elvitegravir/cobicistat/emtricitabine/tenofovir AF (Rx)

HIV Infection

Indicated for ART-naïve or to replace current ART regimen in patients virologically suppressed (HIV-1 RNA <50 copies/mL) on stable ART regimen for ≥6 months with no history of treatment failure and no known substitutions associated with resistance to individual components

1 tablet PO qDay with food

Dosage Modifications

Renal impairment

• Mild-to-moderate (eCrCl ≥30 mL/min): No dosage adjustment required
• Severe (eCrCl 15-30 mL/min) or ESRD (eCrCl <15 mL/min) who are not receiving dialysis: Not recommended; safety has not been established
• Patients (eCrCl <15 mL/min) who are receiving chronic dialysis: On days of dialysis, administer dose after hemodialysis is complete

Hepatic impairment

• Mild-to-moderate (Child Pugh A or B): No dosage adjustment required
• Severe (Child Pugh C): Not recommended; not studied

Dosing Considerations

Testing prior and during treatment

• Prior to initiation, test patients for hepatitis B infection
• Assess serum creatinine, serum phosphorous, estimated CrCl, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate
• Assess serum phosphorus in patients with chronic kidney disease

HIV Infection

Indicated for ART-naïve

Indicated to replace current ART regimen

• In patients virologically suppressed (HIV-1 RNA <50 copies/mL)
• Patients on stable ART regimen for ≥6 months with no history of treatment failure
• No known substitutions associated with resistance to individual components

Dosage

• Weight <25 kg: Safety and efficacy not established
• Weight ≥25 kg: 1 tablet PO qDay with food

Dosage Modifications

Renal impairment

• Mild-to-moderate (eCrCl ≥30 mL/min): No dosage adjustment required
• Severe or ESRD (eCrCl <30 mL/min): Not recommended; safety has not been established

Hepatic impairment

• Mild-to-moderate (Child-Pugh A or B): No dosage adjustment required
• Severe (Child Pugh C): Not recommended; not studied

Dosing Considerations

Testing prior and during treatment

• Prior to initiation, test patients for hepatitis B infection
• Assess serum creatinine, serum phosphorous, estimated CrCl, urine glucose, and urine protein before initiating and during therapy in all patients as clinically appropriate
• Assess serum phosphorus in patients with chronic kidney disease

Contraindicated (15)

• alfuzosin

  cobicistat will increase the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for increased alfuzosin concentrations, which can result in serious or life threatening reactions such as hypotension

• alprazolam

  cobicistat will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• astemizole

  cobicistat will increase the level or effect of astemizole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• cobicistat

  cobicistat, elvitegravir. Other (see comment). Contraindicated. Comment: Coadministration with cobicistat (a strong CYP3A4 and BCRP inhibitor) increases duvelisib (a CYP3A4 and BCRP substrate) levels, which may increase the risk of duvelisib toxicities. Reduce duvelisib dose to 15 mg BID when coadministered with cobicistat.

• cobimetinib

  cobicistat will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• conivaptan

  cobicistat will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  conivaptan will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• dihydroergotamine

  cobicistat will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm, ischemia of the extremities and other tissues)

• dronedarone

  cobicistat will increase the level or effect of dronedarone by Other (see comment). Contraindicated. Dronedarone is a CYP3A4 inhibitor/substrate and a CYP2D6 inhibitor; cobicistat is both an inhibitor and substrate of CYP3A4 and CYP2D6
  
  cobicistat will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• eletriptan

  cobicistat will increase the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• eliglustat

  cobicistat will increase the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindicated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.
  
  cobicistat increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. Strong CYP3A4 inhibitors are contraindicated with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers; eliglustat is contraindicated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

• elvitegravir

  cobicistat, elvitegravir. Other (see comment). Contraindicated. Comment: Coadministration with cobicistat (a strong CYP3A4 and BCRP inhibitor) increases duvelisib (a CYP3A4 and BCRP substrate) levels, which may increase the risk of duvelisib toxicities. Reduce duvelisib dose to 15 mg BID when coadministered with cobicistat.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by pharmacodynamic synergism. Contraindicated. Duplicate therapy
  
  emtricitabine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.
  
  cobicistat will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by pharmacodynamic synergism. Contraindicated. Duplicate therapy

• eplerenone

  cobicistat will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• fezolinetant

  tenofovir AF will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• lamivudine

  emtricitabine and lamivudine both increase risk of immune reconstitution syndrome. Contraindicated. Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.
  
  emtricitabine, lamivudine. Other (see comment). Contraindicated. Comment: Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.

Serious - Use Alternative (161)

• abametapir

  abametapir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
  
  abametapir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Administer at approximately the same time each day after a meal .

• acalabrutinib

  cobicistat will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.

• adagrasib

  elvitegravir will increase the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a CYP3A4 substrate, with strong CYP3A4 inhibitors until adagrasib concentrations have reached steady-state (after ~8 days). If steady state is not reached, concomitant use of strong CYP3A4 inhibitors will increase adagrasib concentrations and risk of its toxicities

• adagrasib

  cobicistat will increase the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a CYP3A4 substrate, with strong CYP3A4 inhibitors until adagrasib concentrations have reached steady-state (after ~8 days). If steady state is not reached, concomitant use of strong CYP3A4 inhibitors will increase adagrasib concentrations and risk of its toxicities

• ado-trastuzumab emtansine

  cobicistat will increase the level or effect of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• alpelisib

  cobicistat will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.
  
  cobicistat will increase the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• apalutamide

  apalutamide will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
  
  apalutamide will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  cobicistat will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• betibeglogene autotemcel

  elvitegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
  
  emtricitabine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.

• armodafinil

  cobicistat will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May increase armotafinil concentration and decrease cobicistat as armodafinil is CYP3A4 inducer and cobicistat is CYP3A4 substrate

• atazanavir

  cobicistat will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  atazanavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• avanafil

  cobicistat will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended; safe/effective dose for avanafil has not been established; coadministration may increase PDE-5 inhibitor adverse effects including hypotension, syncope, visual changes, and prolonged erection

• avapritinib

  cobicistat will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

• axitinib

  cobicistat will increase the level or effect of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• azithromycin

  cobicistat, azithromycin. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• bedaquiline

  cobicistat will increase the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• bosentan

  bosentan will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Bosentan dose reduction required

• bosutinib

  cobicistat will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• cabotegravir

  emtricitabine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
  
  elvitegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

• brigatinib

  cobicistat will increase the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A inhibitor cannot be avoided, reduce the brigatinib once daily dose by about 50% (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). After discontinuation of a strong CYP3A inhibitor, resume the brigatinib dose that was tolerated prior to initiating the strong CYP3A inhibitor.

• carbamazepine

  carbamazepine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• cabozantinib

  cobicistat will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.

• carbamazepine

  carbamazepine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• ceritinib

  cobicistat, ceritinib. Either increases toxicity of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May increase QT prolongation.

• chloramphenicol

  chloramphenicol will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clarithromycin

  cobicistat, clarithromycin. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .
  
  clarithromycin will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• copanlisib

  elvitegravir will increase the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use with strong CYP3A inhibitors cannot be avoided, reduce copanlisib dose to 45 mg.
  
  cobicistat will increase the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use with strong CYP3A inhibitors cannot be avoided, reduce copanlisib dose to 45 mg.

• crizotinib

  cobicistat will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increase in crizotinib levels may result in QT prolongation; May reduce crizotinib dose to 250 mg PO qDay if concomitant administration cannot be avoided.

• dabrafenib

  dabrafenib will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• dabrafenib

  cobicistat will increase the level or effect of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  dabrafenib will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• daridorexant

  cobicistat will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darunavir

  cobicistat will increase the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  darunavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dexamethasone

  cobicistat will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with corticosteroids that are metabolized by CYP3A, particularly for long-term use, may increase the risk for development of systemic corticosteroid effects including Cushing syndrome and adrenal suppression
  
  dexamethasone will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with corticosteroids that induce CYP3A4 may result in loss of therapeutic effect and development of resistance to atazanavir or darunavir
  
  dexamethasone will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• dihydroergotamine intranasal

  cobicistat will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• efavirenz

  efavirenz will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• doxorubicin

  cobicistat will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• doxorubicin liposomal

  cobicistat will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• edoxaban

  cobicistat will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended

• efavirenz

  efavirenz will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with efavirenz may result in loss of therapeutic effect and development of resistance to cobicistat.

• elacestrant

  cobicistat will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elbasvir/grazoprevir

  cobicistat will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of elbasvir/grazoprevir with certain strong CYP3A4 inhibitors

• elivaldogene autotemcel

  elivaldogene autotemcel, elvitegravir. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.
  
  elivaldogene autotemcel, emtricitabine. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.

• encorafenib

  cobicistat will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

• entrectinib

  cobicistat will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

• enzalutamide

  cobicistat will increase the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  enzalutamide will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• erdafitinib

  cobicistat will increase the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP3A4 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP3A4 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• erythromycin base

  cobicistat, erythromycin base. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• erythromycin ethylsuccinate

  cobicistat, erythromycin ethylsuccinate. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• erythromycin lactobionate

  cobicistat, erythromycin lactobionate. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• erythromycin stearate

  cobicistat, erythromycin stearate. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative anticonvulsant or antiretroviral therapy to avoid potential changes in exposures. If coadministration is necessary, monitor for lack or loss of virologic response.

• eszopiclone

  cobicistat will increase the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ethinylestradiol

  elvitegravir will decrease the level or effect of ethinylestradiol by unknown mechanism. Avoid or Use Alternate Drug. Consider alternative nonhormonal methods of contraception to add or replace combination oral contraceptive

• etravirine

  cobicistat will increase the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  etravirine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with etravirine may result in loss of therapeutic effect and development of resistance to cobicistat.
  
  etravirine will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• everolimus

  cobicistat will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fexinidazole

  fexinidazole will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fedratinib

  cobicistat will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

• felbamate

  cobicistat will increase the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fentanyl transdermal

  cobicistat will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl transmucosal

  cobicistat will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fexinidazole

  cobicistat will decrease the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration, monitor fexinidazole for decreased efficacy owing to decreased plasma concentrations of active M1 and M2 metabolites.
  
  fexinidazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fidaxomicin

  cobicistat, fidaxomicin. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• flutamide

  cobicistat will increase the level or effect of flutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fosaprepitant

  cobicistat will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fosphenytoin

  fosphenytoin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  fosphenytoin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• futibatinib

  cobicistat will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

• infigratinib

  elvitegravir will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• gilteritinib

  cobicistat will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.

• glasdegib

  cobicistat will increase the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternate therapies that are not strong CYP3A inhibitors or monitor for increased risk of adverse effects, including QTc interval prolongation.

• guanfacine

  cobicistat will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ibrutinib

  cobicistat will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• idelalisib

  cobicistat will increase the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  idelalisib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• indinavir

  indinavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• infigratinib

  cobicistat will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• itraconazole

  itraconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ivosidenib

  cobicistat will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with ivosidenib or replace with alternate therapies. If coadministration of a strong CYP3A4 inhibitor is unavoidable, reduce ivosidenib dose to 250 mg qDay. If the strong inhibitor is discontinued, increase ivosidenib dose (after at least 5 half-lives of the strong CYP3A4 inhibitor) to the recommended dose of 500 mg qDay. Monitor for increased risk of QTc interval prolongation.
  
  ivosidenib will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ixabepilone

  cobicistat will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ketoconazole

  ketoconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lapatinib

  cobicistat will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant administration cannot be avoided, administer 500 mg lapatinib once daily and increase lapatinib dose to indicated dose once cobicistat discontinued

• larotrectinib

  cobicistat will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lefamulin

  cobicistat will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong CYP3A inhibitors.

• lemborexant

  cobicistat will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

• leniolisib

  leniolisib will increase the level or effect of tenofovir AF by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates
  
  cobicistat will increase the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• letermovir

  tenofovir AF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

• levoketoconazole

  levoketoconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levomilnacipran

  cobicistat will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not esceed 80 mg levominacipram dose once daily if coadministration necessary

• levonorgestrel intrauterine

  cobicistat will increase the level or effect of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lomitapide

  cobicistat will increase the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• lorlatinib

  cobicistat will increase the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering lorlatinib with strong CYP3A inhibitors. If unavoidable, reduce lorlatinib dose by 25 mg/day. If strong CYP3A inhibitor discontinued, increase to previous lorlatinib (dose after 3 plasma half-lives of strong CYP3A inhibitor). See monograph for further details.
  
  lorlatinib will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lurbinectedin

  cobicistat will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mefloquine

  cobicistat will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity. Avoid coadministration during and for 15 weeks after discontinuing mefloquine.

• midazolam intranasal

  cobicistat will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

• midostaurin

  cobicistat will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.

• mifepristone

  mifepristone will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mitotane

  mitotane will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  mitotane will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mobocertinib

  cobicistat will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nafcillin

  nafcillin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• modafinil

  cobicistat will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nafcillin

  nafcillin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• neratinib

  cobicistat will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

• nevirapine

  cobicistat will increase the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  nevirapine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  nevirapine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with etravirine may result in loss of therapeutic effect and development of resistance to cobicistat. Contraindicated with cobicistat coadministered with atazanavir.only; nevirapine substantially decreases atazanavir exposure which may result in loss of therapeutic effect and development of resistance

• nicardipine

  cobicistat will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• nimodipine

  cobicistat will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nisoldipine

  cobicistat will increase the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• olaparib

  cobicistat will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A inhibitors cannot be avoided, reduce olaparib dose to 150 mg (capsule) or 100 mg (tablet) PO BID. Do not substitute tablets with capsules.

