atazanavir/cobicistat (Rx)

Brand and Other Names:Evotaz

Dosing & Uses

AdultPediatric

HIV-1 Infection

Indicated in combination with other antiretroviral (ART) agents for treatment of human immunodeficiency virus type 1 (HIV-1)

1 tablet (300 mg/150 mg) PO qDay with food

Dosage Modifications

Hepatic impairment

  • Do not use in patients with any degree of hepatic impairment

Renal impairment

  • CrCl <70 mL/min: Coadministered with tenofovir disoproxil fumarate (DF) is not recommended
  • End-stage renal disease (ESRD) with hemodialysis: Not recommended
  • Concomitant or recent use of nephrotoxic drug: Atazanavir/cobicistat plus tenofovir DF is not recommended

Dosage Considerations

Limitations of use: Use in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions

Pregnancy

  • Not recommended for use during pregnancy; do not initiate in pregnant individuals
  • Recommend an alternative regimen for females who become pregnant during therapy

Laboratory testing before initiation and during treatment

Assess estimated CrCl, serum creatinine, and urinalysis with microscopic examination

Coadministration with tenofovir DF: Assess estimated CrCl, urine glucose, and urine protein

Patients with chronic kidney disease: Monitor serum phosphorus

Patients with underlying hepatitis B or C viral infections: Perform hepatic laboratory testing

HIV-1 Infection

Indicated in combination with other antiretroviral (ART) agents for treatment of human immunodeficiency virus type 1 (HIV-1) in patients who weigh at least 35 kg

<35 kg: Safety and efficacy not established

≥35 kg

1 tablet (300 mg/150 mg) PO qDay with food

Dosage Modifications

Hepatic impairment

  • Do not use in patients with any degree of hepatic impairment

Renal impairment

  • CrCl <70 mL/min: Coadministered with tenofovir disoproxil fumarate (DF) is not recommended
  • ESRD with hemodialysis: Not recommended
  • Concomitant or recent use of nephrotoxic drug: Atazanavir/cobicistat plus tenofovir DF is not recommended

Dosage Considerations

Indication in children and adolescents is supported by evidence from adequate and well-controlled studies in adults, and by pharmacokinetic, safety, and virologic data from an open-label trial of adolescents with HIV-1 infection aged ≥12 years

Limitations of use: Use in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions

Pregnancy

  • Not recommended for use during pregnancy; do not initiate in pregnant individuals
  • Recommend an alternative regimen for females who become pregnant during therapy

Laboratory testing before initiation and during treatment

  • Assess estimated CrCl, serum creatinine, and urinalysis with microscopic examination
  • Coadministration with tenofovir DF: Assess estimated CrCl, urine glucose, and urine protein
  • Patients with chronic kidney disease: Monitor serum phosphorus
  • Patients with underlying hepatitis B or C viral infections: Perform hepatic laboratory testing
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Interactions

Interaction Checker

and atazanavir/cobicistat

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      Serious - Use Alternative

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            Contraindicated (60)

            • 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

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

            • alprazolam

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

            • carbamazepine

              carbamazepine will decrease the level or effect of atazanavir 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).

              atazanavir 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.

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

              conivaptan will increase the level or effect of atazanavir 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)

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

            • dihydroergotamine intranasal

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

            • 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.

            • elbasvir/grazoprevir

              atazanavir increases levels of elbasvir/grazoprevir by Other (see comment). Contraindicated. Comment: Coadministration with strong OATP1B1/3 inhibitors may increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations.

            • 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.

              atazanavir will increase the level or effect of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 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 contraindiated 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

              atazanavir, elvitegravir/cobicistat/emtricitabine/tenofovir DF. Other (see comment). Contraindicated. Comment: Elvitegravir/cobicistat/emtricitabine/tenofovir is a complete regimen for HIV and should not be administered with other antiretrovirals.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              cobicistat will increase the level or effect of elvitegravir/cobicistat/emtricitabine/tenofovir DF by pharmacodynamic synergism. Contraindicated. Duplicate therapy

            • enzalutamide

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

            • eplerenone

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

            • ergoloid mesylates

              atazanavir will increase the level or effect of ergoloid mesylates 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.

              atazanavir 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

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

            • 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.

              atazanavir 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.

            • gepirone

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

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

            • 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

            • isavuconazonium sulfate

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

            • 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

              atazanavir 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

            • lomitapide

              atazanavir increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

            • 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.

            • lonafarnib

              atazanavir 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

              atazanavir will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors increase systemic statin exposure and risk of myopathy, including rhabdomyolysis

              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

              atazanavir 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.

            • 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)

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

            • 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

              atazanavir will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of naloxegol with strong CYP3A4 inhibitors can significantly increase naloxegol systemic exposure which may precipitate opioid withdrawal symptoms

            • naloxegol

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

            • pacritinib

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

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

            • phenobarbital

              phenobarbital will decrease the level or effect of atazanavir 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.

            • phenytoin

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

            • pimozide

              atazanavir will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Risk of QT interval prolongation.

            • pitavastatin

              atazanavir increases levels of pitavastatin by unknown mechanism. Contraindicated. Potential for increased toxicity. .

            • ranolazine

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

            • regorafenib

              atazanavir, regorafenib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors increase regorafenib levels and decrease exposure of the active metabolites M-2 and M-5.

            • 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.

              rifampin decreases levels of atazanavir by increasing metabolism. Contraindicated. Contraindicated. May result in loss of antiviral efficacy and/or development of viral resistance.

            • ritonavir

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

            • saquinavir

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

            • sildenafil

              atazanavir will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Never use combination with chronic sildenafil for PAH

              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

              atazanavir will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Contraindicated. Increased risk for rhabdomyolysis with drugs that increase simvastatin systemic exposure

            • St John's Wort

              St John's Wort will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • 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

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

              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%.

              atazanavir 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

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

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

            Serious - Use Alternative (248)

            • 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

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

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

            • 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.

              atazanavir increases levels of ado-trastuzumab emtansine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. DM1, the cytotoxic component, is metabolized mainly by CYP3A4; strong CYP3A4 inhibitors may increase DM1 exposure and toxicity.

            • alpelisib

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

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

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

            • aluminum hydroxide

              aluminum hydroxide will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if antacids or buffered medications are coadministered. Administer atazanavir 2 hr before or 1 hr after these medications.

            • 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.

            • aluminum hydroxide/magnesium carbonate

              aluminum hydroxide/magnesium carbonate will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if antacids or buffered medications are coadministered. Administer atazanavir 2 hr before or 1 hr after these medications.

            • aluminum hydroxide/magnesium trisilicate

              aluminum hydroxide/magnesium trisilicate will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if antacids or buffered medications are coadministered. Administer atazanavir 2 hr before or 1 hr after these medications.

            • amiodarone

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

            • apalutamide

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

            • apixaban

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

            • 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

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if antacids or buffered medications are coadministered. Administer atazanavir 2 hr before or 1 hr after these medications.

            • 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

              atazanavir will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; significantly increased levels may result in significant adverse events including severe hypotension, syncope, visual changes, and priapism. Coadministration with strong CYP3A4 is contraindicated.

            • 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.

              atazanavir 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

              atazanavir increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP3A4 inhibitors, reduce axitinib dose by 50%.

