(STAV yoo deen)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Zerit: 15 mg, 20 mg, 30 mg, 40 mg
Generic: 15 mg, 20 mg, 30 mg, 40 mg
Solution Reconstituted, Oral:
Zerit: 1 mg/mL (200 mL) [dye free; fruit flavor]
Generic: 1 mg/mL (200 mL [DSC])
Brand Names: U.S.
- Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV)
Stavudine is a thymidine analog which interferes with HIV viral DNA dependent DNA polymerase resulting in inhibition of viral replication; nucleoside reverse transcriptase inhibitor
Penetrates into the CSF achieving 16% to 97% (mean: 59%) of concomitant plasma concentrations; distributes into extravascular spaces and equally between RBCs and plasma
Vd: Children: 0.73 ± 0.32 L/kg; Adults: 46 ± 21 L
Converted intracellularly to active triphosphate form; metabolism of stavudine plays minimal role in its clearance; minor metabolites include oxidized stavudine and its glucuronide conjugate, glucuronide conjugate of stavudine, N-acetylcysteine conjugate of the ribose after glycosidic cleavage
Urine 95% (74% as unchanged drug); feces 3% (62% as unchanged drug)
Time to Peak
Serum: 1 hour
Note: Half-life is prolonged with renal dysfunction
Newborns (at birth): 5.3 ± 2 hours
Neonates 14 to 28 days old: 1.6 ± 0.3 hours
Children 5 weeks to 15 years: 0.9 ± 0.3 hours
Adults: 1.6 ± 0.2 hours
Intracellular: Adults: 3.5 to 7 hours
Special Populations: Renal Function Impairment
Oral Cl decreases and terminal elimination half-life increases in patients with renal insufficiency. Adjust dosage in patients with reduced CrCl and patients receiving maintenance hemodialysis.
Use: Labeled Indications
HIV-1: Treatment of HIV-1 infection in combination with other antiretroviral agents
Hypersensitivity to stavudine or any component of the formulation
HIV-1 infection, treatment: Oral:
<60 kg: 30 mg every 12 hours
≥60 kg: 40 mg every 12 hours
Note: According to the Department and Health and Human Services (HHS) HIV treatment guidelines, the World Health Organization recommends 30 mg every 12 hours regardless of body weight (HHS [adult] 2016).
Older patients should be closely monitored for signs and symptoms of peripheral neuropathy. Dosage should be carefully adjusted to renal function.
HIV-1 infection, treatment: Oral:
Neonates postnatal age (PNA) 0 to 13 days: 0.5 mg/kg every 12 hours
Neonates PNA ≥14 days: 1 mg/kg/dose every 12 hours
Infants and Children weighing <30 kg: 1 mg/kg/dose every 12 hours; maximum dose: 30 mg/dose
Children and Adolescents weighing 30 to <60 kg: 30 mg every 12 hours
Adolescents ≥60 kg: 30 mg every 12 hours (HHS [pediatric] 2016). Note: Manufacturer's labeling not recommended (40 mg) due to a greater incidence of adverse effects; pharmacokinetic data suggest toxicity may occur at this higher dose (HHS [pediatric] 2016).
Dosing: Renal Impairment
CrCl >50 mL/minute:
<60 kg: 30 mg every 12 hours
≥60 kg: 40 mg every 12 hours
CrCl 26-50 mL/minute:
<60 kg: 15 mg every 12 hours
≥60 kg: 20 mg every 12 hours
CrCl 10-25 mL/minute
<60 kg: 15 mg every 24 hours
≥60 kg: 20 mg every 24 hours
Hemodialysis: Dialyzable (30%); Administer dose after hemodialysis on day of dialysis
<60 kg: 15 mg every 24 hours
≥60 kg: 20 mg every 24 hours
Children: Specific recommendations not available. Reduction in dose or increase in dosing interval should be considered.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution.
Reconstitute powder for oral suspension with 202 mL of purified water as specified on the bottle. Shake vigorously until suspended. Final suspension will be 1 mg/mL (200 mL).
May be administered without regard to meals. Capsule may be opened and dispersed in a small amount of water; administer immediately (HHS [pediatric] 2016). Oral solution should be shaken vigorously prior to use.
May be taken without regard to meals. Some products may contain sucrose.
Capsules and powder for reconstitution may be stored at controlled room temperature of 25°C (77°F). Reconstituted oral solution should be stored in refrigerator at 2°C to 8°C (36°F to 46°F) and is stable for 30 days.
Didanosine: Stavudine may enhance the adverse/toxic effect of Didanosine. Lactic acidosis (possibly fatal) is of particular concern. Management: Use extreme caution and monitor for lactic acidosis with concomitant stavudine and didanosine therapy. Avoid use of stavudine and didanosine (in combination or alone) with hydroxyurea due to increased risk of serious toxicity. Consider therapy modification
DOXOrubicin (Conventional): May diminish the therapeutic effect of Stavudine. Monitor therapy
DOXOrubicin (Liposomal): May diminish the therapeutic effect of Stavudine. Monitor therapy
Hydroxyurea: May enhance the adverse/toxic effect of Stavudine. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Stavudine may enhance the adverse/toxic effect of Hydroxyurea. An increased risk of pancreatitis, hepatotoxicity and/or neuropathy may exist. Avoid combination
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy
Zidovudine: May diminish the therapeutic effect of Stavudine. Avoid combination
Adverse reactions reported below represent experience with combination therapy with other nucleoside analogues and protease inhibitors.
