Adult Antiretroviral Guidelines

US DHHS Guidelines with Australian Commentary

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Drug Interactions Between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)

DHHS Last Updated: May 2023Australian Commentary Last Updated: July 2023

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
RifabutinTAF↓ TAF possibleDo not coadminister unless benefits outweigh risks. If coadministered, monitor for virologic response
TDF↔ AUC TFVNo dose adjustment needed.
RifampinTAF
TAF with Rifampin Compared with TDF Alone

  • TFV-DP AUC ↑ 4.2‑fold

TAF with Rifampin Compared with TAF Alone

  • TAF AUC ↓ 55%

  • TFV-DP AUC ↓ 36%

TAF 25 mg Twice Daily with Rifampin Compared with TAF Once Daily Alone

  • TAF AUC ↓ 14%

  • TFV-DP AUC ↓ 24%


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 TFVNo dose adjustment needed.
RifapentineTAF↓ TAF possibleDo not coadminister unless benefits outweigh risks. If coadministered, monitor for virologic response.
TDF↔ AUC TFVNo 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
AdefovirTAF, TDFNo dataDo not coadminister. Serum concentrations of TDF and/or other renally eliminated drugs may increase.
Ganciclovir, ValganciclovirTAF, TDFNo dataSerum 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/PibrentasvirTAF↔ TFV AUCNo dose adjustment needed.
TDFTFV AUC ↑ 29%No dose adjustment needed.
Ledipasvir/SofosbuvirTAFTFV 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.
RibavirinTDFRibavirin with Sofosbuvir 400 mg
  • ↔ TFV AUC

No dose adjustment needed.
Sofosbuvir/VelpatasvirTAF↔ TFV expectedNo dose adjustment needed.
TDFTFV 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 expectedNo dose adjustment needed.
TDFTFV 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
Buprenorphine3TC, TDF↔ 3TC, TDF, and buprenorphineNo dose adjustment needed.
TAF↔ TAF expectedNo dose adjustment needed.
MethadoneABCMethadone clearance ↑ 22%No dose adjustment needed.
Other Drugs
Anticonvulsants Carbamazepine, oxcarbazepine, phenobarbital, phenytoinTAFWith Carbamazepine
  • TAF AUC ↓ 55%


↓ TAF possible with other anticonvulsants
Do not coadminister.
RiociguatABCRiociguat 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 WortTAF↓ TAF possibleDo not coadminister.
Antiretroviral Drugs
Capsid Inhibitor
LEN (SQ and PO)ABC, FTC, 3TC↔ ABC, FTC, 3TC, LEN expectedNo dose adjustment needed.
TAF
TAF AUC ↑ 32%

↔ LEN
No dose adjustment needed.
TDF
TDF AUC ↑ 47%

↔ LEN
No dose adjustment needed.
INSTIs
DTGTAF↔ TAF AUCNo dose adjustment needed.
TDF
↔ TDF AUC

↔ DTG AUC
No dose adjustment needed.
RALTDFRAL AUC ↑ 49%No dose adjustment needed.
PIs
ATV (Unboosted), ATV/c, ATV/rTAFTAF 10 mg with ATV/r
  • TAF AUC ↑ 91%

TAF 10 mg with ATV/c

  • TAF AUC ↑ 75%

No dose adjustment needed (use TAF 25 mg).
TDFWith ATV (Unboosted)
  • ATV AUC ↓ 25% and Cmin ↓ 23% to 40% (higher Cmin with RTV than without RTV)
     

  • TFV AUC ↑ 24% to 37%


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/cTAFTAF 25 mg with DRV/c
  • ↔ TAF

No dose adjustment needed.
TDFTFV ↑ possibleMonitor for TDF-associated toxicities.
DRV/rTAFTAF 10 mg with DRV/r
  • ↔ TAF AUC

No dose adjustment needed.
TDFTFV AUC ↑ 22% and Cmin ↑37%Clinical significance unknown. If coadministered, monitor for TDF-associated toxicities.
LPV/rTAFTAF 10 mg with LPV/r
  • TAF AUC ↑ 47%

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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