Tenofovir

Proton Pump Inhibitors: e.g., esomeprazole lansoprazole omeprazole pantoprazole rabeprazole ↓ rilpivirine Coadministration is contraindicated with rilpivirine tablets [see Contraindications (4) ] In addition to the drugs included in Table 6, the interaction between rilpivirine tablets and the following drugs was evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology ( 12.3 )] : acetaminophen, atorvastatin, chlorzoxazone, cabotegravir, ethinylestradiol, norethindrone, raltegravir, sildenafil, simeprevir and tenofovir disoproxil fumarate.

( 7.2 ) • HIV-1 Protease Inhibitors: Monitor for evidence of tenofovir toxicity when CIMDUO is coadministrated with atazanavir/ritonavir, darunavir/ritonavir, or lopinavir/ritonavir. ( 7.2 ) • Sorbitol: Avoid chronic administration of sorbitol with CIMDUO.( 7.5 ) 7.1 Drugs Affecting Renal Function Since tenofovir is primarily eliminated by the kidneys [see Clinical Pharmacology (12.3) ] , coadministration of CIMDUO with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of tenofovir and/or increase the concentrations of other renally eliminated drugs. Lopinavir/ritonavir, atazanavir coadministered with ritonavir, and darunavir coadministered with ritonavir have been shown to increase tenofovir concentrations [see Clinical Pharmacology (12.3) ] .

Coadministration with atazanavir may affect plasma concentrations of both drugs.

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 )] .

Hepatitis C Antiviral Agents ledipasvir/sofosbuvir sofosbuvir/velpatasvir ↑ tenofovir Monitor for adverse reactions associated with TDF. Co-administration of DELSTRIGO with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine, tenofovir, and/or other renally eliminated drugs. No clinically significant changes in concentration were observed for tenofovir when co-administered with tacrolimus or entecavir [see Clinical Pharmacology (12.3) ] .

( 4 , 5.4 , 7 ) • HIV-1 protease inhibitors: Coadministration of efavirenz, emtricitabine and tenofovir disoproxil fumarate with either lopinavir/ritonavir or darunavir and ritonavir increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity. Coadministration of efavirenz, emtricitabine and tenofovir disoproxil fumarate with either atazanavir or atazanavir and ritonavir is not recommended.

7 DRUG INTERACTIONS Tenofovir disoproxil fumarate increases didanosine concentrations. ( 7.2 ) Coadministration of TRUVADA with certain HIV-1 protease inhibitors or certain drugs to treat HCV increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity.

Tenofovir disoproxil fumarate Monitor for adverse reactions.

Concomitant Drug Class: Drug Name Effect on Concentration ↓ = decrease, ↑ = increase Clinical Comment tenofovir DF = tenofovir disoproxil fumarate Acid Reducing Agents: ↓ ledipasvir Ledipasvir solubility decreases as pH increases. HIV Antiretrovirals: Regimens containing tenofovir DF without an HIV protease inhibitor/ ritonavir or cobicistat ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving HARVONI concomitantly with a regimen containing tenofovir DF without an HIV protease inhibitor/ritonavir or cobicistat. Regimens containing tenofovir DF and an HIV protease inhibitor/ ritonavir or cobicistat atazanavir/ritonavir or cobicistat + emtricitabine/tenofovir DF darunavir/ritonavir or cobicistat + emtricitabine/tenofovir DF lopinavir/ritonavir + emtricitabine/tenofovir DF ↑ tenofovir The safety of increased tenofovir concentrations in the setting of HARVONI and an HIV protease inhibitor/ritonavir or cobicistat has not been established.

Sedatives/Hypnotics: midazolam (oral) triazolam ↑ midazolam (oral) ↑ triazolam Use with caution when midazolam or triazolam is concomitantly administered with SUNLENCA 7.4 Drugs without Clinically Significant Interactions with SUNLENCA Based on drug interaction studies conducted with SUNLENCA, no clinically significant drug interactions have been observed with: darunavir/cobicistat, cobicistat, famotidine, pitavastatin, rosuvastatin, tenofovir alafenamide, and voriconazole.

tenofovir disoproxil fumarate (tenofovir DF) ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving VOSEVI concomitantly with a regimen containing tenofovir DF. Refer to the prescribing information of the tenofovir DF-containing product for recommendations on renal monitoring. 7.4 Drugs without Clinically Significant Interactions with VOSEVI Based on drug interaction studies conducted with the components of VOSEVI (sofosbuvir, velpatasvir, and/or voxilaprevir) or VOSEVI, no clinically significant drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir: methadone, tacrolimus

7 DRUG INTERACTIONS Tenofovir disoproxil fumarate increases didanosine concentrations. ( 7.2 ) Coadministration of VIREAD with certain HIV-1 protease inhibitors or certain drugs to treat HCV increases tenofovir concentrations. Monitor for evidence of tenofovir toxicity.