              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

              atazanavir will increase the level or effect of bedaquiline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of bedaquiline with strong CYP3A4 inhibitors for >14 consecutive days, unless the benefit of treatment outweighs the risk

            • bedaquiline

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

            • belinostat

              atazanavir will increase the level or effect of belinostat by decreasing metabolism. Avoid or Use Alternate Drug. Strong UGT inhibitors decrease metabolism of belinostat; reduce belinostat starting dose to 750 mg/m2 when coadministered with UGT inhibitors or in patients known to be homozygous for the UGT1A1*28 allele

            • betibeglogene autotemcel

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

            • bosentan

              bosentan will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not coadminister unless atazanavir boosted with ritonavir

              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

              atazanavir increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors increases bosutinib plasma concentration ~5-fold.

              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.

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

            • bromocriptine

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

            • 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.

            • buprenorphine transdermal

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

            • cabergoline

              atazanavir increases levels of cabergoline by decreasing metabolism. Contraindicated.

            • cabotegravir

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

            • cabozantinib

              atazanavir 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.

            • calcitriol

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

            • calcium carbonate

              calcium carbonate will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if antacids or buffered medications are coadministered. Administer atazanavir 2 hr before or 1 hr after these medications.

            • 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.

              atazanavir increases levels of ceritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid if possible; if concomitant use is unavoidable, reduce ceritinib dose by ~33%; after discontinuation of strong CYP3A inhibitor, resume at previous dose.

            • chloramphenicol

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

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

            • cholic acid

              atazanavir increases toxicity of cholic acid by decreasing elimination. Avoid or Use Alternate Drug. Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP). May exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is necessary, monitor serum transaminases and bilirubin.

            • 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.

            • cimetidine

              cimetidine will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if H2-receptor antagonists (H2RA) are coadministered. For treatment-naïve patients, take atazanavir simultaneously with the H2RA or at least 10 h afterwards. See dosage adjustment recommendations if coadministered in treatment-experienced patients.

            • citric acid/sodium bicarbonate

              citric acid/sodium bicarbonate will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if antacids or buffered medications are coadministered. Administer atazanavir 2 hr before or 1 hr after these medications.

            • cobicistat

              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.

            • colchicine

              atazanavir will increase the level or effect of colchicine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid use of colchicine with strong CYP3A4 inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with strong CYP3A4 inhibitors is contraindicated in patients with renal or hepatic impairment.

            • copanlisib

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

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

            • crizotinib

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

            • dabrafenib

              atazanavir increases levels of dabrafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • 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.

              atazanavir 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.

            • dexlansoprazole

              dexlansoprazole will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if PPIs are coadministered. PPI dose should not exceed a dose comparable to omeprazole 20 mg and must be taken ~12 h before atazanavir/ritonavir in treatment naive-patients. PPIs are not recommended in treatment-experienced taking atazanavir.

            • 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.

            • dronedarone

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

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

              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.

              atazanavir 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

              atazanavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • elivaldogene autotemcel

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

            • encorafenib

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

            • eluxadoline

              atazanavir increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

            • encorafenib

              atazanavir 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.

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

            • enzalutamide

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

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

            • 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.

              atazanavir 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.

            • ergoloid mesylates

              atazanavir increases levels of ergoloid mesylates by decreasing metabolism. Contraindicated.

            • 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. .

            • ergotamine

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

              atazanavir increases levels of ergotamine by decreasing metabolism. Contraindicated.

            • erythromycin base

              atazanavir will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin ethylsuccinate

              atazanavir will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              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. .

              atazanavir will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin stearate

              atazanavir will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              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.

            • esomeprazole

              esomeprazole will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if PPIs are coadministered. PPI dose should not exceed a dose comparable to omeprazole 20 mg and must be taken ~12 h before atazanavir/ritonavir in treatment naive-patients. PPIs are not recommended in treatment-experienced taking atazanavir.

            • eszopiclone

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

            • ethinylestradiol

              atazanavir, ethinylestradiol. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended. .

            • 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

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

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

            • famotidine

              famotidine will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if H2-receptor antagonists (H2RA) are coadministered. For treatment-naïve patients, take atazanavir simultaneously with the H2RA or at least 10 h afterwards. See dosage adjustment recommendations if coadministered in treatment-experienced patients.

            • 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.

            • fedratinib

              atazanavir 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

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

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

            • fentanyl

              atazanavir will increase the level or effect of fentanyl 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 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 intranasal

              atazanavir will increase the level or effect of fentanyl intranasal 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 transdermal

              atazanavir 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.

              atazanavir 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

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

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

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

              atazanavir 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.

            • 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. .

            • fluticasone intranasal

              atazanavir will increase the level or effect of fluticasone intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase systemic corticosteroid adverse effects; monitor for signs/symptoms of high corticosteroid concentrations including Cushing type signs/symptoms.

            • 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.

              atazanavir 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.

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

            • glecaprevir/pibrentasvir

              atazanavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. In clinical trials, coadministration of atazanavir (an inhibitor of CYP3A4 and OATP1B1) with glecaprevir (a CYP3A4 and OATP1B1 substrate) increased risk for ALT elevations.

            • 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.

              atazanavir increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

            • ibuprofen/famotidine

              ibuprofen/famotidine will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if H2-receptor antagonists (H2RA) are coadministered. For treatment-naïve patients, take atazanavir simultaneously with the H2RA or at least 10 h afterwards. See dosage adjustment recommendations if coadministered in treatment-experienced patients.

            • 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.

            • idelalisib

              atazanavir will increase the level or effect of idelalisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministered with strong CYP3A inhibitors, monitor for signs of idelalisib toxicity; follow recommendations for dosage modifications if adverse reactions occur

              idelalisib will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indinavir

              atazanavir, indinavir. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive hyperbilirubinemia; concomitant use not recommended.

              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.

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

            • irinotecan

              atazanavir will increase the level or effect of irinotecan by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism

              atazanavir will increase the level or effect of irinotecan 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.

            • irinotecan liposomal

              atazanavir will increase the level or effect of irinotecan liposomal by decreasing metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism

              atazanavir will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. UGT1A1 inhibitors decrease irinotecan metabolism

            • 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.

              atazanavir 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.

              ivosidenib will decrease the level or effect of atazanavir 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.

            • lansoprazole

              lansoprazole will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if PPIs are coadministered. PPI dose should not exceed a dose comparable to omeprazole 20 mg and must be taken ~12 h before atazanavir/ritonavir in treatment naive-patients. PPIs are not recommended in treatment-experienced taking atazanavir.

            • 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

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

              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.

              atazanavir 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.

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

            • lenacapavir

              atazanavir will increase the level or effect of lenacapavir by Other (see comment). Avoid or Use Alternate Drug. Drugs that inhibit P-gp, UGT1A1, and strongly inhibit CYP3A may significantly increase lenacapavir plasma concentrations.

            • leniolisib

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

            • leniolisib

              atazanavir 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.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              atazanavir, levonorgestrel oral/ethinylestradiol/ferrous bisglycinate. Other (see comment). Avoid or Use Alternate Drug. Comment: Significant changes (increase or decrease) can occur in estrogen plasma levels. Efficacy of hormonal contraceptives may be reduced. Use of a nonhormonal contraceptive is recommended.

            • lomitapide

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

            • lopinavir

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

            • lorlatinib

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

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

              lorlatinib will decrease 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 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.

            • lurbinectedin

              atazanavir 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.

              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.

            • macitentan

              atazanavir will increase the level or effect of macitentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministering macitentan with strong CYP3A4 inhibitors

            • 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.

