STAVZOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for STAVZOR (STAVZOR).
Stavudine is a nucleoside analogue reverse transcriptase inhibitor (NRTI). It is phosphorylated intracellularly to stavudine triphosphate, which competes with natural substrate deoxythymidine triphosphate and inhibits HIV-1 reverse transcriptase by incorporating into viral DNA, causing chain termination.
| Metabolism | Stavudine is phosphorylated intracellularly to its active triphosphate metabolite. It is not significantly metabolized by cytochrome P450 enzymes. Approximately 40% of the dose is excreted unchanged in urine via glomerular filtration and active tubular secretion. |
| Excretion | Stavudine is eliminated primarily by renal excretion (approximately 40% of an administered dose is recovered unchanged in urine within 6 hours, with up to 60-70% overall) and to a lesser extent by fecal excretion (approximately 30%). Active tubular secretion contributes to renal elimination. |
| Half-life | Terminal elimination half-life is approximately 1.0-1.6 hours in adults with normal renal function. In patients with renal impairment, half-life is prolonged (up to 8-14 hours with creatinine clearance <10 mL/min), requiring dose adjustment. Intracellular (active triphosphate) half-life is 3.5-7 hours. |
| Protein binding | Negligible (approximately 1-5% bound to plasma proteins). |
| Volume of Distribution | Apparent volume of distribution is 0.6-0.9 L/kg, indicating distribution into total body water and penetration into cells (including cerebrospinal fluid, with CSF/plasma ratio ~0.4). |
| Bioavailability | Oral bioavailability is 86.4% (range 79-99%) for capsules; food does not significantly alter absorption (AUC unchanged, small delay in Tmax). |
| Onset of Action | Oral: Peak plasma concentrations occur within 0.5-1.5 hours; inhibition of HIV-1 reverse transcriptase begins shortly after absorption, but maximal antiviral effect requires several days of steady-state dosing. |
| Duration of Action | Antiviral effect persists throughout the dosing interval (12 hours) with twice-daily dosing. Intracellular stavudine triphosphate concentrations decline slowly, supporting twice-daily regimen despite short plasma half-life. |
| Molecular Weight | 283.3 |
300 mg orally twice daily.
| Dosage form | CAPSULE, DELAYED RELEASE |
| Renal impairment | CrCl ≥50 mL/min: no adjustment; CrCl 30-49 mL/min: 200 mg twice daily; CrCl 15-29 mL/min: 200 mg daily; CrCl <15 mL/min or hemodialysis: 200 mg three times weekly after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 200 mg twice daily; Child-Pugh C: contraindicated. |
| Pediatric use | ≥6 years: 7.5 mg/kg orally twice daily, maximum 300 mg twice daily. |
| Geriatric use | Start at lower end of dosing range due to increased risk of adverse effects; monitor renal function closely; no specific dose adjustment recommended beyond renal adjustment. |
| 1st trimester | Avoid due to potential teratogenicity; limited human data, animal studies show fetal abnormalities. |
| 2nd trimester | Avoid; may cause fetal harm based on animal data. |
| 3rd trimester | Avoid; risk of neonatal hemorrhage and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for STAVZOR (STAVZOR).
| Placental transfer | Crosses placenta; documented in human and animal studies. |
| Breastfeeding | Excreted in breast milk; potential for serious adverse reactions in nursing infant, including bone marrow suppression. Discontinue nursing or drug. |
| Lactation Rating |
■ 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. Fatal lactic acidosis has been reported in pregnant women who received the combination of stavudine and didanosine with other antiretroviral agents.
| Serious Effects |
Hypersensitivity to stavzor or any componentPregnancy
| Precautions | Lactic acidosis and severe hepatomegaly with steatosis, Pancreatitis, especially in combination with didanosine, Peripheral neuropathy, dose-related and may be irreversible, Lipodystrophy and metabolic abnormalities, Immune reconstitution syndrome, Fat redistribution, Hepatic decompensation in patients with hepatitis B or C coinfection |
| Food/Dietary | May be taken with food to decrease gastrointestinal irritation. Avoid alcohol. Grapefruit juice has no significant interaction, but generally monitor for other food effects. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: associated with increased risk of spontaneous abortion and congenital malformations (neural tube defects, cardiovascular anomalies) based on animal data; human data limited but case reports suggest potential for embryotoxicity. Second and third trimesters: risk of preterm birth, low birth weight, and neonatal metabolic disturbances (hypoglycemia, lactic acidosis). Avoid in pregnancy unless benefits outweigh risks. |
| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST), renal function (creatinine, BUN), and blood glucose levels. Fetal surveillance: serial ultrasound for growth and anatomy, nonstress testing in third trimester. Monitor for neonatal hypoglycemia after delivery. |
| Fertility Effects | Animal studies show reduced fertility and spermatogenesis in males; human data insufficient. May cause menstrual irregularities (oligomenorrhea, amenorrhea) in females. Advise contraceptives for women of childbearing age. |
| Clinical Pearls | Stavzor (valproic acid delayed-release capsules) is a Divalproex formulation. Monitor liver function tests (LFTs) and ammonia levels; avoid in patients with hepatic disease. Check for pancreatitis symptoms. Valproate levels should be monitored (therapeutic range 50-100 mcg/mL). Co-administration with lamotrigine increases lamotrigine levels; reduce lamotrigine dose. Use caution in females of childbearing potential due to teratogenicity. |
| Patient Advice | Take with food to reduce GI upset; do not crush or chew capsules. · Report symptoms such as unexplained weakness, vomiting, abdominal pain (pancreatitis), jaundice, or easy bruising/bleeding immediately. · Avoid alcohol while taking this medication. · If you are pregnant or planning pregnancy, discuss risks of neural tube defects with your doctor. · Do not stop suddenly without medical advice to prevent seizure worsening. |