Cobicistat

Other Agents: Alpha 1- adrenoreceptor antagonist: alfuzosin ↑ alfuzosin Coadministration with alfuzosin is contraindicated due to potential for serious and/or life-threatening reactions such as hypotension.

Other HMG-CoA reductase inhibitors: e.g., atorvastatin rosuvastatin ↑ HMG-CoA reductase inhibitors Coadministration of atazanavir and TYBOST with atorvastatin is not recommended. Dosage recommendations with atorvastatin or rosuvastatin are as follows. TYBOST coadministered with atazanavir in adult patients: Rosuvastatin dosage should not exceed 10 mg TYBOST coadministered with darunavir in adult patients: Atorvastatin dosage should not exceed 20 mg Rosuvastatin dosage should not exceed 20 mg Other lipid-modifying agents: lomitapide ↑ lomitapide Coadministration with lomitapide is contraindicated due to potential for markedly increased transaminases.

Strong CYP3A4 inhibitor that increases simvastatin plasma levels, elevating risk of myopathy and rhabdomyolysis.

Antiretroviral Agents: Protease Inhibitors indinavir Contraindicated with TYBOST coadministered with atazanavir only: Both atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia.

Lipid-modifying Agents: HMG-CoA reductase inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Sedative/Hypnotics: midazolam (oral), triazolam ↑ midazolam ↑ triazolam Coadministration with triazolam or oral administered midazolam is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Triazolam and orally administered midazolam are extensively metabolized by CYP3A. Coadministration of triazolam or orally administered midazolam with TYBOST may cause large increases in the concentrations of these benzodiazepines.

Other HMG-CoA reductase inhibitors: e.g., atorvastatin rosuvastatin ↑ HMG-CoA reductase inhibitors Coadministration of atazanavir and TYBOST with atorvastatin is not recommended. Dosage recommendations with atorvastatin or rosuvastatin are as follows. TYBOST coadministered with atazanavir in adult patients: Rosuvastatin dosage should not exceed 10 mg TYBOST coadministered with darunavir in adult patients: Atorvastatin dosage should not exceed 20 mg Rosuvastatin dosage should not exceed 20 mg Other lipid-modifying agents: lomitapide ↑ lomitapide Coadministration with lomitapide is contraindicated due to potential for markedly increased transaminases.

Lipid-modifying Agents: HMG-CoA reductase inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Coadministration with lovastatin or simvastatin is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Sedative/Hypnotics: midazolam (oral), triazolam ↑ midazolam ↑ triazolam Coadministration with triazolam or oral administered midazolam is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression. Triazolam and orally administered midazolam are extensively metabolized by CYP3A. Coadministration of triazolam or orally administered midazolam with TYBOST may cause large increases in the concentrations of these benzodiazepines.

Strong CYP3A4 inhibitor in cobicistat-containing products may increase corticosteroid exposure and risk of systemic side effects.

Strong CYP3A4 inhibitor (in cobicistat-containing products) may cause increased plasma concentration of triamcinolone acetonide.

Strong CYP3A4 inhibitor may increase plasma concentration of triamcinolone acetonide, leading to adverse reactions.

Strong CYP3A4 inhibitor in cobicistat-containing products may increase triamcinolone plasma concentration.

Cobicistat inhibits CYP3A and CYP2D6, potentially increasing plasma concentrations of atazanavir and altering concentrations of concomitant drugs metabolized by these enzymes.

Cobicistat inhibits CYP3A and CYP2D6, potentially increasing plasma concentrations of darunavir and altering concentrations of concomitant drugs metabolized by these enzymes.

Coadministration with TYBOST is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations.

Use with TYBOST is not recommended because lopinavir is co-formulated with ritonavir.

Strong CYP3A4 inhibitor (cobicistat-containing products) may increase systemic exposure to mometasone and risk of systemic corticosteroid side effects; caution advised.

Strong CYP3A4 inhibitor (as cobicistat-containing products) that may increase systemic corticosteroid effects. Use with caution and monitor for systemic corticosteroid side effects.

Strong CYP3A4 inhibitor may increase systemic exposure to mometasone furoate and increase risk of systemic corticosteroid effects. Use with caution.

Strong CYP3A4 inhibitor may increase systemic exposure to mometasone furoate and increase risk for systemic corticosteroid side effects. Caution and monitoring recommended.

Strong CYP3A4 inhibitor that may increase midostaurin concentrations and risk of toxicity. Monitor for increased adverse reactions, especially during first week of administration.

Coadministration with TYBOST is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations.

Coadministration with TYBOST is not recommended because pharmacokinetic data are not available to provide appropriate dosing recommendations.

Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Concomitant Drug Class: Drug Name Potential Effect ↑ = Increase, ↓ = Decrease, ↔ = No change Clinical Comment Antiretroviral Agents: Nucleotide Reverse Transcriptase Inhibitor (NRTI) tenofovir alafenamide ↔tenofovir alafenamide ↑tenofovir alafenamide TYBOST coadministered with darunavir in pediatric patients weighing at least 15 kg: No dose adjustment.

Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nifedipine verapamil ↑ calcium channel blockers Clinical monitoring is recommended for coadministration with calcium channel blockers metabolized by CYP3A.

Antibacterials (macrolide or ketolide antibiotics): clarithromycin erythromycin telithromycin ↑ clarithromycin ↑ erythromycin ↑ telithromycin ↑ cobicistat ↑ atazanavir ↑ darunavir Consider alternative antibiotics with concomitant use of TYBOST coadministered with atazanavir or darunavir.