            • magnesium oxide

              magnesium oxide will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if antacids or buffered medications are coadministered. Administer atazanavir 2 hr before or 1 hr after these medications.

            • mefloquine

              atazanavir increases levels 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. .

              mefloquine increases toxicity of atazanavir by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

            • methylergonovine

              atazanavir increases levels of methylergonovine by decreasing metabolism. Contraindicated.

            • midazolam

              atazanavir increases levels of midazolam by decreasing metabolism. Contraindicated.

            • 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.

              atazanavir 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.

              atazanavir 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

              atazanavir will increase the level or effect of mobocertinib 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.

              atazanavir 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.

            • nefazodone

              atazanavir will increase the level or effect of nefazodone 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.

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

            • nevirapine

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

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

              nevirapine will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with etravirine may result in loss of therapeutic effect and development of resistance to cobicistat. Contraindicated with cobicistat coadministered with atazanavir.only; nevirapine substantially decreases atazanavir exposure which may result in loss of therapeutic effect and development of resistance

            • nicardipine

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

            • nizatidine

              nizatidine will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if H2-receptor antagonists (H2RA) are coadministered. For treatment-naïve patients, take atazanavir simultaneously with the H2RA or at least 10 h afterwards. See dosage adjustment recommendations if coadministered in treatment-experienced patients.

            • 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

              atazanavir will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.

              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.

              atazanavir 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.

            • omeprazole

              omeprazole will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if PPIs are coadministered. PPI dose should not exceed a dose comparable to omeprazole 20 mg and must be taken ~12 h before atazanavir/ritonavir in treatment naive-patients. PPIs are not recommended in treatment-experienced taking atazanavir.

            • 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.

              atazanavir 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.

            • oxycodone

              atazanavir increases levels of oxycodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Oxycodone dose reduction may be warranted when coadministered with strong CYP3A4 inhibitors.

            • 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.

              atazanavir 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.

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

            • pantoprazole

              pantoprazole will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if PPIs are coadministered. PPI dose should not exceed a dose comparable to omeprazole 20 mg and must be taken ~12 h before atazanavir/ritonavir in treatment naive-patients. PPIs are not recommended in treatment-experienced taking atazanavir.

            • pazopanib

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

            • pazopanib

              atazanavir will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of pazopanib with strong CYP3A4 inhibitors if possible; if must coadminister, decrease pazopanib dose to 400 mg/day

            • 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.

              atazanavir 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

              atazanavir 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.

              atazanavir will increase the level or effect of pexidartinib by Other (see comment). Avoid or Use Alternate Drug. Pexdartinib is a UGTA4 substrate. Reduce pexdartinib dose if concomitant use of UGT inhibitors cannot be avoided (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • 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.

              atazanavir 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.

              atazanavir 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.

            • pomalidomide

              atazanavir increases levels of pomalidomide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ponatinib

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

            • ponatinib

              atazanavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.

            • posaconazole

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

            • pralsetinib

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

              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.

            • quetiapine

              atazanavir increases levels of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternative anti-HCV therapy to avoid increases in quetiapine exposures; if coadministration is necessary, reduce quetiapine dose to 1/6th of current dose and monitor for quetiapine associated adverse reactions; refer to quetiapine prescribing information for recommendations on adverse reaction monitoring.

            • 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.

            • rabeprazole

              rabeprazole will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Atazanavir solubility decreases as pH increases. Substantially reduced plasma concentrations of atazanavir are expected if PPIs are coadministered. PPI dose should not exceed a dose comparable to omeprazole 20 mg and must be taken ~12 h before atazanavir/ritonavir in treatment naive-patients. PPIs are not recommended in treatment-experienced taking atazanavir.

            • ranolazine

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

            • red yeast rice

              atazanavir will increase the level or effect of red yeast rice by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. May increase creatine kinase levels and increase risk of myopathy or rhabdomyolysis; red yeast rice contains monocolin K (reportedly identical to lovastatin)

            • repotrectinib

              cobicistat will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.

              atazanavir will increase the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Discontinue strong or moderate CYP3A inhibitors and wait 3-5 elimination half-lives before initiating repotrectinib.

            • 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.

              atazanavir 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.

            • rifampin

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

            • rifapentine

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

            • rifapentine

              rifapentine decreases levels of atazanavir by increasing metabolism. Contraindicated.

            • rimegepant

              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.

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

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

            • riociguat

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

            • romidepsin

              atazanavir will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration with strong 3A4 inhibitors should be avoided if possible.

            • 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

            • rosuvastatin

              atazanavir increases levels of rosuvastatin by unknown mechanism. Avoid or Use Alternate Drug. Potential for increased toxicity. Use alternatives if available. Increased risk of myopathy and rhabdomyolysis. Limit rosuvastatin dose to 10 mg/day; ritonavir component of atazanavir/ritonavir regimen decreases rosuvastatin metabolism.

            • ruxolitinib

              atazanavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L

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

            • ruxolitinib topical

              atazanavir will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L

              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.

            • selpercatinib

              atazanavir will increase the level or effect of selpercatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, reduce selpercatinib dose from 120 mg BID to 40 mg BID, or from 160 mg BID to 80 mg BID. Following discontinuation of the strong CYP3A4 inhibitor, wait at least 3 to 5 half-lives of the discontinued drug before resuming the selpercatinib dose administered before use of the strong CYP3A4 inhibitor.

            • 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.

              atazanavir 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.

            • silodosin

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

            • 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.

            • siponimod

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

            • sirolimus

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

            • sodium bicarbonate

              sodium bicarbonate will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • sodium citrate/citric acid

              sodium citrate/citric acid will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • solifenacin

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

            • sonidegib

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

            • sotorasib

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

            • sparsentan

              atazanavir 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.

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

            • St John's Wort

              St John's Wort decreases levels of atazanavir by increasing metabolism. Contraindicated.

            • sunitinib

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

            • stiripentol

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

            • suvorexant

              atazanavir increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.

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

            • tadalafil

              atazanavir will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Stop tadalafil >24 hours prior to protease inhibitor (PI) initiation, restart 7 days after PI initiation at 20 mg once daily, and increase to 40 mg once daily based on tolerability.

              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

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

            • 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.

              atazanavir increases levels of tamsulosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Potential for increased toxicity. .

            • 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.

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

            • teniposide

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

            • tepotinib

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

            • ticagrelor

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

            • tipranavir

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

              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.

              atazanavir 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

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

            • 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

              atazanavir 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

              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.

            • triazolam

              atazanavir increases levels of triazolam by decreasing metabolism. Contraindicated.

            • tucatinib

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

              tucatinib will increase the level or effect of atazanavir 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

              atazanavir increases levels of vemurafenib 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

              atazanavir increases levels of vilazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong CYP3A4 inhibitors may increase vilazodone plasma levels by 50% - Reduce daily dose to 20 mg.

              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.

            • vonoprazan

              vonoprazan will decrease the level or effect of atazanavir by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug.

            • vorapaxar

              atazanavir increases levels of vorapaxar by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

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

            • voriconazole

              voriconazole 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 voriconazole 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.

            • voxelotor

              voxelotor will increase the level or effect of atazanavir 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.

            • voxilaprevir

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

            • zolpidem

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

            Monitor Closely (409)

            • abacavir

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

            • abemaciclib

              atazanavir 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 strong CYP3A4 inhibitor is discontinued, increase abemaciclib to the dose prior to initiating the strong inhibitor.

