cobicistat (Rx)

Brand and Other Names:Tybost

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 150mg

Pharmacokinetic Enhancer for HIV Treatment

Indicated to increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents (ARTs) in the treatment of HIV-1 infection

Coadministered with atazanavir

  • May use for treatment-naïve or experienced
  • 150 mg PO qDay with atazanavir 300 mg PO qDay plus other ARTs

Coadministered with darunavir

  • May use for treatment-naïve or treatment-experienced with no darunavir resistance-associated substitutions
  • 150 mg PO qDay with darunavir 800 mg PO qDay plus other ARTs

Dosage Modifications

Refer to prescribing information for darunavir and atazanavir for dosage modifications

Renal impairment

  • Mild-to-severe: No dosage adjustment necessary
  • Coadministered with tenofovir DF
    • CrCl <70 mL/min: Coadministration with tenofovir DF not recommended
    • Dose adjustment of tenofovir is required for CrCl <50 mL/min, and such dose adjustments not established for coadministration with cobicistat

Hepatic impairment

  • Mild-to-moderate: No dosage adjustment necessary
  • Severe: No data

Dosing Considerations

Limitations of use

  • Cobicistat is not interchangeable with ritonavir and cobicistat use is not recommended to increase systemic exposure of darunavir 600 mg BID, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data
  • Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain cobicistat interactions
  • Cobicistat and ritonavir when administered with either atazanavir or darunavir may result in different drug interactions when used with concomitant medications

Laboratory testing before and during treatment

  • Before initiating: Test for hepatitis B infection
  • Before initiating and during treatment: Assess eCrCl; cobicistat decreases eCrCl because of tubular secretion inhibition of creatinine; however, it does not affect actual renal glomerular function
  • Coadministration with tenofovir DF: Assess eCrCl, urine glucose, and urine protein at baseline
  • Patients with chronic kidney disease: Assess eCrCl, urine glucose, urine protein, and serum phosphorus at baseline

Not recommended during pregnancy

  • Do not initiate cobicistat with darunavir or atazanavir during pregnancy
  • Coadministered with darunavir or atazanavir is not recommended during pregnancy owing to substantially lower systemic exposures of darunavir and cobicistat during the second and third trimesters

Dosage Forms & Strengths

tablet

  • 150mg

Pharmacokinetic Enhancer for HIV Treatment

Indicated to increase systemic exposure of atazanavir or darunavir (once daily dosing regimen) in combination with other antiretroviral agents (ARTs) in the treatment of HIV-1 infection in pediatric patients

Coadministration with atazanavir

  • Indicated for treatment-naïve or treatment experienced patients
  • <35 kg: Safety and efficacy not established
  • ≥35 kg: Cobicistat 150 mg PO qDay plus atazanavir (300 mg PO qDay) plus other ARTs

Coadministration with darunavir

  • Indicated for treatment-naïve or treatment experienced patients with no darunavir resistance-associated substitutions
  • <40 kg: Safety and efficacy not established
  • ≥40 kg: Cobicistat 150 mg PO qDay plus darunavir (800 mg PO qDay) plus other ARTs

Dosage Modifications

Refer to prescribing information for darunavir and atazanavir for dosage modifications

Renal impairment

  • Mild-to-severe: No dosage adjustment necessary
  • Coadministered with tenofovir DF
    • CrCl <70 mL/min: Coadministration with tenofovir DF not recommended
    • Dose adjustment of tenofovir is required for CrCl <50 mL/min, and such dose adjustments not established for coadministration with cobicistat

Hepatic impairment

  • Mild-to-moderate: No dosage adjustment necessary
  • Severe: No data

Dosing Considerations

Limitations of use

  • Cobicistat is not interchangeable with ritonavir and cobicistat use is not recommended to increase systemic exposure of darunavir 600 mg BID, fosamprenavir, saquinavir, or tipranavir due to lack of exposure data
  • Complex or unknown mechanisms of drug interactions preclude extrapolation of ritonavir drug interactions to certain cobicistat interactions
  • Cobicistat and ritonavir when administered with either atazanavir or darunavir may result in different drug interactions when used with concomitant medications

Laboratory testing before and during treatment

  • Before initiating: Test for hepatitis B infection
  • Before initiating and during treatment: Assess eCrCl; cobicistat decreases eCrCl because of tubular secretion inhibition of creatinine; however, it does not affect actual renal glomerular function
  • Coadministration with tenofovir DF: Assess eCrCl, urine glucose, and urine protein at baseline
  • Patients with chronic kidney disease: Assess eCrCl, urine glucose, urine protein, and serum phosphorus at baseline

Not recommended during pregnancy

  • Do not initiate cobicistat with darunavir or atazanavir during pregnancy
  • Coadministered with darunavir or atazanavir is not recommended during pregnancy owing to substantially lower systemic exposures of darunavir and cobicistat during the second and third trimesters
Next:

Interactions

Interaction Checker

and cobicistat

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      Serious - Use Alternative

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            Contraindicated (40)

            • 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.