May increase serum concentration of trospium and/or tenofovir due to competition for renal tubular secretion. Careful patient monitoring is recommended.

Regimens containing tenofovir DF ↑ tenofovir Monitor for tenofovir-associated adverse reactions in patients receiving EPCLUSA concomitantly with a regimen containing tenofovir DF. Refer to the prescribing information of the tenofovir DF-containing product for recommendations on renal monitoring. 7.4 Drugs without Clinically Significant Interactions with EPCLUSA Based on drug interaction studies conducted with the components of EPCLUSA (sofosbuvir or velpatasvir) or EPCLUSA, no clinically significant drug interactions have been observed or are expected with the following drugs [see Clinical Pharmacology (12.3) ]: EPCLUSA: atazanavir/ritonavir, buprenorphine/naloxone, cyclosporine, darunavir/ritonavir, dolutegravir, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, methadone, naltrexone, raltegravir, or rilpivirine.

However, in vivo, dolutegravir did not alter the plasma concentrations of tenofovir or para-amino hippurate, substrates of OAT1 and OAT3. In drug interaction trials, dolutegravir did not have a clinically relevant effect on the pharmacokinetics of the following drugs: tenofovir, methadone, midazolam, rilpivirine, and oral contraceptives containing norgestimate and ethinyl estradiol. Darunavir/ritonavir, lopinavir/ritonavir, rilpivirine, tenofovir, boceprevir, prednisone, rifabutin, and omeprazole had no clinically significant effect on the pharmacokinetics of dolutegravir.

Drugs that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption (see Table 4 ). Drugs that induce P-gp activity are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentrations of tenofovir alafenamide, which may lead to loss of therapeutic effect of VEMLIDY. Coadministration of VEMLIDY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of tenofovir alafenamide.

tenofovir disoproxil fumarate ↓ atazanavir ↑ tenofovir Patients receiving EVOTAZ and tenofovir should be monitored for tenofovir-associated adverse reactions [see Warnings and Precautions (5.4) ] . H 2 ‑Receptor antagonists (H 2 RA ) : (e.g., famotidine) ↓ atazanavir Coadministration of EVOTAZ with tenofovir DF and an H 2 RA in treatment-experienced patients 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.

7.4 Drugs Affecting Renal Function Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions.

Rilpivirine Based on drug interaction study results, the following drugs can be coadministered with rilpivirine (non-antiretrovirals and cabotegravir) or given after discontinuation of rilpivirine (antiretrovirals and non-antiretrovirals): acetaminophen, atorvastatin, cabotegravir, chlorzoxazone, dolutegravir, ethinyl estradiol, norethindrone, raltegravir, ritonavir-boosted atazanavir, ritonavir-boosted darunavir, sildenafil, tenofovir alafenamide, and tenofovir disoproxil fumarate [see Clinical Pharmacology ( 12.3 )] .

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.

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).

Tenofovir alafenamide (TAF) is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3. 7.4 Drugs Affecting Renal Function Because emtricitabine and tenofovir are primarily excreted by the kidneys through glomerular filtration and active tubular secretion, co-administration of SYMTUZA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. Drug interaction trials have been conducted with darunavir co-administered with ritonavir or cobicistat or with emtricitabine and tenofovir prodrugs.

However, in vivo, dolutegravir did not alter the plasma concentrations of tenofovir or para-amino hippurate, substrates of OAT1 and OAT3. b 7.4 Drugs without Clinically Significant Interactions with Dolutegravir Based on drug interaction trial results, the following drugs can be coadministered with dolutegravir without a dose adjustment: atazanavir/ritonavir, darunavir/ritonavir, elbasvir/grazoprevir, methadone, midazolam, omeprazole, oral contraceptives containing norgestimate and ethinyl estradiol, prednisone, rifabutin, rilpivirine, sofosbuvir/velpatasvir, and tenofovir [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.