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

            • acalabrutinib

              atazanavir will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

            • alfentanil

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

            • acarbose

              atazanavir decreases effects of acarbose by pharmacodynamic antagonism. Use Caution/Monitor. New onset or exacerbation of diabetes mellitus and hyperglycemia have been reported with protease inhibitors.

            • acebutolol

              atazanavir increases effects of acebutolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • albiglutide

              atazanavir decreases effects of albiglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • almotriptan

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

            • alprazolam

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

            • 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

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

              atazanavir increases levels of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor.

              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.

              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

            • amlodipine

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

            • amoxapine

              atazanavir increases levels of amoxapine by unspecified interaction mechanism. 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.

              atazanavir 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.

            • aprepitant

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

            • aripiprazole

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

              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.

              atazanavir increases levels of artemether by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. Use alternatives if available.

            • artemether/lumefantrine

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

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

            • atenolol

              atazanavir increases effects of atenolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • 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.

            • atogepant

              atazanavir 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.

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

            • 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.

            • bazedoxifene/conjugated estrogens

              atazanavir, bazedoxifene/conjugated estrogens. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estrogens conjugated . Use alternatives if available.

            • 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.

              belzutifan will decrease the level or effect of atazanavir 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

              atazanavir 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.

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

            • betaxolol

              atazanavir increases effects of betaxolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • 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.

            • bexarotene

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

            • bisoprolol

              atazanavir increases effects of bisoprolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • bortezomib

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

              atazanavir 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

              atazanavir increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor patients for adverse reactions. .

            • 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.

              atazanavir 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.

              atazanavir increases levels of bromocriptine by decreasing metabolism. Use Caution/Monitor.

            • budesonide

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

              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

              atazanavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.

            • buprenorphine

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

            • buprenorphine buccal

              atazanavir increases levels of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.

            • 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.

              atazanavir 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

              atazanavir 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.

            • 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

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

            • cabazitaxel

              atazanavir increases levels of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Avoid coadministration.

            • 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.

            • calcifediol

              atazanavir, 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

              atazanavir 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.

              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.

              atazanavir 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.

              atazanavir will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor plasma levels when used concomitantly

            • 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.

              atazanavir 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.

              atazanavir increases effects of carvedilol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • cenobamate

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

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

            • ceritinib

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

            • chlordiazepoxide

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

            • chlordiazepoxide

              atazanavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

            • chlorpropamide

              atazanavir decreases effects of chlorpropamide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • ciclesonide inhaled

              atazanavir increases levels of ciclesonide inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. Increased risk of Cushing's syndrome or adrenal suppression.

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

            • cilostazol

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

              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.

            • cimetidine

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

            • 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.

            • cinacalcet

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

            • citalopram

              atazanavir increases levels of citalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clarithromycin

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

            • clomipramine

              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.

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

              atazanavir increases levels of clomipramine by unspecified interaction mechanism. Use Caution/Monitor.

              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

            • clonazepam

              atazanavir increases levels of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              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.

            • clopidogrel

              atazanavir will decrease the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Inhibition of CYP3A4 will reduce clopidogrel bioactivation

            • 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

            • clorazepate

              atazanavir increases levels of clorazepate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

            • clozapine

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

            • 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.

            • conjugated estrogens

              atazanavir, conjugated estrogens. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estrogens conjugated . Use alternatives if available.

            • conjugated estrogens, vaginal

              atazanavir, conjugated estrogens, vaginal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estrogens conjugated . Use alternatives if available.

            • cortisone

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

            • crizotinib

              atazanavir increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use of strong CYP3A inducers should be avoided. .

              crizotinib increases levels of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • crofelemer

              crofelemer increases levels of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclophosphamide

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

              atazanavir increases toxicity of cyclophosphamide by unspecified interaction mechanism. Use Caution/Monitor.

            • cyclosporine

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

              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

            • dabrafenib

              dabrafenib will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dapsone

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

            • darifenacin

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

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

            • darolutamide

              cobicistat will increase the level or effect of darolutamide by Other (see comment). Modify Therapy/Monitor Closely. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.

            • darunavir

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

              atazanavir and darunavir both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • dasatinib

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

              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.

            • deferasirox

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

            • 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.

            • deflazacort

              atazanavir 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 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.

              atazanavir increases levels of desipramine by unspecified interaction mechanism. Use Caution/Monitor.

              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

            • desogestrel

              atazanavir, desogestrel. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of desogestrel. Use alternatives if available.

            • dexlansoprazole

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

            • desvenlafaxine

              atazanavir increases levels of desvenlafaxine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • dexamethasone

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

            • diazepam

              atazanavir increases levels of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              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.

              atazanavir 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.

            • diazoxide

              atazanavir increases effects of diazoxide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • 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.

            • diclofenac

              atazanavir increases levels of diclofenac by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • didanosine

              didanosine will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Use Caution/Monitor.

              atazanavir and didanosine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • dienogest/estradiol valerate

              atazanavir, dienogest/estradiol valerate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of dienogest/estradiol valerate. Use alternatives if available. .

            • digoxin

              atazanavir increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of AV block.

            • diltiazem

              atazanavir will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of atazanavir with diltiazem may increase diltiazem levels and toxicities (eg, hypotension, AV block). Consider reducing diltiazem dose by 50%. Monitor blood pressure and ECG.

              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.

            • dofetilide

              atazanavir increases levels of dofetilide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Increased risk of QT prolongation and cardiac arrhythmias.

            • 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

            • dolasetron

              atazanavir increases levels of dolasetron by QTc interval. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Increased risk of cardiac arrhythmias.

            • 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.

              atazanavir 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.

            • dosulepin

              atazanavir increases levels of dosulepin by unspecified interaction mechanism. Use Caution/Monitor.

            • 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

              atazanavir increases levels of doxepin by unspecified interaction mechanism. Use Caution/Monitor.

            • doxepin cream

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

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

            • doxorubicin

              atazanavir will increase the level or effect of doxorubicin 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.

            • doxorubicin liposomal

              atazanavir will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dronabinol

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

            • drospirenone

              atazanavir, drospirenone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of drospirenone. Use alternatives if available.

            • duvelisib

              atazanavir will increase the level or effect of duvelisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with a strong CYP3A4 inhibitor increases duvelisib AUC, which may increase the risk of duvelisib toxicities. Reduce duvelisib dose to 15 mg BID when coadministered with a strong CYP3A4 inhibitor.

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

            • efavirenz

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

              atazanavir and efavirenz both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • 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.

              atazanavir 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.

              elagolix will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

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

            • 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

            • eltrombopag

              atazanavir increases levels of eltrombopag by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

            • elvitegravir

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

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

            • emtricitabine

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

            • 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.

              encorafenib, atazanavir. 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

              atazanavir 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.

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

            • enfuvirtide

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

            • enzalutamide

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

            • erlotinib

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

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

            • erythromycin base

              erythromycin base will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • 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.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • escitalopram

              atazanavir increases levels of escitalopram by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased risk of serotonin syndrome.

            • esmolol

              atazanavir increases effects of esmolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • esomeprazole

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

            • estradiol

              atazanavir, estradiol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estradiol. Use alternatives if available.

            • 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.

              atazanavir 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.

            • estrogens conjugated synthetic

              atazanavir, estrogens conjugated synthetic. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estrogens conjugated synthetic. Use alternatives if available.

            • ethosuximide

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

            • estrogens esterified

              atazanavir, estrogens esterified. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estrogens esterified. Use alternatives if available.

