Dosing & Uses
Dosage Forms & Strengths
elvitegravir/cobicistat/emtricitabine/tenofovir AF
tablet
- 150mg/150mg/200mg/10mg
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
Dosage Forms & Strengths
elvitegravir/cobicistat/emtricitabine/tenofovir AF (tenofovir alafenamide)
tablet
- 150mg/150mg/200mg/10mg
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
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

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.
Adverse Effects
1-10%
Nausea (10%)
Diarrhea (7%)
Creatine kinase ≥10 x ULN (7%)
Headache (6%)
Fatigue (5%)
LDL-C >190 mg/dL (5%)
Total cholesterol >300 mg/dL (2%)
Postmarketing Reports
Suicidal ideation, suicidal behavior, and suicide attempt
Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome
Warnings
Black Box Warnings
Post treatment acute exacerbation of hepatitis B
- Severe acute exacerbations of hepatitis B reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation treatment
- Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue treatment
- If appropriate, antihepatitis B therapy may be warranted
Contraindications
Coadministration with drugs highly dependent on CYP3A for clearance
- Alfuzosin
- Carbamazepine, phenobarbital, phenytoin
- Rifampin
- Lurasidone, pimozide
- Dihydroergotamine, ergotamine, methylergonovine
- Cisapride
- St. John’s wort (Hypericum perforatum)
- Lomitapide, lovastatin, simvastatin
- Phosphodiesterase-5 (PDE-5) inhibitor: Sildenafil when administered for treatment of pulmonary arterial hypertension
- Midazolam, triazolam
Cautions
Lactic acidosis and severe hepatomegaly with steatosis reported; treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations)
Test patients with HIV-1 infection for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy (ART); not approved for the treatment of chronic HBV infection (see Black Box Warnings)
Fat redistribution and accumulation observed with ART therapy
Immune reconstitution syndrome reported, including the occurrence of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barre syndrome) with variable time to onset; autoimmune disorder can occur many months after initiation of treatment; during initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment
New-onset or worsening renal impairment
- Measure serum creatinine, serum phosphorous, estimated CrCl, urine glucose, and urine protein before initiating drug and during therapy in all patients as clinically appropriate
- Avoid concurrent or recent use of nephrotoxic drugs; patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions
- Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome reported with tenofovir AF-containing products; monitor estimated CrCl, urine glucose, and urine protein in all patients prior to initiating and during therapy; additionally, monitor serum phosphorus in patients with or at risk for renal impairment
- Discontinue drug if clinically significant decreases in renal function or evidence of Fanconi syndrome develop
- Cobicistat may cause modest increases in serum creatinine and modest declines in CrCl without affecting renal glomerular function; the elevation is typically seen within 2 weeks of starting therapy and is reversible after discontinuation; serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety
- Do not initiate with CrCl <30 mL/min
Drug interactions overview
- Avoid coadministration of Genvoya and other antiretroviral medications for HIV-1 since Genvoya is a complete HIV infection
- Concomitant use with other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effects and possible development of resistance
- Concomitant use with other drugs may result in known or potentially significant drug interactions, some of which may lead to loss of therapeutic effects and possible development of resistance
- Cobicistat an inhibitor of CYP3A and CYP2D6 and an inhibitor of the following transporters: P-glycoprotein (P-gp), BCRP, OATP1B1 and OATP1B3; coadministration with drugs that are primarily metabolized by CYP3A or CYP2D6, or P-gp, BCRP, OATP1B1 or OATP1B3 substrates may result in increased plasma concentrations of such drugs
- Elvitegravir is a modest CYP2C9 inducer and may decrease plasma concentrations of CYP2C9 substrates TAF is a weak CYP3A inhibitor
- Emtricitabine and tenofovir are primarily excreted by the kidneys; coadministration of Genvoya with drugs that reduce renal function or compete for active tubular secretion may increase concentrations and effects of emtricitabine, tenofovir, and other renally eliminated drugs
Pregnancy
Pregnancy
Not recommended for use during pregnancy; substantially lower exposures of cobicistat and elvitegravir reported during second and third trimesters
