REZIPAS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REZIPAS (REZIPAS).
Inhibits cell wall synthesis by blocking incorporation of mycolic acids into the mycobacterial cell wall via inhibition of the enzyme InhA, a NADH-dependent enoyl-acyl carrier protein reductase.
| Metabolism | Primarily hepatic via acetylation by N-acetyltransferase 2 (NAT2); also metabolized by cytochrome P450 isoenzymes (CYP2E1, CYP3A4). |
| Excretion | Primarily renal excretion (70-80%) as unchanged drug; approximately 20-30% fecal excretion via biliary elimination. |
| Half-life | Terminal elimination half-life is 1.5-2.5 hours. In patients with renal impairment (CrCl <30 mL/min), half-life may extend to 8-12 hours, requiring dose adjustment. |
| Protein binding | Approximately 40% bound to albumin. |
| Volume of Distribution | 0.25-0.35 L/kg, indicating distribution primarily into extracellular fluid and well-perfused tissues. |
| Bioavailability | Oral bioavailability is 60-75% due to first-pass metabolism. Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes. Intravenous: immediate onset. |
| Duration of Action | Duration is 4-6 hours after oral administration; 6-8 hours for intravenous dosing. Short-acting; frequent dosing required (every 6-8 hours). |
150 mg orally every 6 hours (600 mg/day) for 2 days, then 150 mg orally every 12 hours for up to 90 days
| Dosage form | POWDER |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR <30 mL/min or dialysis: 150 mg every 12 hours for 2 days, then 150 mg every 24 hours |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 150 mg every 12 hours; Child-Pugh C: not recommended |
| Pediatric use | For infants ≥3 months and children <12 years: 5 mg/kg/dose every 12 hours for 2 days, then 5 mg/kg/dose every 24 hours; maximum 300 mg/day |
| Geriatric use | No specific dose adjustment; monitor renal function and consider starting at lower end of dosing range due to age-related renal decline |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REZIPAS (REZIPAS).
| Breastfeeding | Stavudine is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 0.9, indicating extensive transfer. In nursing infants, the estimated daily dose from breast milk is about 0.3-0.5 mg/kg/day, which is subtherapeutic but may select for resistance. Given the potential for adverse effects including mitochondrial toxicity and the availability of safer alternatives, breastfeeding is not recommended during stavudine therapy. The WHO advises against breastfeeding for HIV-positive mothers taking stavudine, especially in resource-rich settings. |
| Teratogenic Risk | Based on its mechanism as a nucleotide analogue reverse transcriptase inhibitor, rezispas (stavudine) is classified as FDA Pregnancy Category C. In animal studies, stavudine demonstrated embryotoxicity and fetal toxicity at systemic exposures similar to human therapeutic levels. Human data from the Antiretroviral Pregnancy Registry show no increased risk of overall birth defects above the background rate, but there is evidence of mitochondrial toxicity in infants exposed in utero. Specifically, first trimester exposure is associated with a low absolute risk of neural tube defects (0.3% vs 0.1% background). Second and third trimester exposure may cause transient lactic acidosis and hepatic steatosis in the newborn, and has been linked to an increased incidence of anemia and hyperbilirubinemia. Long-term effects include possible mitochondrial dysfunction manifesting as neurological or growth abnormalities. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hepatic impairment","Acute liver disease of any etiology","Hypersensitivity to isoniazid or any component of the formulation"]
| Precautions | ["Hepatotoxicity, including fatal hepatitis; monitor liver function tests","Peripheral neuropathy, prevented or treated with pyridoxine (vitamin B6)","Hypersensitivity reactions, including rash and flu-like syndrome"] |
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| Fetal Monitoring | Maternal monitoring should include complete blood count (CBC) with differential, serum chemistry including hepatic transaminases, bilirubin, amylase, and lactate levels at baseline and every 2-4 weeks during the first 3 months, then monthly thereafter. Peripheral neuropathy should be assessed clinically. Fetal monitoring includes ultrasound assessment of growth and anatomy at 18-22 weeks, with follow-up growth scans in the third trimester given the risk of intrauterine growth restriction. Neonatal monitoring includes serum lactate within the first 24 hours of life, and evaluation for metabolic acidosis, neurologic symptoms, and hematologic abnormalities. Newborns should be followed for signs of mitochondrial toxicity up to age 1 year. |
| Fertility Effects | There is no evidence that stavudine impairs fertility in men or women. Animal studies showed no adverse effects on mating, fertility, or reproductive performance. In humans, HIV-infected patients on stavudine-containing regimens have not demonstrated reduced fertility rates compared to those on other antiretrovirals. However, stavudine is associated with lipodystrophy and mitochondrial toxicity, which could theoretically affect reproductive outcomes, but no direct fertility impairment has been documented. |