January 10, 2011

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Page 34 

Table 15c. Drug Interactions between NRTIs and Other Drugs (Including ARV Agents)

(Updated January 10, 2011)

Concomitant 

Drug 

Class/Name

NRTI

Effect on NRTI or 

Concomitant Drug 

Concentrations

Dosage Recommendations and Clinical Comments

Antivirals

Ganciclovir

Valganciclovir

TDF No data Serum concentrations of these drugs and/or TDF may be increased. 

Monitor for dose-related toxicities. 

ZDV No significant pharmacokinetic effects Potential increase in hematologic toxicities

Ribavirin

ddI ↑ intracellular ddI Contraindicated. Do not coadminister. Fatal hepatic failure and 

other ddI-related toxicities have been reported with coadministration.

ZDV Ribavirin inhibits phosphorylation of 

ZDV.

Avoid coadministration if possible or closely monitor virologic 

response and hematologic toxicities.

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% and Cmax ↓ 44% No dosage adjustment necessary

ZDV ZDV AUC ↑ 29%–43% Monitor for ZDV-related adverse effects.

NRTIs

ddI d4T No significant PK interaction

Avoid coadministration. Additive toxicities of peripheral 

neuropathy, lactic acidosis, and pancreatitis seen with this 

combination.

TDF ddI-EC AUC and Cmax ↑ 48%–60% Avoid coadministration.

Other

Allopurinol ddI ddI AUC ↑ 113%

ddI AUC ↑ 312% with renal impairment

Contraindicated. Do not coadminister. Potential for increased ddIassociated 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 didanosine. 

TDF

ATV AUC↓ 25% and Cmin ↓ 23%–40% 

(higher Cmin with RTV than without)

TDF AUC ↑ 24%–37%

Dose: ATV/r 300/100 mg daily coadministered 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 ↓ 35%–44% with TPV/r 1,250/100 

mg BID Appropriate doses for this combination have not been established. 

ddI ddI-EC ↓ 10% and TPV Cmin ↓34% with 

TPV/r 1,250/100 mg BID Separate doses by at least 2 hours. 

ZDV ZDV AUC ↓ 31%–43% and Cmax ↓ 46%–

51% with TPV/r 1,250/100 mg BID Appropriate doses for this combination have not been established. 

Acronyms: 3TC = lamivudine, ABC = abacavir, ARV = antiretroviral, ATV = atazanavir, AUC = area under the curve, BID = twice daily, 

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.