Drug-Drug Interactions
Table 24c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)
This table provides information on the known or predicted interactions between nucleoside reverse transcriptase inhibitors (NRTIs) and non-antiretroviral drugs.
2BRecommendations for managing a particular drug interaction may differ depending on whether a new antiretroviral (ARV) drug is being initiated in a patient on a stable concomitant medication or whether a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly. In cases where an interacting drug needs to be replaced with an alternative, providers should exercise their clinical judgment to select the most appropriate alternative medication.
This table focuses on interactions with pharmacokinetic study data and interactions without study data but where there is a clinical recommendation. Interactions associated with zidovudine (ZDV) are not included in this table. Please refer to the U.S. Food and Drug Administration product labels for information regarding drug interactions between ZDV and other drugs.
| Concomitant Drug | NRTI | Effect on NRTI and/or Concomitant Drug Concentrations | Dosing Recommendations and Clinical Comments |
|---|---|---|---|
| Antibacterials—Antimycobacterials | |||
| Rifabutin | 3TC, ABC, FTC, | ↔ expected | No dose adjustment needed |
| TAF | ↓ TAF possible | Use with caution. If coadministered, monitor virologic response. | |
| TDF | ↔ AUC TFV | No dose adjustment needed | |
| Rifampin | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF With Rifampin Compared With TDF Alone
TAF With Rifampin Compared With TAF Alone
TAF 25 mg Twice Daily With Rifampin Compared With TAF Once Daily Alone
| Use with caution. If coadministered, monitor virologic response. Intracellular TFV-DP levels are higher when TAF is coadministered with rifampin than when TDF is administered alone, but clinical outcomes have not been studied. | |
| TDF | ↔ AUC TFV | No dose adjustment needed | |
| Rifapentine | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↓ TAF possible | Use with caution. If coadministered, monitor virologic response. | |
| TDF | ↔ AUC TFV | No dose adjustment needed | |
| Antiseizure | |||
| Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin | ABC | ↑ carbamazepine possible ↓ ABC possible with oxcarbazepine, phenobarbital, phenytoin | No dose adjustment needed |
| 3TC, FTC, TDF | ↔ expected | No dose adjustment needed | |
| TAF | With Carbamazepine
| Do not coadminister. | |
| Antivirals—Hepatitis C | |||
| Glecaprevir/Pibrentasvir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↔ TFV AUC | No dose adjustment needed | |
| TDF | TFV AUC ↑ 29% | No dose adjustment needed | |
| Ledipasvir/Sofosbuvir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TFV AUC ↑ 27% | No dose adjustment needed | |
| TDF | Ledipasvir ↑ TFV AUC 35% to 98% when TDF is given with various PIs and NNRTIs. Ledipasvir ↑ TFV Cmin 55% to 80% when TDF is given with various PIs, NNRTIs, or INSTIs. Further ↑ TFV AUC and Cmax possible when TDF, ledipasvir/sofosbuvir, and PIs are coadministered. | Do not coadminister with EVG/c, TDF, or FTC. If TDF is used, monitor for TDF toxicities. Consider using TAF in patients at risk of TDF-associated adverse events. Consider using TAF or alternative HCV therapy in patients on TDF plus a PI/r or PI/c. The safety of increased TFV exposure with this combination has not been established. | |
| Ribavirin | 3TC | ↔ 3TC AUC | No dose adjustment needed |
| ABC, FTC, TAF | ↔ expected | No dose adjustment needed | |
| TDF | Ribavirin With Sofosbuvir 400 mg
| No dose adjustment needed | |