• omaveloxolone

  cobicistat will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 50 mg/day. Closely monitor and discontinue if adverse effects emerge.

• ombitasvir/paritaprevir/ritonavir

  cobicistat will increase the level or effect of ombitasvir/paritaprevir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  cobicistat will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• osimertinib

  cobicistat will increase the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of osimertinib with strong CYP3A4 inhibitors. If no other alternative treatment exists, monitor patient more closely for adverse effects.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative anticonvulsant or antiretroviral therapy to avoid potential changes in exposures. If coadministration is necessary, monitor for lack or loss of virologic response.

• ozanimod

  cobicistat increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .

• palbociclib

  cobicistat will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of palbociclib with strong CYP3A inhibitors. If unable to avoid, reduce palbociclib dose to 75 mg/day.

• pazopanib

  cobicistat will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pemigatinib

  cobicistat will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

• pentobarbital

  pentobarbital will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• perampanel

  cobicistat will increase the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pexidartinib

  cobicistat will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

• phenobarbital

  phenobarbital will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  phenobarbital will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• phenytoin

  phenytoin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  phenytoin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• pimavanserin

  cobicistat will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.

• primidone

  primidone will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• ponatinib

  cobicistat will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• posaconazole

  posaconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pralsetinib

  cobicistat will increase the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• primidone

  primidone will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• progesterone intravaginal gel

  cobicistat will increase the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• progesterone micronized

  cobicistat will increase the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• progesterone, natural

  cobicistat will increase the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• quetiapine

  cobicistat increases levels of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with atazanavir and cobicistat in patients taking quetiapine. If coadministration is necessary, reduce quetiapine dose to one-sixth of the current dose and monitor for quetiapine-associated adverse reactions. Refer to quetiapine prescribing information for initial dosing and titration of quetiapine.

• ribociclib

  cobicistat will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.
  
  ribociclib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifabutin

  rifabutin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  rifampin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• rifapentine

  rifapentine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  rifapentine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• St John's Wort

  St John's Wort will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• rimegepant

  cobicistat will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.

• riociguat

  cobicistat will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ritonavir

  ritonavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rivaroxaban

  cobicistat will increase the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cobicistat with rivaroxaban; may result in increased exposure of rivaroxaban and increased risk of bleeding

• ruxolitinib

  cobicistat will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ruxolitinib topical

  cobicistat will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• salmeterol

  cobicistat increases levels of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration not recommended; may result in increased cardiovascular effects associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.

• saquinavir

  cobicistat will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  saquinavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• saxagliptin

  cobicistat will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selumetinib

  cobicistat will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

• siponimod

  cobicistat will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

• solifenacin

  cobicistat will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sonidegib

  cobicistat will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong CYP3A4 inhibitors.

• sotorasib

  sotorasib will decrease the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

• sparsentan

  cobicistat will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration.

• sunitinib

  cobicistat will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• suvorexant

  cobicistat will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tadalafil

  cobicistat will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Adjust tadalafil dose for PAH; if on cobicistat, start tadalafil 20 mg/day and may increase up to 40 mg/day; avoid tadalafil when starting cobicistat; for ED, may take a single dose of tadalafil not exceeding 10 mg in 72 hr.

• talazoparib

  cobicistat will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.

• tamoxifen

  cobicistat decreases effects of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Affecting hepatic/intestinal enzyme CYP3A4 metabolism. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

• tamsulosin

  cobicistat will increase the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tazemetostat

  cobicistat will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with strong CYP3A4 inhibitors.

• teniposide

  cobicistat will increase the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tepotinib

  tepotinib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

• ticagrelor

  cobicistat will increase the level or effect of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

Monitor Closely (279)

• abacavir

  abacavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• abemaciclib

  cobicistat will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a patient taking abemaciclib discontinues a strong CYP3A inhibitor, increase abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.

• acalabrutinib

  acalabrutinib increases levels of tenofovir AF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.

• acyclovir

  acyclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• adefovir

  adefovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• alfentanil

  cobicistat will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• aluminum hydroxide

  aluminum hydroxide will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• amiodarone

  cobicistat will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• amitriptyline

  cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• amlodipine

  cobicistat will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amoxapine

  cobicistat will increase the level or effect of amoxapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of amoxapine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• apalutamide

  cobicistat will increase the level or effect of apalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of apalutamide with strong CYP3A4 or CYP2C8 inhibitors does not require initial dosage modification; however, dose reduction may be needed based on tolerability.
  
  apalutamide will decrease the level or effect of tenofovir AF by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.

• apixaban

  cobicistat will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• berotralstat

  berotralstat will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

• aripiprazole

  cobicistat will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce aripiprazole dose by 25% and by approximately 50% if administered with CYP3A4 inhibitor and CYP206 inhibitor

• artemether

  cobicistat, artemether. unknown mechanism. Use Caution/Monitor. Monitor for potential decrease of antimalarial efficacy or potential QT prolongation.

• artemether/lumefantrine

  cobicistat will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• atazanavir

  atazanavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Atazanavir significantly increases elvitegravir levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 85 mg PO once daily with atazanavir/ritonavir other than 300/100 mg once daily.
  
  atazanavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• atogepant

  cobicistat will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage is 10 mg PO qDay when coadministered with strong CYP3A4 inhibitors.

• atorvastatin

  cobicistat will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, dose should not exceed 20 mg/day.

• avatrombopag

  cobicistat will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose. Refer to drug monograph for specific recommendations.

• belzutifan

  belzutifan will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
  
  belzutifan will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• benzhydrocodone/acetaminophen

  cobicistat will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors may increase hydrocodone (benzhydrocodone is prodrug of hydrocodone) plasma concentrations and can result in potentially fatal respiratory depression

• bosentan

  elvitegravir, bosentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elvitegravir increases bosentan levels, and bosentan decreases elvitegravir levels; if elvitegravir received for >10 days, start bosentan at 62.5 mg/day or every other day; if patient taking bosentan and starting elvitegravir, discontinue bosentan at least 36 hr beforehand, may resume bosentan at 62.5 mg/day or every other day after 10 days.

• cabozantinib

  tenofovir AF will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicity

• calcium carbonate

  calcium carbonate will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• celecoxib

  emtricitabine, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• berotralstat

  cobicistat increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

• betrixaban

  cobicistat increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

• bortezomib

  cobicistat will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bosentan

  bosentan will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Bosentan dose reduction required. Refer to the prescribing information of bosentan and cobicistat for recommended dosage adjustments.

• brentuximab vedotin

  cobicistat will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexpiprazole

  cobicistat will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  cobicistat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• bromocriptine

  cobicistat will increase the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• budesonide

  cobicistat will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• budesonide inhaled

  cobicistat increases levels of budesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine

  cobicistat will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• buprenorphine subdermal implant

  cobicistat will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• buprenorphine transdermal

  cobicistat will increase the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• buprenorphine, long-acting injection

  cobicistat will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

• buspirone

  cobicistat will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of buspirone may be required

• calcifediol

  cobicistat, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

• cannabidiol

  cobicistat will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

• capmatinib

  cobicistat will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbamazepine

  cobicistat will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cariprazine

  cobicistat will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

• carvedilol

  cobicistat will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• cenobamate

  cenobamate will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
  
  cenobamate will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• chlordiazepoxide

  cobicistat will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cidofovir

  cidofovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• ciclesonide inhaled

  cobicistat will increase the level or effect of ciclesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cilostazol

  cobicistat will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce cilostazol dose to 50 mg twice daily when administered concomitantly; monitor for increase in cilostazole related adverse effects.

• citalopram

  cobicistat will increase the level or effect of citalopram by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.
  
  cobicistat will increase the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clarithromycin

  clarithromycin increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• clomipramine

  cobicistat will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of clomipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• clonazepam

  cobicistat will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with anticonvulsants.

• clorazepate

  cobicistat will increase the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dose of clorazepate if necessary

• colchicine

  cobicistat will increase the level or effect of colchicine by Other (see comment). Modify Therapy/Monitor Closely. Coadministration with colchicine is contraindicated in patients with renal and/or hepatic impairment due to potential for serious and/or life-threatening reactions. Dosage adjustment of colchicine may be necessary upon coadministration with cobicistat. Refer colchicine prescribing information for dosing instructions.

• conivaptan

  conivaptan increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• cyclosporine

  cobicistat will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dabigatran

  cobicistat will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min

• dapsone

  cobicistat will increase the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darifenacin

  cobicistat will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Darifenacin daily dose should not exceed 7.5 mg PO when administered concomitantly.

• darolutamide

  cobicistat will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
  
  darolutamide will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).

• darunavir

  darunavir, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; unknown if darunavir will elevate levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 150 mg PO once daily with darunavir/ritonavir 600/100 mg PO BID.

• duvelisib

  tenofovir AF will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• dasatinib

  cobicistat will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dosage adjustment of dasatinib may be necessary upon coadministration with cobicistat coadministered with atazanavir or darunavir. Refer dasatinib prescribing information for dosing instructions.

• deflazacort

  cobicistat will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

• delavirdine

  cobicistat will increase the level or effect of delavirdine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• desipramine

  cobicistat will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of desipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• dexlansoprazole

  cobicistat will increase the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diazepam

  cobicistat will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of diazepam may be required

• diazepam intranasal

  cobicistat will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• diclofenac

  emtricitabine, diclofenac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• didanosine

  didanosine, elvitegravir. Other (see comment). Use Caution/Monitor. Comment: Didanosine must be administered on an empty stomach; administer didanosine at least 1 hr before or 2 hr after elvitegravir (which is administered with food).

• diflunisal

  emtricitabine, diflunisal. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• digoxin

  cobicistat will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Measure serum digoxin concentrations before initiating concomitant drugs. Titrate the digoxin dose by ~30-50% or by modifying the dosing frequency and continue monitoring.

• diltiazem

  cobicistat will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• disopyramide

  cobicistat will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• docetaxel

  cobicistat will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. May consider reducing docetaxel dosing 50% if concomitant administration cannot be avoided

• doravirine

  cobicistat will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

• doxepin

  cobicistat will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of doxepin by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• doxepin cream

  cobicistat will increase the level or effect of doxepin cream by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• dronabinol

  cobicistat will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• efavirenz

  efavirenz and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
  
  cobicistat will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• elagolix

  elagolix will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
  
  elagolix will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  cobicistat will increase the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of elagolix 200 mg BID with strong CYP3A inhibitors for >1 month is not recommended. Limit elagolix dose to 150 mg qDay and CYP3A inhibitor duration of use to 6 months if coadministered.
  
  elagolix, cobicistat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Combination of elagolix (weak-to-moderate CYP3A4 inducer) with cobicistat (a CYP3A4 inhibitor and substrate) may increase elagolix levels and may decrease cobicistat levels. Refer to the prescribing information of elagolix and cobicistat for recommended dosage adjustments.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  cobicistat will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Cobicistat inhibits P-gp

• encorafenib

  encorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

• encorafenib

  encorafenib, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• encorafenib

  encorafenib, cobicistat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enfortumab vedotin

  cobicistat increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.
  
  cobicistat will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs of toxicities.

• enfuvirtide

  emtricitabine and enfuvirtide both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• enzalutamide

  enzalutamide will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• erdafitinib

  elvitegravir will decrease the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. If a moderate CYP2C9 inducer must be coadministered, administer 8-mg/day dose initially, with potential to increase to 9 mg/day based on serum phosphate levels on Days 14-21 and tolerability. If a moderate CYP2C9 inducer must be coadministered after the initial dose increase period based on serum phosphate levels and tolerability, increase erdafitinib dose up to 9 mg. When a moderate inducer discontinued, continue erdafitinib at same dose, in absence of drug-related toxicity.

• erlotinib

  cobicistat will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avaoided, reduce erlotinib dose by 50 mg decrements and monitor for adverse effects

• escitalopram

  cobicistat will increase the level or effect of escitalopram by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.
  
  cobicistat will increase the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• esomeprazole

  cobicistat will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol vaginal

  cobicistat will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.

• ethosuximide

  cobicistat will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etodolac

  emtricitabine, etodolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• fedratinib

  fedratinib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felodipine

  cobicistat will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fenoprofen

  emtricitabine, fenoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• fentanyl

  cobicistat will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl intranasal

  cobicistat will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• flecainide

  cobicistat will increase the level or effect of flecainide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• fluoxetine

  cobicistat will increase the level or effect of fluoxetine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.

• flurazepam

  cobicistat will increase the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• flurbiprofen

  emtricitabine, flurbiprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• fluticasone furoate

  cobicistat increases levels of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluticasone inhaled

  cobicistat increases levels of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluvastatin

  cobicistat will increase the level or effect of fluvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, start with the lowest recommended dose and titrate while monitoring for safety.

