Version May 2024
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 and other antiretrovirals. Fatal lactic acidosis has been reported in pregnant individuals who received the combination of stavudine and didanosine with other antiretroviral agents. Coadministration of stavudine and didanosine is contraindicated because of increased risk of serious and/or life-threatening events. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
Fatal and nonfatal pancreatitis has occurred during therapy when stavudine was part of a combination regimen that included didanosine in both treatment-naive and treatment-experienced patients, regardless of degree of immunosuppression.
HIV-1 infection, treatment: Oral:
Note: Stavudine is no longer recommended for use in the treatment of HIV (HHS [adult] 2019).
<60 kg: 30 mg every 12 hours
≥60 kg: 40 mg every 12 hours
Note: 30 mg every 12 hours, regardless of body weight, may be sufficient for efficacy and associated with improved tolerability (Maskew 2012).
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
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution.
Older patients should be closely monitored for signs and symptoms of peripheral neuropathy. Dosage should be carefully adjusted to renal function.
(For additional information see "Stavudine: Pediatric drug information")
Note: Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer to www.iasusa.org for more information) when necessary.
HIV-1 infection, treatment: Note: Although FDA approved, stavudine is no longer recommended for use in pediatric patients due to higher rates of adverse effects than other nucleoside reverse transcriptase inhibitors (HHS [adult, pediatric] 2018). If used, it should be in combination with other ARV agents.
Infants and Children <30 kg: Oral: 1 mg/kg/dose every 12 hours; maximum dose: 30 mg/dose.
Children and Adolescents weighing 30 to <60 kg: Oral: 30 mg every 12 hours.
Adolescents weighing ≥60 kg: AIDSInfo and WHO recommendation: Oral: 30 mg every 12 hours (HHS [pediatric] 2018). Note: The manufacturer's labeling (40 mg) is not recommended due to a greater incidence of adverse effects (HHS [pediatric] 2018).
Infants, Children, and Adolescents: A decrease in dose should be considered in pediatric patients with renal impairment. Dialyzable (30%). The following guidelines have been used by some clinicians (Aronoff 2007):
Weight <30 kg:
GFR >50 mL/minute/1.73 m2: No adjustment required.
GFR 30 to 50 mL/minute/1.73 m2: 0.5 mg/kg/dose every 12 hours.
GFR <30 mL/minute/1.73 m2: 0.25 mg/kg/dose every 24 hours.
Hemodialysis or peritoneal dialysis: 0.25 mg/kg/dose every 24 hours.
Continuous renal replacement therapy (CRRT): 0.5 mg/kg/dose every 12 hours.
Weight 30 to 59 kg:
GFR >50 mL/minute/1.73 m2: No adjustment required.
GFR 30 to 50 mL/minute/1.73 m2: 15 mg every 12 hours.
GFR <30 mL/minute/1.73 m2: 7.5 mg every 24 hours.
Hemodialysis or peritoneal dialysis: 7.5 mg every 24 hours.
Continuous renal replacement therapy (CRRT): 15 mg every 12 hours.
There are no dosage adjustments provided in the manufacturer labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported below represent experience with combination therapy with other nucleoside analogues and protease inhibitors.
>10%:
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%, postmarketing, and/or case reports: 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
Hypersensitivity to stavudine or any component of the formulation; coadministration with didanosine
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• 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; coadministration of stavudine and didanosine is contraindicated. 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).
• Lipoatrophy: May cause loss of subcutaneous fat, especially in the face, limbs, and buttocks. Lipoatrophy incidence and severity are related to cumulative exposure and may be only partially reversible. Monitor patients for signs of lipoatrophy and consider switching to a nonstavudine-containing regimen if lipoatrophy occurs.
• 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. Coadministration of stavudine and didanosine is contraindicated. Suspend stavudine and any agents toxic to the pancreas in patients with suspected pancreatitis. If pancreatitis diagnosis is 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. Consider discontinuation of therapy if peripheral neuropathy develops; effect may be reversible if therapy discontinued immediately. Symptoms may worsen initially when therapy is discontinued.
