STAVZOR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for STAVZOR (STAVZOR).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for STAVZOR (STAVZOR).

Breastfeeding

Excreted into breast milk; M/P ratio approximately 0.5–0.8. Limited human data; potential for infant adverse effects (diarrhea, rash). Caution advised; consider alternative agents or discontinue breastfeeding during therapy.

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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to stavudine or any component of the formulation","Do not coadminister with didanosine due to increased risk of lactic acidosis, pancreatitis, and peripheral neuropathy"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

STAVZOR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for STAVZOR (STAVZOR).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for STAVZOR (STAVZOR).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to stavudine or any component of the formulation","Do not coadminister with didanosine due to increased risk of lactic acidosis, pancreatitis, and peripheral neuropathy"]