• fluvoxamine

  fluvoxamine will increase the level or effect of cobicistat by Other (see comment). Use Caution/Monitor. Carfully titrate dose of antidepressant to desired effect, including using lowest feasible initial or maintenance dose , and monitor its response during coadministration with SSRIs and cobicistat

• fosamprenavir

  fosamprenavir, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; unknown if fosamprenavir will elevate levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 150 mg PO once daily with fosamprenavir/ritonavir 700/100 mg PO BID.
  
  fosamprenavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• fostamatinib

  fostamatinib will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.
  
  cobicistat will increase the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors may increase exposure to R406 (fostamatinib major active metabolite). Monitor for toxicities that may require fostamatinib dose reduction.

• ganciclovir

  ganciclovir, emtricitabine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.
  
  ganciclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• glecaprevir/pibrentasvir

  glecaprevir/pibrentasvir will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

• gefitinib

  cobicistat increases levels of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of strong CYP3A4 inhibitors may increase risk for gefitinib adverse effects.

• glecaprevir/pibrentasvir

  cobicistat will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• grapefruit

  grapefruit increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• haloperidol

  cobicistat will increase the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydrocodone

  cobicistat will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

• ibuprofen

  emtricitabine, ibuprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• ibuprofen IV

  emtricitabine, ibuprofen IV. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• idelalisib

  idelalisib increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• ifosfamide

  cobicistat will decrease the level or effect of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inhibitors may decrease the metabolism of ifosfamide to its active alkylating metabolites and decrease the efficacy of ifosfamide.
  
  ifosfamide, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Monitor electrolytes and renal function.

• imatinib

  imatinib increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  cobicistat will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• imipramine

  cobicistat will increase the level or effect of imipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• indinavir

  indinavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
  
  indinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• indomethacin

  emtricitabine, indomethacin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• isoniazid

  isoniazid will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  isoniazid increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• isradipine

  cobicistat will increase the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• istradefylline

  cobicistat will increase the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed istradefylline 20 mg/day if coadministered with strong CYP3A4 inhibitors.
  
  istradefylline will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  cobicistat, itraconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for itraconazole are not available when coadministered with cobicistat.
  
  itraconazole increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When coadministered with elvitegravir, limit dose of itraconazole should not exceed 200 mg/day.

• ivacaftor

  cobicistat will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

• ketoconazole

  ketoconazole, elvitegravir. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministered, do not exceed ketoconazole 200 mg/day; no dose adjustment needed for elvitegravir.

• ketoconazole

  cobicistat, ketoconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for ketoconazole are not available when coadministered with cobicistat.

• ketoprofen

  emtricitabine, ketoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• ketorolac

  emtricitabine, ketorolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• lansoprazole

  cobicistat will increase the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lenacapavir

  lenacapavir will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
  
  lenacapavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

  cobicistat increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

• levoketoconazole

  levoketoconazole, elvitegravir. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministered, do not exceed ketoconazole 200 mg/day; no dose adjustment needed for elvitegravir.

• levamlodipine

  cobicistat will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

• levoketoconazole

  cobicistat, levoketoconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for ketoconazole are not available when coadministered with cobicistat.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  cobicistat will increase the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase the plasma hormone concentrations. Use of a nonhormonal contraceptive is recommended.

• lidocaine

  cobicistat will increase the level or effect of lidocaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• lonafarnib

  lonafarnib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

• lopinavir

  lopinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lopinavir/ritonavir significantly increases elvitegravir levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 85 mg PO once daily with lopinavir/ritonavir other than 400/100 mg BID.

• lorlatinib

  lorlatinib will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• losartan

  cobicistat will increase the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lumacaftor/ivacaftor

  cobicistat increases levels of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A inhibitors do not impact lumacaftor exposure, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg q12hr (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking lumacaftor/ivacaftor. However, when initiating lumacaftor/ivacaftor in patients taking strong CYP3A inhibitors, reduce the dose to 1 tablet daily (lumacaftor 200 mg/ivacaftor 125 mg total daily dose) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. No dose adjustment is required for moderate or weak CYP3A4 inhibitors.

• lumateperone

  cobicistat will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.

• lumefantrine

  cobicistat, lumefantrine. unknown mechanism. Use Caution/Monitor. Monitor for potential decrease of antimalarial efficacy or potential QT prolongation.
  
  cobicistat will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• magnesium oxide

  magnesium oxide will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• maraviroc

  cobicistat will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Maraviroc is a CYP3A4 substrate. Decrease maraviroc dose to 150 mg BID when coadministered with strong CYP3A4 inhibitors

• meclofenamate

  emtricitabine, meclofenamate. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• mefenamic acid

  emtricitabine, mefenamic acid. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• meloxicam

  emtricitabine, meloxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• methadone

  cobicistat will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Methadone dose may require an adjustment
  
  elvitegravir decreases levels of methadone by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dosage of methadone may need to be increased.

• methylprednisolone

  cobicistat will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nabumetone

  emtricitabine, nabumetone. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• metoprolol

  cobicistat will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mexiletine

  cobicistat will increase the level or effect of mexiletine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• mifepristone

  cobicistat will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, administer 300 mg mifepristone initially; not to exceed 600 mg; if cobicistat initiated in patient receiving 600 mg mifepristone, reduce mirepristone dose to 300 mg; if cobicistat initiated in patient receiving 900-1200 mg mifepristone, reduce mifepristone dose to 600 mg; if initiated in patient receiving 300 mg mifepristone, no change in dose necessary

• mirtazapine

  cobicistat will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mirvetuximab soravtansine

  cobicistat will increase the level or effect of mirvetuximab soravtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with strong CYP3A4 inhibitors may increase unconjugated DM4 (a CYP3A4 substrate and the cytotoxic component of the antibody drug conjugate for mirvetuximab soravtansine) exposure, which may increase the risk of adverse reactions.

• mometasone inhaled

  cobicistat will increase the level or effect of mometasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increases risk for systemic corticosteroid side effects

• mometasone, intranasal

  cobicistat will increase the level or effect of mometasone, intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• naldemedine

  cobicistat increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.
  
  cobicistat increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

• naproxen

  emtricitabine, naproxen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• nefazodone

  cobicistat will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  nefazodone increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  nefazodone will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  nelfinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  nelfinavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• netupitant/palonosetron

  cobicistat will increase the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Netupitant is mainly metabolized by CYP3A4; no dosage adjustment is required

• nevirapine

  emtricitabine and nevirapine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• nicardipine

  nicardipine increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• nifedipine

  cobicistat will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nilotinib

  cobicistat will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dosage adjustment of nilotinib may be necessary upon coadministration with cobicistat coadministered with atazanavir or darunavir. Refer nilotinib prescribing information for dosing instructions.

• nintedanib

  cobicistat increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy.

• nirmatrelvir

  nirmatrelvir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures.

• nirmatrelvir/ritonavir

  nirmatrelvir/ritonavir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures.

• nortriptyline

  cobicistat will increase the level or effect of nortriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• oliceridine

  cobicistat will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
  
  cobicistat will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• omeprazole

  cobicistat will increase the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ondansetron

  cobicistat will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• orlistat

  orlistat will decrease the level or effect of elvitegravir by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
  
  orlistat will decrease the level or effect of tenofovir AF by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
  
  orlistat will decrease the level or effect of emtricitabine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.

• osilodrostat

  cobicistat will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

• oteseconazole

  oteseconazole will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.

• ospemifene

  cobicistat will increase the level or effect of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oxaprozin

  emtricitabine, oxaprozin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• oxycodone

  cobicistat will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• paclitaxel

  cobicistat will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paclitaxel protein bound

  cobicistat will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• panobinostat

  cobicistat increases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce panobinostat starting dose to 10 mg if coadministered with strong CYP3A4 inhibitors.

• paricalcitol

  cobicistat will increase the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paroxetine

  cobicistat will increase the level or effect of paroxetine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.

• perphenazine

  cobicistat will increase the level or effect of perphenazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.

• pitavastatin

  cobicistat will increase the level or effect of pitavastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, start with the lowest recommended dose and titrate while monitoring for safety.

• polatuzumab vedotin

  cobicistat will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

• posaconazole

  posaconazole increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• piroxicam

  emtricitabine, piroxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• pravastatin

  cobicistat will increase the level or effect of pravastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, start with the lowest recommended dose and titrate while monitoring for safety.

• praziquantel

  cobicistat will increase the level or effect of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• propafenone

  cobicistat will increase the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• protriptyline

  cobicistat will increase the level or effect of protriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• quazepam

  cobicistat will increase the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinidine

  quinidine increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  cobicistat will increase the level or effect of quinidine by Other (see comment). Modify Therapy/Monitor Closely. Quinidine is a substrate of CYP3A4 and P-gp, and inhibits CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both isoenzymes and a P-gp inhibitor
  
  cobicistat will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinine

  cobicistat will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• regorafenib

  regorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.

• ribavirin

  ribavirin increases toxicity of emtricitabine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of lactic acidosis.

• rabeprazole

  cobicistat will increase the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• repaglinide

  cobicistat will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifabutin

  rifabutin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose for rifabutin to 150 mg PO every other day when coadministered with cobicistat. Monitor rifabutin associated adverse reactions.
  
  cobicistat will increase the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease rifabutin dose to 150 mg PO every other day; monitor for rifabutin associated neutropenia and uveitis
  
  elvitegravir, rifabutin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elvitegravir increases rifabutin levels, and rifabutin decreases elvitegravir levels; when rifabutin, a potent CYP3A inducer is used with elvitegravir (with a protease inhibitor and ritonavir), reduce dose of rifabutin by at least 75%; no dose adjustment of elvitegravir is required.

• ripretinib

  cobicistat will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.

• ritonavir

  ritonavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
  
  ritonavir will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risperidone

  cobicistat will increase the level or effect of risperidone by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.

• roflumilast

  cobicistat will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• romidepsin

  cobicistat will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rosuvastatin

  cobicistat will increase the level or effect of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, dose should not exceed 20 mg/day.

• rucaparib

  rucaparib will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
  
  rucaparib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• safinamide

  safinamide will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

• saquinavir

  saquinavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• sarecycline

  sarecycline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• selexipag

  cobicistat will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.

• saquinavir

  saquinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• selpercatinib

  cobicistat will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, reduce dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily and to 80 mg PO twice daily if original dose was 160 mg twice daily; monitor for side effects

• sertraline

  cobicistat will increase the level or effect of sertraline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.

• sirolimus

  cobicistat will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• stavudine

  emtricitabine and stavudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• stiripentol

  stiripentol, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol, cobicistat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.

• sufentanil

  cobicistat will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tafamidis

  tafamidis will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

• sulindac

  emtricitabine, sulindac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• sufentanil SL

  cobicistat will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

• tacrolimus

  cobicistat will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• tafamidis meglumine

  tafamidis meglumine will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

• tazemetostat

  tazemetostat will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  tazemetostat will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  tecovirimat will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
  
  tecovirimat will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• temsirolimus

  cobicistat will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, consider reducing temsirolimus dose to 12.5 mg per week; after discontinuing cobicistat, allow one week washout period before increaing cobicistat dose to its original level

• tenofovir DF

  emtricitabine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• terbinafine

  cobicistat will increase the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tezacaftor

  cobicistat will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

• theophylline

  cobicistat will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• thioridazine

  cobicistat will increase the level or effect of thioridazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.

• tiagabine

  cobicistat will increase the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• timolol

  cobicistat will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tinidazole

  cobicistat will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  tipranavir, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; unknown if tipranavir will elevate levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 150 mg PO once daily with tipranavir/ritonavir 500/200 mg PO BID.
  
  tipranavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• tisotumab vedotin

  cobicistat increases levels of tisotumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tisotumab vedotin?s active metabolite (MMAE) is a CYP3A4 substrate. Coadministration with strong CYP3A4 inhibitors may increase unconjugated MMAE systemic exposure and increase risk of adverse effects.

• tolmetin

  emtricitabine, tolmetin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• tramadol

  cobicistat will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required
  
  cobicistat will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required

• trazodone

  cobicistat will increase the level or effect of trazodone by Other (see comment). Use Caution/Monitor. Trazodone is a substrate of CYP3A4 and CYP2D6; cobicistat inhibits CYP3A4 and CYP2D6

• triamcinolone acetonide injectable suspension

  cobicistat will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• trimipramine

  cobicistat will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of trimipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.
  
  cobicistat will increase the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tucatinib

  tucatinib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

• ublituximab

  ublituximab decreases effects of elvitegravir by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.

• ublituximab

  ublituximab decreases effects of emtricitabine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.

• ulipristal

  cobicistat will increase the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• umeclidinium bromide/vilanterol inhaled

  cobicistat will increase the level or effect of umeclidinium bromide/vilanterol inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• upadacitinib

  cobicistat will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.

• valacyclovir

  valacyclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• valbenazine

  cobicistat will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Reduce valbenazine dose to 40 mg once daily when coadministered with a strong CYP3A4 inhibitor.