            • estropipate

              atazanavir, estropipate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of estropipate. Use alternatives if available. .

            • eszopiclone

              atazanavir increases levels of eszopiclone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce eszopiclone starting dose to 1 mg/day.

            • ethosuximide

              atazanavir increases levels of ethosuximide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • etonogestrel

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

            • etoposide

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

            • etravirine

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

            • etynodiol

              atazanavir, etynodiol. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of etynodiol. Use alternatives if available. .

            • exenatide injectable solution

              atazanavir decreases effects of exenatide injectable solution by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • exenatide injectable suspension

              atazanavir decreases effects of exenatide injectable suspension by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors.

            • fedratinib

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

              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.

              atazanavir 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.

            • fesoterodine

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

            • 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.

            • fludrocortisone

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

            • 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

              atazanavir increases levels of flurazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              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.

              atazanavir will increase the level or effect of fluticasone furoate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase fluticasone systemic exposure

            • fluticasone inhaled

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

              atazanavir will increase the level or effect of fluticasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inhibitors may increase fluticasone systemic exposure

            • 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.

            • fosamprenavir

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

              atazanavir and fosamprenavir both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • 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

            • fosaprepitant

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

            • fostamatinib

              cobicistat will increase the level or effect of fostamatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong CYP3A4 inhibitors may increase exposure to R406 (fostamatinib major active metabolite). Monitor for toxicities that may require fostamatinib dose reduction.

              atazanavir 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.

            • garlic

              garlic decreases levels of atazanavir by unknown mechanism. Use Caution/Monitor.

            • 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.

            • gefitinib

              atazanavir 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.

            • glimepiride

              atazanavir decreases effects of glimepiride by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • glipizide

              atazanavir decreases effects of glipizide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • glyburide

              atazanavir decreases effects of glyburide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • guanfacine

              atazanavir will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

            • haloperidol

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

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

            • hydrocodone

              atazanavir 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

              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

            • hydrocortisone

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

            • 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.

            • hydroxyprogesterone caproate (DSC)

              atazanavir will increase the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ifosfamide

              atazanavir 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.

            • iloperidone

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

              iloperidone increases levels of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imatinib

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

            • imipramine

              atazanavir increases levels of imipramine by unspecified interaction mechanism. Use Caution/Monitor.

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

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

            • indinavir

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

              atazanavir and indinavir both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • isoniazid

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

            • insulin aspart

              atazanavir decreases effects of insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • insulin degludec

              atazanavir decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

            • insulin degludec/insulin aspart

              atazanavir decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

            • insulin detemir

              atazanavir decreases effects of insulin detemir by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • insulin glargine

              atazanavir decreases effects of insulin glargine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • insulin glulisine

              atazanavir decreases effects of insulin glulisine by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • insulin inhaled

              atazanavir decreases effects of insulin inhaled by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. HIV protease inhibitors may cause new onset diabetes mellitus (DM), exacerbate existing DM, and cause hyperglycemia due to insulin resistance.

            • insulin lispro

              atazanavir decreases effects of insulin lispro by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • insulin NPH

              atazanavir decreases effects of insulin NPH by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • insulin regular human

              atazanavir decreases effects of insulin regular human by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • isoniazid

              isoniazid will increase the level or effect of atazanavir 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

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

              cobicistat will increase the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed istradefylline 20 mg/day if coadministered with strong CYP3A4 inhibitors.

              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.

              atazanavir will increase the level or effect of istradefylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed istradefylline 20 mg/day if coadministered with strong CYP3A4 inhibitors.

            • itraconazole

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

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

            • 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.

              atazanavir 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.

            • ixabepilone

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

            • 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.

            • ketamine

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

            • ketoconazole

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

            • labetalol

              atazanavir increases effects of labetalol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • lacosamide

              atazanavir increases effects of lacosamide by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of PR prolongation and cardiac arrhythmias.

              atazanavir increases levels of lacosamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider decreasing lacosamide dose when coadministered with strong CYP3A4 inhibitors.

            • lamivudine

              atazanavir and lamivudine both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • lamotrigine

              atazanavir will decrease the level or effect of lamotrigine by increasing metabolism. Use Caution/Monitor. Interaction is of greater clinical significance with ritonavir-boosted atazanavir than with unboosted atazanavir

            • lansoprazole

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

            • lapatinib

              atazanavir will increase the level or effect of lapatinib 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.

              lenacapavir will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of lenacapavir with atazanavir/cobicistat or atazanavir/ritonavir should be avoided. Use with atazanavir alone may be used with caution.

            • letermovir

              letermovir increases levels of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              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.

              atazanavir 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.

            • levobunolol

              atazanavir increases effects of levobunolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • 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.

            • levoketoconazole

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

            • levomilnacipran

              atazanavir will increase the level or effect of levomilnacipran by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Do not exceed 80 mg/day of levomilnacipran when coadministered with strong CYP3A4 inhibitors

            • levonorgestrel intrauterine

              atazanavir, levonorgestrel intrauterine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of levonorgestrel. Use alternatives if available.

            • levonorgestrel oral

              atazanavir, levonorgestrel oral. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of levonorgestrel oral. Use alternatives if available. .

            • 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.

            • linagliptin

              atazanavir decreases effects of linagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

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

            • liraglutide

              atazanavir decreases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • lofepramine

              atazanavir increases levels of lofepramine by unspecified interaction mechanism. Use Caution/Monitor.

            • lopinavir

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

            • loratadine

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

            • losartan

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

              atazanavir 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.

              atazanavir 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.

              atazanavir 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.

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

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

            • lurasidone

              atazanavir will increase the level or effect of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Manufacturer recommends decreasing starting dose of lurasidone to 20 mg/day and maximum daily dose of lurasidone 80 mg when coadministered with moderate CYP3A4 inhibitors. Concurrent use may increase risk of lurasidone-related adverse reactions.

            • 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

            • maprotiline

              atazanavir increases levels of maprotiline by unspecified interaction mechanism. Use Caution/Monitor.

            • maraviroc

              atazanavir will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Decrease maraviroc dose to 150 mg BID when coadministered with strong CYP3A4 inhibitors

            • medroxyprogesterone

              atazanavir, medroxyprogesterone. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available.

            • meperidine

              atazanavir increases levels of meperidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • mestranol

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

            • metformin

              atazanavir decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease 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

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

            • methylprednisolone

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

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

            • metoprolol

              atazanavir increases effects of metoprolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

              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.

            • midazolam

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

            • mifepristone

              atazanavir will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Do not exceed mifepristone 300 mg/day for Cushing syndrome when coadministered with strong CYP3A4 inhibitors. Potential for increased toxicity

              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

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

            • miglitol

              atazanavir decreases effects of miglitol by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • mirtazapine

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

            • mipomersen

              mipomersen, atazanavir. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • 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.

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

            • mitotane

              mitotane decreases levels of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • 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 inhaled

              atazanavir increases levels of mometasone inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. Increased risk of Cushing's syndrome or adrenal suppression.

            • mometasone, intranasal

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

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

            • nadolol

              atazanavir increases effects of nadolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • 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.

            • naldemedine

              atazanavir 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.

            • nateglinide

              atazanavir decreases effects of nateglinide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • nebivolol

              atazanavir increases effects of nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • 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.