7 DRUG INTERACTIONS Efavirenz, lamivudine and tenofovir disoproxil fumarate should not be administered with other antiretroviral medications for the treatment of HIV-1 infection. ( 7.1 ) Coadministration of efavirenz, lamivudine and tenofovir disoproxil fumarate can alter the concentrations of other drugs and other drugs may alter the concentration of efavirenz, lamivudine and tenofovir disoproxil fumarate. ( 5.3 , 7 ) 7.1 Not Recommended with Other Antiretroviral Medications Efavirenz, lamivudine and tenofovir disoproxil fumarate is a complete regimen for the treatment of HIV-1 infection; therefore, it should not be administered with other antiretroviral medications for treatment of HIV-1 infection.

Elvitegravir/ cobicistat/ emtricitabine/ tenofovir (disoproxil fumarate or alafenamide) ↑ EBR ↑ GZR Co-administration of cobicistat-containing regimens is not recommended. 7.3 Drugs without Clinically Significant Interactions with ZEPATIER The interaction between the components of ZEPATIER (elbasvir or grazoprevir) or ZEPATIER and the following drugs were evaluated in clinical studies, and no dose adjustments are needed when ZEPATIER is used with the following drugs individually: acid reducing agents (proton pump inhibitors, H2 blockers, antacids), buprenorphine/naloxone, digoxin, dolutegravir, methadone, mycophenolate mofetil, oral contraceptive pills, phosphate binders, pitavastatin, pravastatin, prednisone, raltegravir, ribavirin, rilpivirine, tenofovir disoproxil fumarate, and sofosbuvir [see Clinical Pharmacology (12.3) ] .

7.4 Drugs Affecting Renal Function Because emtricitabine and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of GENVOYA with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. The drug interactions described are based on studies conducted with either GENVOYA, the components of GENVOYA (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) as individual agents and/or in combination, or are predicted drug interactions that may occur with GENVOYA [for magnitude of interaction, see Clinical Pharmacology (12.3) ] .

7.4 Drugs Affecting Renal Function Because emtricitabine and tenofovir, components of STRIBILD, are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of STRIBILD with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. Hepatitis C Antiviral Agents: ledipasvir/sofosbuvir sofosbuvir/velpatasvir sofosbuvir/velpatasvir/voxilaprevir ↑ tenofovir The safety of increased tenofovir concentrations in the setting of HARVONI ® (ledipasvir/sofosbuvir) and STRIBILD has not been established. Patients receiving STRIBILD concomitantly with EPCLUSA ® (sofosbuvir/velpatasvir) or VOSEVI ® (sofosbuvir/velpatasvir/voxilaprevir) should be monitored for adverse reactions associated with tenofovir disoproxil fumarate.

7 DRUG INTERACTIONS The potential for drug interactions with EMTRIVA has been studied in combination with AZT, indinavir, d4T, famciclovir, and tenofovir DF (TDF).

7.2 Drugs Affecting Renal Function Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of DESCOVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. The drug interactions described are based on studies conducted with either DESCOVY, the components of DESCOVY (emtricitabine and tenofovir alafenamide) as individual agents, or are predicted drug interactions that may occur with DESCOVY.

7.4 Drugs Affecting Renal Function Because FTC and tenofovir are primarily eliminated by the kidneys through a combination of glomerular filtration and active tubular secretion, coadministration of COMPLERA with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of FTC, tenofovir, and/or other renally eliminated drugs. Hepatitis C Antiviral Agents: ledipasvir/sofosbuvir sofosbuvir/velpatasvir sofosbuvir/velpatasvir/voxilaprevir ↑ tenofovir Patients receiving COMPLERA concomitantly with HARVONI ® (ledipasvir/sofosbuvir), EPCLUSA ® (sofosbuvir/velpatasvir), or VOSEVI ® (sofosbuvir/velpatasvir/voxilaprevir) should be monitored for adverse reactions associated with TDF. Narcotic Analgesics : methadone ↓ R(–) methadone ↓ S(+) methadone ↔ RPV ↔ methadone (when used with tenofovir) No dose adjustments are required when initiating coadministration of methadone with COMPLERA.

