Alafenamide

Tenofovir alafenamide (TAF) is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3. Anticonvulsants: carbamazepine, phenobarbital, phenytoin ↓ cobicistat ↓ darunavir ↓ tenofovir alafenamide Co-administration is contraindicated due to potential for loss of therapeutic effect and development of resistance. Anticonvulsants with CYP3A induction effects that are NOT contraindicated: e.g., eslicarbazepine, oxcarbazepine ↓ cobicistat ↓ tenofovir alafenamide darunavir: effect unknown Consider alternative anticonvulsant or antiretroviral therapy to avoid potential changes in exposures.

P-gp inducer that decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

P-gp inducer that decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

P-gp inducer that decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

Decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

Decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

Decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

Eliminated by active tubular secretion; coadministration may increase tenofovir and acyclovir concentrations, increasing adverse reaction risk.

P-gp inducer that decreases tenofovir alafenamide absorption and plasma concentrations. Dose adjustment to two tablets once daily is recommended.

Eliminated by active tubular secretion; coadministration may increase tenofovir and cidofovir concentrations, increasing adverse reaction risk.

Eliminated by active tubular secretion; coadministration may increase tenofovir and ganciclovir concentrations, increasing adverse reaction risk.

Aminoglycoside eliminated by active tubular secretion; coadministration may increase tenofovir and gentamicin concentrations, increasing adverse reaction risk.

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.

Eliminated by active tubular secretion; coadministration may increase tenofovir and valacyclovir concentrations, increasing adverse reaction risk.

Eliminated by active tubular secretion; coadministration may increase tenofovir and valganciclovir concentrations, increasing adverse reaction risk.

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.

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).

Elvitegravir/ cobicistat/ emtricitabine/ tenofovir (disoproxil fumarate or alafenamide) ↑ EBR ↑ GZR Co-administration of cobicistat-containing regimens is not recommended.

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) ] .

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.

7.5 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.

John's wort (Hypericum perforatum) 7.4 Drugs without Clinically Significant Interactions with VEMLIDY Based on drug interaction studies conducted with VEMLIDY, no clinically significant drug interactions have been observed with: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.

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.

John's wort (Hypericum perforatum) 7.4 Drugs without Clinically Significant Interactions with VEMLIDY Based on drug interaction studies conducted with VEMLIDY, no clinically significant drug interactions have been observed with: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.

There is no predicted pharmacokinetic drug interaction between ISENTRESS and tenofovir alafenamide. There is no predicted pharmacokinetic drug interaction between ISENTRESS HD and tenofovir alafenamide.

John's wort (Hypericum perforatum) 7.4 Drugs without Clinically Significant Interactions with VEMLIDY Based on drug interaction studies conducted with VEMLIDY, no clinically significant drug interactions have been observed with: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.

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

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.

John's wort (Hypericum perforatum) 7.4 Drugs without Clinically Significant Interactions with VEMLIDY Based on drug interaction studies conducted with VEMLIDY, no clinically significant drug interactions have been observed with: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.

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.

John's wort (Hypericum perforatum) 7.4 Drugs without Clinically Significant Interactions with VEMLIDY Based on drug interaction studies conducted with VEMLIDY, no clinically significant drug interactions have been observed with: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.