Available data from the Antiretroviral Pregnancy Registry (APR) show no statistically significant difference in the overall risk of major birth defects for emtricitabine (FTC), rilpivirine (RPV) or tenofovir alafenamide (TAF)
Avoid use in pregnant individuals; an alternative regimen is recommended for individuals who become pregnant during therapy
Pregnancy exposure registry
- Monitors pregnancy outcomes in individuals exposed to drug during pregnancy
- Register patients by calling the APR at 1-800-258 4263
Animal data
-
No adverse developmental effects observed in following
- Elvitegravir (EVG): In rats and rabbits exposed to up to 23x and 0.2x during organogenesis
- Cobicistat (COBI): In rats and rabbits exposed to up to 1.6x and 3.8x during organogenesis
- FTC: In mice and rabbits exposed to up to 60x and 108x during organogenesis
- TAF: In rats and rabbits exposed to 53x during organogenesis
Lactation
The Centers for Disease Control and Prevention do not recommend HIV-infected mothers breastfeed their infants due to potential risk for postnatal transmission of HIV
FTC has been shown to be present in human breast milk; it is unknown if EVG, COBI, and TAF are present in human breast milk
EVG and COBI are present in rat milk, and tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration of TDF
Owing to the potential for HIV transmission (in HIV-negative infants); developing viral resistance (in HIV-positive infants); and adverse reactions in a breastfed infant like those seen in adults, instruct mothers not to breastfeed
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Elvitegravir: Integrase inhibitor; inhibits catalytic activity (ie, strand transfer) of HIV-1 integrase, an HIV encoded enzyme required for viral replication; CYP3A4 substrate
Cobicistat: CYP3A4 inhibitor; mechanism-based pharmaco-enhancer, first product to be developed and submitted solely as pharmacokinetic booster for elvitegravir; enhances the systemic exposure of CYP3A substrates, such as elvitegravir, where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism
Emtricitabine: Synthetic nucleoside analog of cytidine and is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate (active); inhibits the activity of the HIV-1 RT by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA, which results in chain termination
Tenofovir alafenamide (AF): Prodrug of tenofovir; compared with tenofovir disoproxil fumarate (tenofovir DF, Viread), tenofovir AF is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile; inhibits HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination
Absorption
Food increases mean systemic exposure of elvitegravir by 34%
A high fat meal (~800 kcal, 50% fat) increases mean systemic exposure of elvitegravir by 87%
Elvitegravir
- Peak plasma time: 4 hr
- Peak plasma concentration: 1.7 mcg/mL
- Trough plasma concentration: 0.45 mcg/mL
- AUC: 23 mcg•hr/mL
Cobicistat
- Peak plasma time: 3 hr
- Peak plasma concentration: 1.1 mcg/mL
- Trough plasma concentration: 0.05 mcg/mL
- AUC: 8.3 mcg•hr/mL
Emtricitabine
- Peak plasma time: 3 hr
- Peak plasma concentration: 1.9 mcg/mL
- Trough plasma concentration: 0.14 mcg/mL
- AUC: 12.7 mcg•hr/mL
Tenofovir
- Peak plasma time: 1 hr
- Peak plasma concentration: 0.16 mcg/mL
- AUC: 0.21 mcg•hr/mL
Distribution
Elvitegravir
- Protein Bound: 98-99%
Cobicistat
- Protein Bound: 97-98%
Emtricitabine
- Protein Bound: <4%
Tenofovir
- Protein Bound: 80%
- Vd: 1.2-1.3 L/kg
Metabolism
Elvitegravir
- Metabolized by CY3A4 (major)
- Also undergoes glucuronidation via UGT1A1/3 enzymes
Cobicistat
- Metabolized by CYP3A4 (major) and CYP2D6 (minor)
- Strong CYP3A4 inhibitor
Emtricitabine
- Not significantly metabolized
- Metabolized by oxidation
Tenofovir
- Tenofovir AF (TAF) is hydrolyzed within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate
- In vitro studies have shown that TAF is metabolized to tenofovir by cathepsin A in PBMCs and macrophages; and by CES1 in hepatocytes
- Upon coadministration with the moderate CYP3A inducer probe efavirenz, TAF exposure was unaffected
Elimination
Elvitegravir
- Half-life: 12.9 hr
- Excretion: 94.8% feces; 6.7% urine
Cobicistat
- Half-life: 3.5 hr
- Excretion: 86.2% feces; 8.2% urine
Emtricitabine
- Half-life: 10 hr
- Dialyzable: 30% removed by hemodialysis
- Excretion: 70% urine; 14% feces
Tenofovir
- Half-life: 0.51 hr
- Excretion: 31.7% feces; <1% urine
Administration
Oral Administration
For oral use only
Take with food
Storage
Store below 30°C (86°F)
Keep container tightly closed
Dispense only in original container
Do not use if seal over bottle opening is broken or missing
Images
Formulary
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