            • 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

              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.

            • 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.

            • mavacamten

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

            • 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.

            • pacritinib

              cobicistat will increase the level or effect of pacritinib 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.

            • 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.

            • ritonavir

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

            • sildenafil

              cobicistat will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. When used chronically for PAH, sildenafil is contraindicated for use with cobicistat; if used for erectile dysfunction, do not exceed sildenafil 25 mg q48hr

            • simvastatin

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

            • tipranavir

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

            • triazolam

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

            • ubrogepant

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

            • venetoclax

              cobicistat will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Use of strong CYP3A4 inhibitors is contraindicated with venetoclax during the initial ramp-up dosing phase. If a strong CYP3A inhibitor must be used after the ramp-up phase, reduce the venetoclax dose by at least 75%.

            • voclosporin

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

            Serious - Use Alternative (157)

            • acalabrutinib

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

            • adagrasib

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

            • ado-trastuzumab emtansine

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

            • alpelisib

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

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

            • apalutamide

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

            • 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

              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.

            • 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

            • ceritinib

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

            • chloramphenicol

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

            • clarithromycin

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

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

            • copanlisib

              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 cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • daridorexant

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

            • darunavir

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

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

            • dexamethasone

              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.

            • elacestrant

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

            • elbasvir/grazoprevir

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

            • 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.

            • eszopiclone

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

            • etravirine

              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.

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

            • everolimus

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

            • fedratinib

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

            • felbamate

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

            • fentanyl transdermal

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

            • fentanyl transmucosal

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

            • fexinidazole

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

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

            • fidaxomicin

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

            • flutamide

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

            • fosaprepitant

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

            • fosphenytoin

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

            • futibatinib

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

            • gilteritinib

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

            • glasdegib

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

            • guanfacine

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

            • ibrutinib

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

            • idelalisib

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

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

            • indinavir

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

            • infigratinib

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

            • itraconazole

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

            • ivosidenib

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

              ivosidenib will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ixabepilone

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

            • ketoconazole

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

            • lapatinib

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

            • larotrectinib

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

            • lefamulin

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

            • lemborexant

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

            • leniolisib

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

            • levoketoconazole

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

            • levomilnacipran

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

            • levonorgestrel intrauterine

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

            • lomitapide

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

            • lorlatinib

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

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

            • lurbinectedin

              cobicistat will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce lurbinectedin dose by 50%. After strong CYP3A inhibitor discontinued for 5 half-lives, increase lurbinectedin to dose used before coadministration.

            • 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.

            • mitotane

              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.

            • 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

              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

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

            • nicardipine

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

            • nimodipine

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

            • nisoldipine

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

            • olaparib

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

            • omaveloxolone

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

            • ombitasvir/paritaprevir/ritonavir

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

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

            • osimertinib

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

            • oxcarbazepine

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

            • ozanimod

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

            • palbociclib

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

            • palovarotene

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

            • 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.

            • 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 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 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.

            • pirtobrutinib

              cobicistat will increase the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration is unavoidable, reduce pirtobrutinib by 50 mg. If current pirtobrutinib dose is 50 mg qDay, discontinue pirtobrutinib for duration of strong CYP3A inhibitor use. Once strong CYP3A inhibitor discontinued for 5 half-lives, resume pirtobrutinib at the dose taken before initiating the strong CYP3A inhibitor.

            • 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.

            • rifapentine

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

            • rimegepant

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

              cobicistat will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP.

            • riociguat

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

            • ritonavir

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

            • rivaroxaban

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

            • ruxolitinib

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

            • ruxolitinib topical

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

            • salmeterol

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

            • saquinavir

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

              cobicistat will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

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

            • saxagliptin

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

            • selumetinib

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

            • siponimod

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

            • solifenacin

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

            • sonidegib

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

            • sparsentan

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

            • sunitinib

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

            • suvorexant

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

            • tadalafil

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

            • talazoparib

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

            • tamoxifen

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

            • tamsulosin

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

            • tazemetostat

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

            • teniposide

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

            • 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.

            • valbenazine

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

            • vemurafenib

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

            • vilanterol/fluticasone furoate inhaled

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

            • vilazodone

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

            • vincristine liposomal

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

            • vorapaxar

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

            • voxelotor

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

            • zolpidem

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

            Monitor Closely (198)

            • 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.

