(STAV yoo deen)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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)
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.
Special Populations: Hepatic Function Impairment
Pharmacokinetics were not altered in patients with Child-Pugh class B or C hepatic impairment.
Special Populations: Elderly
Pharmacokinetics have not been studied.
Special Populations: Gender
No clinically important differences in pharmacokinetics occurred between men and women.
Special Populations: Race
No clinically important pharmacokinetic differences were associated with race.
Use: Labeled Indications
Treatment of HIV infection in combination with other antiretroviral agents
Hypersensitivity to stavudine or any component of the formulation
HIV infection (in combination with other antiretrovirals): 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 in all adult and adolescent patients regardless of body weight (HHS [adult] 2015).
Older patients should be closely monitored for signs and symptoms of peripheral neuropathy. Dosage should be carefully adjusted to renal function.
HIV infection: Oral:
Newborns (Birth to 13 days): 0.5 mg/kg every 12 hours
≥14 days and <30 kg: 1 mg/kg every 12 hours
≥30 kg: Refer to adult dosing.
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, hemodialysis (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. 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. Consider therapy modification
DOXOrubicin (Liposomal): May diminish the therapeutic effect of Stavudine. Consider therapy modification
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
Ribavirin (Oral Inhalation): May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Monitor therapy
Ribavirin (Systemic): May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). 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%)
Dermatologic: Rash (18% to 30%)
Gastrointestinal: Nausea (43% to 53%; less than comparator group), vomiting (18% to 30%; less than comparator group), diarrhea (34% to 45%)
Hepatic: Hyperbilirubinemia (65% to 68%; grade 3/4: 7% to 16%), AST increased (42% to 53%; grade 3/4: 5% to 7%), ALT increased (40% to 50%; grade 3/4: 6% to 8%), GGT increased (15% to 28%; grade 3/4: 2% to 5%)
Neuromuscular & skeletal: Peripheral neuropathy (8% to 21%)
Miscellaneous: Amylase increased (21% to 31%; grade 3/4: 4% to 8%), lipase increased (~27%; grade 3/4: 5% to 6%)
Postmarketing and/or case reports: Abdominal pain, allergic reaction, anemia, anorexia, chills, diabetes mellitus, fever, hepatic failure, hepatitis, hepatomegaly (with steatosis; some fatal), hyperglycemia, hyperlactatemia (symptomatic), hyperlipidemia, immune reconstitution syndrome, insomnia, insulin resistance, lactic acidosis (some fatal), leukopenia, macrocytosis, myalgia, neuromuscular weakness (severe-resembling Guillain-Barré), neutropenia, pancreatitis (some fatal), redistribution/accumulation/atrophy of body fat, 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. Cases of lactic acidosis/hepatic steatosis syndrome related to mitochondrial toxicity have been reported with use of nucleoside analogues. In addition, 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. The HHS Perinatal HIV Guidelines recommend stavudine to be used only in special circumstances during pregnancy; do not use with didanosine or zidovudine; not recommended for initial therapy in antiretroviral-naive pregnant women due to toxicity. Pharmacokinetics of stavudine are not significantly altered during pregnancy; dose adjustments are not needed.
Combination antiretroviral therapy (cART) therapy is recommended for all HIV-infected pregnant women. The goal of therapy is to keep the viral load below the limit of detection and prevent perinatal transmission. Therapy must be individualized. In general, women who become pregnant on a stable cART regimen may continue that regimen if viral suppression is effective, contraindications for use in pregnancy are not present, and the regimen is well tolerated. For HIV-infected couples planning a pregnancy, maximum viral suppression with cART is recommended prior to conception for the HIV-infected partner(s). When HIV is diagnosed during pregnancy in a woman who has never received antiretroviral therapy, cART should be considered as soon as possible after diagnosis to reduce the risk of perinatal transmission. If antiretroviral drug-resistance testing is done, treatment may be started prior to obtaining results, then adjusted accordingly. Monitoring during pregnancy is more frequent than in non-pregnant adults. If cART must be interrupted for <24 hours, stop then restart all medications simultaneously in order to decrease the chance of developing resistance. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children who develop significant organ system abnormalities (particularly of the CNS or heart) should be evaluated for potential mitochondrial dysfunction.
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] 2015).
• 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 a pancreas problem (pancreatitis; severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of too much lactic acid in the blood (lactic acidosis; fast breathing, fast heartbeat, abnormal heartbeat, vomiting, drowsiness, shortness of breath, feeling very tired or weak, severe dizziness, feeling cold, or muscle pain or cramps), signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), signs of infection, 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.
More about stavudine
- Other brands: Zerit