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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: May 1, 2014; last reviewed: May 1, 2014)

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Talbe 18c. 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
Non-ARV—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 effect 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 effect 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.
Simeprevir
TDF No significant PK effects
No dose adjustment necessary.
Telaprevir TDF TDF AUC ↑ 30%, Cmin ↑ 6% to 41% Monitor for TDF-associated toxicity.
INSTIs
DTG TDF TDF AUC ↑ 12%, Cmin ↑ 19%

DTG ↔
No dosage adjustment necessary.
RAL TDF RAL AUC ↑ 49% 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% No dosage adjustment necessary.
ZDV ZDV AUC ↑ 29% to 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% to 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.
Atovaquone
ZDV ZDV AUC ↑ 31%
Monitor for ZDV-related adverse effects.
PIs
ATV ddI With ddI-EC Plus 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%, Cmin ↓ 23% to 40% (higher Cmin with RTV than without RTV)

TDF AUC ↑ 24% to 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%, 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% to 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%, Cmin ↓ 12% to 21%
No dosage adjustment necessary.
ZDV ZDV AUC ↓ 35%
TPV/r AUC ↓ 31% to 43%
Appropriate doses for this combination have not been established.
Key to Acronyms: 3TC = lamivudine; ABC = abacavir; ART = antiretroviral; ARV = antiretroviral; ATV = atazanavir; ATV/r = ritonavir-boosted atazanavir; AUC = area under the curve; Cmax  = maximum plasma concentration; Cmin = minimum plasma concentration; d4T = stavudine; ddI = didanosine; DRV/r = ritonavir-boosted darunavir; EC = enteric coated; LPV/r = ritonavir-boosted lopinavir; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RTV = ritonavir; TDF = tenofovir disoproxil fumarate; TPV/r = ritonavir-boosted tipranavir; ZDV = zidovudine

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