            • alfentanil

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

            • 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.

            • 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 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

            • 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.

            • chlordiazepoxide

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

            • 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.

            • 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.

            • 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.

            • 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.

            • 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

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

            • elagolix

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

            • enfortumab vedotin

              cobicistat increases toxicity of enfortumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Enfortumab vedotin is an antibody-drug conjugate that releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE is primarily metabolized by CYP3A4 in vitro. Coadministration with strong CYP3A4 inhibitors may increase free MMAE exposure, which may increase the incidence or severity of toxicities.

              cobicistat will increase the level or effect of enfortumab vedotin by Other (see comment). Use Caution/Monitor. Coadministration with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) exposure, which may increase the risk of enfortumab vedotin toxicities. Closely monitor for signs of toxicities.

            • enzalutamide

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

            • 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.

            • 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.

            • 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.

            • 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

            • 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.

            • 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.

            • 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

            • 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

              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.

            • isoniazid

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

            • isradipine

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

            • 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.

            • 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

              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.

            • lansoprazole

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

            • lenacapavir

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

            • letermovir

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

            • levamlodipine

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

            • levoketoconazole

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

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

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

            • lidocaine

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

            • losartan

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

            • lumacaftor/ivacaftor

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

            • lumateperone

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

            • lumefantrine

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

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

            • 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

            • 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

            • methylprednisolone

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

            • metoprolol

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

            • mexiletine

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

            • mifepristone

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

            • mirtazapine

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

            • mirvetuximab soravtansine

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

            • mometasone inhaled

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

            • mometasone, intranasal

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

            • naldemedine

              cobicistat increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

              cobicistat increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

            • nefazodone

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

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

            • 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.

            • norgestrel

              cobicistat will increase the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may increase systemic concentration of norgestrel, which may increase risk for adverse effects

            • 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.

            • 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.

            • 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.

            • 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

              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.

            • quizartinib

              cobicistat will increase the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce quizartinib dosage to 26.5 mg qDay (if current dosage is 53 mg/day) or 17.7 mg qDay (if current dosage is 26.5 mg/day or 35.4 mg/day) when coadministered with strong CYP3A inhibitors. If current dosage is 17.7 mg qDay, interrupt quizartinib for the duration of strong CYP3A inhibitor use. After discontinuation of a strong CYP3A inhibitor for 5 half-lives, resume quizartinib dose that was taken before initiating the strong inhibitor.

            • 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

              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

              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.

            • 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.

            • 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 cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • 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.

            • 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.

            • stiripentol

              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.

            • 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 cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              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

            • 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.

            • 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.

            • 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.

            • vardenafil

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

            • velpatasvir

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

            • venlafaxine

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

            • verapamil

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

            • vinblastine

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

            • vincristine

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

            • vinorelbine

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

            • voriconazole

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

            • zanubrutinib

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

            Minor (5)

            • acetazolamide

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

            • anastrozole

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

            • cyclophosphamide

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

            • ganaxolone

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

            • ixazomib

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

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            Adverse Effects

            Note: Adverse effects listed below are for cobicistat coadministered with atazanavir

            >10%

            Total bilirubin >2.5x ULN (65%)

            Ocular icterus, all grades (15%)

            Jaundice, all grades (13%)

            Nausea, all grades (12%)

            1-10%

            Creatine kinase >10x ULN (5%)

            Jaundice, Grades 2-4 (5%)

            Rash, Grades 2-4 (5%)

            Serum amylase >2x ULN (4%)

            ALT or AST >5x ULN (3%)

            Glycosuria >1000 mg/dL (3%)

            Urine RBC >75 RBC/HPF (3%)

            Ocular icterus Grades 2-4 (3%)

            GGT >5x ULN (2%)

            Nausea, Grades 2-4 (2%)

            <2%

            Gastrointestinal disorders: Diarrhea, vomiting, upper abdominal pain

            General disorders and administration site conditions: Fatigue

            Musculoskeletal and connective-tissue disorders: Rhabdomyolysis

            Nervous system disorders: Headache

            Psychiatric disorders: Depression, abnormal dreams, insomnia

            Renal and urinary disorders: Nephropathy, Fanconi syndrome acquired

            Frequency Not Defined

            Increased triglycerides, +15 from baseline

            Increased LDL-C, +5 from baseline

            Increased total cholesterol, +4 from baseline

            Increased HDL-C, +3 from baseline

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            Warnings

            Contraindications

            Coadministration of cobicistat with atazanavir or darunavir and the following drugs is contraindicated owing to potential for serious and/or life-threatening events or loss of therapeutic effect