| Sofosbuvir/Velpatasvir | 3TC, ABC, FTC, TAF | ↔ expected | No dose adjustment needed |
| TDF | TFV Cmax ↑ 44% to 46% and AUC ↑ 40% when coadministered with various ARV combinations. | If TDF is used in these patients, monitor for TDF-related toxicities. Consider using TAF in patients at risk of TDF-related adverse events. | |
| Sofosbuvir/Velpatasvir/ Voxilaprevir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF AUC ↑ 52% to 57% | No dose adjustment needed | |
| TDF | TFV Cmax ↑ 48% and AUC ↑ 39% when coadministered with various ARV combinations. | Monitor for TDF-related toxicities. Consider using TAF in patients at risk of TDF-related adverse events. | |
| Antivirals—Miscellaneous (e.g., for Herpesvirus, CMV, HBV, Mpox) | |||
| Adefovir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↑ TFV possible | Do not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may increase. | |
| TDF | ↔ TFV | Do not coadminister. | |
| Brincidofovir | 3TC, ABC, FTC, TAF, TDF | ↔ brincidofovir expected | No dose adjustment needed |
| Cidofovir | 3TC, ABC, FTC, TAF | ↔ cidofovir expected | No dose adjustment needed |
| TDF | ↑ TDF and cidofovir possible | Potential for renal toxicity when TDF is given with a nephrotoxic agent, such as cidofovir. If concomitant use is necessary, closely monitor renal function. | |
| Famciclovir | 3TC, ABC, TAF, TDF | ↔ expected | No dose adjustment needed |
| FTC | ↔ AUC FTC, famciclovir | No dose adjustment needed | |
| Ganciclovir, Valganciclovir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF, TDF | ↑ ganciclovir or TFV possible | No dose adjustment needed | |
| Tecovirimat | 3TC, ABC, FTC, TAF, TDF | ↔ tecovirimat expected | No dose adjustment needed |
| Antivirals—SARS-CoV-2 | |||
| Molnupiravir | 3TC, ABC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| Remdesivir | 3TC, ABC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| Ritonavir-Boosted Nirmatrelvir | 3TC, ABC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| Hormonal Therapies—Contraceptives | |||
| Injectable Contraceptives Depot MPA | 3TC, ABC, TAF | ↔ expected | No dose adjustment needed |
| FTC, TDF | ↔ FTC AUC ↔ TFV AUC | No dose adjustment needed | |
| Oral Contraceptives (e.g., desogestrel, drospirenone, ethinyl estradiol, levonorgestrel, norelgestromin, norgestimate, norgestrel) | 3TC, ABC, FTC, TDF | ↔ expected | No dose adjustment needed |
| TAF | ↔ ethinyl estradiol AUC ↔ norelgestromin AUC ↔ norgestrel AUC | No dose adjustment needed | |
| Hormonal Therapies—Gender Affirming and Menopause | |||
| Estradiol Valerate | 3TC, ABC, TAF | ↔ expected | No dose adjustment needed |
| FTC | ↔ FTC AUC ↔ estradiol AUC | ||
| TDF | ↔ TFV AUC ↔ estradiol | ||
| 17-β-estradiol | 3TC, ABC, TAF | ↔ expected | No dose adjustment needed |
| FTC | FTC AUC ↓ 14% to 24% | ||
| TDF | TFV AUC ↓ 12% to 27% | ||
| Other Medications Used for Gender-Affirming Therapy or Menopausal Replacement Therapy | ABC, 3TC, FTC, TAF, TDF | ↔ NRTI expected | No dose adjustment needed |
| Narcotics and Treatment for Opioid Dependence | |||
| Buprenorphine | ABC, FTC | ↔ expected | No dose adjustment needed |
| 3TC, TDF | ↔ 3TC, TDF, and buprenorphine | No dose adjustment needed | |
| TAF | ↔ TAF expected | No dose adjustment needed | |
| Methadone | 3TC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| ABC | Methadone clearance ↑ 22% | No dose adjustment needed | |
| Miscellaneous | |||
| Ethanol | ABC | ABC AUC ↑ 41% | No dose adjustment needed |
| Riociguat | 3TC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| ABC | Riociguat AUC ↑ 200% | If coadministered, initiate riociguat at 0.5 mg three times daily and monitor for riociguat-related adverse effects (e.g., hypotension). | |