• valganciclovir

  valganciclovir, emtricitabine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.
  
  valganciclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• vardenafil

  cobicistat will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit vardenafil dose to 2.5 mg/72 hr

• velpatasvir

  cobicistat will increase the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• venlafaxine

  cobicistat will increase the level or effect of venlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• verapamil

  cobicistat will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vinblastine

  cobicistat will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for hematologic or GI adverse effects that may be associated with increased systemic exposure to vinblastine. Consider temporarily withholding antiretroviral regimen in patients who develop significant hematologic or gastrointestinal side effects. If the antiretroviral regimen must be withheld for a prolonged period, consider initiating a revised regimen that does not include a CYP3A or P-gp inhibitor.

• vincristine

  cobicistat will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for hematologic or GI adverse effects that may be associated with increased systemic exposure to vincristine. Consider temporarily withholding antiretroviral regimen in patients who develop significant hematologic or gastrointestinal side effects. If the antiretroviral regimen must be withheld for a prolonged period, consider initiating a revised regimen that does not include a CYP3A or P-gp inhibitor.

• vinorelbine

  cobicistat will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• voclosporin

  voclosporin, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.
  
  voclosporin, elvitegravir. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• voriconazole

  voriconazole increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  cobicistat will increase the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of cobicistat with voriconazole is not recommended unless the benefit/risk assessment justifies the use.

• warfarin

  elvitegravir will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.
  
  cobicistat will increase the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inhibitors of these isoenzymes and adjust warfarin dose if needed.

• zanubrutinib

  cobicistat will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous zanubrutinib dose.

• zidovudine

  emtricitabine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• zinc

  zinc will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer elvitegravir 2 hr before or 6 hr after administration of polyvalent cation containing products.

Minor (9)

• acetazolamide

  acetazolamide will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  acetazolamide will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anastrozole

  anastrozole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  anastrozole will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• buprenorphine

  elvitegravir increases levels of buprenorphine by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• buprenorphine buccal

  elvitegravir increases levels of buprenorphine buccal by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ganaxolone

  cobicistat, ganaxolone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Changes in ganaxolone exposures when coadministered with strong, moderate, or weak CYP3A4 inhibitors are not expected to be clinically significant.

• ixazomib

  cobicistat, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

• larotrectinib

  larotrectinib will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• abacavir

  Monitor Closely (1)abacavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• abametapir

  Serious - Use Alternative (2)abametapir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
  
  abametapir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Administer at approximately the same time each day after a meal .

• abemaciclib

  Monitor Closely (1)cobicistat will increase the level or effect of abemaciclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors increase plasma levels of abemaciclib and its metabolites. Abemaciclib dose reduction required. If a patient taking abemaciclib discontinues a strong CYP3A inhibitor, increase abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.

• acalabrutinib

  Monitor Closely (1)acalabrutinib increases levels of tenofovir AF by Other (see comment). Use Caution/Monitor. Comment: Acalabrutinib may increase exposure to coadministered BCRP substrates by inhibition of intestinal BCRP.Serious - Use Alternative (1)cobicistat will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of acalabrutinib with strong CYP3A inhibitors. If a strong CYP3A inhibitor must be used short-term (eg, up to 7 days), temporarily interrupt treatment with acalabrutinib.

• acetazolamide

  Minor (2)acetazolamide will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  acetazolamide will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acyclovir

  Monitor Closely (1)acyclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• adagrasib

  Serious - Use Alternative (2)elvitegravir will increase the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a CYP3A4 substrate, with strong CYP3A4 inhibitors until adagrasib concentrations have reached steady-state (after ~8 days). If steady state is not reached, concomitant use of strong CYP3A4 inhibitors will increase adagrasib concentrations and risk of its toxicities
  
  cobicistat will increase the level or effect of adagrasib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a CYP3A4 substrate, with strong CYP3A4 inhibitors until adagrasib concentrations have reached steady-state (after ~8 days). If steady state is not reached, concomitant use of strong CYP3A4 inhibitors will increase adagrasib concentrations and risk of its toxicities

• adefovir

  Monitor Closely (1)adefovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• ado-trastuzumab emtansine

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• alfentanil

  Monitor Closely (1)cobicistat will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• alfuzosin

  Contraindicated (1)cobicistat will increase the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for increased alfuzosin concentrations, which can result in serious or life threatening reactions such as hypotension

• alpelisib

  Serious - Use Alternative (2)cobicistat will increase the level or effect of alpelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.

• alprazolam

  Contraindicated (1)cobicistat will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• aluminum hydroxide

  Monitor Closely (1)aluminum hydroxide will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• amiodarone

  Monitor Closely (1)cobicistat will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• amitriptyline

  Monitor Closely (2)cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• amlodipine

  Monitor Closely (1)cobicistat will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• amoxapine

  Monitor Closely (2)cobicistat will increase the level or effect of amoxapine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of amoxapine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• anastrozole

  Minor (2)anastrozole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  anastrozole will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Monitor Closely (2)cobicistat will increase the level or effect of apalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of apalutamide with strong CYP3A4 or CYP2C8 inhibitors does not require initial dosage modification; however, dose reduction may be needed based on tolerability.
  
  apalutamide will decrease the level or effect of tenofovir AF by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces BCRP and may decrease systemic exposure of drugs that are BCRP substrates.Serious - Use Alternative (2)apalutamide will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
  
  apalutamide will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• apixaban

  Monitor Closely (1)cobicistat will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• aprepitant

  Serious - Use Alternative (1)cobicistat will increase the level or effect of aprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• aripiprazole

  Monitor Closely (1)cobicistat will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce aripiprazole dose by 25% and by approximately 50% if administered with CYP3A4 inhibitor and CYP206 inhibitor

• armodafinil

  Serious - Use Alternative (1)cobicistat will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May increase armotafinil concentration and decrease cobicistat as armodafinil is CYP3A4 inducer and cobicistat is CYP3A4 substrate

• artemether

  Monitor Closely (1)cobicistat, artemether. unknown mechanism. Use Caution/Monitor. Monitor for potential decrease of antimalarial efficacy or potential QT prolongation.

• artemether/lumefantrine

  Monitor Closely (1)cobicistat will decrease the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• aspirin/citric acid/sodium bicarbonate

  Monitor Closely (1)aspirin/citric acid/sodium bicarbonate will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• astemizole

  Contraindicated (1)cobicistat will increase the level or effect of astemizole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• atazanavir

  Monitor Closely (2)atazanavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Atazanavir significantly increases elvitegravir levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 85 mg PO once daily with atazanavir/ritonavir other than 300/100 mg once daily.
  
  atazanavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.Serious - Use Alternative (2)cobicistat will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  atazanavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• atogepant

  Monitor Closely (1)cobicistat will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Recommended atogepant dosage is 10 mg PO qDay when coadministered with strong CYP3A4 inhibitors.

• atorvastatin

  Monitor Closely (1)cobicistat will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, dose should not exceed 20 mg/day.

• avanafil

  Serious - Use Alternative (1)cobicistat will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended; safe/effective dose for avanafil has not been established; coadministration may increase PDE-5 inhibitor adverse effects including hypotension, syncope, visual changes, and prolonged erection

• avapritinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

• avatrombopag

  Monitor Closely (1)cobicistat will increase the level or effect of avatrombopag by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. When treating ITP, coadministration of avatrombopag with a moderate or strong dual CYP2C9/3A4 inhibitor requires a decreased avatrombopag starting dose. Refer to drug monograph for specific recommendations.

• axitinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• azithromycin

  Serious - Use Alternative (1)cobicistat, azithromycin. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• bedaquiline

  Serious - Use Alternative (1)cobicistat will increase the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• belzutifan

  Monitor Closely (2)belzutifan will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.
  
  belzutifan will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)cobicistat will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors may increase hydrocodone (benzhydrocodone is prodrug of hydrocodone) plasma concentrations and can result in potentially fatal respiratory depression

• berotralstat

  Monitor Closely (2)berotralstat will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
  
  cobicistat increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors.

• betibeglogene autotemcel

  Serious - Use Alternative (2)elvitegravir, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.
  
  emtricitabine, betibeglogene autotemcel. Other (see comment). Avoid or Use Alternate Drug. Comment: Do not take antiretroviral medications for at least 1 month before mobilization or expected duration for elimination of the medications, and until all cycles of apheresis are completed. Antiretroviral medications may interfere with manufacturing of apheresed cells.

• betrixaban

  Monitor Closely (1)cobicistat increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

• bortezomib

  Monitor Closely (1)cobicistat will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• bosentan

  Monitor Closely (2)elvitegravir, bosentan. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elvitegravir increases bosentan levels, and bosentan decreases elvitegravir levels; if elvitegravir received for >10 days, start bosentan at 62.5 mg/day or every other day; if patient taking bosentan and starting elvitegravir, discontinue bosentan at least 36 hr beforehand, may resume bosentan at 62.5 mg/day or every other day after 10 days.
  
  bosentan will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Bosentan dose reduction required. Refer to the prescribing information of bosentan and cobicistat for recommended dosage adjustments.Serious - Use Alternative (2)bosentan will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Bosentan dose reduction required

• bosutinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• brentuximab vedotin

  Monitor Closely (1)cobicistat will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (2)cobicistat will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer half of the usual brexpiprazole dose when coadministered with strong CYP3A4 inhibitors. If also administered with a strong/moderate CYP2D6 inhibitor, administer a quarter of brexpiprazole dose.
  
  cobicistat will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.

• brigatinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of brigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A inhibitor cannot be avoided, reduce the brigatinib once daily dose by about 50% (ie, from 180 mg to 90 mg, or from 90 mg to 60 mg). After discontinuation of a strong CYP3A inhibitor, resume the brigatinib dose that was tolerated prior to initiating the strong CYP3A inhibitor.

• bromocriptine

  Monitor Closely (1)cobicistat will increase the level or effect of bromocriptine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• budesonide

  Monitor Closely (1)cobicistat will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• budesonide inhaled

  Monitor Closely (1)cobicistat increases levels of budesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• buprenorphine

  Monitor Closely (1)cobicistat will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Minor (1)elvitegravir increases levels of buprenorphine by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.

• buprenorphine buccal

  Minor (1)elvitegravir increases levels of buprenorphine buccal by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.

• buprenorphine subdermal implant

  Monitor Closely (1)cobicistat will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• buprenorphine transdermal

  Monitor Closely (1)cobicistat will increase the level or effect of buprenorphine transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• buprenorphine, long-acting injection

  Monitor Closely (1)cobicistat will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

• buspirone

  Monitor Closely (1)cobicistat will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of buspirone may be required

• cabotegravir

  Serious - Use Alternative (2)emtricitabine, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.
  
  elvitegravir, cabotegravir. Other (see comment). Avoid or Use Alternate Drug. Comment: Cabotegravir plus rilpivirine is a complete regimen. Coadministration with other antiretroviral medications for treating HIV-1 infection is not recommended.

• cabozantinib

  Monitor Closely (1)tenofovir AF will increase the level or effect of cabozantinib by Other (see comment). Use Caution/Monitor. MRP2 inhibitors increase cabozantinib toxicitySerious - Use Alternative (1)cobicistat will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cabozantinib with strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor is required, decrease cabozantinib dose by 40 mg/day (Cometriq) or by 20 mg/day (Cabometyx). Resume previous dose 2-3 days after strong CYP3A4 inhibitor discontinued.

• calcifediol

  Monitor Closely (1)cobicistat, calcifediol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1). This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol. Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor.

• calcium carbonate

  Monitor Closely (1)calcium carbonate will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• cannabidiol

  Monitor Closely (1)cobicistat will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a strong CYP3A4 inhibitor.

• capmatinib

  Monitor Closely (1)cobicistat will increase the level or effect of capmatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbamazepine

  Monitor Closely (1)cobicistat will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)carbamazepine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  carbamazepine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• cariprazine

  Monitor Closely (1)cobicistat will increase the level or effect of cariprazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with strong CYP3A4 inhibitors requires cariprazine dose reduction. See Dosage Modification section in drug monograph.

• carvedilol

  Monitor Closely (1)cobicistat will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• celecoxib

  Monitor Closely (1)emtricitabine, celecoxib. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• cenobamate

  Monitor Closely (2)cenobamate will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
  
  cenobamate will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Serious - Use Alternative (1)cobicistat, ceritinib. Either increases toxicity of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May increase QT prolongation.

• chloramphenicol

  Serious - Use Alternative (1)chloramphenicol will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• chlordiazepoxide

  Monitor Closely (1)cobicistat will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ciclesonide inhaled

  Monitor Closely (1)cobicistat will increase the level or effect of ciclesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cidofovir

  Monitor Closely (1)cidofovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• cilostazol

  Monitor Closely (1)cobicistat will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce cilostazol dose to 50 mg twice daily when administered concomitantly; monitor for increase in cilostazole related adverse effects.

• citalopram

  Monitor Closely (2)cobicistat will increase the level or effect of citalopram by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.
  
  cobicistat will increase the level or effect of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• clarithromycin

  Monitor Closely (1)clarithromycin increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.Serious - Use Alternative (2)clarithromycin will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat, clarithromycin. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• clomipramine

  Monitor Closely (2)cobicistat will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of clomipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• clonazepam

  Monitor Closely (1)cobicistat will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with anticonvulsants.