            • Alfuzosin
            • Amiodarone
            • Carbamazepine, phenobarbital, phenytoin
            • Rifampin
            • Irinotecan (when administered with atazanavir)
            • Lurasidone, pimozide
            • Dihydroergotamine, ergotamine, methylergonovine
            • Cisapride
            • St. John’s wort (Hypericum perforatum)
            • Drospirenone/ethinyl estradiol (when administered with atazanavir)
            • Lomitapide, lovastatin, simvastatin
            • Nevirapine (when administered with atazanavir)
            • Sildenafil when administered for pulmonary arterial hypertension
            • Indinavir (when administered with atazanavir)
            • Triazolam, orally administered midazolam

            Cautions

            Cobicistat may cause modest increases in serum creatinine and modest declines in CrCl without affecting renal glomerular function; serum creatinine >0.4 mg/dL from baseline should be closely monitored for renal safety; assess CrCl before administering

            New-onset or worsening renal impairment reported when used with antiretroviral regimens containing tenofovir; do not use with tenofovir if CrCl <70 mL/min

            Assess urine glucose and urine protein at baseline and monitor ClCr, urine glucose, and urine protein when using with tenofovir; monitor serum phosphorus in patients with or at risk for renal impairment

            CYP inducers may lower systemic exposure of cobicistat and atazanavir or darunavir, resulting in loss of virologic response

            Cobicistat is an inhibitor of CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3; plasma concentration of drugs that are substrates of the aforementioned isoenzymes or transporters may be increased if coadministered with cobicistat

            Antiretrovirals that are not recommended

            • The following are NOT recommended in combination with cobicistat because dosing recommendations for the combinations have not been established
            • Coadministration may result in decreased plasma concentrations of the antiretroviral agents, leading to loss of therapeutic effect and development of resistance
            • More than 1 antiretroviral that requires pharmacokinetic enhancement (ie, 2 protease inhibitors or a protease inhibitor in combination with elvitegravir)
            • Darunavir in combination with efavirenz, nevirapine, or etravirine
            • Atazanavir in combination with etravirine
            • Atazanavir in combination with efavirenz in treatment-experienced patients
            • Darunavir 600 mg BID
            • Other HIV-1 protease inhibitors, including fosamprenavir, saquinavir, or tipranavir
            • Stribild fixed-dose combination tablets (elvitegravir, cobicistat, emtricitabine, tenofovir) are not recommended because cobicistat is a component of Stribild
            • Cobicistat in combination with lopinavir/ritonavir or regimens containing ritonavir are not recommended, owing to similar effects of cobicistat and ritonavir on CYP3A
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            Pregnancy & Lactation

            Pregnancy

            Coadministration with darunavir or atazanavir is not recommended during pregnancy

            In a clinical trial of individuals taking cobicistat coadministered with darunavir, exposures of cobicistat and darunavir were substantially lower during the second and third trimesters of pregnancy

            Refer to prescribing information of darunavir and atazanavir about pregnancy

            Animal data

            • In animal reproduction studies in rats and rabbits, no evidence of fetal harm was observed with oral administration of cobicistat during organogenesis at doses that produced exposures up to 1.4x and 3.3x the maximal recommended human dose (MRHD) of 150 mg

            ART pregnancy registry

            • Pregnancy exposure registry that monitors fetal outcomes in individuals exposed to drug during pregnancy
            • Encourage to register patients by calling Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

            Contraception

            • Cobicistat interacts with certain oral contraceptives

            Lactation

            There is no information regarding presence of cobicistat in human milk, the effects on the breastfed infant, or the effects on milk production

            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

            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

            CYP3A4 inhibitor; mechanism-based pharmaco-enhancer, first product to be developed and submitted solely as pharmacokinetic booster for elvitegravir; enhances the systemic exposure of ART CYP3A substrates (ie, atazanavir, darunavir), where bioavailability is limited and half-life is shortened by CYP3A-dependent metabolism

            Absorption

            Peak Plasma Time: 3.5 hr

            Peak Plasma Concentration: 0.99 mcg/mL

            Trough Plasma Concentration: 0.03 mcg/mL

            AUC: 7.6 mcg•hr/mL

            Distribution

            Protein bound: 97-98%

            Metabolism

            Metabolized by CYP3A4 and CYP2D6 (minor)

            Inhibits CYP3A, CYP2D6, p-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3

            Elimination

            Half-life: 3-4 hr

            Excretion: 86.2% feces; 8.2% urine

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            Administration

            Oral Administration

            Must be coadministered with atazanavir or darunavir at the same time, with food, and in combination with other HIV-1 antiretroviral agents

