Paul A. Pham, Pharm. D. and John G. Bartlett, M.D
- Coformulation: d4T (30 mg) + 3TC (150 mg) + NVP (200 mg); Dose: 1 tab twice daily.
- 40 mg twice daily dosing no longer recommended due to increased risk of mitochondrial toxicity.
- Co-administration with ddI, INH, phenytoin, and vincristine may increase the risk of peripheral neuropathy.
- Contraindicated with AZT due to in vitro and in vivo antagonism.
Zambia Information Author: Paul A. Pham, Pharm.D.
- Treatment of HIV infection in combination with other antiretrovirals.
| Zerit ||Stavudine (d4T)||Bristol-Myers Squibb||oral|
15 mg; 20 mg; 30 mg; 40 mg
|$6.76; $7.03; $7.45; $7.60
1 mg/mL (200 mL bottle)
|Stavudine ||Stavudine ||Camber pharmaceuticals and other generic manufacturers ||oral |
15 mg; 20 mg; 30 mg; 40 mg
|$6.09; $6.33; $6.73; $6.86
*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.
Wt >60 kg: 40 mg PO twice-daily (WHO recommends and data supports 30 mg PO twice-daily, less toxic and equally effective).
Wt <60 kg: 30 mg PO twice-daily.
- Package insert recommends dose reduction (wt >60 kg: 20 mg twice-daily, wt <60 kg 15 mg twice-daily) for peripheral neuropathy; however, treatment with alternate agent preferred due to limited efficacy data with lower doses and potential for irreversible neuropathy with continued use.
- WHO recommends 30 mg PO twice-daily
Wt >60 kg dose: 30 mg twice-daily (WHO recommendation), wt <60 kg dose: 30 mg twice-daily. May consider 30 mg twice-daily.
Wt >60 kg Cr clearance 26-50 mL: 20 mg twice-daily, wt >60 kg Cr clearance 10-25 mL/min: 20 mg once-daily ; wt <60 kg Cr clearance 26-50 mL/min:15mg twice-daily, wt <60 kg Cr clearance 10-25 mL/min:15 mg once-daily.
Wt >60 kg: 20 mg q24h, wt <60 kg: 15mg q24h.
Wt >60 kg dose: 20 mg q24h, wt <60 kg dose: 15 mg q24h, on days of dialysis dose post-dialysis.
Wt >60 kg dose: 20 mg q24h. Wt <60 kg dose: 15 mg q24h, on days of dialysis dose post-dialysis.
No data: Consider ½ of standard dose.
Peripheral neuropathy (5-24%). Onset is usually 2 to 6 mos. Reversible with early discontinuation.
- Macrocytosis (inconsequential).
Lipoatrophy: caused by mitochondrial toxicity; d4T most common cause; dose dependent--may be less common or severe with 30 mg twice-daily.
Few pharmacokinetic drug interactions.
- HIV-associated neuromuscular weakness syndrome (HANWS): ascending motor weakness, generally accompanied by lactic acidosis.
- Esophageal ulcer (association unclear).
- TAMs (41L, 67N, 70R, 210W, 215Y/F, 219 Q/E): selected by d4T and AZT; increasing d4T resistance (and NRTI cross-resistance) with increasing number of TAMs.
- 151M complex and 69S insertion confer high-level resistance to d4T in setting of multi-NRTI resistance.
- 184V: as with AZT, 184V mutation (associated with 3TC resistance) may increase susceptibility or delay resistance to d4T
- 65R: can be selected by d4T, especially with non-subtype B virus; causes low-level d4T resistance
d4T no longer recommended due to long-term toxicity, including peripheral neuropathy, lipoatrophy, and potentially fatal lactic acidosis. Nevertheless it remains a potent agent for pts who need a thymidine analog but cannot tolerate AZT. ddI + d4T should be avoided, especially in pregnant pts.
Pros: well studied NRTI. Well tolerated in short term; gradual emergence of TAM-medicated resistance.
Cons: NRTI most commonly associated with mitochondrial toxicity, including lipoatrophy, lactic acidosis, and hepatic steatosis; ddI+d4T+EFV inferior to AZT+3TC+EFV in ACTG 384; d4T+3TC+EFV non-inferior to TDF+3TC+EFV in GS903, but with greater toxicity (neuropathy, lipoatrophy, hyperlipidemia). No longer a recommended drug in guidelines used in developed countries. Important to refrigerate (10C or lower) oral liquid formulation since significant loss of stability was observed after 4 weeks at 25C.