| St. John’s Wort | 3TC, ABC, FTC, TDF | ↔ expected | No dose adjustment needed |
| TAF | ↓ TAF possible | Do not coadminister. | |
| Antiretrovirals | |||
| Capsid Inhibitor | |||
| LEN (SQ and PO) | 3TC, ABC, FTC | ↔ 3TC, ABC, FTC, LEN expected | No dose adjustment needed |
| TAF | TAF AUC ↑ 32% ↔ LEN | No dose adjustment needed | |
| TDF | TDF AUC ↑ 47% ↔ LEN | No dose adjustment needed | |
| INSTIs | |||
| DTG | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↔ TAF AUC | No dose adjustment needed | |
| TDF | ↔ TDF AUC ↔ DTG AUC | No dose adjustment needed | |
| RAL | 3TC, ABC, FTC, TAF | ↔ expected | No dose adjustment needed |
| TDF | RAL AUC ↑ 49% | No dose adjustment needed | |
| PIs | |||
| ATV/c, ATV/r | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF 10 mg With ATV/r
TAF 10 mg With ATV/c
| No dose adjustment needed (use TAF 25 mg) | |
| TDF | With ATV (Unboosted)
| Use ATV 300 mg plus (RTV 100 mg or COBI 150 mg) daily when coadministering TDF 300 mg daily. If using TDF and an H2 receptor antagonist in an ART‑experienced patient, use ATV 400 mg plus (RTV 100 mg or COBI 150 mg) daily. Monitor for TDF-associated toxicities. | |
| DRV/c | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF 25 mg With DRV/c
| No dose adjustment needed | |
| TDF | TFV ↑ possible | Monitor for TDF-associated toxicities. | |
| DRV/r | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF 10 mg With DRV/r
| No dose adjustment needed | |
| TDF | TFV AUC ↑ 22% and Cmin ↑ 37% | Clinical significance is unknown. If coadministered, monitor for TDF-associated toxicities. | |
| Key to Symbols: ↑ = increase ↓ = decrease ↔ = less than 20% change in AUC Key: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; CMV = cytomegalovirus; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; HBV = hepatitis B virus; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitor; LEN = lenacapavir; MPA = medroxyprogesterone acetate; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; PO: oral; RAL = raltegravir; RTV = ritonavir; SQ = subcutaneous; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TFV = tenofovir; TFV-DP = tenofovir diphosphate | |||
Drug-Drug Interactions
Table 24c. Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)
| Concomitant Drug | NRTI | Effect on NRTI and/or Concomitant Drug Concentrations | Dosing Recommendations and Clinical Comments |
|---|---|---|---|
| Antibacterials—Antimycobacterials | |||
| Rifabutin | 3TC, ABC, FTC, | ↔ expected | No dose adjustment needed |
| TAF | ↓ TAF possible | Use with caution. If coadministered, monitor virologic response. | |
| TDF | ↔ AUC TFV | No dose adjustment needed | |
| Rifampin | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF With Rifampin Compared With TDF Alone
TAF With Rifampin Compared With TAF Alone
TAF 25 mg Twice Daily With Rifampin Compared With TAF Once Daily Alone
| Use with caution. If coadministered, monitor virologic response. Intracellular TFV-DP levels are higher when TAF is coadministered with rifampin than when TDF is administered alone, but clinical outcomes have not been studied. | |
| TDF | ↔ AUC TFV | No dose adjustment needed | |
| Rifapentine | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↓ TAF possible | Use with caution. If coadministered, monitor virologic response. | |
| TDF | ↔ AUC TFV | No dose adjustment needed | |
| Antiseizure | |||
| Carbamazepine, Oxcarbazepine, Phenobarbital, Phenytoin | ABC | ↑ carbamazepine possible ↓ ABC possible with oxcarbazepine, phenobarbital, phenytoin | No dose adjustment needed |
