|
|
Tenofovir DF
Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
06-18-2008
-
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 hepatitis in HIV-HBV co-infected pts. or in HBV mono-infected pts.
brand
name
| generic
| Mfg
| brand
forms
| cost*
|
|
Viread
| Tenofovir Disoproxil Fumarate (TDF) | Gilead Sciences | oral
tablet
300 mg | $23.00 |
|
Truvada
| TDF + emtricitabine (FTC) | Gilead Sciences | oral
tablet
300/200 mg | $35.00 |
| Atripla | TDF + FTC + EFV | Bristol-Myers Squibb & Gilead | oral
tablet
EFV 600mg + TDF 300 mg + FTC 200mg | $55.10 |
*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 with initial therapy to decrease EFV-associated side effects.
Usual dose
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 and transaminase levels in 10%. Neutropenia in 7% and increased amylase in 6%.
- Pts with underlying renal insufficiency or other conditions predisposing to renal insufficiency may be at increased risk for nephrotoxicity.
- 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 hyperlactemia (>2.2 mmol/L) compared to TDF (27% vs 4%, p <0.0001).
Low likelihood drug-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.
| 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 PI or 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). Limited data with EFV/TDF/FTC coformulation and ATV co-administration. 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. Use standard dose of both TDF and LPV/r. |
| Etravirine (ETR) | ETR AUC decreased by 19%, TDF AUC increased by 15% | Use standard dose |
| 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; 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.
- Cons: potential for nephrotoxicity; resistance with selection of K65R.
|
|
![Johns Hopkins POC-IT: Point of Care Information Technology [Home]](../../images/pocit_logo.gif){kind=logo}
Help