• clorazepate

  Monitor Closely (1)cobicistat will increase the level or effect of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dose of clorazepate if necessary

• cobicistat

  Contraindicated (1)cobicistat, elvitegravir. Other (see comment). Contraindicated. Comment: Coadministration with cobicistat (a strong CYP3A4 and BCRP inhibitor) increases duvelisib (a CYP3A4 and BCRP substrate) levels, which may increase the risk of duvelisib toxicities. Reduce duvelisib dose to 15 mg BID when coadministered with cobicistat.

• cobimetinib

  Contraindicated (1)cobicistat will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Avoid coadministration with strong CYP3A4 inhibitors with (increases cobimetinib systemic exposure by 6.7-fold).

• colchicine

  Monitor Closely (1)cobicistat will increase the level or effect of colchicine by Other (see comment). Modify Therapy/Monitor Closely. Coadministration with colchicine is contraindicated in patients with renal and/or hepatic impairment due to potential for serious and/or life-threatening reactions. Dosage adjustment of colchicine may be necessary upon coadministration with cobicistat. Refer colchicine prescribing information for dosing instructions.

• conivaptan

  Contraindicated (2)cobicistat will increase the level or effect of conivaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  conivaptan will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Monitor Closely (1)conivaptan increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• copanlisib

  Serious - Use Alternative (2)elvitegravir will increase the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use with strong CYP3A inhibitors cannot be avoided, reduce copanlisib dose to 45 mg.
  
  cobicistat will increase the level or effect of copanlisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use with strong CYP3A inhibitors cannot be avoided, reduce copanlisib dose to 45 mg.

• crizotinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increase in crizotinib levels may result in QT prolongation; May reduce crizotinib dose to 250 mg PO qDay if concomitant administration cannot be avoided.

• cyclophosphamide

  Minor (2)cyclophosphamide will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  cyclophosphamide will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (1)cobicistat will increase the level or effect of cyclosporine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dabigatran

  Monitor Closely (1)cobicistat will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min

• dabrafenib

  Serious - Use Alternative (3)cobicistat will increase the level or effect of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  dabrafenib will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  dabrafenib will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dapsone

  Monitor Closely (1)cobicistat will increase the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• daridorexant

  Serious - Use Alternative (1)cobicistat will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• darifenacin

  Monitor Closely (1)cobicistat will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Darifenacin daily dose should not exceed 7.5 mg PO when administered concomitantly.

• darolutamide

  Monitor Closely (2)cobicistat will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.
  
  darolutamide will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a BCRP inhibitor. Avoid coadministration with BCRP inhibitors. If use is unavoidable, closely monitor for adverse reactions and consider dose reduction of BCRP substrate drug (refer BCRP substrate prescribing information).

• darunavir

  Monitor Closely (1)darunavir, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; unknown if darunavir will elevate levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 150 mg PO once daily with darunavir/ritonavir 600/100 mg PO BID.Serious - Use Alternative (2)cobicistat will increase the level or effect of darunavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  darunavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dasatinib

  Monitor Closely (1)cobicistat will increase the level or effect of dasatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dosage adjustment of dasatinib may be necessary upon coadministration with cobicistat coadministered with atazanavir or darunavir. Refer dasatinib prescribing information for dosing instructions.

• deflazacort

  Monitor Closely (1)cobicistat will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

• delavirdine

  Monitor Closely (1)cobicistat will increase the level or effect of delavirdine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• desipramine

  Monitor Closely (2)cobicistat will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of desipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• dexamethasone

  Serious - Use Alternative (3)cobicistat will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with corticosteroids that are metabolized by CYP3A, particularly for long-term use, may increase the risk for development of systemic corticosteroid effects including Cushing syndrome and adrenal suppression
  
  dexamethasone will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with corticosteroids that induce CYP3A4 may result in loss of therapeutic effect and development of resistance to atazanavir or darunavir
  
  dexamethasone will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• dexlansoprazole

  Monitor Closely (1)cobicistat will increase the level or effect of dexlansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)cobicistat will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of diazepam may be required

• diazepam intranasal

  Monitor Closely (1)cobicistat will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

• diclofenac

  Monitor Closely (1)emtricitabine, diclofenac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• didanosine

  Monitor Closely (1)didanosine, elvitegravir. Other (see comment). Use Caution/Monitor. Comment: Didanosine must be administered on an empty stomach; administer didanosine at least 1 hr before or 2 hr after elvitegravir (which is administered with food).

• diflunisal

  Monitor Closely (1)emtricitabine, diflunisal. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• digoxin

  Monitor Closely (1)cobicistat will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Measure serum digoxin concentrations before initiating concomitant drugs. Titrate the digoxin dose by ~30-50% or by modifying the dosing frequency and continue monitoring.

• dihydroergotamine

  Contraindicated (1)cobicistat will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm, ischemia of the extremities and other tissues)

• dihydroergotamine intranasal

  Serious - Use Alternative (1)cobicistat will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• diltiazem

  Monitor Closely (1)cobicistat will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• disopyramide

  Monitor Closely (1)cobicistat will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• docetaxel

  Monitor Closely (1)cobicistat will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. May consider reducing docetaxel dosing 50% if concomitant administration cannot be avoided

• doravirine

  Monitor Closely (1)cobicistat will increase the level or effect of doravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of doravirine and CYP3A4 inhibitors may increase plasma concentrations and toxicities of doravirine.

• doxepin

  Monitor Closely (2)cobicistat will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of doxepin by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• doxepin cream

  Monitor Closely (1)cobicistat will increase the level or effect of doxepin cream by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• doxorubicin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• doxorubicin liposomal

  Serious - Use Alternative (1)cobicistat will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• dronabinol

  Monitor Closely (1)cobicistat will increase the level or effect of dronabinol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dronabinol is a CYP3A4 substrate.

• dronedarone

  Contraindicated (2)cobicistat will increase the level or effect of dronedarone by Other (see comment). Contraindicated. Dronedarone is a CYP3A4 inhibitor/substrate and a CYP2D6 inhibitor; cobicistat is both an inhibitor and substrate of CYP3A4 and CYP2D6
  
  cobicistat will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• duvelisib

  Monitor Closely (1)tenofovir AF will decrease the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• edoxaban

  Serious - Use Alternative (1)cobicistat will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended

• efavirenz

  Monitor Closely (2)efavirenz and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
  
  cobicistat will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)efavirenz will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with efavirenz may result in loss of therapeutic effect and development of resistance to cobicistat.
  
  efavirenz will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• elacestrant

  Serious - Use Alternative (1)cobicistat will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (4)elagolix will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
  
  elagolix will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  cobicistat will increase the level or effect of elagolix by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of elagolix 200 mg BID with strong CYP3A inhibitors for >1 month is not recommended. Limit elagolix dose to 150 mg qDay and CYP3A inhibitor duration of use to 6 months if coadministered.
  
  elagolix, cobicistat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Combination of elagolix (weak-to-moderate CYP3A4 inducer) with cobicistat (a CYP3A4 inhibitor and substrate) may increase elagolix levels and may decrease cobicistat levels. Refer to the prescribing information of elagolix and cobicistat for recommended dosage adjustments.

• elbasvir/grazoprevir

  Serious - Use Alternative (1)cobicistat will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of elbasvir/grazoprevir with certain strong CYP3A4 inhibitors

• eletriptan

  Contraindicated (1)cobicistat will increase the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• eliglustat

  Contraindicated (2)cobicistat will increase the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. If coadministered with strong or moderate CYP2D6 inhibitors, reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive and intermediate metabolizers; eliglustat is contraindicated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.
  
  cobicistat increases levels of eliglustat by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. Strong CYP3A4 inhibitors are contraindicated with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers; eliglustat is contraindicated if strong or moderate CYP2D6 inhibitors are given concomitantly with strong or moderate CYP3A inhibitors.

• elivaldogene autotemcel

  Serious - Use Alternative (2)elivaldogene autotemcel, elvitegravir. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.
  
  elivaldogene autotemcel, emtricitabine. Either decreases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Patients should not take antiretroviral medications for at least 1 month before initiating medications for stem cell mobilization, for the duration of the medications? elimination, and until all cycles of apheresis are completed.

• elvitegravir

  Contraindicated (1)cobicistat, elvitegravir. Other (see comment). Contraindicated. Comment: Coadministration with cobicistat (a strong CYP3A4 and BCRP inhibitor) increases duvelisib (a CYP3A4 and BCRP substrate) levels, which may increase the risk of duvelisib toxicities. Reduce duvelisib dose to 15 mg BID when coadministered with cobicistat.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Contraindicated (3)emtricitabine, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.
  
  elvitegravir will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by pharmacodynamic synergism. Contraindicated. Duplicate therapy
  
  cobicistat will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by pharmacodynamic synergism. Contraindicated. Duplicate therapyMonitor Closely (1)cobicistat will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Cobicistat inhibits P-gp

• encorafenib

  Monitor Closely (3)encorafenib, cobicistat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
  
  encorafenib, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
  
  encorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a BCRP inhibitor) may increase the concentration and toxicities of BCRP substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.Serious - Use Alternative (1)cobicistat will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a strong CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-third of the dose (eg, reduce from 450 mg/day to 150 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

• enfortumab vedotin

  Monitor Closely (2)cobicistat increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.
  
  cobicistat will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs of toxicities.

• enfuvirtide

  Monitor Closely (1)emtricitabine and enfuvirtide both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• entrectinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce entrectinib dose to 100 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing strong CYP3A inhibitor for 3-5 elimination half-lives.

• enzalutamide

  Monitor Closely (1)enzalutamide will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)cobicistat will increase the level or effect of enzalutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  enzalutamide will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• eplerenone

  Contraindicated (1)cobicistat will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• erdafitinib

  Monitor Closely (1)elvitegravir will decrease the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. If a moderate CYP2C9 inducer must be coadministered, administer 8-mg/day dose initially, with potential to increase to 9 mg/day based on serum phosphate levels on Days 14-21 and tolerability. If a moderate CYP2C9 inducer must be coadministered after the initial dose increase period based on serum phosphate levels and tolerability, increase erdafitinib dose up to 9 mg. When a moderate inducer discontinued, continue erdafitinib at same dose, in absence of drug-related toxicity.Serious - Use Alternative (1)cobicistat will increase the level or effect of erdafitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP3A4 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP3A4 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

• ergonovine

  Contraindicated (1)cobicistat will increase the level or effect of ergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ergotamine

  Contraindicated (1)cobicistat will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm, ischemia of the extremities and other tissues)

• erlotinib

  Monitor Closely (1)cobicistat will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration cannot be avaoided, reduce erlotinib dose by 50 mg decrements and monitor for adverse effects

• erythromycin base

  Serious - Use Alternative (1)cobicistat, erythromycin base. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)cobicistat, erythromycin ethylsuccinate. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• erythromycin lactobionate

  Serious - Use Alternative (1)cobicistat, erythromycin lactobionate. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• erythromycin stearate

  Serious - Use Alternative (1)cobicistat, erythromycin stearate. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• escitalopram

  Monitor Closely (2)cobicistat will increase the level or effect of escitalopram by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.
  
  cobicistat will increase the level or effect of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• eslicarbazepine acetate

  Serious - Use Alternative (2)eslicarbazepine acetate will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative anticonvulsant or antiretroviral therapy to avoid potential changes in exposures. If coadministration is necessary, monitor for lack or loss of virologic response.
  
  eslicarbazepine acetate will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• esomeprazole

  Monitor Closely (1)cobicistat will increase the level or effect of esomeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• estradiol vaginal

  Monitor Closely (1)cobicistat will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase plasma concentrations of estrogens and toxicities.

• eszopiclone

  Serious - Use Alternative (1)cobicistat will increase the level or effect of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ethinylestradiol

  Serious - Use Alternative (1)elvitegravir will decrease the level or effect of ethinylestradiol by unknown mechanism. Avoid or Use Alternate Drug. Consider alternative nonhormonal methods of contraception to add or replace combination oral contraceptive

• ethosuximide

  Monitor Closely (1)cobicistat will increase the level or effect of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• etodolac

  Monitor Closely (1)emtricitabine, etodolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• etravirine

  Serious - Use Alternative (3)cobicistat will increase the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  etravirine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with etravirine may result in loss of therapeutic effect and development of resistance to cobicistat.
  
  etravirine will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• everolimus

  Serious - Use Alternative (1)cobicistat will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.Serious - Use Alternative (1)cobicistat will increase the level or effect of fedratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid fedratinib coadministration with strong CYP3A4 inhibitors, decrease fedratinib dose to 200 mg/day. If CYP3A4 inhibitor discontinued, increase fedratinib dose to 300 mg/day for 2 weeks, and then 400 mg/day thereafter as tolerated.

• felbamate

  Serious - Use Alternative (1)cobicistat will increase the level or effect of felbamate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• felodipine

  Monitor Closely (1)cobicistat will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fenoprofen

  Monitor Closely (1)emtricitabine, fenoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• fentanyl

  Monitor Closely (1)cobicistat will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl intranasal

  Monitor Closely (1)cobicistat will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl transdermal

  Serious - Use Alternative (1)cobicistat will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fentanyl transmucosal

  Serious - Use Alternative (1)cobicistat will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fexinidazole

  Serious - Use Alternative (3)fexinidazole will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
  
  cobicistat will decrease the level or effect of fexinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration, monitor fexinidazole for decreased efficacy owing to decreased plasma concentrations of active M1 and M2 metabolites.
  
  fexinidazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fezolinetant

  Contraindicated (1)tenofovir AF will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• fidaxomicin

  Serious - Use Alternative (1)cobicistat, fidaxomicin. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative antibiotics with concomitant use of cobicistat coadministered with atazanavir or darunavir. .