| 3TC, FTC, TDF | ↔ expected | No dose adjustment needed | |
| TAF | With Carbamazepine
| Do not coadminister. | |
| Antivirals—Hepatitis C | |||
| Glecaprevir/Pibrentasvir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↔ TFV AUC | No dose adjustment needed | |
| TDF | TFV AUC ↑ 29% | No dose adjustment needed | |
| Ledipasvir/Sofosbuvir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TFV AUC ↑ 27% | No dose adjustment needed | |
| TDF | Ledipasvir ↑ TFV AUC 35% to 98% when TDF is given with various PIs and NNRTIs. Ledipasvir ↑ TFV Cmin 55% to 80% when TDF is given with various PIs, NNRTIs, or INSTIs. Further ↑ TFV AUC and Cmax possible when TDF, ledipasvir/sofosbuvir, and PIs are coadministered. | Do not coadminister with EVG/c, TDF, or FTC. If TDF is used, monitor for TDF toxicities. Consider using TAF in patients at risk of TDF-associated adverse events. Consider using TAF or alternative HCV therapy in patients on TDF plus a PI/r or PI/c. The safety of increased TFV exposure with this combination has not been established. | |
| Ribavirin | 3TC | ↔ 3TC AUC | No dose adjustment needed |
| ABC, FTC, TAF | ↔ expected | No dose adjustment needed | |
| TDF | Ribavirin With Sofosbuvir 400 mg
| No dose adjustment needed | |
| Sofosbuvir/Velpatasvir | 3TC, ABC, FTC, TAF | ↔ expected | No dose adjustment needed |
| TDF | TFV Cmax ↑ 44% to 46% and AUC ↑ 40% when coadministered with various ARV combinations. | If TDF is used in these patients, monitor for TDF-related toxicities. Consider using TAF in patients at risk of TDF-related adverse events. | |
| Sofosbuvir/Velpatasvir/ Voxilaprevir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF AUC ↑ 52% to 57% | No dose adjustment needed | |
| TDF | TFV Cmax ↑ 48% and AUC ↑ 39% when coadministered with various ARV combinations. | Monitor for TDF-related toxicities. Consider using TAF in patients at risk of TDF-related adverse events. | |
| Antivirals—Miscellaneous (e.g., for Herpesvirus, CMV, HBV, Mpox) | |||
| Adefovir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↑ TFV possible | Do not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may increase. | |
| TDF | ↔ TFV | Do not coadminister. | |
| Brincidofovir | 3TC, ABC, FTC, TAF, TDF | ↔ brincidofovir expected | No dose adjustment needed |
| Cidofovir | 3TC, ABC, FTC, TAF | ↔ cidofovir expected | No dose adjustment needed |
| TDF | ↑ TDF and cidofovir possible | Potential for renal toxicity when TDF is given with a nephrotoxic agent, such as cidofovir. If concomitant use is necessary, closely monitor renal function. | |
| Famciclovir | 3TC, ABC, TAF, TDF | ↔ expected | No dose adjustment needed |
| FTC | ↔ AUC FTC, famciclovir | No dose adjustment needed | |
| Ganciclovir, Valganciclovir | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF, TDF | ↑ ganciclovir or TFV possible | No dose adjustment needed | |
| Tecovirimat | 3TC, ABC, FTC, TAF, TDF | ↔ tecovirimat expected | No dose adjustment needed |
| Antivirals—SARS-CoV-2 | |||
| Molnupiravir | 3TC, ABC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| Remdesivir | 3TC, ABC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| Ritonavir-Boosted Nirmatrelvir | 3TC, ABC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| Hormonal Therapies—Contraceptives | |||
| Injectable Contraceptives Depot MPA | 3TC, ABC, TAF | ↔ expected | No dose adjustment needed |
| FTC, TDF | ↔ FTC AUC ↔ TFV AUC | No dose adjustment needed | |
| Oral Contraceptives (e.g., desogestrel, drospirenone, ethinyl estradiol, levonorgestrel, norelgestromin, norgestimate, norgestrel) | 3TC, ABC, FTC, TDF | ↔ expected | No dose adjustment needed |
