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Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Drug Interactions

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

(Last updated:2/12/2013; last reviewed:2/12/2013)

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Table 15c. Drug Interactions between Nucleoside Reverse Transcriptase Inhibitors and Other Drugs (Including Antiretroviral Agents)
Concomitant Drug
Class/Name
NRTI Effect on NRTI or Concomitant Drug Concentrations Dosage Recommendations and Clinical Comments
Antivirals
Adefovir TDF No data Do not co-administer. Serum concentrations of TDF and/or other renally eliminated drugs may be increased.
Boceprevir TDF No significant PK effects No dose adjustment necessary.
Ganciclovir
Valganciclovir
TDF No data Serum concentrations of these drugs and/or TDF may be increased. Monitor for dose-related toxicities.
ZDV No significant PK effects Potential increase in hematologic toxicities
Ribavirin ddI ↑ intracellular ddI Contraindicated. Do not co-administer. Fatal hepatic failure and other ddI-related toxicities have been reported with co administration.
ZDV Ribavirin inhibits phosphorylation of ZDV. Avoid co-administration if possible, or closely monitor virologic response and hematologic toxicities.
Telaprevir TDF TDF AUC ↑ 30%, Cmin ↑ 6%–41% Monitor for TDF-associated toxicity.
Integrase Inhibitor
RAL TDF RAL AUC ↑ 49%, Cmax ↑ 64% No dosage adjustment necessary.
Narcotics/Treatment for Opioid Dependence
Buprenorphine 3TC, ddI, TDF, ZDV No significant effect No dosage adjustment necessary.
Methadone ABC methadone clearance ↑ 22% No dosage adjustment necessary.
d4T d4T AUC ↓ 23%, Cmax ↓ 44% No dosage adjustment necessary.
ZDV ZDV AUC ↑ 29%–43% Monitor for ZDV-related adverse effects.
NRTIs
ddI d4T No significant PK interaction Do not co-administer. Additive toxicities of peripheral neuropathy, lactic acidosis, and pancreatitis seen with this combination.
TDF ddI-EC AUC and Cmax ↑ 48%–60% Avoid co-administration.
Other
Allopurinol ddI ddI AUC ↑ 113%
In patients with renal impairment:
ddI AUC ↑ 312%
Contraindicated. Potential for increased ddI-associated toxicities.
PIs
ATV ddI With ddI-EC + ATV (with food): ddI AUC ↓ 34%; ATV no change Administer ATV with food 2 hours before or 1 hour after ddI.
TDF ATV AUC ↓ 25% and Cmin  23%–40% (higher Cmin with RTV than without RTV)

TDF AUC ↑ 24%–37%
Dose: ATV/r 300/100 mg daily co-administered with TDF 300 mg daily. Avoid concomitant use without RTV. If using TDF and H2 receptor antagonist in ART-experienced patients, use ATV/r 400 mg/100 mg daily. Monitor for TDF-associated toxicity.
ZDV ZDV Cmin  30%, no change in AUC Clinical significance unknown.
DRV/r TDF TDF AUC ↑ 22%, Cmax ↑ 24%, and
Cmin ↑ 37%
Clinical significance unknown. Monitor for TDF toxicity.
LPV/r TDF LPV/r AUC 15%
TDF AUC ↑ 34%
Clinical significance unknown. Monitor for TDF toxicity.
TPV/r ABC ABC AUC  35%–44% Appropriate doses for this combination have not been established.
ddI ddI-EC AUC ←→ and Cmin  34%
TPV/r ↔
Separate doses by at least 2 hours.
TDF TDF AUC ←→
TPV/r AUC ↓ 9%–18% and
Cmin ↓ 12%–21%
No dosage adjustment necessary.
ZDV ZDV AUC ↓ 35%
TPV/r AUC ↓ 31%–43%
Appropriate doses for this combination have not been established.
Key to Abbreviations: 3TC = lamivudine, ABC = abacavir, ART = antiretroviral, ATV = atazanavir, ATV/r = atazanavir/ritonavir, AUC = area under the curve, Cmax  = maximum plasma concentration, Cmin = minimum plasma concentration, d4T = stavudine, ddI = didanosine, DRV/r = darunavir/ritonavir, EC = enteric coated, LPV/r = lopinavir/ritonavir, NRTI = nucleoside reverse transcriptase inhibitor, PI = protease inhibitor, PK = pharmacokinetic, RAL = raltegravir, TDF = tenofovir, TPV/r = tipranavir/ritonavir, ZDV = zidovudine