            Coadministration with acid-modifying drugs

            • Atazanavir systemic exposure is decreased if administered comcomitantly with acid modifying drugs
            • Antacids containing aluminum or magnesium hydroxide: Administer antacids at least 2 hr before or after cobicistat with atazanavir
            • H2-receptor antagonists: Administer either at the same time or take cobicistat with atazanavir a minimum of 10 hr after administering H2-receptor antagonists
            • Proton pump inhibitors: Take cobicistat with atazanavir a minimum of 12 hr after administering proton pump inhibitors

            Storage

            Tablets: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Tybost oral
            -
            150 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            cobicistat oral

            COBICISTAT - ORAL

            (koe-BIK-i-stat)

            COMMON BRAND NAME(S): Tybost

            USES: This drug is used to increase ("boost") the levels of certain HIV protease inhibitors (atazanavir and darunavir). This helps them work better to help control HIV infection.Cobicistat is not a cure for HIV infection. To decrease your risk of spreading HIV disease to others, continue to take all HIV medications exactly as prescribed by your doctor. Use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity as directed by your doctor. Do not share personal items (such as needles/syringes, toothbrushes, and razors) that may have contacted blood or other body fluids. Consult your doctor or pharmacist for more details.

            HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking cobicistat and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with food as directed by your doctor, usually once daily. Take cobicistat at the same time as your HIV protease inhibitor.It is very important to continue taking this medication (and other HIV medications) exactly as prescribed by your doctor. Do not skip any doses.This medication works best when the amount of drug in your body is kept at a constant level. Take this drug at evenly spaced intervals. To help you remember, take it at the same time each day.Do not take more or less of this drug than prescribed or stop taking it (or other HIV medicines) even for a short time unless directed to do so by your doctor. Doing so may cause the amount of virus to increase, make the infection more difficult to treat (resistant), or worsen side effects.

            SIDE EFFECTS: Nausea may occur. If this lasts or gets worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.As your immune system gets stronger, it can begin to fight off infections you already had, possibly causing disease symptoms to come back. You could also have symptoms if your immune system becomes overactive. This reaction may happen at any time (soon after starting HIV treatment or many months later). Get medical help right away if you have any serious symptoms, including: unexplained weight loss, severe tiredness, muscle aches/weakness that doesn't go away, headaches that are severe or don't go away, joint pain, numbness/tingling of the hands/feet/arms/legs, vision changes, signs of infection (such as fever, chills, swollen lymph nodes, trouble breathing, cough, non-healing skin sores), signs of an overactive thyroid (such as irritability, nervousness, heat intolerance, fast/pounding/irregular heartbeat, bulging eyes, unusual growth in the neck/thyroid known as a goiter), signs of a certain nerve problem known as Guillain-Barre syndrome (such as unsteadiness, loss of coordination, trouble swallowing/speaking/chewing, trouble moving your eyes).Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn't stop, loss of appetite, stomach/abdominal pain, yellowing eyes/skin, dark urine.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking cobicistat, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication is not recommended for use during pregnancy. It may not work well in a pregnant woman. If you become pregnant or think you may be pregnant, tell your doctor right away. Your doctor may change your HIV medications.It is unknown if this medication passes into breast milk. Because breast milk can transmit HIV, do not breast-feed.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: elvitegravir, orlistat, ritonavir.This medication can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include certain alpha blockers (such as alfuzosin, tamsulosin), certain benzodiazepines (such as midazolam, triazolam), dronedarone, ergot alkaloids (such as dihydroergotamine, ergotamine), quinidine, pimozide, ranolazine, rivaroxaban, salmeterol, certain drugs to treat erectile dysfunction-ED or pulmonary hypertension (such as avanafil, sildenafil), certain "statin" cholesterol drugs (lovastatin, simvastatin), among others.Other medications can affect the removal of cobicistat from your body, which may affect how cobicistat works. Examples include certain drugs used to treat seizures (such as carbamazepine, phenobarbital, phenytoin, primidone), enzalutamide, certain HIV NNRTI drugs (such as efavirenz, etravirine, nevirapine), mitotane, rifampin, St. John's wort, among others.This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Talk to your doctor about additional or alternative reliable forms of birth control, and use an effective barrier method (latex or polyurethane condoms/dental dams) during sexual activity to decrease the risk of spreading HIV to others. Tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your hormonal birth control is not working well.Do not take this medication with other products that contain cobicistat.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.Lab and/or medical tests (such as kidney function) may be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember, unless it is less than 12 hours until the next dose. In that case, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store in the original container at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised December 2022. Copyright(c) 2023 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.