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

            • nelfinavir

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

              atazanavir and nelfinavir both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • netupitant/palonosetron

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

            • netupitant/palonosetron

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

            • nevirapine

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

            • nicardipine

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

            • nifedipine

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

            • nilotinib

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

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

            • nintedanib

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

            • nirmatrelvir

              nirmatrelvir will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased nirmatrelvir/ritonavir or protease inhibitor adverse events with concomitant use.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Patients on ritonavir- or cobicistat-containing HIV regimens should continue their treatment as indicated. Monitor for increased nirmatrelvir/ritonavir or protease inhibitor adverse events with concomitant use.

            • nisoldipine

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

            • norelgestromin

              atazanavir, norelgestromin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of norelgestromin. Use alternatives if available.

            • norethindrone

              atazanavir, norethindrone. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of norethindrone. Use alternatives if available.

            • norethindrone acetate

              atazanavir, norethindrone acetate. Either decreases effects of the other by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available.

            • norgestimate

              atazanavir, norgestimate. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Atazanavir may increase or decrease levels of norgestimate. Use alternatives if available.

            • 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

              atazanavir 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

              atazanavir increases levels of nortriptyline by unspecified interaction mechanism. Use Caution/Monitor.

              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/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.

              atazanavir 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.

              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.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              atazanavir will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increased levels of paritaprevir when coadministered with atazanavir/ritonavir; give atazanavir 300 mg (without ritonavir) in the morning when coadministered with Viekira Pak

            • omeprazole

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

            • ondansetron

              atazanavir will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP-450 inhibitors may decrease clearance of ondansetron. However, no dosage adjustment for ondansetron is recommended.

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

            • orlistat

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

            • osilodrostat

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

            • osilodrostat

              atazanavir 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

              atazanavir increases levels of ospemifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              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.

            • panobinostat

              atazanavir 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.

            • 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.

              atazanavir increases levels of paricalcitol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • 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.

            • penbutolol

              atazanavir increases effects of penbutolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • perampanel

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

            • 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.

            • pindolol

              atazanavir increases effects of pindolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • 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.

              atazanavir 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.

            • pramlintide

              atazanavir decreases effects of pramlintide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • 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.

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

            • prednisolone

              atazanavir will increase the level or effect of prednisolone 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.

            • prednisone

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

            • progesterone intravaginal gel

              atazanavir will increase the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • progesterone micronized

              atazanavir will increase the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • progesterone, natural

              atazanavir will increase the level or effect of progesterone, natural by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • protriptyline

              atazanavir increases levels of protriptyline by unspecified interaction mechanism. Use Caution/Monitor.

              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

              atazanavir will increase the level or effect of quinidine 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.

              atazanavir 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

              atazanavir will increase the level or effect of repaglinide 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.

            • ribociclib

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

            • rifabutin

              atazanavir will increase the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce rifabutin dose by up to 75% (eg, 150 mg every other day or 3 times per week). Closely monitor for rifabutin-associated adverse reactions.

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

              rifabutin will decrease the level or effect of cobicistat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce dose for rifabutin to 150 mg PO every other day when coadministered with cobicistat. Monitor rifabutin associated adverse reactions.

              cobicistat will increase the level or effect of rifabutin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease rifabutin dose to 150 mg PO every other day; monitor for rifabutin associated neutropenia and uveitis

            • rilpivirine

              atazanavir increases levels of rilpivirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Rilpivirine is not expected to affect the plasma concentrations of co-administered protease inhibitors. .

            • 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.

            • riociguat

              atazanavir will increase the level or effect of riociguat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider a starting dose of 0.5 mg 3 times a day when initiating riociguat in patients receiving atazanavir (a strong CYP3A4 and P-gp inhibitor). Monitor for signs and symptoms of hypotension on initiation and on treatment with atazanavir.

            • ripretinib

              atazanavir 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.

            • ritonavir

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

              atazanavir and ritonavir both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • rivaroxaban

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

            • 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.

            • ropivacaine

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

            • rosiglitazone

              atazanavir decreases effects of rosiglitazone by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • rosuvastatin

              atazanavir increases levels of rosuvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Increased risk of myopathy and rhabdomyolysis. .

              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.

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

            • salmeterol

              atazanavir increases levels of salmeterol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Increased risk of systemic effects.

            • selexipag

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

            • saquinavir

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

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

            • saxagliptin

              atazanavir will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limit saxagliptin dose to 2.5 mg/day when coadministered with strong CYP3A4 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

              atazanavir increases levels of sertraline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

              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.

            • sitagliptin

              atazanavir decreases effects of sitagliptin by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • sodium zirconium cyclosilicate

              sodium zirconium cyclosilicate will decrease the level or effect of atazanavir by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.

            • sofosbuvir/velpatasvir

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

            • solifenacin

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

            • sonidegib

              atazanavir will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.

            • sorafenib

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

            • stavudine

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

            • stiripentol

              stiripentol, atazanavir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol, cobicistat. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

            • sufentanil

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

            • sufentanil SL

              atazanavir 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.

            • 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.

            • sunitinib

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

            • tacrolimus

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

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

            • tadalafil

              atazanavir increases levels of tadalafil by decreasing metabolism. Use Caution/Monitor. Stop tadalafil >24 hours prior to protease inhibitor (PI) initiation, restart 7 days after PI initiation at 20 mg once daily, and increase to 40 mg once daily based on tolerability.

            • tazemetostat

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

            • tasimelteon

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

            • tazemetostat

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

            • tecovirimat

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

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

            • temsirolimus

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

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

            • teniposide

              atazanavir increases levels of teniposide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • terbinafine

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

            • tenofovir DF

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

              tenofovir DF decreases levels of atazanavir by unknown mechanism. Use Caution/Monitor. May result in loss of atazanavir antiviral activity; ritonavir boosting may help to compensate.

            • terbinafine

              atazanavir 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.

              atazanavir 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.

              atazanavir 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

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

            • tiagabine

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

            • ticagrelor

              atazanavir increases levels of ticagrelor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Ticagrelor is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors.

            • timolol

              atazanavir increases effects of timolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

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

            • tinidazole

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

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

            • tipranavir

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

              atazanavir and tipranavir both increase risk of immune reconstitution syndrome. Use Caution/Monitor.

            • tisotumab vedotin

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

            • tisotumab vedotin

              atazanavir 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.

            • tolazamide

              atazanavir decreases effects of tolazamide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • tolbutamide

              atazanavir decreases effects of tolbutamide by Other (see comment). Use Caution/Monitor. Comment: Reports of hyperglycemia due to insulin resistance with protease inhibitors. .

            • tolterodine

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

            • toremifene

              atazanavir increases levels of toremifene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Metabolism of toremifene may be inhibited by drugs known to inhibit CYP3A4.

            • tramadol

              atazanavir increases levels of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

              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

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

              atazanavir increases levels of trazodone by unspecified interaction mechanism. Use Caution/Monitor.

              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.

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

            • triazolam

              atazanavir will increase the level or effect of triazolam 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.

            • trimipramine

              atazanavir increases levels of trimipramine by unspecified interaction mechanism. Use Caution/Monitor.

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

            • tucatinib

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

            • ublituximab

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

            • ulipristal

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

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

            • umeclidinium bromide/vilanterol inhaled

              atazanavir will increase the level or effect of umeclidinium bromide/vilanterol inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vilanterol is a CYP3A4 substrate; coadministration with potent CYP3A4 inhibitors may increase systemic exposure

              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.

              atazanavir 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.

              atazanavir will increase the level or effect of valbenazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce valbenazine dose to 40 mg daily when coadministered with strong CYP3A4 inhibitors.