• finerenone

  Contraindicated (1)cobicistat will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• flecainide

  Monitor Closely (1)cobicistat will increase the level or effect of flecainide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• flibanserin

  Contraindicated (1)cobicistat will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of flibanserin with moderate or strong CYP3A4 inhibitors is contraindicated. Severe hypotension or syncope can occur.

• fluoxetine

  Monitor Closely (1)cobicistat will increase the level or effect of fluoxetine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.

• flurazepam

  Monitor Closely (1)cobicistat will increase the level or effect of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• flurbiprofen

  Monitor Closely (1)emtricitabine, flurbiprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• flutamide

  Serious - Use Alternative (1)cobicistat will increase the level or effect of flutamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fluticasone furoate

  Monitor Closely (1)cobicistat increases levels of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluticasone inhaled

  Monitor Closely (1)cobicistat increases levels of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluvastatin

  Monitor Closely (1)cobicistat will increase the level or effect of fluvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, start with the lowest recommended dose and titrate while monitoring for safety.

• fluvoxamine

  Monitor Closely (1)fluvoxamine will increase the level or effect of cobicistat by Other (see comment). Use Caution/Monitor. Carfully titrate dose of antidepressant to desired effect, including using lowest feasible initial or maintenance dose , and monitor its response during coadministration with SSRIs and cobicistat

• fosamprenavir

  Monitor Closely (2)fosamprenavir, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; unknown if fosamprenavir will elevate levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 150 mg PO once daily with fosamprenavir/ritonavir 700/100 mg PO BID.
  
  fosamprenavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• fosaprepitant

  Serious - Use Alternative (1)cobicistat will increase the level or effect of fosaprepitant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• fosphenytoin

  Serious - Use Alternative (2)fosphenytoin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  fosphenytoin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• fostamatinib

  Monitor Closely (2)fostamatinib will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of BCRP substrate drugs. Monitor for toxicities of BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.
  
  cobicistat will increase the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors may increase exposure to R406 (fostamatinib major active metabolite). Monitor for toxicities that may require fostamatinib dose reduction.

• futibatinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

• ganaxolone

  Minor (1)cobicistat, ganaxolone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Changes in ganaxolone exposures when coadministered with strong, moderate, or weak CYP3A4 inhibitors are not expected to be clinically significant.

• ganciclovir

  Monitor Closely (2)ganciclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.
  
  ganciclovir, emtricitabine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.

• gefitinib

  Monitor Closely (1)cobicistat increases levels of gefitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of strong CYP3A4 inhibitors may increase risk for gefitinib adverse effects.

• gilteritinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.

• glasdegib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of glasdegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternate therapies that are not strong CYP3A inhibitors or monitor for increased risk of adverse effects, including QTc interval prolongation.

• glecaprevir/pibrentasvir

  Monitor Closely (2)glecaprevir/pibrentasvir will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.
  
  cobicistat will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• grapefruit

  Monitor Closely (1)grapefruit increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• guanfacine

  Serious - Use Alternative (1)cobicistat will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• haloperidol

  Monitor Closely (1)cobicistat will increase the level or effect of haloperidol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• hydrocodone

  Monitor Closely (1)cobicistat will increase the level or effect of hydrocodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with CYP3A4 inhibitors may increase hydrocodone plasma concentrations and can result in potentially fatal respiratory depression

• ibrutinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ibuprofen

  Monitor Closely (1)emtricitabine, ibuprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• ibuprofen IV

  Monitor Closely (1)emtricitabine, ibuprofen IV. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• idelalisib

  Monitor Closely (1)idelalisib increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.Serious - Use Alternative (2)cobicistat will increase the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  idelalisib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ifosfamide

  Monitor Closely (2)cobicistat will decrease the level or effect of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of CYP3A4 inhibitors may decrease the metabolism of ifosfamide to its active alkylating metabolites and decrease the efficacy of ifosfamide.
  
  ifosfamide, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Monitor electrolytes and renal function.

• imatinib

  Monitor Closely (2)imatinib increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  cobicistat will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• imipramine

  Monitor Closely (1)cobicistat will increase the level or effect of imipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• indinavir

  Contraindicated (1)cobicistat will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with cobicistat coadministered with atazanavir only; both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemiaMonitor Closely (2)indinavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
  
  indinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.Serious - Use Alternative (1)indinavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• indomethacin

  Monitor Closely (1)emtricitabine, indomethacin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• infigratinib

  Serious - Use Alternative (2)elvitegravir will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• irinotecan

  Contraindicated (1)cobicistat will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with cobicistat coadministered with atazanavir and irinotecan. Coadministration of atazanavir with irinotecan is contraindicated due to potential for increased irinotecan toxicity.

• irinotecan liposomal

  Contraindicated (1)cobicistat will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. UGT1A1 inhibitors decrease irinotecan metabolism

• isavuconazonium sulfate

  Contraindicated (1)cobicistat will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• isoniazid

  Monitor Closely (2)isoniazid will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  isoniazid increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.

• isradipine

  Monitor Closely (1)cobicistat will increase the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• istradefylline

  Monitor Closely (4)istradefylline will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
  
  istradefylline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.
  
  istradefylline will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
  
  cobicistat will increase the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed istradefylline 20 mg/day if coadministered with strong CYP3A4 inhibitors.

• itraconazole

  Monitor Closely (2)cobicistat, itraconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for itraconazole are not available when coadministered with cobicistat.
  
  itraconazole increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When coadministered with elvitegravir, limit dose of itraconazole should not exceed 200 mg/day.Serious - Use Alternative (1)itraconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ivabradine

  Contraindicated (1)cobicistat will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of ivabradine with strong CYP3A4 inhibitors is contraindicated

• ivacaftor

  Monitor Closely (1)cobicistat will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with strong CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

• ivosidenib

  Serious - Use Alternative (2)cobicistat will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of strong CYP3A4 inhibitors with ivosidenib or replace with alternate therapies. If coadministration of a strong CYP3A4 inhibitor is unavoidable, reduce ivosidenib dose to 250 mg qDay. If the strong inhibitor is discontinued, increase ivosidenib dose (after at least 5 half-lives of the strong CYP3A4 inhibitor) to the recommended dose of 500 mg qDay. Monitor for increased risk of QTc interval prolongation.
  
  ivosidenib will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ixabepilone

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ixazomib

  Minor (1)cobicistat, ixazomib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. In clinical trials, coadministration of ixazomib with strong CYP3A inhibitors did not result in a clinically meaningful change in the systemic exposure of ixazomib.

• ketoconazole

  Monitor Closely (2)cobicistat, ketoconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for ketoconazole are not available when coadministered with cobicistat.
  
  ketoconazole, elvitegravir. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministered, do not exceed ketoconazole 200 mg/day; no dose adjustment needed for elvitegravir.Serious - Use Alternative (1)ketoconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ketoprofen

  Monitor Closely (1)emtricitabine, ketoprofen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• ketorolac

  Monitor Closely (1)emtricitabine, ketorolac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• lamivudine

  Contraindicated (2)emtricitabine and lamivudine both increase risk of immune reconstitution syndrome. Contraindicated. Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.
  
  emtricitabine, lamivudine. Other (see comment). Contraindicated. Comment: Coadministration of emtricitabine containing products and lamivudine containing products should be avoided. Combination will result in therapeutic duplication.

• lansoprazole

  Monitor Closely (1)cobicistat will increase the level or effect of lansoprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lapatinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of lapatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant administration cannot be avoided, administer 500 mg lapatinib once daily and increase lapatinib dose to indicated dose once cobicistat discontinued

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)cobicistat will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• lefamulin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lefamulin with strong CYP3A inhibitors.

• lemborexant

  Serious - Use Alternative (1)cobicistat will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

• lenacapavir

  Monitor Closely (2)lenacapavir will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
  
  lenacapavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• leniolisib

  Serious - Use Alternative (2)leniolisib will increase the level or effect of tenofovir AF by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, a BCRP inhibitor, may increase systemic exposure of BCRP substrates
  
  cobicistat will increase the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• letermovir

  Monitor Closely (1)cobicistat increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.Serious - Use Alternative (1)tenofovir AF will decrease the level or effect of letermovir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of letermovir with P-gp inducers is not recommended.

• levamlodipine

  Monitor Closely (1)cobicistat will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

• levoketoconazole

  Monitor Closely (2)cobicistat, levoketoconazole. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Specific dosage recommendations for ketoconazole are not available when coadministered with cobicistat.
  
  levoketoconazole, elvitegravir. Either increases levels of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministered, do not exceed ketoconazole 200 mg/day; no dose adjustment needed for elvitegravir.Serious - Use Alternative (1)levoketoconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levomilnacipran

  Serious - Use Alternative (1)cobicistat will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not esceed 80 mg levominacipram dose once daily if coadministration necessary

• levonorgestrel intrauterine

  Serious - Use Alternative (1)cobicistat will increase the level or effect of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (1)cobicistat will increase the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with CYP3A4 inhibitors may increase the plasma hormone concentrations. Use of a nonhormonal contraceptive is recommended.

• lidocaine

  Monitor Closely (1)cobicistat will increase the level or effect of lidocaine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• lomitapide

  Serious - Use Alternative (1)cobicistat will increase the level or effect of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• lonafarnib

  Contraindicated (1)cobicistat will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.Monitor Closely (1)lonafarnib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

• lopinavir

  Monitor Closely (1)lopinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lopinavir/ritonavir significantly increases elvitegravir levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 85 mg PO once daily with lopinavir/ritonavir other than 400/100 mg BID.

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)lorlatinib will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of lorlatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering lorlatinib with strong CYP3A inhibitors. If unavoidable, reduce lorlatinib dose by 25 mg/day. If strong CYP3A inhibitor discontinued, increase to previous lorlatinib (dose after 3 plasma half-lives of strong CYP3A inhibitor). See monograph for further details.

• losartan

  Monitor Closely (1)cobicistat will increase the level or effect of losartan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lovastatin

  Contraindicated (1)cobicistat will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious reactions such as myopathy including rhabdomyolysis

• lumacaftor/ivacaftor

  Monitor Closely (1)cobicistat increases levels of lumacaftor/ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A inhibitors do not impact lumacaftor exposure, but increased ivacaftor exposure by 4.3-fold. Due to the induction effect of lumacaftor on CYP3A, at steady-state the net exposure of ivacaftor is not expected to exceed that when given in the absence of lumacaftor at a dose of 150 mg q12hr (the approved dose of ivacaftor monotherapy). Therefore, no dose adjustment is necessary when CYP3A inhibitors are initiated in patients currently taking lumacaftor/ivacaftor. However, when initiating lumacaftor/ivacaftor in patients taking strong CYP3A inhibitors, reduce the dose to 1 tablet daily (lumacaftor 200 mg/ivacaftor 125 mg total daily dose) for the first week of treatment to allow for the steady-state induction effect of lumacaftor. Following this period, continue with the recommended daily dose. No dose adjustment is required for moderate or weak CYP3A4 inhibitors.

• lumateperone

  Monitor Closely (1)cobicistat will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 10.5 mg/day if coadministered with strong CYP3A4 inhibitors.

• lumefantrine

  Monitor Closely (2)cobicistat, lumefantrine. unknown mechanism. Use Caution/Monitor. Monitor for potential decrease of antimalarial efficacy or potential QT prolongation.
  
  cobicistat will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lurasidone

  Contraindicated (1)cobicistat will increase the level or effect of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for increased systemic exposure of lurasidone resulting in increased risk for QT prolongation.

• lurbinectedin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• magnesium oxide

  Monitor Closely (1)magnesium oxide will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Elvitegravir plasma concentrations are lower with antacids due to the formation of ionic complexes in the GI tract and not due to changes in gastric pH; separate dose from antacid by at least 2 hr

• maraviroc

  Monitor Closely (1)cobicistat will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Maraviroc is a CYP3A4 substrate. Decrease maraviroc dose to 150 mg BID when coadministered with strong CYP3A4 inhibitors

• mavacamten

  Contraindicated (1)cobicistat will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

• meclofenamate

  Monitor Closely (1)emtricitabine, meclofenamate. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• mefenamic acid

  Monitor Closely (1)emtricitabine, mefenamic acid. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• mefloquine

  Serious - Use Alternative (1)cobicistat will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity. Avoid coadministration during and for 15 weeks after discontinuing mefloquine.

• meloxicam

  Monitor Closely (1)emtricitabine, meloxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• methadone

  Monitor Closely (2)cobicistat will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Methadone dose may require an adjustment
  
  elvitegravir decreases levels of methadone by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dosage of methadone may need to be increased.

