Atazanavir Sulfate

Other Agents Alpha 1-Adrenoreceptor Antagonist: alfuzosin ↑ alfuzosin Coadministration of atazanavir with alfuzosin is contraindicated due to risk for hypotension [see Contraindications (4)].

Antineoplastics: irinotecan apalutamide ivosidenib encorafenib ↑ irinotecan ↓ atazanavir ↓ atazanavir ↑ ivosidenib ↓ atazanavir ↑ encorafenib Coadministration of atazanavir with irinotecan is contraindicated. Coadministration of atazanavir (with or without ritonavir) and apalutamide is contraindicated due to the potential for subsequent loss of virologic response and possible resistance to the class of protease inhibitors [see Contraindications (4)] .

Hepatitis C Antiviral Agents elbasvir/grazoprevir ↑ grazoprevir Coadministration of atazanavir with grazoprevir is contraindicated due to the potential for increased risk of ALT elevations [see Contraindications (4)].

Antineoplastics: irinotecan apalutamide ivosidenib encorafenib ↑ irinotecan ↓ atazanavir ↓ atazanavir ↑ ivosidenib ↓ atazanavir ↑ encorafenib Coadministration of atazanavir with irinotecan is contraindicated. Coadministration of encorafenib with atazanavir (with or without ritonavir) is contraindicated due to the potential for the loss of virologic response and risk of serious adverse events such as QT interval prolongation.

glecaprevir/pibrentasvir ↑ glecaprevir ↑ pibrentasvir Coadministration of atazanavir with glecaprevir/pibrentasvir is contraindicated due to the potential for increased the risk of ALT elevations [see Contraindications (4)].

Hepatitis C Antiviral Agents elbasvir/grazoprevir ↑ grazoprevir Coadministration of atazanavir with grazoprevir is contraindicated due to the potential for increased risk of ALT elevations [see Contraindications (4)].

indinavir Coadministration of atazanavir with indinavir is contraindicated. Both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia [see Contraindications (4)].

Antineoplastics: irinotecan apalutamide ivosidenib encorafenib ↑ irinotecan ↓ atazanavir ↓ atazanavir ↑ ivosidenib ↓ atazanavir ↑ encorafenib Coadministration of atazanavir with irinotecan is contraindicated. Coadministration of ivosidenib with atazanavir (with or without ritonavir) is contraindicated due to the potential for loss of virologic response and risk of serious adverse events such as QT interval prolongation.

Lipid-modifying agents HMG-CoA reductase inhibitors: lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Coadministration of atazanavir with lovastatin or simvastatin is contraindicated.

Benzodiazepines: midazolam (oral) triazolam ↑ midazolam ↑ triazolam Coadministration of atazanavir with either orally administered midazolam or triazolam is contraindicated. Triazolam and orally administered midazolam are extensively metabolized by CYP3A4, and coadministration with atazanavir can lead to the potential for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression [see Contraindications (4)]. parenterally administered midazolam b ↑ midazolam Coadministration with parenteral midazolam should be done in a setting which ensures close clinical monitoring and appropriate medical management in case of respiratory depression and/or prolonged sedation.

glecaprevir/pibrentasvir ↑ glecaprevir ↑ pibrentasvir Coadministration of atazanavir with glecaprevir/pibrentasvir is contraindicated due to the potential for increased the risk of ALT elevations [see Contraindications (4)].

Lipid-modifying agents HMG-CoA reductase inhibitors: lovastatin, simvastatin ↑ lovastatin ↑ simvastatin Coadministration of atazanavir with lovastatin or simvastatin is contraindicated.

Benzodiazepines: midazolam (oral) triazolam ↑ midazolam ↑ triazolam Coadministration of atazanavir with either orally administered midazolam or triazolam is contraindicated. Triazolam and orally administered midazolam are extensively metabolized by CYP3A4, and coadministration with atazanavir can lead to the potential for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression [see Contraindications (4)].

Coadministration decreases both atazanavir and didanosine concentrations. Atazanavir should be given 2 hours before or 1 hour after didanosine buffered formulations.

Simultaneous administration with atazanavir and food decreases didanosine exposure. Separate administration times are required.

felodipine, nifedipine, nicardipine, and verapamil ↑ calcium channel blocker Caution is warranted.

Kinase inhibitors: fostamatinib ↑ R406 (active metabolite of fostamatinib) When coadministering fostamatinib with atazanavir (with or without ritonavir), monitor for toxicities of R406 exposure resulting in dose-related adverse events such as hepatotoxicity and neutropenia. Fostamatinib dose reduction may be required.

felodipine, nifedipine, nicardipine, and verapamil ↑ calcium channel blocker Caution is warranted.

felodipine, nifedipine, nicardipine, and verapamil ↑ calcium channel blocker Caution is warranted.

Atazanavir without ritonavir is not recommended when coadministered with paclitaxel due to CYP2C8 inhibition and narrow therapeutic index.

Atazanavir without ritonavir is not recommended when coadministered with repaglinide due to CYP2C8 inhibition and narrow therapeutic index.

7 DRUG INTERACTIONS Coadministration of atazanavir can alter the concentration of other drugs and other drugs may alter the concentration of atazanavir. ( 4 , 7 , 12.3 ) 7.1 Potential for Atazanavir to Affect Other Drugs Atazanavir is an inhibitor of CYP3A and UGT1A1. Coadministration of atazanavir and drugs primarily metabolized by CYP3A or UGT1A1 may result in increased plasma concentrations of the other drug that could increase or prolong its therapeutic and adverse effects.