Central nervous system: Headache (25% to 46%), peripheral neuropathy (8% to 21%)
Dermatologic: Skin rash (18% to 30%)
Endocrine & metabolic: Increased amylase (21% to 31%; grades 3/4: 4% to 8%), increased gamma-glutamyl transferase (15% to 28%; grades 3/4: 2% to 5%)
Gastrointestinal: Nausea (43% to 53%), diarrhea (34% to 45%), vomiting (18% to 30%), increased serum lipase (27%; grades 3/4: 5% to 6%)
Hepatic: Hyperbilirubinemia (65% to 68%; grades 3/4: 7% to 16%), increased serum AST (42% to 53%; grades 3/4: 5% to 7%), increased serum ALT (40% to 50%; grades 3/4: 6% to 8%)
<1% (Limited to important or life-threatening): Abdominal pain, anemia, anorexia, chills, diabetes mellitus, fever, hepatic failure, hepatitis, hepatomegaly with steatosis (some fatal), hyperglycemia, hyperlipidemia, hypersensitivity reaction, immune reconstitution syndrome, insomnia, insulin resistance, lactic acidosis (some fatal), leukopenia, lipoatrophy, lipotrophy, macrocytosis, myalgia, neutropenia, pancreatitis (some fatal), redistribution of body fat, severe weakness (severe neuromuscular weakness resembling Guillain-Barré), thrombocytopenia
Concerns related to adverse effects:
• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves’ disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; combination therapy with didanosine may increase risk; use with caution in patients with risk factors for liver disease (although acidosis has occurred in patients without known risk factors, risk may be increased with female gender, obesity, pregnancy, or prolonged exposure). Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Motor weakness: Severe motor weakness (resembling Guillain-Barré syndrome) has been reported (including fatal cases, usually in association with lactic acidosis); manufacturer recommends discontinuation if motor weakness develops (with or without lactic acidosis).
• Pancreatitis: [US Boxed Warning]: Pancreatitis (including some fatal cases) has occurred during combination therapy with didanosine. Suspend stavudine and didanosine combination therapy, and any other agents toxic to the pancreas, in patients with suspected pancreatitis. If pancreatitis diagnosis confirmed, use extreme caution if reinitiating stavudine; monitor closely and do not use didanosine in regimen.
• Peripheral neuropathy: May be treatment-limiting, especially with higher doses; use with caution in patients with pre-existing peripheral neuropathy, advanced HIV, and/or in combination with other medications known to cause neuropathy (eg, didanosine). Consider discontinuation of therapy if peripheral neuropathy develops; effect may be reversible if therapy discontinued immediately. Symptoms may worsen initially when therapy is discontinued.
• Bone marrow suppression: Use with caution in patients with pre-existing bone marrow suppression.
• Hepatic impairment: Use with caution in patients with hepatic impairment; discontinue or interrupt therapy if worsening liver function occurs.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Concurrent drug therapy issues:
• Combination with didanosine or hydroxyurea: May increase risk of hepatotoxicity/pancreatitis or severe peripheral neuropathy; avoid stavudine or hydroxyurea combination.
• Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
• Zidovudine: Should not use zidovudine in combination with stavudine.
Monitor liver function tests and renal function tests; signs and symptoms of peripheral neuropathy; monitor viral load and CD4 count
Pregnancy Risk Factor
Adverse events were observed in some animal reproduction studies. Stavudine has a high level of transfer across the human placenta. No increased risk of overall birth defects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy may increase the risk of preterm delivery, although available information is conflicting possibly due to variability of maternal factors (disease severity; initiation of therapy); however, maternal antiretroviral medication should not be withheld due to concerns of preterm birth. Information related to stillbirth, low birth weight, and small for gestational age infants is limited. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
[US Boxed Warning]: Fatal lactic acidosis has been reported in pregnant women using didanosine and stavudine in combination with other antiretroviral agents. Cases of lactic acidosis and hepatic steatosis related to mitochondrial toxicity have been reported with use of nucleoside reverse transcriptase inhibitors (NRTIs). These adverse events are similar to other rare but life-threatening syndromes which occur during pregnancy (eg, HELLP syndrome). In general nucleoside reverse transcriptase inhibitors are well tolerated and the benefits of use generally outweigh potential risk. However, due to reports of potentially fatal lactic acidosis, didanosine and stavudine should not be used in combination during pregnancy.
Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women to keep the viral load below the limit of detection and reduce the risk of perinatal transmission. When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should begin as soon as possible after diagnosis. The Health and Human Services (HHS) Perinatal HIV Guidelines do not recommend stavudine for initial therapy in antiretroviral-naive pregnant women due to toxicity; do not use with didanosine or zidovudine. Pharmacokinetics of stavudine are not significantly altered during pregnancy; dose adjustments are not needed. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated. However, because stavudine has a high risk of toxicity, women should be switched to a preferred or alternative regimen. Monitoring during pregnancy is more frequent than in non-pregnant adults; cART should be continued postpartum.
For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s) and expert consultation is recommended; modification of therapy (if needed) and optimization of the woman's health should be done prior to conception. HIV-infected women not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. In addition, consistent use of condoms is also recommended (even during pregnancy) to prevent transmission of HIV or other sexually transmitted diseases.
Health care providers are encouraged to enroll pregnant women exposed to antiretroviral medications as early in pregnancy as possible in the Antiretroviral Pregnancy Registry (1-800-258-4263 or www.APRegistry.com). Health care providers caring for HIV-infected women and their infants may contact the National Perinatal HIV Hotline (888-448-8765) for clinical consultation (HHS [perinatal] 2016).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, nausea, vomiting, or diarrhea. Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of lactic acidosis (fast breathing, tachycardia, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of infection, muscle weakness, burning or numbness feeling, or change in body fat (HCAHPS)
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
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- Drug class: nucleoside reverse transcriptase inhibitors (NRTIs)
Other brands: Zerit