• methylergonovine

  Contraindicated (1)cobicistat will increase the level or effect of methylergonovine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm, ischemia of the extremities and other tissues)

• methylprednisolone

  Monitor Closely (1)cobicistat will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• metoprolol

  Monitor Closely (1)cobicistat will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mexiletine

  Monitor Closely (1)cobicistat will increase the level or effect of mexiletine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• midazolam

  Contraindicated (1)cobicistat will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Triazolam and midazolam (PO) are extensively metabolized by CYP3A. Coadministration of triazolam or midazolam (PO) may cause large increases in the concentrations of these benzodiazepines. Potential for serious and/or life-threatening events (eg, prolonged or increased sedation or respiratory depression).

• midazolam intranasal

  Serious - Use Alternative (1)cobicistat will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of strong CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

• midostaurin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of midostaurin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A4 inhibitors cannot be avoided, monitor midostaurin for increased risk of adverse reactions, especially during the first week of treatment.

• mifepristone

  Monitor Closely (1)cobicistat will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, administer 300 mg mifepristone initially; not to exceed 600 mg; if cobicistat initiated in patient receiving 600 mg mifepristone, reduce mirepristone dose to 300 mg; if cobicistat initiated in patient receiving 900-1200 mg mifepristone, reduce mifepristone dose to 600 mg; if initiated in patient receiving 300 mg mifepristone, no change in dose necessarySerious - Use Alternative (1)mifepristone will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mirtazapine

  Monitor Closely (1)cobicistat will increase the level or effect of mirtazapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• mirvetuximab soravtansine

  Monitor Closely (1)cobicistat will increase the level or effect of mirvetuximab soravtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with strong CYP3A4 inhibitors may increase unconjugated DM4 (a CYP3A4 substrate and the cytotoxic component of the antibody drug conjugate for mirvetuximab soravtansine) exposure, which may increase the risk of adverse reactions.

• mitotane

  Serious - Use Alternative (2)mitotane will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  mitotane will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mobocertinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• modafinil

  Serious - Use Alternative (1)cobicistat will increase the level or effect of modafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mometasone inhaled

  Monitor Closely (1)cobicistat will increase the level or effect of mometasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increases risk for systemic corticosteroid side effects

• mometasone, intranasal

  Monitor Closely (1)cobicistat will increase the level or effect of mometasone, intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nabumetone

  Monitor Closely (1)emtricitabine, nabumetone. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• nafcillin

  Serious - Use Alternative (2)nafcillin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  nafcillin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• naldemedine

  Monitor Closely (2)cobicistat increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.
  
  cobicistat increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

• naloxegol

  Contraindicated (1)cobicistat will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• naloxone

  Minor (1)elvitegravir decreases levels of naloxone by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.

• naproxen

  Monitor Closely (1)emtricitabine, naproxen. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• nefazodone

  Monitor Closely (3)cobicistat will increase the level or effect of nefazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  nefazodone increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  nefazodone will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nelfinavir

  Monitor Closely (2)nelfinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  nelfinavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• neratinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

• netupitant/palonosetron

  Monitor Closely (1)cobicistat will increase the level or effect of netupitant/palonosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Netupitant is mainly metabolized by CYP3A4; no dosage adjustment is required

• nevirapine

  Monitor Closely (1)emtricitabine and nevirapine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.Serious - Use Alternative (3)cobicistat will increase the level or effect of nevirapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  nevirapine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  nevirapine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with etravirine may result in loss of therapeutic effect and development of resistance to cobicistat. Contraindicated with cobicistat coadministered with atazanavir.only; nevirapine substantially decreases atazanavir exposure which may result in loss of therapeutic effect and development of resistance

• nicardipine

  Monitor Closely (1)nicardipine increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.Serious - Use Alternative (1)cobicistat will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nifedipine

  Monitor Closely (1)cobicistat will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nilotinib

  Monitor Closely (1)cobicistat will increase the level or effect of nilotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Dosage adjustment of nilotinib may be necessary upon coadministration with cobicistat coadministered with atazanavir or darunavir. Refer nilotinib prescribing information for dosing instructions.

• nimodipine

  Serious - Use Alternative (1)cobicistat will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nintedanib

  Monitor Closely (1)cobicistat increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy.

• nirmatrelvir

  Monitor Closely (1)nirmatrelvir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures.

• nirmatrelvir/ritonavir

  Monitor Closely (1)nirmatrelvir/ritonavir will increase the level or effect of tenofovir AF by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration may increase tenofovir systemic exposures.Minor (1)nirmatrelvir/ritonavir will increase the level or effect of emtricitabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nisoldipine

  Serious - Use Alternative (1)cobicistat will increase the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nortriptyline

  Monitor Closely (1)cobicistat will increase the level or effect of nortriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• olaparib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong CYP3A inhibitors cannot be avoided, reduce olaparib dose to 150 mg (capsule) or 100 mg (tablet) PO BID. Do not substitute tablets with capsules.

• oliceridine

  Monitor Closely (2)cobicistat will increase the level or effect of oliceridine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.
  
  cobicistat will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

• omaveloxolone

  Serious - Use Alternative (1)cobicistat will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 50 mg/day. Closely monitor and discontinue if adverse effects emerge.

• ombitasvir/paritaprevir/ritonavir

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ombitasvir/paritaprevir/ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• omeprazole

  Monitor Closely (1)cobicistat will increase the level or effect of omeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ondansetron

  Monitor Closely (1)cobicistat will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• orlistat

  Monitor Closely (3)orlistat will decrease the level or effect of elvitegravir by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
  
  orlistat will decrease the level or effect of tenofovir AF by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.
  
  orlistat will decrease the level or effect of emtricitabine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Loss of virological control reported in HIV-infected patients taking orlistat concomitantly. Exact mechanism is unclear, but may include a drug-drug interaction that inhibits systemic absorption of the antiretroviral drug. Monitor HIV RNA levels frequently and if increased HIV viral load confirmed, discontinue orlistat.

• osilodrostat

  Monitor Closely (1)cobicistat will increase the level or effect of osilodrostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose of osilodrostat, a CYP3A4 substrate, by half when coadministered with a strong CYP3A4 inhibitor.

• osimertinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of osimertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of osimertinib with strong CYP3A4 inhibitors. If no other alternative treatment exists, monitor patient more closely for adverse effects.

• ospemifene

  Monitor Closely (1)cobicistat will increase the level or effect of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• oteseconazole

  Monitor Closely (1)oteseconazole will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Otesezonale, a BCRP inhibitor, may increase the effects and risk of toxicities of BCRP substrates. Use lowest starting dose of BCRP substrate, or consider reducing BCRP substrate dose.

• oxaprozin

  Monitor Closely (1)emtricitabine, oxaprozin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• oxcarbazepine

  Serious - Use Alternative (2)oxcarbazepine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative anticonvulsant or antiretroviral therapy to avoid potential changes in exposures. If coadministration is necessary, monitor for lack or loss of virologic response.
  
  oxcarbazepine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• oxycodone

  Monitor Closely (1)cobicistat will increase the level or effect of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• ozanimod

  Serious - Use Alternative (1)cobicistat increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .

• paclitaxel

  Monitor Closely (1)cobicistat will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paclitaxel protein bound

  Monitor Closely (1)cobicistat will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• pacritinib

  Contraindicated (1)cobicistat will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• palbociclib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of palbociclib with strong CYP3A inhibitors. If unable to avoid, reduce palbociclib dose to 75 mg/day.

• panobinostat

  Monitor Closely (1)cobicistat increases levels of panobinostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce panobinostat starting dose to 10 mg if coadministered with strong CYP3A4 inhibitors.

• paricalcitol

  Monitor Closely (1)cobicistat will increase the level or effect of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• paroxetine

  Monitor Closely (1)cobicistat will increase the level or effect of paroxetine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.

• pazopanib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pemigatinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

• pentobarbital

  Serious - Use Alternative (1)pentobarbital will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• perampanel

  Serious - Use Alternative (1)cobicistat will increase the level or effect of perampanel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• perphenazine

  Monitor Closely (1)cobicistat will increase the level or effect of perphenazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.

• pexidartinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

• phenobarbital

  Serious - Use Alternative (2)phenobarbital will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  phenobarbital will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• phenytoin

  Serious - Use Alternative (2)phenytoin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  phenytoin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is necessary, monitor for lack or loss of virologic response from cobicistat

• pimavanserin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of pimavanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease dose to 17 mg/day if pimavanserin is coadministered with strong CYP3A4 inhibitors.

• pimozide

  Contraindicated (2)cobicistat will increase the level or effect of pimozide by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated. Potential for increased systemic exposure of pimozide resulting in increased risk for QT prolongation
  
  cobicistat will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for increased systemic exposure of pimozide resulting in increased risk for QT prolongation.

• piroxicam

  Monitor Closely (1)emtricitabine, piroxicam. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• pitavastatin

  Monitor Closely (1)cobicistat will increase the level or effect of pitavastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, start with the lowest recommended dose and titrate while monitoring for safety.

• polatuzumab vedotin

  Monitor Closely (1)cobicistat will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

• ponatinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• posaconazole

  Monitor Closely (1)posaconazole increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.Serious - Use Alternative (1)posaconazole will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pralsetinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of pralsetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• pravastatin

  Monitor Closely (1)cobicistat will increase the level or effect of pravastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, start with the lowest recommended dose and titrate while monitoring for safety.

• praziquantel

  Monitor Closely (1)cobicistat will increase the level or effect of praziquantel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• primidone

  Serious - Use Alternative (2)primidone will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  primidone will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• progesterone intravaginal gel

  Serious - Use Alternative (1)cobicistat will increase the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• progesterone micronized

  Serious - Use Alternative (1)cobicistat will increase the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• progesterone, natural

  Serious - Use Alternative (1)cobicistat will increase the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• propafenone

  Monitor Closely (1)cobicistat will increase the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Clinical monitoring is recommended upon coadministration with antiarrhythmics.

• protriptyline

  Monitor Closely (1)cobicistat will increase the level or effect of protriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• quazepam

  Monitor Closely (1)cobicistat will increase the level or effect of quazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quetiapine

  Serious - Use Alternative (1)cobicistat increases levels of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with atazanavir and cobicistat in patients taking quetiapine. If coadministration is necessary, reduce quetiapine dose to one-sixth of the current dose and monitor for quetiapine-associated adverse reactions. Refer to quetiapine prescribing information for initial dosing and titration of quetiapine.

• quinidine

  Monitor Closely (3)quinidine increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  cobicistat will increase the level or effect of quinidine by Other (see comment). Modify Therapy/Monitor Closely. Quinidine is a substrate of CYP3A4 and P-gp, and inhibits CYP2D6 and P-gp; cobicistat is a substrate and inhibitor of both isoenzymes and a P-gp inhibitor
  
  cobicistat will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• quinine

  Monitor Closely (1)cobicistat will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rabeprazole

  Monitor Closely (1)cobicistat will increase the level or effect of rabeprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ranolazine

  Contraindicated (1)cobicistat will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• regorafenib

  Monitor Closely (1)regorafenib will increase the level or effect of tenofovir AF by Other (see comment). Modify Therapy/Monitor Closely. Regorafenib likely inhibits BCRP (ABCG2) transport. Coadministration with a BCRP substrate may increase systemic exposure to the substrate and related toxicity.

• repaglinide

  Monitor Closely (1)cobicistat will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ribavirin

  Monitor Closely (1)ribavirin increases toxicity of emtricitabine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of lactic acidosis.

• ribociclib

  Contraindicated (1)ribociclib will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Serious - Use Alternative (2)cobicistat will increase the level or effect of ribociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a strong CYP3A inhibitor must be coadministered with ribociclib, reduce the ribociclib starting dose to 400 mg/day.
  
  ribociclib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifabutin

  Monitor Closely (3)rifabutin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose for rifabutin to 150 mg PO every other day when coadministered with cobicistat. Monitor rifabutin associated adverse reactions.
  
  cobicistat will increase the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease rifabutin dose to 150 mg PO every other day; monitor for rifabutin associated neutropenia and uveitis
  
  elvitegravir, rifabutin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elvitegravir increases rifabutin levels, and rifabutin decreases elvitegravir levels; when rifabutin, a potent CYP3A inducer is used with elvitegravir (with a protease inhibitor and ritonavir), reduce dose of rifabutin by at least 75%; no dose adjustment of elvitegravir is required.Serious - Use Alternative (1)rifabutin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rifampin

  Contraindicated (1)rifampin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with rifampin is contraindicated due to potential for loss of therapeutic effect and development of resistance. Serious - Use Alternative (1)rifampin will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• rifapentine

  Serious - Use Alternative (2)rifapentine will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance
  
  rifapentine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• rimegepant

  Serious - Use Alternative (2)cobicistat will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.

• riociguat

  Serious - Use Alternative (1)cobicistat will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ripretinib

  Monitor Closely (1)cobicistat will increase the level or effect of ripretinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with a strong CYP3A inhibitor will increase systemic exposure to ripretinib and its active metabolite (DP-5439), which may increase risk of adverse reactions.

• risperidone

  Monitor Closely (1)cobicistat will increase the level or effect of risperidone by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.

