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

 (Last updated:5/9/2015; last reviewed:5/9/2015)

Table 19c. 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
Ledipasvir/ Sofosbuvir TDF

• Ledipasvir ↑ TDF AUC 40% to 98% when TDF given with RPV and EFV

• Further ↑ TDF possible if TDF given with PIs

No dose adjustment necessary.

Monitor for TDF toxicity. The safety of increased TDF exposure when ledipasvir/sofosbuvir is coadministered with TDF and a PI/r, ATV/c, or DRV/c has not been established. Consider alternative HCV or ARV drugs to avoid increased TDF toxicities. If coadministration is necessary, monitor for TDF-associated adverse reactions.

Coadministration of ledipasvir/sofosbuvir with EVG/c/TDF/FTC is not recommended.

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.
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 +/- RTV or COBI 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%

Avoid concomitant use without RTV or COBI

Dose:

• ATV 300 mg daily plus (RTV 100 mg or COBI 150 mg) daily when coadministered with TDF 300 mg daily.

• If using TDF and H2 receptor antagonist in ARTexperienced patients, use ATV 400 mg daily plus (RTV 100 mg or COBI 150 mg) daily. Monitor for TDF-associated toxicity.

 

ZDV ZDV Cmin  30%, no change in AUC Clinical significance unknown.
DRV/c TDF Increased TDF possible Monitor for TDF-associated toxicity.
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; COBI = cobicistat; d4T = stavudine; ddI = didanosine; DRV/c = darunavir/cobicistat; DRV/r = ritonavir-boosted darunavir; EC = enteric coated; HCV = hepatitis C virus; 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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