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.
Recommendations 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 judgement to select the most appropriate alternative medication to use.
Interactions associated with zidovudine are not included in this table. Please refer to the U.S. Food and Drug Administration product labels for information regarding drug interactions between these NRTIs and other drugs.
Concomitant Drug | NRTI | Effect on NRTI and/or Concomitant Drug Concentrations | Dosing Recommendations and Clinical Comments |
|---|---|---|---|
| Antimycobacterials | |||
| Rifabutin | TAF | ↓ TAF possible | Do not coadminister unless benefits outweigh risks. If coadministered, monitor for virologic response |
| TDF | ↔ AUC TFV | No dose adjustment needed. | |
| Rifampin | TAF | TAF with Rifampin Compared with TDF Alone
| Do not coadminister unless benefits outweigh risks. 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. If coadministered, monitor virologic response. |
| TDF | ↔ AUC TFV | No dose adjustment needed. | |
| Rifapentine | TAF | ↓ TAF possible | Do not coadminister unless benefits outweigh risks. If coadministered, monitor for virologic response. |
| TDF | ↔ AUC TFV | No dose adjustment needed. | |
| Antivirals – Orthopoxviruses (Smallpox, Mpox) | |||
Brincidofovir | All NRTIs | ↔ brincidofovir expected | No dose adjustment needed. |
Cidofovir | ABC, 3TC, 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. |
|
Tecovirimat | All NRTIs | ↔ tecovirimat expected | No dose adjustment needed. |
| Cytomegalovirus and Hepatitis B Antivirals | |||
| Adefovir | TAF, TDF | No data | Do not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may increase. |
| Ganciclovir, Valganciclovir | TAF, TDF | No data | Serum concentrations of ganciclovir and/or TFV may increase. Monitor for dose-related toxicities. |
| Hormonal Therapies | |||
17-β-estradiol | FTC | FTC AUC ↓ 14% to 24% | No dose adjustment needed. |
TDF | TFV AUC ↓ 12% to 27% | No dose adjustment needed. |
|
Other hormones used for contraception, gender affirming therapy, or menopausal replacement therapy | All NRTIs | No change expected. | No dose adjustment needed. |
| Hepatitis C Antiviral Agents | |||
| Glecaprevir/Pibrentasvir | TAF | ↔ TFV AUC | No dose adjustment needed. |
| TDF | TFV AUC ↑ 29% | No dose adjustment needed. | |
| Ledipasvir/Sofosbuvir | 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 | TDF | Ribavirin with Sofosbuvir 400 mg
| No dose adjustment needed. |
| Sofosbuvir/Velpatasvir | TAF | ↔ TFV 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 | TAF | ↔ TAF expected | No dose adjustment needed. |
| TDF | TFV Cmax ↑ 48% and AUC ↑39% 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. | |
| Narcotics and Treatment for Opioid Dependence | |||
| Buprenorphine | 3TC, TDF | ↔ 3TC, TDF, and buprenorphine | No dose adjustment needed. |
| TAF | ↔ TAF expected | No dose adjustment needed. | |
| Methadone | ABC | Methadone clearance ↑ 22% | No dose adjustment needed. |
| Other Drugs | |||
| Anticonvulsants Carbamazepine, oxcarbazepine, phenobarbital, phenytoin | TAF | With Carbamazepine
↓ TAF possible with other anticonvulsants | Do not coadminister. |
| Riociguat | 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 | TAF | ↓ TAF possible | Do not coadminister. |
| Antiretroviral Drugs | |||
| Capsid Inhibitor | |||
| LEN (SQ and PO) | ABC, FTC, 3TC | ↔ ABC, FTC, 3TC, 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 | TAF | ↔ TAF AUC | No dose adjustment needed. |
| TDF | ↔ TDF AUC ↔ DTG AUC | No dose adjustment needed. | |
| RAL | TDF | RAL AUC ↑ 49% | No dose adjustment needed. |
| PIs | |||
| ATV (Unboosted), ATV/c, ATV/r | TAF | TAF 10 mg with ATV/r
| No dose adjustment needed (use TAF 25 mg). |
| TDF | With ATV (Unboosted)
| Do not coadminister unboosted ATV with TDF. 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 | TAF | TAF 25 mg with DRV/c
| No dose adjustment needed. |
| TDF | TFV ↑ possible | Monitor for TDF-associated toxicities. | |
| DRV/r | TAF | TAF 10 mg with DRV/r
| No dose adjustment needed. |
| TDF | TFV AUC ↑ 22% and Cmin ↑37% | Clinical significance unknown. If coadministered, monitor for TDF-associated toxicities. | |
| LPV/r | TAF | TAF 10 mg with LPV/r
| No dose adjustment needed. |
| TDF | ↔ LPV/r AUC TFV AUC ↑32% | Clinical significance unknown. If coadministered, monitor for TDF-associated toxicities. | |
| Key to Symbols: ↑ = increase ↓ = decrease ↔ = no change 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; Cmin = minimum plasmaconcentration; COBI = cobicistat; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; HCV = hepatitis C virus; INSTI = integrase strand transferinhibitor; LEN = lenacapavir; LPV/r = lopinavir/ritonavir; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/c = protease inhibitor/cobicistat; PI/r =protease inhibitor/ritonavir; RAL = raltegravir; RTV = ritonavir; SQ = subcutaneous; TAF = tenofovir alafenamide; TDF = tenofovirdisoproxil fumarate; TFV = tenofovir; TFV-DP = tenofovir diphosphate |
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