7.4 Drugs with No Observed Interactions with Atazanavir No clinically significant drug interactions were observed when atazanavir was coadministered with methadone, fluconazole, acetaminophen, atenolol, or the nucleoside reverse transcriptase inhibitors lamivudine or zidovudine [see Clinical Pharmacology, Tables 21 and 22 ( 12.3 )] .

atorvastatin, rosuvastatin ↑ atorvastatin ↑ rosuvastatin Titrate atorvastatin dose carefully and use the lowest necessary dose.

Macrolide antibiotics: clarithromycin ↑ clarithromycin ↓ 14-OH clarithromycin ↑ atazanavir Increased concentrations of clarithromycin may cause QTc prolongations; therefore, a dose reduction of clarithromycin by 50% should be considered when it is coadministered with atazanavir. In addition, concentrations of the active metabolite 14-OH clarithromycin are significantly reduced; consider alternative therapy for indications other than infections due to Mycobacterium avium complex. Coadministration of atazanavir with ritonavir and clarithromycin has not been studied.

7.4 Drugs with No Observed Interactions with Atazanavir No clinically significant drug interactions were observed when atazanavir was coadministered with methadone, fluconazole, acetaminophen, atenolol, or the nucleoside reverse transcriptase inhibitors lamivudine or zidovudine [see Clinical Pharmacology, Tables 21 and 22 ( 12.3 )] .

Antifungals: ketoconazole, itraconazole Atazanavir with ritonavir: ↑ ketoconazole ↑ itraconazole Coadministration of ketoconazole has only been studied with atazanavir without ritonavir (negligible increase in atazanavir AUC and C max ). Due to the effect of ritonavir on ketoconazole, high doses of ketoconazole and itraconazole (>200 mg/day) should be used cautiously when administering atazanavir with ritonavir.

Antifungals: ketoconazole, itraconazole Atazanavir with ritonavir: ↑ ketoconazole ↑ itraconazole Coadministration of ketoconazole has only been studied with atazanavir without ritonavir (negligible increase in atazanavir AUC and C max ). Due to the effect of ritonavir on ketoconazole, high doses of ketoconazole and itraconazole (>200 mg/day) should be used cautiously when administering atazanavir with ritonavir.

Proton-pump inhibitors: omeprazole ↓ atazanavir Coadministration of atazanavir with or without ritonavir and omeprazole may result in loss of virologic response and development of resistance. In HIV-treatment-naive adult patients: The proton-pump inhibitor (PPI) dose should not exceed a dose comparable to omeprazole 20 mg and must be taken approximately 12 hours prior to the atazanavir 300 mg with ritonavir 100 mg dose.

Potential safety risks include substantial increases in progesterone exposure.

Use of atazanavir without ritonavir is not recommended when coadministered with drugs highly dependent on CYP2C8 with narrow therapeutic indices (eg, paclitaxel, repaglinide). When atazanavir with ritonavir is coadministered with substrates of CYP2C8, clinically significant interactions are not expected [see Clinical Pharmacology, Table 22 ( 12.3 )]. The magnitude of CYP3A-mediated drug interactions on coadministered drug may change when atazanavir is coadministered with ritonavir.

atorvastatin, rosuvastatin ↑ atorvastatin ↑ rosuvastatin Titrate atorvastatin dose carefully and use the lowest necessary dose. Rosuvastatin dose should not exceed 10 mg/day.

Protease Inhibitors: saquinavir (soft gelatin capsules) ↑ saquinavir Appropriate dosing recommendations for this combination, with or without ritonavir, with respect to efficacy and safety have not been established. In a clinical study, saquinavir 1200 mg coadministered with atazanavir 400 mg and tenofovir DF 300 mg (all given once daily), and nucleoside analogue reverse transcriptase inhibitors did not provide adequate efficacy [see Clinical Studies (14.2)] .

voxilaprevir/sofosbuvir/ velpatasvir ↑ voxilaprevir Coadministration with atazanavir is not recommended.

Nucleotide Reverse Transcriptase Inhibitors: tenofovir disoproxil fumarate (DF) ↓ atazanavir ↑ tenofovir When coadministered with tenofovir DF in adults, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg and tenofovir DF 300 mg (all as a single daily dose with food). Higher tenofovir concentrations could potentiate tenofovir-associated adverse reactions, including renal disorders. Patients receiving atazanavir and tenofovir DF should be monitored for tenofovir-associated adverse reactions.

voxilaprevir/sofosbuvir/ velpatasvir ↑ voxilaprevir Coadministration with atazanavir is not recommended.

voriconazole Atazanavir with ritonavir in participants with a functional CYP2C19 allele: ↓ voriconazole ↓ atazanavir Atazanavir with ritonavir in participants without a functional CYP2C19 allele: ↑ voriconazole ↓ atazanavir The use of voriconazole in patients receiving atazanavir with ritonavir is not recommended unless an assessment of the benefit/risk to the patient justifies the use of voriconazole. Patients should be carefully monitored for voriconazole-associated adverse reactions and loss of either voriconazole or atazanavir efficacy during the coadministration of voriconazole and atazanavir with ritonavir. Coadministration of voriconazole with atazanavir (without ritonavir) may affect atazanavir concentrations; however, no data are available.

voxilaprevir/sofosbuvir/ velpatasvir ↑ voxilaprevir Coadministration with atazanavir is not recommended.