            • vamorolone

              cobicistat will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.

              atazanavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.

            • vardenafil

              atazanavir 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/24 hr

              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

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

              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

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

              verapamil will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution advised, may increase risk of AV block

            • verapamil

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

            • vilanterol/fluticasone furoate inhaled

              atazanavir will increase the level or effect of vilanterol/fluticasone furoate inhaled by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Fluticasone furoate and vilanterol are both CYP3A4 substrates; coadministration with potent CYP3A4 inhibitors may increase systemic exposure

            • 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.

              atazanavir 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.

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

            • zidovudine

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

            • zileuton

              atazanavir increases levels of zileuton by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            Minor (99)

            • acetazolamide

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

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

            • alfentanil

              atazanavir will increase the level or effect of alfentanil 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.

            • aliskiren

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

            • alosetron

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

            • ambrisentan

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

            • amlodipine

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

            • amobarbital

              amobarbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anastrozole

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

            • aprepitant

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

            • armodafinil

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

              armodafinil will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • bosentan

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

            • budesonide

              budesonide will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • butabarbital

              butabarbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • butalbital

              butalbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cevimeline

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

            • clarithromycin

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

            • cortisone

              cortisone will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclophosphamide

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

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

            • cyclosporine

              cyclosporine will increase the level or effect of atazanavir 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.

            • dapsone

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

            • darifenacin

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

            • darunavir

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

            • dasatinib

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

            • dexamethasone

              dexamethasone will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • disopyramide

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

            • docetaxel

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

            • donepezil

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

            • dutasteride

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

            • efavirenz

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

              efavirenz decreases levels of atazanavir by unspecified interaction mechanism. Minor/Significance Unknown. May be coadministered; see atazanavir monograph for dosing info.

            • eplerenone

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

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • etravirine

              etravirine will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Packaging labeling states that etravirine and atazanavir/ritonavir can be coadministered without dose adjustments. Decrease in atazanavir not clinically relevant when all three drugs are used.

            • eucalyptus

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

            • finasteride

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

            • fluconazole

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

            • fludrocortisone

              fludrocortisone will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • flutamide

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

            • fosamprenavir

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

            • fosaprepitant

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

            • fosphenytoin

              fosphenytoin will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • galantamine

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

            • ganaxolone

              atazanavir, 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.

            • grapefruit

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

            • griseofulvin

              griseofulvin will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • imatinib

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

            • indinavir

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

            • isradipine

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

            • 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.

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

            • ketoconazole

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

            • lansoprazole

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

            • lapatinib

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

            • levoketoconazole

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

            • lumefantrine

              lumefantrine will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • marijuana

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

            • methylprednisolone

              methylprednisolone will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metronidazole

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

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • montelukast

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

            • nelfinavir

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

            • nevirapine

              nevirapine will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

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

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

            • nilotinib

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

            • nimodipine

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

            • nitrendipine

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

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • oxybutynin

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

            • paclitaxel

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

            • paclitaxel protein bound

              atazanavir will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • parecoxib

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

            • pentobarbital

              pentobarbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pioglitazone

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

            • posaconazole

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

            • prednisone

              prednisone will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • primidone

              primidone will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • propafenone

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

            • quinine

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

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rabeprazole

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

            • ramelteon

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

            • rifapentine

              rifapentine will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ritonavir

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

            • rufinamide

              rufinamide will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sufentanil

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

            • topiramate

              topiramate will decrease the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vinblastine

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

            • vincristine

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

            • vincristine liposomal

              atazanavir will increase the level or effect of vincristine liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • vinorelbine

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

            • zafirlukast

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

            • zaleplon

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

            • ziprasidone

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

            • zolpidem

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

            • zonisamide

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

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            Adverse Effects

            >10%

            Total bilirubin >2.5 xULN (65%)

            Ocular icterus, all grades (15%)

            Jaundice, all grades (13%)

            Nausea, all grades (12%)

            1-10%

            Jaundice, grades 2-4 (5%)

            Rash, grades 2-4 (5%)

            Creatinine kinase >10 xULN (5%)

            Serum amylase >2 xULN (4%)

            ALT/AST >5 xULN (3%)

            Ocular icterus, grades 2-4 (3%)

            Glycosuria ≥1000 mcg/dL (3%)

            Hematuria >75 RBC/HPF (3%)

            GGT >5 xULN (2%)

            Nausea, grades 2-4 (2%)

            Nephrolithiasis (2%)

            Gastrointestinal disorders: Diarrhea, vomiting, upper abdominal pain (<2%)

            General disorders and administration site conditions: Fatigue (<2%)

            Musculoskeletal and connective tissue disorders: Rhabdomyolysis (<2%)

            Nervous system disorders: Headache (<2%)

            Psychiatric disorders: Depression, abnormal dreams, insomnia (<2%)

            Renal and urinary disorders: Nephropathy, Fanconi syndrome (<2%)

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            Warnings

            Contraindications

            Previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions)

            Coadministration with drugs that are highly dependent on CYP3A or UGT1A1 for clearance, and for which elevated plasma concentrations of the interacting drugs are associated with serious and/or life-threatening events

            Coadministration with drugs that strongly induce CYP3A and may lead to lower exposure and loss of efficacy of atazanavir/cobicistat

            Contraindicated drugs

            • Alfuzosin: Potential for increased alfuzosin concentrations, which can result in serious or life-threatening reactions (eg, hypotension)
            • Dronedarone, ranolazine: Potential for increased dronedarone and ranolazine concentrations that may result in prolonged QT interval
            • Colchicine: Contraindicated in patients with renal and/or hepatic impairment due to the potential for serious and/or life-threatening reactions
            • CYP inducers (rifampin, St. John’s wort): Rifampin is a potent inducer of CYP metabolism, and coadministration may cause a significant decrease in the plasma concentrations of darunavir and result in loss of therapeutic effect and development of resistance
            • Carbamazepine: Potential for decreased atazanavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance
            • Cisapride, pimozide, lurasidone: Potential for serious and/or life-threatening reactions (eg, cardiac arrhythmias)
            • Elbasvir/grazoprevir: Atazanavir OATP1B1/3 inhibition may cause a significant increase in grazoprevir levels, and therefore increase risk of elevated ALT
            • Ergot derivatives (dihydroergotamine, ergotamine, methylergonovine): Potential for serious and/or life-threatening reactions (eg, acute ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues)
            • Lipid-modifying agents, lovastatin, simvastatin, lomitapide: Potential for serious reactions (eg, myopathy, including rhabdomyolysis)
            • Indinavir: Both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia
            • Irinotecan: UGT1A1 inhibition by atazanavir may interfere with the metabolism of irinotecan, resulting in increased toxicity
            • Nevirapine: Nevirapine substantially decreases atazanavir exposure which may result in loss of therapeutic effect and development of resistance; potential risk for nevirapine-associated adverse reactions due to increased nevirapine exposures
            • PDE5 inhibitors (long-term administration [eg, sildenafil as Revatio for PAH]): Potential for sildenafil-associated adverse reactions (eg, visual disturbances, hypotension, priapism, syncope)
            • Phenobarbital, phenytoin: Potential for decreased atazanavir plasma concentrations, which may result in loss of therapeutic effect and development of resistance
            • Triazolam, midazolam PO: These are extensively metabolized by CYP3A4; potential for prolonged or increased sedation or respiratory depression

