Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
Available formulations in Zambia: Tablet: 300 mg (tenofovir disoproxil fumarate - equivalent to 245 mg tenofovir disoproxil). TDF 300 mg/FTC 200 mg combination tab. EFV 600 mg/TDF 300 mg/FTC 200 mg combination tab
- TDF/FTC plus EFV or NVP is now the preferred first line regimen due to long-term potency and favorable mutation pathway.
- Avoid TDF based regimen in patients with renal insufficiency (CrCl <50 ml/min).
ABC/3TC/EFV recommended in patients with renal dysfunction.
- AZT/TDF/FTC plus LPV/r is one of recommended second line regimen after TDF/FTC/EFV failure.
- TDF mutations can increase HIV susceptibility to AZT, while TDF may maintain some activity.
Zambia Information Author: Paul A. Pham, Pharm. D.
- Treatment of HIV-infection in combination with other antiretroviral drugs.
- Treatment of HBV
- Treatment of hepatitis in HIV-HBV co-infected pts.
| Viread ||Tenofovir disoproxil fumarate (TDF)||Gilead Sciences||oral|
| Truvada ||TDF + emtricitabine (FTC) ||Gilead Sciences ||oral |
| Atripla ||TDF + FTC + EFV||Bristol-Myers Squibb & Gilead||oral|
EFV600mg + TDF 300mg + FTC200mg
*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP).
AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's
information, and the McKesson database.
^Dosage is indicated in mg unless otherwise noted.
Pill burden: 1 tab per day.
- TDF: 1 tab once-daily without regard to meals. Fatty meals improve absorption by 40% (clinical significance unknown but not thought to be significant).
- TDF/FTC (Truvada): 1 tab once-daily without regard to meals.
EFV/TDF/FTC (Atripla): 1 tab once-daily. Evening dosing on an empty stomach recommended at first to decrease EFV-associated side effects.
30-49 mL/min TDF 300 mg q48h or Truvada (TDF/FTC co-formulation) 1 tab q48h . <30 mL/min: TDF 300 mg q72-96h . Atripla (TDF/TDF/FTC co-formulation) not recommended with GFR <50 ml/min.
TDF 300 mg q 7 days. Atripla (TDF/TDF/FTC co-formulation) not recommended with GFR <50 ml/min.
TDF 300 mg q 7 days following HD (may require more if more than three 4-hr HD session). Atripla (TDF/TDF/FTC co-formulation) not recommended with GFR <50 ml/min.
No data. Consider dose reduction. Atripla (TDF/TDF/FTC co-formulation) not recommended with GFR <50 ml/min.
No data. Consider dose reduction.
- Generally well tolerated. For Atripla, see EFV for EFV-associated side effects.
- Flatulence, nausea, and vomiting. Asymptomatic elevation of CPK in 12%; transaminase elevation in 4-5%. Neutropenia in 3% and increased amylase in 9%.
- Pts with underlying renal insufficiency or other conditions predisposing to renal insufficiency may be at increased risk for nephrotoxicity.
Low likelihood drug interactions with PIs (with the exception of ATV and LPV) and NNRTIs, since TDF is not a substrate, inhibitor, or inducer of CYP 3A4.
- Case reports of nephrotoxicity with characteristic features of Fanconi syndrome (hypophosphatemia, hypouricemia, proteinuria, and normoglycemic glycosuria), especially in pts with prior history of Fanconi syndrome on adefovir.
LACTIC ACIDOSIS AND HEPATIC STEATOSIS: Causal relationship not established. In vitro, TDF is one of the NRTIs least associated with mitochondrial toxicity. In a clinical trial, d4T resulted in significantly more hyperlactatemia (>2.2 mmol/L) compared to TDF (27% vs 4%, p <0.0001).
|Drug||Effect of Interaction||Recommendations/Comments
| ABC ||No evidence of drug-drug interactions.||ABC +TDF + 3TC once-daily associated with suboptimal viral suppression. Effect probably due to increased selection for resistance (K65R) rather than drug interaction. Preliminary analysis of AZT/ABC/3TC + TDF as a twice-daily regimen showed more favorable results, though unclear whether better than AZT/3TC/ABC alone. Do not co-administer ABC/TDF/3TC without a PIor thymidine analog.
| ATV ||ATV: AUC decreased by 25%; Cmin decreased by 26% (with RTV); tenofovir not measured. ATV AUC decreased by 25% and Cmin decreased by 40% (without RTV);tenofovir AUC: increased by 24%.||With co-administration use RTV-boosted ATV (ATV 300 mg+ RTV 100 mg once-daily). Avoid unboosted ATV and use boosted ATV with caution.
| ddI ||ddI EC AUC: increased by 48% (fasted); ddI EC AUC: increased by 60% (fed state). Tenofovir: No change.||Dose adjust ddI EC to 250 mg once-daily (for >60kg) or 200 mg once-daily (for <60kg) with TDF co-administration. Suboptimal virologic response in 91% of pts treated with ddI + TDF + 3TC once-daily. Do not use ddI + TDF +3TC as a triple-NRTI regimen.
| FTC ||No significant drug interaction.||Use standard dose, usually in coformulated version (TDF/FTC or TDF/FTC/EFV).
| LPV/r ||Tenofovir AUC increased by 34%.||Unlikely to be clinically significant, but monitor for TDF-associated nephrotoxicity. Use standard dose of both TDF and LPV/r
| Etravirine ||ETR AUC decreased by 19%, TDF AUC increased by 15% ||Use standard dose
| Ganciclovir ||May theoretically increase serum concentrations of TDF and/or ganciclovir. ||No data. Monitor for dose-related toxicities.
| Valganciclovir ||May theoretically increase serum concentrations of TDF and/or ganciclovir. ||No data. Monitor for dose-related toxicities.
| Darunavir ||TDF AUC increased 22%. ||Unlikely to be clinically significant, but monitor for TDF-associated nephrotoxicity. Use standard dose of both TDF and DRV/r.
|Food||Increased bioavailability with food (AUC increased 60%), especially high-fat meals, but levels adequate in fasting state.||Take with or without food.
|Norgestimate/ethinyl estradiol||No significant drug interaction.||Use standard dose.
|Probenecid||Tenofovir levels may be increased due to probenecid-induced inhibition of the renal tubular secretion.||Clinical significance unknown.
- TAMs (41L, 210W, 215Y/F, 219Q/E, 67N, 70R): high-level resistance with 3 or more TAMs that include 41L and 210W.
- 65R: selected by TDF, causing intermediate tenofovir resistance, and intermediate resistance to ddI, 3TC, FTC, low-level resistance to ABC and possibly d4T. Susceptibility to AZT retained (may be hypersusceptible).
- 184V: increased susceptibility; may partially reverse 65R- or TAM-mediated resistance.
- T69 insertion: intermediate resistance in setting of multi-NRTI resistance.
- Q151M complex: tenofovir sensitivity retained.
- 74V: increased susceptibility to tenofovir (clinical significance unknown).
Pros: once-daily administration; well tolerated with few short-term side effects and no clear mitochondrial or other long-term toxicity; few drug interactions; less effect on lipids than other NRTIs; activity against some NRTI-resistant strains; longer intracellular half-life than most NRTIs; active against HBV. Coformulations available, including the only single-pill, once-daily regimen. TDF/FTC is now the preferred NRTI backbone for initial therapy in DHHS guidelines.
Cons: potential for nephrotoxicity (may be increased when coadministered with PIs); may decrease bone density more than other NRTIs (generally modest and non-progressive); resistance with selection of K65R.