Abacavir

Monitor patients for increased toxicity when MRP2 inhibitors (e.g., abacavir, adefovir, cidofovir, furosemide, lamivudine, nevirapine, ritonavir, probenecid, saquinavir, and tenofovir) are co-administered with COMETRIQ [see Clinical Pharmacology ( 12.3 )] .

Abacavir increases oral methadone clearance. An increased methadone dose may be required in a small number of patients receiving methadone-maintenance therapy.

Coadministration with abacavir/dolutegravir/lamivudine results in increased riociguat exposure, which may increase the risk of riociguat adverse reactions. Riociguat dose may need to be reduced.

( 7.3 ) 7.1 Abacavir Methadone In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of ZIAGEN ® twice daily (twice the currently recommended dose), oral methadone clearance increased [see CLINICAL PHARMACOLOGY ( 12.3 )] . Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [ see Clinical Pharmacology ( 12.3 ) ].

7.3 Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3) ] .

( 7.2 ) 7.1 Methadone In a trial of 11 HIV-1–infected subjects receiving methadone-maintenance therapy with 600 mg of abacavir twice daily (twice the currently recommended dose), oral methadone clearance increased [see Clinical Pharmacology (12.3) ]. 7.2 Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3) ] .

7.3 Established and Other Potentially Significant Drug Interactions There were no drug-drug interaction trials conducted with the abacavir, dolutegravir, and lamivudine fixed-dose combination tablets. Methadone Abacavir: In a trial of 11 HIV-1–infected subjects receiving methadone-maintenance therapy with 600 mg of abacavir twice daily (twice the currently recommended dose), oral methadone clearance increased [see Clinical Pharmacology ( 12.3 )] . Riociguat Abacavir: Coadministration with TRIUMEQ resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology ( 12.3 )] .

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.

7.4 Drugs without Clinically Significant Interactions with PREZCOBIX Clinically relevant drug-drug interactions have not been observed or are not anticipated with concomitant use of darunavir and cobicistat with rilpivirine, dolutegravir, raltegravir, abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, tenofovir DF, lamivudine, stavudine, zidovudine, or acid modifying medications (antacids, H 2 -receptor antagonists, proton pump inhibitors).

7.2 Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3) ].

7.5 Drugs Without Clinically Significant Interactions with Efavirenz No dosage adjustment is recommended when efavirenz is given with the following: aluminum/magnesium hydroxide antacids, azithromycin, cetirizine, famotidine, fluconazole, lorazepam, nelfinavir, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), paroxetine, and raltegravir.

No clinically relevant drug-drug interaction is expected when ZEPATIER is co-administered with abacavir, emtricitabine, entecavir, and lamivudine.

n % Change in Amprenavir Pharmacokinetic Parameters (90% CI) C max AUC C min Abacavir 300 mg twice daily for 2 to 3 weeks 900 mg twice daily for 2 to 3 weeks 4 ↔ ↔ ↔ Clarithromycin 500 mg twice daily for 4 days 1,200 mg twice daily for 4 days 12 ↑15 (↑1 to ↑31) ↑18 (↑8 to ↑29) ↑39 (↑31 to ↑47) Delavirdine 600 mg twice daily for 10 days 600 mg twice daily for 10 days 9 ↑40 Median percent change; confidence interval not reported. Coadministered Drug(s) and Dose(s) Dose of AGENERASE n % Change in Pharmacokinetic Parameters of Coadministered Drug (90% CI) C max AUC C min Abacavir 300 mg twice daily for 2 to 3 weeks 900 mg twice daily for 2 to 3 weeks 4 ↔ Compared with historical data.

7.5 Drugs with No Observed Clinically Significant Interactions with MAVYRET No dose adjustment is required when MAVYRET is coadministered with the following medications: abacavir, amlodipine, caffeine, dextromethorphan, dolutegravir, elvitegravir/ cobicistat, emtricitabine, ethinyl estradiol of 20 mcg or less, felodipine, lamivudine, lamotrigine, losartan, midazolam, norethindrone or other progestin-only contraceptives, omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir alafenamide, tenofovir disoproxil fumarate, tolbutamide, and valsartan.

7.3 Drugs without Clinically Significant Interactions with HARVONI Based on drug interaction studies conducted with the components of HARVONI (ledipasvir or sofosbuvir) or HARVONI, no clinically significant drug interactions have been either observed or are expected when HARVONI is used with the following drugs [see Clinical Pharmacology (12.3) ]: abacavir, atazanavir/ritonavir, cyclosporine, darunavir/ritonavir, dolutegravir, efavirenz, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, lamivudine, methadone, midazolam, oral contraceptives, pravastatin, raltegravir, rilpivirine, tacrolimus, or verapamil.

Nucleoside Reverse Transcriptase Inhibitors: abacavir zidovudine ↓ abacavir ↓ zidovudine The clinical significance of this potential interaction is unknown.

Paradoxical Effects of Anti-Retroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranvir+ritonavir, has resulted in increased clearance or decreased plasma levels of methadone.

No clinically relevant drug-drug interaction is expected when rilpivirine tablets are coadministered with maraviroc, ribavirin or the NRTIs abacavir, emtricitabine, lamivudine, stavudine and zidovudine.

No clinically relevant drug-drug interaction is expected when EDURANT or EDURANT PED is coadministered with maraviroc, ribavirin or the NRTIs abacavir, emtricitabine, lamivudine, stavudine and zidovudine.

Nucleoside Reverse Transcriptase Inhibitors: Abacavir ↓ Abacavir AUC by approximately 40% Clinical relevance of reduction in abacavir levels not established. Dose adjustment of abacavir cannot be recommended at this time.