Anticonvulsants that are metabolized by CYP3A e.g., clonazepam ↑ clonazepam Clinical monitoring of anticonvulsants is recommended.

dasatinib nilotinib vinblastine vincristine ↑ anticancer agents A decrease in the dosage or an adjustment of the dosing interval of dasatinib or nilotinib may be necessary upon coadministration with TYBOST coadministered with atazanavir or darunavir. Consult the dasatinib and nilotinib prescribing information for dosing instructions.

Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Coadministration with parenteral midazolam may increase plasma concentrations of midazolam.

Other antiarrhythmics: e.g., amiodarone disopyramide flecainide mexiletine propafenone quinidine ↑ antiarrhythmics Clinical monitoring is recommended upon coadministration with antiarrhythmics.

Antibacterials (macrolide or ketolide antibiotics): clarithromycin erythromycin telithromycin ↑ clarithromycin ↑ erythromycin ↑ telithromycin ↑ cobicistat ↑ atazanavir ↑ darunavir Consider alternative antibiotics with concomitant use of TYBOST coadministered with atazanavir or darunavir.

Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Coadministration with parenteral midazolam may increase plasma concentrations of midazolam.

Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nifedipine verapamil ↑ calcium channel blockers Clinical monitoring is recommended for coadministration with calcium channel blockers metabolized by CYP3A.

Other benzodiazepines: e.g., parenterally administered midazolam clorazepate diazepam estazolam flurazepam ↑ sedatives/hypnotics Coadministration with parenteral midazolam may increase plasma concentrations of midazolam.

Antifungals: itraconazole ketoconazole ↑ itraconazole ↑ ketoconazole Specific dosing recommendations are not available for coadministration with itraconazole or ketoconazole.

Antifungals: itraconazole ketoconazole ↑ itraconazole ↑ ketoconazole Specific dosing recommendations are not available for coadministration with itraconazole or ketoconazole.

Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone triamcinolone ↓ cobicistat ↓ atazanavir ↓ darunavir ↑ corticosteroids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to atazanavir or darunavir.

Beta-Blockers: e.g., metoprolol carvedilol timolol ↑ beta-blockers Clinical monitoring is recommended for coadministration with beta-blockers that are metabolized by CYP2D6.

Calcium Channel Blockers: e.g., amlodipine diltiazem felodipine nifedipine verapamil ↑ calcium channel blockers Clinical monitoring is recommended for coadministration with calcium channel blockers metabolized by CYP3A.

dasatinib nilotinib vinblastine vincristine ↑ anticancer agents A decrease in the dosage or an adjustment of the dosing interval of dasatinib or nilotinib may be necessary upon coadministration with TYBOST coadministered with atazanavir or darunavir. Consult the dasatinib and nilotinib prescribing information for dosing instructions.

Proton-pump Inhibitors (PPIs) e.g., omeprazole ↓ atazanavir TYBOST coadministered with atazanavir in adult patients: In treatment-naïve adult patients, administer TYBOST with atazanavir a minimum of 12 hours after administering PPIs. The dose of the PPI should not exceed a dose comparable to omeprazole 20 mg daily.

Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone triamcinolone ↓ cobicistat ↓ atazanavir ↓ darunavir ↑ corticosteroids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to atazanavir or darunavir. Alternative corticosteroids including beclomethasone, prednisone, and prednisolone (whose PK and/or PD are less affected by strong CYP3A inhibitors relative to other studied steroids) should be considered, particularly for long-term use .

Use of TYBOST with lopinavir is not recommended because lopinavir is co-formulated with ritonavir. In addition to the drug interactions noted in Table 7 , TYBOST is not recommended for use in combination with fixed-dose combination tablets that contain cobicistat, lopinavir/ritonavir or regimens containing ritonavir, or in combination with more than one antiretroviral agent that requires pharmacokinetic enhancement [see Warnings and Precautions (5.4) ]. Switching from ritonavir to TYBOST coadministered with atazanavir or darunavir: Maintain bosentan dose.

Antibacterials (macrolide or ketolide antibiotics): clarithromycin erythromycin telithromycin ↑ clarithromycin ↑ erythromycin ↑ telithromycin ↑ cobicistat ↑ atazanavir ↑ darunavir Consider alternative antibiotics with concomitant use of TYBOST coadministered with atazanavir or darunavir.

Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or Predicted Interaction Concomitant Drug Class: Drug Name Potential Effect ↑ = Increase, ↓ = Decrease, ↔ = No change Clinical Comment Antiretroviral Agents: Nucleotide Reverse Transcriptase Inhibitor (NRTI) tenofovir alafenamide ↔tenofovir alafenamide ↑tenofovir alafenamide TYBOST coadministered with darunavir in pediatric patients weighing at least 15 kg: No dose adjustment. TYBOST coadministered with atazanavir and TDF in adult patients: Treatment-experienced adult patients: The recommended once daily dosage regimen is TYBOST 150 mg coadministered with atazanavir 400 mg with concomitant use of H 2 -receptor antagonists and tenofovir DF. In treatment-experienced adult patients, coadministration with PPIs, with or without tenofovir, is not recommended.

Beta-Blockers: e.g., metoprolol carvedilol timolol ↑ beta-blockers Clinical monitoring is recommended for coadministration with beta-blockers that are metabolized by CYP2D6.

Corticosteroids: e.g., betamethasone budesonide ciclesonide dexamethasone fluticasone methylprednisolone mometasone triamcinolone ↓ cobicistat ↓ atazanavir ↓ darunavir ↑ corticosteroids Coadministration with oral dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to atazanavir or darunavir.

voriconazole Voriconazole: effects unknown ↑ cobicistat ↑ atazanavir ↑ darunavir Coadministration with voriconazole is not recommended unless the benefit/risk assessment justifies the use of voriconazole.