ZERIT XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZERIT XR (ZERIT XR).
ZERIT XR (stavudine extended-release) is a nucleoside analog reverse transcriptase inhibitor (NRTI). It is phosphorylated intracellularly to stavudine triphosphate, which competes with natural thymidine triphosphate for incorporation into viral DNA, causing chain termination and inhibition of HIV-1 reverse transcriptase.
| Metabolism | Stavudine is phosphorylated intracellularly to active metabolite; it is not significantly metabolized by cytochrome P450 enzymes. Approximately 40% of an oral dose is excreted unchanged in urine via glomerular filtration and active tubular secretion. |
| Excretion | Approximately 94% of the dose is excreted unchanged in urine via glomerular filtration and tubular secretion; <1% is eliminated in feces. |
| Half-life | 5.7 hours (range 4–8 hours) in patients with normal renal function; prolonged to 13–20 hours in renal impairment (CrCl <30 mL/min). |
| Protein binding | <5% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.83–1.14 L/kg (total body water distribution); extensive tissue penetration including CSF, semen, and fetal tissues. |
| Bioavailability | 68–89% after oral administration (mean 86%); food slightly delays absorption but no significant change in AUC. |
| Onset of Action | Peak plasma concentrations achieved 1.5–3 hours after oral administration; antiretroviral effect begins with first dose but maximal viral suppression takes weeks. |
| Duration of Action | Dosing interval 12 hours due to short half-life; clinical effect requires consistent adherence. For XR formulation, dosing interval is 24 hours. |
| Molecular Weight | 224.21 |
ZERIT XR (stavudine extended-release) is administered orally once daily. Adult dose: 100 mg once daily for patients ≥60 kg; 75 mg once daily for patients <60 kg.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | Creatinine clearance (CrCl) >50 mL/min: no adjustment. CrCl 26-50 mL/min: 50 mg once daily (if ≥60 kg) or 30 mg once daily (if <60 kg). CrCl 10-25 mL/min: 50 mg once daily (if ≥60 kg) or 30 mg once daily (if <60 kg). CrCl <10 mL/min or hemodialysis: 50 mg once daily (if ≥60 kg) or 30 mg once daily (if <60 kg) for patients not on dialysis; for hemodialysis, administer after dialysis. |
| Liver impairment | No specific guidelines for Child-Pugh classification. Use with caution in hepatic impairment; consider dose reduction or alternative therapy due to potential for hepatotoxicity. |
| Pediatric use | Weight-based dosing for ZERIT XR not established; use immediate-release stavudine. For IR: 1 mg/kg/dose twice daily (maximum 30 mg/dose) for <30 kg; 30 mg twice daily for ≥30 kg. |
| Geriatric use | Elderly patients may have age-related renal impairment; adjust dose based on creatinine clearance. Monitor renal function and neuropathy risk. |
| 1st trimester | Avoid use unless no alternative; associated with mitochondrial toxicity and lactic acidosis; preferred use later in pregnancy. |
| 2nd trimester | Avoid use unless no alternative; monitor for lactic acidosis and hepatic steatosis. |
| 3rd trimester | Avoid use unless no alternative; monitor for lactic acidosis and hepatic steatosis. |
Clinical note
Comprehensive clinical and safety monograph for ZERIT XR (ZERIT XR).
| Placental transfer | Crosses placenta; cord blood concentrations similar to maternal levels. |
| Breastfeeding | Contraindicated in breastfeeding due to potential for HIV transmission via breast milk and possible infant toxicity; alternative antiretrovirals preferred. |
| Lactation Rating |
■ FDA Black Box Warning
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including stavudine. Fatal lactic acidosis has been reported in pregnant women who received stavudine and didanosine with other antiretroviral agents. Co-administration of stavudine with didanosine is contraindicated due to increased risk of toxicity, including pancreatitis, peripheral neuropathy, and lactic acidosis.
| Serious Effects |
Hypersensitivity to stavudine or any componentPre-existing peripheral neuropathyLactic acidosis or severe hepatomegaly with steatosis
| Precautions | Lactic acidosis/hepatomegaly with steatosis, Pancreatitis (especially with didanosine co-administration), Peripheral neuropathy, Lipoatrophy/lipodystrophy, Immune reconstitution syndrome, Mitochondrial toxicity (including in infants exposed in utero), Hepatic decompensation in patients with hepatitis co-infection |
| Food/Dietary | May be taken with or without food. Avoid high-fat meals as they may alter absorption. No specific food restrictions. |
Loading safety data…
| Avoid |
| Teratogenic Risk | FDA Pregnancy Category C. Stavudine crosses the placenta. First trimester: limited human data, but animal studies show decreased fetal weight and increased incidence of skeletal variations at doses producing maternal toxicity. Second and third trimesters: no evidence of teratogenicity in prospective cohort studies, but mitochondrial toxicity may occur with prolonged exposure. Not recommended for use in pregnancy unless benefit outweighs risk; preferred alternatives (e.g., zidovudine) exist. |
| Fetal Monitoring | Monitor maternal: baseline and periodic serum lactate (risk of lactic acidosis), liver enzymes, amylase, and neurologic symptoms for peripheral neuropathy. Fetal: ultrasound fetal growth and anatomy if used in first trimester (limited data). Monitor neonate for signs of mitochondrial toxicity (hypotonia, seizures, lactic acidosis) if exposed in utero. |
| Fertility Effects | No direct studies on fertility. In animal studies, no impact on mating or fertility at systemic exposures similar to human therapeutic levels. However, stavudine may cause mitochondrial dysfunction in oocytes/sperm, potentially affecting fertility, but clinical significance unknown. |
| Clinical Pearls | ZERIT XR (stavudine extended-release) is a nucleoside reverse transcriptase inhibitor (NRTI) for HIV-1 infection. Monitor for peripheral neuropathy, which may require dose adjustment or discontinuation. Avoid use with didanosine due to increased risk of pancreatitis and peripheral neuropathy. Warn patients about lactic acidosis and severe hepatomegaly with steatosis, especially in women and obese patients. |
| Patient Advice | Take once daily at bedtime to minimize daytime side effects. · Do not crush or chew the extended-release capsule; swallow whole. · Report tingling or numbness in hands/feet immediately. · Avoid alcohol due to increased risk of liver toxicity. · Do not take with other stavudine products or didanosine. · If pregnant, discuss risks of lactic acidosis in the fetus. |