| TAF | ↔ ethinyl estradiol AUC ↔ norelgestromin AUC ↔ norgestrel AUC | No dose adjustment needed | |
| Hormonal Therapies—Gender Affirming and Menopause | |||
| Estradiol Valerate | 3TC, ABC, TAF | ↔ expected | No dose adjustment needed |
| FTC | ↔ FTC AUC ↔ estradiol AUC | ||
| TDF | ↔ TFV AUC ↔ estradiol | ||
| 17-β-estradiol | 3TC, ABC, TAF | ↔ expected | No dose adjustment needed |
| FTC | FTC AUC ↓ 14% to 24% | ||
| TDF | TFV AUC ↓ 12% to 27% | ||
| Other Medications Used for Gender-Affirming Therapy or Menopausal Replacement Therapy | ABC, 3TC, FTC, TAF, TDF | ↔ NRTI expected | No dose adjustment needed |
| Narcotics and Treatment for Opioid Dependence | |||
| Buprenorphine | ABC, FTC | ↔ expected | No dose adjustment needed |
| 3TC, TDF | ↔ 3TC, TDF, and buprenorphine | No dose adjustment needed | |
| TAF | ↔ TAF expected | No dose adjustment needed | |
| Methadone | 3TC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| ABC | Methadone clearance ↑ 22% | No dose adjustment needed | |
| Miscellaneous | |||
| Ethanol | ABC | ABC AUC ↑ 41% | No dose adjustment needed |
| Riociguat | 3TC, FTC, TAF, TDF | ↔ expected | No dose adjustment needed |
| ABC | Riociguat AUC ↑ 200% | If coadministered, initiate riociguat at 0.5 mg three times daily and monitor for riociguat-related adverse effects (e.g., hypotension). | |
| St. John’s Wort | 3TC, ABC, FTC, TDF | ↔ expected | No dose adjustment needed |
| TAF | ↓ TAF possible | Do not coadminister. | |
| Antiretrovirals | |||
| Capsid Inhibitor | |||
| LEN (SQ and PO) | 3TC, ABC, FTC | ↔ 3TC, ABC, FTC, LEN expected | No dose adjustment needed |
| TAF | TAF AUC ↑ 32% ↔ LEN | No dose adjustment needed | |
| TDF | TDF AUC ↑ 47% ↔ LEN | No dose adjustment needed | |
| INSTIs | |||
| DTG | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | ↔ TAF AUC | No dose adjustment needed | |
| TDF | ↔ TDF AUC ↔ DTG AUC | No dose adjustment needed | |
| RAL | 3TC, ABC, FTC, TAF | ↔ expected | No dose adjustment needed |
| TDF | RAL AUC ↑ 49% | No dose adjustment needed | |
| PIs | |||
| ATV/c, ATV/r | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF 10 mg With ATV/r
TAF 10 mg With ATV/c
| No dose adjustment needed (use TAF 25 mg) | |
| TDF | With ATV (Unboosted)
| Use ATV 300 mg plus (RTV 100 mg or COBI 150 mg) daily when coadministering TDF 300 mg daily. If using TDF and an H2 receptor antagonist in an ART‑experienced patient, use ATV 400 mg plus (RTV 100 mg or COBI 150 mg) daily. Monitor for TDF-associated toxicities. | |
| DRV/c | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF 25 mg With DRV/c
| No dose adjustment needed | |
| TDF | TFV ↑ possible | Monitor for TDF-associated toxicities. | |
| DRV/r | 3TC, ABC, FTC | ↔ expected | No dose adjustment needed |
| TAF | TAF 10 mg With DRV/r
| No dose adjustment needed | |
| TDF | TFV AUC ↑ 22% and Cmin ↑ 37% | Clinical significance is unknown. If coadministered, monitor for TDF-associated toxicities. | |
| Key to Symbols: ↑ = increase ↓ = decrease ↔ = less than 20% change in AUC Key: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; COBI = cobicistat; CMV = cytomegalovirus; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; HBV = hepatitis B virus; HCV = hepatitis C virus; INSTI = integrase strand transfer inhibitor; LEN = lenacapavir; MPA = medroxyprogesterone acetate; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r = protease inhibitor/ritonavir; PO: oral; RAL = raltegravir; RTV = ritonavir; SQ = subcutaneous; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate; TFV = tenofovir; TFV-DP = tenofovir diphosphate | |||
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