STAVUDINE; LAMIVUDINE
Clinical safety rating: safe
Other drugs that cause peripheral neuropathy or pancreatitis increase risk Can cause peripheral neuropathy and pancreatitis.
Stavudine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV-1 reverse transcriptase by competing with natural substrate thymidine triphosphate and causing chain termination after incorporation. Lamivudine is also an NRTI that inhibits HIV-1 reverse transcriptase via similar competition and chain termination.
| Metabolism | Stavudine: Undergoes intracellular phosphorylation to active triphosphate; eliminated renally (~40% unchanged) and via metabolism (not extensively metabolized by CYP450). Lamivudine: Undergoes intracellular phosphorylation; eliminated renally predominantly as unchanged drug (~70%), with minor metabolism to trans-sulfoxide metabolite. |
| Excretion | Stavudine: 40% renal (unchanged) via glomerular filtration and tubular secretion. Lamivudine: 70% renal (unchanged) via glomerular filtration and tubular secretion. Both: minimal biliary/fecal elimination (<5%). |
| Half-life | Stavudine: 1.5-2 h (adults) but intracellular active triphosphate t1/2 3.5-6 h; Lamivudine: 5-7 h (adults) with intracellular triphosphate t1/2 10.5-15.5 h. Renal impairment prolongs elimination; dose adjustment needed for CrCl <50 mL/min. |
| Protein binding | Stavudine: <5% bound to plasma proteins. Lamivudine: <36% bound (predominantly albumin). Binding is negligible and clinically insignificant. |
| Volume of Distribution | Stavudine: 1.0 L/kg (total body water; extensive tissue distribution including CSF). Lamivudine: 1.3 L/kg (large Vd due to penetration into tissues, including CSF). Both distribute well into CNS. |
| Bioavailability | Stavudine: 86-100% (oral) with food reducing Cmax but not AUC. Lamivudine: 86-88% (oral) with food delaying absorption but not reducing AUC. Both well absorbed; no parenteral formulation. |
| Onset of Action | Stavudine: 1-2 h (oral) to peak plasma concentration; Lamivudine: 1-2 h (oral) to peak plasma concentration. Antiviral effect begins within days; maximal suppression >2 weeks. |
| Duration of Action | Stavudine: dosing interval 12 h (plasma) but intracellular effect 8-12 h; Lamivudine: dosing interval 12-24 h; intracellular triphosphate supports once-daily dosing. Duration tailored to maintain trough above IC50. |
Stavudine 30 mg plus lamivudine 150 mg orally twice daily. For weight <60 kg: stavudine 30 mg twice daily; for weight ≥60 kg: stavudine 40 mg twice daily (but fixed-dose combination typically uses 30 mg).
| Dosage form | TABLET |
| Renal impairment | For CrCl 26-50 mL/min: stavudine 20 mg twice daily, lamivudine 150 mg once daily. CrCl 15-25 mL/min: stavudine 15 mg twice daily, lamivudine 150 mg once daily. CrCl <15 mL/min or hemodialysis: stavudine 15 mg once daily, lamivudine 25-50 mg once daily (or 150 mg first dose then 25-50 mg daily). |
| Liver impairment | Stavudine: no adjustment recommended; monitor for hepatotoxicity. Lamivudine: no adjustment recommended for mild to moderate hepatic impairment; no data for severe impairment. |
| Pediatric use | Weight-based: for weight 14-20 kg: stavudine 20 mg + lamivudine 75 mg twice daily; 20-25 kg: stavudine 20 mg + lamivudine 75 mg twice daily; 25-30 kg: stavudine 22.5 mg + lamivudine 75 mg twice daily; 30-40 kg: stavudine 30 mg + lamivudine 75 mg twice daily; ≥40 kg: adult dose. Alternatively, based on BSA: stavudine 1 mg/kg twice daily, lamivudine 4 mg/kg twice daily (max adult dose). |
| Geriatric use | Consider age-related renal impairment; monitor renal function and adjust stavudine and lamivudine doses accordingly. Use lower starting doses if CrCl <50 mL/min. No specific dose adjustment for age alone. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other drugs that cause peripheral neuropathy or pancreatitis increase risk Can cause peripheral neuropathy and pancreatitis.
| FDA category | Animal |
| Breastfeeding | Both agents are excreted into human milk. Lamivudine M/P ratio 0.6-3.3; stavudine M/P ratio 0.7-1.0. Concentrations in milk are subtherapeutic for infants. WHO recommends avoidance of breastfeeding for HIV-positive mothers where replacement feeding is acceptable; otherwise, limited data suggest low risk. |
| Teratogenic Risk |
■ FDA Black Box Warning
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including stavudine and lamivudine. Pancreatitis, including fatal cases, has been reported in patients receiving stavudine.
| Common Effects | Peripheral neuropathy |
| Serious Effects |
Hypersensitivity to stavudine or lamivudine; combination with doxorubicin (due to increased risk of toxicity); caution in patients with pre-existing peripheral neuropathy or pancreatitis.
| Precautions | Lactic acidosis/hepatomegaly with steatosis; pancreatitis; peripheral neuropathy; lipodystrophy; immune reconstitution syndrome; hepatic decompensation in patients co-infected with HIV and HBV; renal impairment (dose adjustment needed). |
Loading safety data…
| First trimester: No increased risk of major birth defects based on data from the Antiretroviral Pregnancy Registry; limited data on specific organ malformations. Second and third trimesters: Potential risk for lactic acidosis and hepatic steatosis with prolonged use; case reports of mitochondrial toxicity. Animal studies showed no teratogenicity at clinically relevant doses. |
| Fetal Monitoring | Monitor maternal complete blood count, hepatic function, serum lactate, and lipase every 2-4 weeks. Fetal ultrasound for growth and anatomy in second trimester. Newborns require monitoring for hyperlactatemia and anemia in first 4-6 weeks. Consider mitochondrial toxicity surveillance if prolonged in utero exposure. |
| Fertility Effects | No known adverse effects on female or male fertility. Lamivudine and stavudine do not impair spermatogenesis or oocyte quality in animal studies. |