• ritonavir

  Contraindicated (1)cobicistat will increase the level or effect of ritonavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Monitor Closely (2)ritonavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.
  
  ritonavir will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ritonavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• rivaroxaban

  Serious - Use Alternative (1)cobicistat will increase the level or effect of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of cobicistat with rivaroxaban; may result in increased exposure of rivaroxaban and increased risk of bleeding

• roflumilast

  Monitor Closely (1)cobicistat will increase the level or effect of roflumilast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• romidepsin

  Monitor Closely (1)cobicistat will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rosuvastatin

  Monitor Closely (1)cobicistat will increase the level or effect of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. For HMG-CoA reductase inhibitors that are not contraindicated with cobicistat, dose should not exceed 20 mg/day.

• rucaparib

  Monitor Closely (2)rucaparib will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
  
  rucaparib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• ruxolitinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ruxolitinib topical

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• safinamide

  Monitor Closely (1)safinamide will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Safinamide and its major metabolite may inhibit intestinal BCRP. Monitor BCRP substrates for increased pharmacologic or adverse effects.

• salmeterol

  Serious - Use Alternative (1)cobicistat increases levels of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration not recommended; may result in increased cardiovascular effects associated with salmeterol, including QT prolongation, palpitations, and sinus tachycardia.

• saquinavir

  Monitor Closely (2)saquinavir increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  saquinavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.Serious - Use Alternative (3)cobicistat will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  cobicistat will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  saquinavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• sarecycline

  Monitor Closely (1)sarecycline will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• saxagliptin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• selexipag

  Monitor Closely (1)cobicistat will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.

• selpercatinib

  Monitor Closely (1)cobicistat will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, reduce dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily and to 80 mg PO twice daily if original dose was 160 mg twice daily; monitor for side effects

• selumetinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

• sertraline

  Monitor Closely (1)cobicistat will increase the level or effect of sertraline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with SSRIs and cobicistat.

• sildenafil

  Contraindicated (1)cobicistat will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. When used chronically for PAH, sildenafil is contraindicated for use with cobicistat; if used for erectile dysfunction, do not exceed sildenafil 25 mg q48hr

• simvastatin

  Contraindicated (1)cobicistat will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Potential for serious reactions such as myopathy including rhabdomyolysis

• siponimod

  Serious - Use Alternative (1)cobicistat will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

• sirolimus

  Monitor Closely (1)cobicistat will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• solifenacin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• sonidegib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sonidegib with strong CYP3A4 inhibitors.

• sotorasib

  Serious - Use Alternative (1)sotorasib will decrease the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

• sparsentan

  Serious - Use Alternative (1)cobicistat will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, interrupt treatment with sparsentan. When resuming sparsentan, consider dose titration.

• St John's Wort

  Serious - Use Alternative (1)St John's Wort will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid; coadministration with CYP3A inducers may result in decreased plasma concentrations of elvitegravir and/or a concomitantly administered protease inhibitor and lead to loss of therapeutic effect and to possible resistance

• stavudine

  Monitor Closely (1)emtricitabine and stavudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• stiripentol

  Monitor Closely (3)stiripentol, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol, cobicistat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  stiripentol will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Stiripentol is a BCRP transport inhibitor. Consider dosage reduction for BCRP substrates if adverse effects are experienced when coadministered.

• sufentanil

  Monitor Closely (1)cobicistat will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• sufentanil SL

  Monitor Closely (1)cobicistat will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

• sulindac

  Monitor Closely (1)emtricitabine, sulindac. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• sunitinib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• suvorexant

  Serious - Use Alternative (1)cobicistat will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tacrolimus

  Monitor Closely (1)cobicistat will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• tadalafil

  Serious - Use Alternative (1)cobicistat will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Adjust tadalafil dose for PAH; if on cobicistat, start tadalafil 20 mg/day and may increase up to 40 mg/day; avoid tadalafil when starting cobicistat; for ED, may take a single dose of tadalafil not exceeding 10 mg in 72 hr.

• tafamidis

  Monitor Closely (1)tafamidis will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

• tafamidis meglumine

  Monitor Closely (1)tafamidis meglumine will increase the level or effect of tenofovir AF by Other (see comment). Use Caution/Monitor. Tafamidis inhibits breast cancer resistant protein (BCRP) in vitro and may increase exposure of BCRP substrates following tafamidis or tafamidis meglumine administration. Dosage adjustment of these BCRP substrates may be necessary.

• talazoparib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.

• tamoxifen

  Serious - Use Alternative (1)cobicistat decreases effects of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Affecting hepatic/intestinal enzyme CYP3A4 metabolism. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity).

• tamsulosin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tazemetostat

  Monitor Closely (2)tazemetostat will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  tazemetostat will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)cobicistat will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with strong CYP3A4 inhibitors.

• tecovirimat

  Monitor Closely (2)tecovirimat will decrease the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
  
  tecovirimat will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• temsirolimus

  Monitor Closely (1)cobicistat will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration necessary, consider reducing temsirolimus dose to 12.5 mg per week; after discontinuing cobicistat, allow one week washout period before increaing cobicistat dose to its original level

• teniposide

  Serious - Use Alternative (1)cobicistat will increase the level or effect of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tenofovir DF

  Monitor Closely (1)emtricitabine and tenofovir DF both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• tepotinib

  Serious - Use Alternative (1)tepotinib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

• terbinafine

  Monitor Closely (1)cobicistat will increase the level or effect of terbinafine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tezacaftor

  Monitor Closely (1)cobicistat will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a strong CYP3A inhibitor.

• theophylline

  Monitor Closely (1)cobicistat will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• thioridazine

  Monitor Closely (1)cobicistat will increase the level or effect of thioridazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.

• tiagabine

  Monitor Closely (1)cobicistat will increase the level or effect of tiagabine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• ticagrelor

  Serious - Use Alternative (1)cobicistat will increase the level or effect of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• timolol

  Monitor Closely (1)cobicistat will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tinidazole

  Monitor Closely (1)cobicistat will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tipranavir

  Contraindicated (1)cobicistat will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Monitor Closely (2)tipranavir, elvitegravir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; unknown if tipranavir will elevate levels; there are no data available to alter current dosing recommendations; recommended dose is elvitegravir 150 mg PO once daily with tipranavir/ritonavir 500/200 mg PO BID.
  
  tipranavir and emtricitabine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.Serious - Use Alternative (1)tipranavir will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• tisotumab vedotin

  Monitor Closely (1)cobicistat increases levels of tisotumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tisotumab vedotin?s active metabolite (MMAE) is a CYP3A4 substrate. Coadministration with strong CYP3A4 inhibitors may increase unconjugated MMAE systemic exposure and increase risk of adverse effects.

• tofacitinib

  Serious - Use Alternative (1)cobicistat increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce tofacitinib dose to 5 mg qDay when coadministered with potent CYP3A4 inhibitors.

• tolmetin

  Monitor Closely (1)emtricitabine, tolmetin. Either increases levels of the other by decreasing renal clearance. Modify Therapy/Monitor Closely. Toxicity may result from coadministration of emtricitabine with other drugs that are also primarily excreted by glomerular filtration and/or active tubular secretion including high-dose or multiple-dose NSAIDs; alternatives to NSAIDs should be considered.

• tolterodine

  Serious - Use Alternative (1)cobicistat will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• tolvaptan

  Serious - Use Alternative (1)cobicistat will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• topotecan

  Serious - Use Alternative (1)cobicistat will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance

• toremifene

  Serious - Use Alternative (1)cobicistat will increase the level or effect of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• trabectedin

  Serious - Use Alternative (1)cobicistat will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

• tramadol

  Monitor Closely (2)cobicistat will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required
  
  cobicistat will increase the level or effect of tramadol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. A decreased dose of tramadol may be required

• trazodone

  Monitor Closely (1)cobicistat will increase the level or effect of trazodone by Other (see comment). Use Caution/Monitor. Trazodone is a substrate of CYP3A4 and CYP2D6; cobicistat inhibits CYP3A4 and CYP2D6 Serious - Use Alternative (1)cobicistat will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• triamcinolone acetonide injectable suspension

  Monitor Closely (1)cobicistat will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• triazolam

  Contraindicated (1)cobicistat will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Triazolam and midazolam (PO) are extensively metabolized by CYP3A. Coadministration of triazolam or midazolam (PO) may cause large increases in the concentrations of these benzodiazepines. Potential for serious and/or life-threatening events (eg, prolonged or increased sedation or respiratory depression).

• trimipramine

  Monitor Closely (3)cobicistat will increase the level or effect of trimipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of trimipramine by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.
  
  cobicistat will increase the level or effect of trimipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tucatinib

  Monitor Closely (1)tucatinib will increase the level or effect of tenofovir AF by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.Serious - Use Alternative (2)tucatinib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
  
  tucatinib will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• ublituximab

  Monitor Closely (2)ublituximab decreases effects of elvitegravir by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.
  
  ublituximab decreases effects of emtricitabine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely.

• ubrogepant

  Contraindicated (1)cobicistat will increase the level or effect of ubrogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

• ulipristal

  Monitor Closely (1)cobicistat will increase the level or effect of ulipristal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• umeclidinium bromide/vilanterol inhaled

  Monitor Closely (1)cobicistat will increase the level or effect of umeclidinium bromide/vilanterol inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• upadacitinib

  Monitor Closely (1)cobicistat will increase the level or effect of upadacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution if upadacitinib is coadministered with strong CYP3A4 inhibitors.

• valacyclovir

  Monitor Closely (1)valacyclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.

• valbenazine

  Monitor Closely (1)cobicistat will increase the level or effect of valbenazine by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Reduce valbenazine dose to 40 mg once daily when coadministered with a strong CYP3A4 inhibitor. Serious - Use Alternative (1)cobicistat will increase the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• valganciclovir

  Monitor Closely (2)valganciclovir increases levels of emtricitabine by Other (see comment). Use Caution/Monitor. Comment: Coadministration of emtricitabine with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of emtricitabine.
  
  valganciclovir, emtricitabine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of hematologic toxicity.

• vardenafil

  Monitor Closely (1)cobicistat will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit vardenafil dose to 2.5 mg/72 hr

• velpatasvir

  Monitor Closely (1)cobicistat will increase the level or effect of velpatasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vemurafenib

  Serious - Use Alternative (1)cobicistat will increase the level or effect of vemurafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• venetoclax

  Contraindicated (1)cobicistat will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of strong CYP3A4 inhibitors is contraindicated with venetoclax during the initial ramp-up dosing phase. If a strong CYP3A inhibitor must be used after the ramp-up phase, reduce the venetoclax dose by at least 75%.

• venlafaxine

  Monitor Closely (1)cobicistat will increase the level or effect of venlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• verapamil

  Monitor Closely (1)cobicistat will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (1)cobicistat will increase the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vilazodone

  Serious - Use Alternative (1)cobicistat will increase the level or effect of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vinblastine

  Monitor Closely (1)cobicistat will increase the level or effect of vinblastine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for hematologic or GI adverse effects that may be associated with increased systemic exposure to vinblastine. Consider temporarily withholding antiretroviral regimen in patients who develop significant hematologic or gastrointestinal side effects. If the antiretroviral regimen must be withheld for a prolonged period, consider initiating a revised regimen that does not include a CYP3A or P-gp inhibitor.

• vincristine

  Monitor Closely (1)cobicistat will increase the level or effect of vincristine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for hematologic or GI adverse effects that may be associated with increased systemic exposure to vincristine. Consider temporarily withholding antiretroviral regimen in patients who develop significant hematologic or gastrointestinal side effects. If the antiretroviral regimen must be withheld for a prolonged period, consider initiating a revised regimen that does not include a CYP3A or P-gp inhibitor.

• vincristine liposomal

  Serious - Use Alternative (1)cobicistat will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• vinorelbine

  Monitor Closely (1)cobicistat will increase the level or effect of vinorelbine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• voclosporin

  Contraindicated (1)cobicistat will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.Monitor Closely (2)voclosporin, tenofovir AF. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.
  
  voclosporin, elvitegravir. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

• vorapaxar

  Serious - Use Alternative (1)cobicistat will increase the level or effect of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• voriconazole

  Monitor Closely (2)voriconazole increases levels of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elvitegravir is a CYP3A4 substrate; if coadministered with strong CYP3A4 inhibitors may increase levels.
  
  cobicistat will increase the level or effect of voriconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of cobicistat with voriconazole is not recommended unless the benefit/risk assessment justifies the use.

• voxelotor

  Serious - Use Alternative (2)voxelotor will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
  
  voxelotor will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• warfarin

  Monitor Closely (2)elvitegravir will decrease the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.
  
  cobicistat will increase the level or effect of warfarin by Other (see comment). Use Caution/Monitor. Warfarin's less potent R-enantiomer is metabolized in part by CYP3A4 (and also CYP1A2 and CYP2C19). Monitor INR more frequently if coadministered with inhibitors of these isoenzymes and adjust warfarin dose if needed.

• zanubrutinib

  Monitor Closely (1)cobicistat will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous zanubrutinib dose.

• zidovudine

  Monitor Closely (1)emtricitabine and zidovudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

• zinc

  Monitor Closely (1)zinc will decrease the level or effect of elvitegravir by cation binding in GI tract. Modify Therapy/Monitor Closely. Administer elvitegravir 2 hr before or 6 hr after administration of polyvalent cation containing products.

• zolpidem

  Serious - Use Alternative (1)cobicistat will increase the level or effect of zolpidem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.