Darunavir 600 Mg

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

Lipid Modifying Agents: HMG-CoA reductase inhibitors : lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid modifying agents: lomitapide ↑ lovastatin ↑ simvastatin ↑ HMG-CoA reductase inhibitors ↑ lomitapide Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis. Titrate atorvastatin, pravastatin or rosuvastatin dose carefully and use the lowest necessary dose while monitoring for adverse events. Do not exceed atorvastatin 20 mg/day.

buspirone, diazepam, estazolam, zolpidem parenterally administered midazolam ↑ midazolam ↑ triazolam ↑ sedatives/hypnotics Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.

amiodarone, bepridil, disopyramide, flecainide, lidocaine (systemic), mexiletine, propafenone, quinidine digoxin ↑ ranolazine ↑ ivabradine ↑ dronedarone ↑ antiarrhythmics ↑ digoxin Co-administration is contraindicated due to potential for serious and/or life-threatening reactions.

Hepatitis C virus (HCV): Direct-Acting Antivirals: elbasvir/grazoprevir glecaprevir/pibrentasvir ↑ elbasvir/grazoprevir ↑ glecaprevir ↑ pibrentasvir Co-administration is contraindicated due to potential for the increased risk of alanine transaminase (ALT) elevations.

buspirone, diazepam, estazolam, zolpidem parenterally administered midazolam ↑ midazolam ↑ triazolam ↑ sedatives/hypnotics Co-administration is contraindicated due to potential for serious and/or life-threatening reactions such as prolonged or increased sedation or respiratory depression.

Hepatitis C virus (HCV): Direct-Acting Antivirals: elbasvir/grazoprevir glecaprevir/pibrentasvir ↑ elbasvir/grazoprevir ↑ glecaprevir ↑ pibrentasvir Co-administration is contraindicated due to potential for the increased risk of alanine transaminase (ALT) elevations. Co-administration of darunavir /ritonavir with glecaprevir/pibrentasvir is not recommended.

Hepatitis C virus (HCV): Direct-Acting Antivirals: elbasvir/grazoprevir glecaprevir/pibrentasvir ↑ elbasvir/grazoprevir ↑ glecaprevir ↑ pibrentasvir Co-administration is contraindicated due to potential for the increased risk of alanine transaminase (ALT) elevations.

Lipid Modifying Agents: HMG-CoA reductase inhibitors : lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid modifying agents: lomitapide ↑ lovastatin ↑ simvastatin ↑ HMG-CoA reductase inhibitors ↑ lomitapide Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Sedatives/hypnotics: orally administered midazolam, triazolam metabolized by CYP3A e.g. buspirone, diazepam, estazolam, zolpidem parenterally administered midazolam ↑ midazolam ↑ triazolam ↑ sedatives/hypnotics Co-administration 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.

Hepatitis C virus (HCV): Direct-Acting Antivirals: elbasvir/grazoprevir glecaprevir/pibrentasvir ↑ elbasvir/grazoprevir ↑ glecaprevir ↑ pibrentasvir Co-administration is contraindicated due to potential for the increased risk of alanine transaminase (ALT) elevations. Co-administration of darunavir /ritonavir with glecaprevir/pibrentasvir is not recommended.

Lipid Modifying Agents: HMG-CoA reductase inhibitors : lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid modifying agents: lomitapide ↑ lovastatin ↑ simvastatin ↑ HMG-CoA reductase inhibitors ↑ lomitapide Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis. Titrate atorvastatin, pravastatin or rosuvastatin dose carefully and use the lowest necessary dose while monitoring for adverse events.

Lipid Modifying Agents: HMG-CoA reductase inhibitors : lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid modifying agents: lomitapide ↑ lovastatin ↑ simvastatin ↑ HMG-CoA reductase inhibitors ↑ lomitapide Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis. Titrate atorvastatin, pravastatin or rosuvastatin dose carefully and use the lowest necessary dose while monitoring for adverse events.

Lipid Modifying Agents: HMG-CoA reductase inhibitors : lovastatin, simvastatin atorvastatin, pravastatin, rosuvastatin Other lipid modifying agents: lomitapide ↑ lovastatin ↑ simvastatin ↑ HMG-CoA reductase inhibitors ↑ lomitapide Co-administration is contraindicated due to potential for serious reactions such as myopathy including rhabdomyolysis.

Sedatives/hypnotics: orally administered midazolam, triazolam metabolized by CYP3A e.g. buspirone, diazepam, estazolam, zolpidem parenterally administered midazolam ↑ midazolam ↑ triazolam ↑ sedatives/hypnotics Co-administration 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.

Proton pump inhibitor: omeprazole ↓ omeprazole ↔ darunavir When omeprazole is co-administered with darunavir/ritonavir, monitor patients for decreased efficacy of omeprazole. Consider increasing the omeprazole dose in patients whose symptoms are not well controlled; avoid use of more than 40 mg per day of omeprazole.

fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration.

Didanosine should be administered one hour before or two hours after darunavir/ritonavir due to potential interaction. Requires dosing separation.

Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole voriconazole ↑ darunavir ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole ↓ voriconazole Monitor for increased darunavir/ritonavir and/or antifungal adverse events with concomitant use of these antifungals.

Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole voriconazole ↑ darunavir ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole ↓ voriconazole Monitor for increased darunavir/ritonavir and/or antifungal adverse events with concomitant use of these antifungals. When co-administration is required, the daily dose of ketoconazole or itraconazole should not exceed 200 mg with monitoring for increased antifungal adverse events.

Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole voriconazole ↑ darunavir ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole ↓ voriconazole Monitor for increased darunavir/ritonavir and/or antifungal adverse events with concomitant use of these antifungals. When co-administration is required, the daily dose of ketoconazole or itraconazole should not exceed 200 mg with monitoring for increased antifungal adverse events.

Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole voriconazole ↑ darunavir ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole ↓ voriconazole Monitor for increased darunavir/ritonavir and/or antifungal adverse events with concomitant use of these antifungals.

Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole voriconazole ↑ darunavir ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole ↓ voriconazole Monitor for increased darunavir/ritonavir and/or antifungal adverse events with concomitant use of these antifungals. Voriconazole is not recommended for patients receiving darunavir/ritonavir unless an assessment comparing predicted benefit to risk ratio justifies the use of voriconazole.

7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.

7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.

Calcium Channel Blockers: amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring of patients is recommended.

Other HIV protease inhibitors, except atazanavir [see Drug Interactions (7.4)] As co-administration with darunavir/ritonavir has not been studied, co-administration is not recommended. 7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.

Antibacterial: clarithromycin ↔ darunavir ↑ clarithromycin No dose adjustment of the combination is required for patients with normal renal function. For co-administration of clarithromycin and darunavir/ritonavir in patients with renal impairment, the following dose adjustments should be considered: For subjects with CLcr of 30-60 mL/min, the dose of clarithromycin should be reduced by 50%. For subjects with CLcr of <30 mL/min, the dose of clarithromycin should be reduced by 75%.

clonazepam phenobarbital, phenytoin ↑ clonazepam ↔ darunavir ↓ phenytoin ↓ phenobarbital Clinical monitoring of anticonvulsants that are metabolized by CYP3A is recommended.

7 DRUG INTERACTIONS Co-administration of darunavir/ritonavir with other drugs can alter the concentrations of other drugs and other drugs may alter the concentrations of darunavir. ( 4 , 5.5 , 7 , 12.3 ) 7.1 Potential for Darunavir/ritonavir to Affect Other Drugs Darunavir co-administered with ritonavir is an inhibitor of CYP3A, CYP2D6, and P-gp. Co-administration of darunavir and ritonavir with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and adverse events.

Antineoplastics: dasatinib, nilotinib vinblastine, vincristine ↑ antineoplastics A decrease in the dosage or an adjustment of the dosing interval of dasatinib and nilotinib may be necessary for patients. Please refer to the dasatinib and nilotinib prescribing information for dosing instructions.

7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.

Calcium Channel Blockers: amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring of patients is recommended.

HIV-1-Antiviral Agents: HIV-Protease Inhibitors (PIs) indinavir (The reference regimen for indinavir was indinavir/ritonavir 800/100 mg twice daily.) ↑ darunavir ↑ indinavir The appropriate dose of indinavir in combination with darunavir/ritonavir has not been established.

lopinavir/ritonavir ↓ darunavir ↔ lopinavir Appropriate doses of the combination have not been established. Hence, it is not recommended to co-administer lopinavir/ritonavir and darunavir, with or without ritonavir.

betamethasone budesonide ciclesonide fluticasone methylprednisolone mometasone triamcinolone ↓ darunavir ↑ corticosteroids Co-administration of darunavir/ritonavir with systemic dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to darunavir.

carvedilol, metoprolol, timolol ↑ beta-blockers Clinical monitoring of patients is recommended.

Calcium Channel Blockers: amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring of patients is recommended.

Calcium Channel Blockers: amlodipine, diltiazem, felodipine, nicardipine, nifedipine, verapamil ↑ calcium channel blockers Clinical monitoring of patients is recommended.

Antineoplastics: dasatinib, nilotinib vinblastine, vincristine ↑ antineoplastics A decrease in the dosage or an adjustment of the dosing interval of dasatinib and nilotinib may be necessary for patients. Please refer to the dasatinib and nilotinib prescribing information for dosing instructions.

7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.

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

7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.

7 DRUG INTERACTIONS Co-administration of darunavir/ritonavir with other drugs can alter the concentrations of other drugs and other drugs may alter the concentrations of darunavir. ( 4 , 5.5 , 7 , 12.3 ) 7.1 Potential for Darunavir/ritonavir to Affect Other Drugs Darunavir co-administered with ritonavir is an inhibitor of CYP3A, CYP2D6, and P-gp. Co-administration of darunavir and ritonavir with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp may result in increased plasma concentrations of such drugs, which could increase or prolong their therapeutic effect and adverse events.

saquinavir ↓ darunavir ↔ saquinavir Appropriate doses of the combination have not been established. Hence, it is not recommended to co-administer saquinavir and darunavir, with or without ritonavir.

7.4 Drugs without Clinically Significant Interactions with Darunavir No dosage adjustments are recommended when darunavir/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine.

carvedilol, metoprolol, timolol ↑ beta-blockers Clinical monitoring of patients is recommended.

betamethasone budesonide ciclesonide fluticasone methylprednisolone mometasone triamcinolone ↓ darunavir ↑ corticosteroids Co-administration of darunavir/ritonavir with systemic dexamethasone or other systemic corticosteroids that induce CYP3A may result in loss of therapeutic effect and development of resistance to darunavir.