            Cautions

            Atazanavir prolongs the PR interval of the electrocardiogram in healthy subjects and in subjects with HIV-1 infection treated with atazanavir, abnormalities in atrioventricular (AV) conduction were asymptomatic and generally limited to first-degree AV block; reports of second-degree AV block and other conduction abnormalities

            Cases of Stevens-Johnson syndrome, erythema multiforme, and toxic skin eruptions, including drug rash, eosinophilia and systemic symptoms (DRESS) syndrome, have been reported; mild-to-moderate maculopapular skin eruptions have also been reported in atazanavir clinical trials and generally did not result in treatment discontinuation

            Effects on serum creatinine: Assess eCrCl before initiating; cobicistat decreases estimated creatinine clearance, owing to inhibition of tubular secretion of creatinine, without affecting actual renal glomerular function

            Chronic kidney disease in HIV-infected patients treated with atazanavir, with or without ritonavir reported; consider alternatives to therapy in patients at high risk for renal disease or with preexisting renal disease; renal laboratory testing (including serum creatinine, estimated creatinine clearance, and urinalysis with microscopic examination) should be conducted in all patients prior to initiating therapy and continued during treatment

            Cases of nephrolithiasis and/or cholelithiasis have been reported during postmarketing surveillance in patients receiving atazanavir

            Patients with underlying hepatitis B or C viral infections or marked elevations in transaminases may be at increased risk for developing further transaminase elevations or hepatic decompensation

            Most patients taking atazanavir experience asymptomatic elevations in indirect (unconjugated) bilirubin related to inhibition of UDP-glucuronosyltransferase (UGT)

            New-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, and hyperglycemia reported during postmarketing surveillance in HIV-infected patients receiving protease inhibitors

            Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been observed in patients receiving ARTs

            Immune reconstitution syndrome reported in patients treated with combination ART therapy; during the initial phase of combination ART treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, CMV, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment; autoimmune disorders (eg, Graves disease, polymyositis, autoimmune hepatitis, Guillan-Barre syndrome) have also been reported

            Increased bleeding, including spontaneous skin hematomas and hemarthrosis, reported in patients with hemophilia type A and B treated with HIV protease inhibitors

            Renal impairment

            • Renal impairment, including cases of acute renal failure and Fanconi syndrome, reported when cobicistat was used in an ART regimen that contained tenofovir DF
            • Do not use with tenofovir DF if CrCl <70 mL/min
            • Document urine glucose and urine protein at baseline and perform routine monitoring of eCrCl, urine glucose, and urine protein during treatment
            • Measure serum phosphorus in patients at risk for renal impairment
            • Coadministration of atazanavir/cobicistat plus tenofovir DF in combination with concomitant or recent use of a nephrotoxic agent is not recommended

            Drug interaction overview

            • Drugs that induce CYP3A4 may lead to lower exposure of atazanavir and loss of virologic response
            • Atazanavir inhibits CYP3A4 and is a substrate for CYP3A4
            • Cobicistat inhibits CYP3A and CYP2D6
            • Cobicistat inhibits the following transporters: P-glycoprotein (P-gp), BCRP, OATP1B1, and OATP1B3
            • Drugs that are metabolized by CYP3A and CYP2D6, or are substrates of the transporters P-gp, BCRP, OATP1B1, or OATP1B3, may show increased systemic exposure if coadministered with darunavir/cobicistat
            • Atazanavir solubility decreases as pH increases; reduced plasma concentrations of atazanavir are expected if proton-pump inhibitors, antacids, buffered medications, or H2-receptor antagonists are administered
            • ART agents that are not recommended
              • Not recommended in combination with other ART drugs that require pharmacokinetic boosting (ie, another protease inhibitor or elvitegravir) because dosing recommendations for such combinations have not been established and coadministration may result in decreased plasma concentrations of the ART agents, leading to loss of therapeutic effect and development of resistance
              • Not recommended in combination with products containing the individual components (atazanavir and cobicistat) or with ritonavir
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            Pregnancy & Lactation

            Pregnancy

            Cases of lactic acidosis syndrome, sometimes fatal, and symptomatic hyperlactatemia have occurred in pregnant women using atazanavir in combination with nucleoside analogues

            Nucleoside analogues are associated with an increased risk of lactic acidosis syndrome

            Hyperbilirubinemia occurs frequently in patients who take atazanavir, including pregnant women

            All infants, including neonates exposed to atazanavir in utero, should be monitored for the development of severe hyperbilirubinemia during the first few days of life

            Not recommended for use during pregnancy and should not be initiated in pregnant individuals; an alternative regimen is recommended for individuals who become pregnant during therapy

            Components of drug combination interact with certain oral contraceptives; nonhormonal forms of contraceptive should be considered

            Animal data

            • Atazanavir
              • In animal reproduction studies, there was no evidence of teratogenicity in offspring born to animals at systemic drug exposure levels (AUC) 0.7 (in rabbits) to 1.2 (in rats) times those observed at the human clinical dose (300 mg/day atazanavir coadministered with 100 mg/day ritonavir)
              • In prenatal and postnatal development studies in the rat, atazanavir caused body weight loss or weight gain suppression in the animal offspring with maternal drug exposure (AUC) 1.3 times the human exposure at this clinical dose; however, maternal toxicity also occurred at this exposure level
            • Cobicistat
              • Studies in animals have shown no evidence of teratogenicity or an effect on reproductive function
              • In offspring from rat and rabbit dams treated with cobicistat during pregnancy, there were no toxicologically significant effects on developmental endpoints
              • The exposures at the embryo-fetal No Observed Adverse Effects Levels (NOAELs) in rats and rabbits were respectively 1.4 and 3.3 times higher than the exposure in humans at the recommended daily dose of 150 mg

            Lactation

            The CDC recommends that HIV infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV to infant

            Unknown whether atazanavir or cobicistat are secreted in human milk

            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

            Atazanavir: Protease inhibitor; selectively inhibits cleavage of Gag-Pol polyprotein precursors, thereby preventing the formation of mature virus particles

            Cobicistat: CYP3A4 inhibitor; mechanism-based pharmacokinetic enhancer, increases the systemic exposure of atazanavir (a CYP3A4 substrate)

            Absorption

            Peak plasma time: 3.5 hr (atazanavir); 3 hr (cobicistat)

            Peak plasma concentration, atazanavir: 3.91 mcg/mL

            AUC, atazanavir: 46.13 mcg•hr/mL

            Distribution

            Protein bound: 86% (atazanavir); 97-98% (cobicistat)

            Metabolism

            Atazanavir

            • Extensively metabolized by CYP3A
            • Other minor biotransformation pathways for atazanavir or its metabolites consisted of glucuronidation, N-dealkylation, hydrolysis, and oxygenation with dehydrogenation

            Cobicistat

            • Metabolized by CYP3A and to a minor extent by CYP2D6 enzymes
            • Does not undergo glucuronidation

            Elimination

            Half-life: 7.5 hr (atazanavir); 3-4 hr (cobicistat)

            Elimination, cobicistat: 86.2% feces; 8.2% urine

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            Administration

            Oral Administration

            Take with food

            Separate dose by at least 2 hr apart when coadministered with H2-receptor antagonists or proton-pump inhibitors

            Missed dose

            • Missed dose: Take missed dose as soon as possible and then return to normal dosing schedule; do not double the next dose

            Storage

            Store tablets at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)

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            Images

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            Patient Handout

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

            FormularyPatient Discounts

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            Tier Description
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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.