elvitegravir/cobicistat/emtricitabine/tenofovir AF (Rx)

Brand and Other Names:Genvoya
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

elvitegravir/cobicistat/emtricitabine/tenofovir AF

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

1 tablet PO qDay with food

See also Administration

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

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
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Interactions

Interaction Checker

and elvitegravir/cobicistat/emtricitabine/tenofovir AF

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            Contraindicated (33)

            • 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.

            • 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.

            • ergonovine

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

            • ergotamine

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

            • finerenone

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

            • flibanserin

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

            • indinavir

              cobicistat will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated with cobicistat coadministered with atazanavir only; both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia

            • irinotecan

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

            • irinotecan liposomal

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

            • isavuconazonium sulfate

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

            • ivabradine

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

            • lonafarnib

              cobicistat will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            • lovastatin

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

            • lurasidone

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

            • methylergonovine

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

            • midazolam

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

            • naloxegol

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

            • pimozide

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

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

            • ranolazine

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

            • ribociclib

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

            • rifampin

              rifampin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration with rifampin is contraindicated due to potential for loss of therapeutic effect and development of resistance.

            Serious - Use Alternative (156)

            • 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.

            • apalutamide

              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.

            • 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.

            • aprepitant

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

            • 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.

            • 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

              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

            • 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.

            • 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.

            • 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

              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

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

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

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

            • 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

              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

            • dexamethasone

              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

              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

            • dihydroergotamine intranasal

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

            • 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.

              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

            • 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

            • enzalutamide

              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

            • 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.

            • 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.

            • 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.

              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

            • 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.

            • 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

            • 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.

            • infigratinib

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

            • 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. If coadministration of larotrectinib with strong CYP3A4 inhibitors is unavoidable, reduce larotrectinib dose by 50%. Resume prior larotrectinib dose once CYP3A4 inhibitor discontinued for 3-5 half-lives.

            • 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.

            • 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.

            • 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

              cobicistat will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir 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.

            • 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.

            • 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.

            • ticagrelor

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

            • tipranavir

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

            • tofacitinib

              cobicistat increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce tofacitinib dose to 5 mg qDay when coadministered with potent CYP3A4 inhibitors.

            • tolterodine

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

            • tolvaptan

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

            • topotecan

              cobicistat will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance

            • toremifene

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

            • trabectedin

              cobicistat will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If strong CYP3A inhibitor must be used, short-term (eg, less than 14 days), administer strong CYP3A inhibitor 1 week after trabectedin infusion, and discontinue the day prior to next trabectedin infusion

            • trazodone

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

            • tucatinib

              tucatinib will increase the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              tucatinib will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • valbenazine

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

            • voxelotor

              voxelotor will increase the level or effect of elvitegravir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (255)

            • 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.

            • 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.

            • apixaban

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

            • 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.

            • 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.

            • 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.

            • 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.

              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, 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.

            • 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

              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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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 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.

            • 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.

            • 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.

            • saquinavir

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

            • 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.

            • sofosbuvir/velpatasvir

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

            • 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.

            • sufentanil

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

            • 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.

            • 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.

            • 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.

            • 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.

            • 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, 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.

            • 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.

            • 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.

            • 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

              cobicistat, warfarin. Other (see comment). Use Caution/Monitor. Comment: Effect unknown; monitor INR .

            • zidovudine

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

            • zanubrutinib

              cobicistat will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib dose when coadministered with a strong CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib. See zanubrutinib Dosage Modifications for precise recommendation.

            • 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 (5)

            • abiraterone

              cobicistat will increase the level or effect of abiraterone 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.

            • 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.

            • 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.

            • naloxone

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

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            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

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            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
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            Pregnancy

            Pregnancy

            An ART pregnancy registry has been established (1-800-258-4263); Available data from the APR show no statistically significant difference in the overall risk of major birth defects for emtricitabine (FTC), rilpivirine (RPV) or tenofovir alafenamide (TAF) compared with the background rate for major birth defects of 2.7% in a US reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data); the rate of miscarriage is not reported in the APR

            Not recommended for use during pregnancy because of substantially lower exposures of cobicistat and elvitegravir during second and third trimesters

            Avoid use in pregnant individuals; an alternative regimen is recommended for individuals who become pregnant during therapy

            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

            Emtricitabine has been shown to be present in human breast milk; it is unknown if elvitegravir, cobicistat, and TAF are present in human breast milk

            Elvitegravir and cobicistat 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 similar to 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.

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            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
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            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

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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.