|
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. |