7.6 Drugs Affecting Renal Function Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of ODEFSEY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. Narcotic Analgesics: methadone ↓ R(–) methadone ↓ S(+) methadone ↔ RPV ↔ methadone (when used with tenofovir) No dosage adjustments are required when initiating coadministration of methadone with ODEFSEY.

7 DRUG INTERACTIONS • Emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. ( 4 , 5.7 , 7 ) 7.1 Not Recommended with Other Antiretroviral Medications Because emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets are a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. This section describes clinically relevant drug interactions with emtricitabine, rilpivirine and tenofovir disoproxil fumarate tablets.

7.1 Drugs Affecting Renal Function FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion [see CLINICAL PHARMACOLOGY (12.3)]. No drug-drug interactions due to competition for renal excretion have been observed; however, coadministration of emtricitabine and tenofovir disoproxil fumarate with drugs that are eliminated by active tubular secretion may increase concentrations of FTC, tenofovir, and/or the coadministered drug. Drugs that decrease renal function may increase concentrations of FTC and/or tenofovir.

Co-administration of entecavir with lamivudine, adefovir dipivoxil, or tenofovir disoproxil fumarate did not result in significant drug interactions.

Coadministration of entecavir with lamivudine, adefovir dipivoxil, or tenofovir disoproxil fumarate did not result in significant drug interactions.

7.4 Drugs Without Clinically Significant Interactions with Etravirine Tablets In addition to the drugs included in Table 4, the interaction between etravirine tablets and the following drugs were evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology (12.3) ] : didanosine, enfuvirtide (ENF), ethinylestradiol/norethindrone, omeprazole, paroxetine, raltegravir, ranitidine, and tenofovir disoproxil fumarate. 7.4 Drugs Without Clinically Significant Interactions with Etravirine Tablets In addition to the drugs included in Table 4, the interaction between etravirine tablets and the following drugs were evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology (12.3) ] : didanosine, enfuvirtide (ENF), ethinylestradiol/norethindrone, omeprazole, paroxetine, raltegravir, ranitidine, and tenofovir disoproxil fumarate.

14 ↓15 (↓27 to ↓1) ↓17 (↓27 to ↓6) ↓32 (↓53 to ↓1) 700 mg twice daily plus ritonavir 100 mg twice daily for 14 days (fasted) 14 ↓14 (↓39 to ↑20) ↓17 (↓38 to ↑12) ↓20 (↓45 to ↑17) 700 mg twice daily plus ritonavir 100 mg twice daily for 14 days 12 ↓25 (↓42 to ↓2) ↓25 (↓44 to ↔) ↓33 (↓52 to ↓7) Raltegravir 400 mg twice daily for 14 days 1,400 mg once daily plus ritonavir 100 mg once daily for 14 days (fasted) 13 ↓18 (↓34 to ↔) ↓24 (↓41 to ↔) ↓50 (↓64 to ↓31) 1,400 mg once daily plus ritonavir 100 mg once daily for 14 days 14 ↑27 (↓1 to ↑62) ↑13 (↓7 to ↑38) ↓17 (↓45 to ↑26) Ranitidine 300-mg single dose (administered 1 hour before fosamprenavir) 1,400-mg single dose 30 ↓51 (↓43 to ↓58) ↓30 (↓22 to ↓37) ↔ (↓19 to ↑21) Rifabutin 150 mg every other day for 2 weeks 700 mg twice daily plus ritonavir 100 mg twice daily for 2 weeks 15 ↑36 (↑18 to ↑55) ↑35 (↑17 to ↑56) ↑17 (↓1 to ↑39) Tenofovir 300 mg once daily for 4 to 48 weeks 700 mg twice daily plus ritonavir 100 mg twice daily for 4 to 48 weeks 45 NA NA ↔ Compared with parallel control group. Tenofovir 300 mg once daily for 4 to 48 weeks 1,400 mg once daily plus ritonavir 200 mg once daily for 4 to 48 weeks 60 NA NA ↔ Table 11.

7.5 Drugs without Clinically Significant Interactions with RUKOBIA Based on drug interaction study results, the following drugs can be coadministered with RUKOBIA without a dose adjustment: atazanavir/ritonavir, buprenorphine/naloxone, cobicistat, darunavir/cobicistat, darunavir/ritonavir with and without etravirine, etravirine, famotidine, maraviroc, methadone, norethindrone, raltegravir, ritonavir, rifabutin with and without ritonavir, tenofovir disoproxil fumarate [see Clinical Pharmacology ( 12.3 )] .

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.

Nucleoside Reverse Transcriptase Inhibitor: tenofovir disoproxil fumarate* ↑ tenofovir Patients receiving lopinavir and ritonavir and tenofovir should be monitored for adverse reactions associated with tenofovir.

Anti-HIV efavirenz, maraviroc, nevirapine, zidovudine, bictegravir/ emtricitabine/ tenofovir ↑ efavirenz ↑ maraviroc ↑ nevirapine ↓ zidovudine ↑ bictegravir ↔ emtricitabine ↑ tenofovir For further information, refer to the respective anti-HIV drugs prescribing information.

7.7 Antiretroviral Drugs Loss of virological control has been reported in HIV-infected patients taking orlistat concomitantly with antiretroviral drugs such as atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, and with the combinations lopinavir/ritonavir and emtricitabine/efavirenz/tenofovir disoproxil fumarate.

7.2 Drugs without Clinically Significant Interactions with ISENTRESS or ISENTRESS HD ISENTRESS In drug interaction studies performed using ISENTRESS film-coated tablets 400 mg twice daily dose, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of the following: ethinyl estradiol/norgestimate, methadone, midazolam, lamivudine, tenofovir disoproxil fumarate, etravirine, darunavir/ritonavir, or boceprevir. There is no predicted pharmacokinetic drug interaction between ISENTRESS and tenofovir alafenamide. No dose adjustment is recommended when ISENTRESS HD 1200 mg once daily is coadministered with atazanavir, atazanavir/ritonavir, hormonal contraceptives, methadone, lamivudine, tenofovir disoproxil fumarate, darunavir/ritonavir, boceprevir, efavirenz and omeprazole.

Bictegravir 75 mg once a day 300 mg once a day (fasted) Healthy subjects ND ↓ AUC 38% ↓ C min 56% ↓ C max 20% Co-administration of rifabutin with Biktarvy (bictegravir/ emtricitabine/tenofovir alafenamide) is not recommended due to an expected decrease in tenofovir alafenamide in addition to the reported reduction in bictegravir. Rilpivirine 25 mg once a day 300 mg once a day Healthy subjects (18) ND ↓ AUC by 42% ↓ C min by 48% ↓ C max by 31% Co-administration of rifabutin with Odefsey (rilpivirine/ tenofovir alafenamide/ emtricitabine) is not recommended, due to an expected decrease in tenofovir alafenamide in addition to the reported reduction in rilpivirine.

7.2 Fixed-Dose Combination of Efavirenz, Emtricitabine, and Tenofovir Once-weekly coadministration of 900 mg PRIFTIN with the antiretroviral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in HIV-infected patients did not result in any substantial change in steady state exposures of efavirenz, emtricitabine, and tenofovir.

In addition to the drugs included in Table 6, the interaction between EDURANT and the following drugs was evaluated in clinical studies and no dose adjustment is needed for either drug [see Clinical Pharmacology (12.3) ] : acetaminophen, atorvastatin, chlorzoxazone, cabotegravir, ethinylestradiol, norethindrone, raltegravir, sildenafil, simeprevir and tenofovir disoproxil fumarate.

7.2 Drugs without Clinically Significant Interactions with SOVALDI Based on drug interaction studies conducted with SOVALDI, no clinically significant drug interactions have been either observed or are expected when SOVALDI is combined with the following drugs [see Clinical Pharmacology (12.3) ]: cyclosporine, darunavir/ritonavir, efavirenz, emtricitabine, methadone, oral contraceptives, raltegravir, rilpivirine, tacrolimus, or tenofovir disoproxil fumarate.

7.2 Efavirenz One HIV positive patient treated with ROCTAVIAN at a dose of 4 × 10 13 vg/kg ROCTAVIAN while on an antiretroviral therapy regimen consisting of efavirenz, lamivudine, and tenofovir experienced asymptomatic elevations of ALT, AST, and GGT (> 5.0 × ULN) and serum bilirubin (> ULN and up to 1.5 × ULN) at Week 4 [see Use in Specific Populations (8.6) ] .