Disease-related concerns:
• 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; lactic acidosis may also occur with concomitant didanosine administration. Use with hydroxyurea should be avoided; coadministration with didanosine is contraindicated.
• 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.
Due to an increased risk of toxicities and the availability of alternate agents, stavudine is not recommended as part of an antiretroviral regimen in pediatric patients (HHS [pediatric] 2018) or in adolescents (HHS [adult] 2018).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 15 mg [DSC], 20 mg [DSC], 30 mg [DSC], 40 mg [DSC]
Yes
Capsules (Stavudine Oral)
15 mg (per each): $7.38
20 mg (per each): $7.67
30 mg (per each): $8.15
40 mg (per each): $8.30
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Zerit: 20 mg [DSC], 30 mg [DSC], 40 mg [DSC]
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.
Oral: Administer with or without food
Oral capsule: May be opened and dispersed in a small amount of water; administer immediately (HHS [pediatric] 2016).
Oral solution: Shake well before using
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020412s040,020413s032lbl.pdf#page=28, must be dispensed with this medication.
HIV-1: Treatment of HIV-1 infection in combination with other antiretroviral agents. Note: Stavudine is no longer recommended for use in the treatment of HIV (HHS [adult] 2019).
Stavudine may be confused with cetirizine
Zerit may be confused with Zestril, Ziac, ZyrTEC
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Didanosine: Stavudine may enhance the adverse/toxic effect of Didanosine. The risk of lactic acidosis (possibly fatal), hepatomegaly, and pancreatitis may be increased with this combination. Risk X: Avoid combination
DOXOrubicin (Conventional): May diminish the therapeutic effect of Stavudine. Risk C: Monitor therapy
DOXOrubicin (Liposomal): May diminish the therapeutic effect of Stavudine. Risk C: Monitor therapy
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
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. Risk X: Avoid combination
Levomethadone: May decrease the serum concentration of Stavudine. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Methadone: May decrease the serum concentration of Stavudine. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Zidovudine: May diminish the therapeutic effect of Stavudine. Risk X: Avoid combination
Contraception is not required to initiate or continue antiretroviral therapy (ART).
Based on the Health and Humans Services perinatal HIV guidelines, stavudine is not one of the recommended antiretroviral agents for use in patients with HIV who are trying to conceive.
Maximum viral suppression sustained below the limits of detection prior to conception is recommended for all persons with HIV who are planning a pregnancy. Optimization of the health of the person who will become pregnant is recommended. Selection of or changes to a specific antiretroviral regimen prior to pregnancy should be done as part of a shared decision-making process. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
Stavudine crosses the placenta.
Outcome information specific to stavudine use in pregnancy is no longer being reviewed and updated in the Health and Humans Services (HHS) perinatal guidelines. Fatal lactic acidosis has been reported in pregnant individuals using didanosine and stavudine in combination with other antiretroviral agents; coadministration of stavudine and didanosine is contraindicated. The HHS perinatal HIV guidelines do not recommend stavudine use in pregnant patients due to toxicity, and patients who are pregnant should be changed to a preferred or alternative therapy.
Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes, including preterm birth, low birth weight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, gestational age at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.
ART is recommended for all pregnant people with HIV to maximize their health, maintain the viral load below the limit of detection and reduce the risk of perinatal transmission. Selection of or changes to a specific antiretroviral regimen during pregnancy should be done as part of a shared decision-making process. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth.
Data collection to monitor pregnancy and infant outcomes following exposure to ART is ongoing. Health care providers should enroll all patients exposed to antiretroviral medications during pregnancy in the Antiretroviral Pregnancy Registry (1-800-258-4263). Enrollment should be done as early in pregnancy as possible.
Health care providers caring for pregnant patients with HIV and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
Stavudine is present in breast milk.
Maintaining maximum viral suppression during pregnancy and postpartum decreases but does not eliminate the risk of HIV transmission via breast milk. In addition, multiclass-resistant virus has been detected in breastfeeding infants who acquire HIV despite maternal therapy. In the United States, where formula is usually accessible, affordable, safe, and sustainable, and the risk of infant mortality due to diarrhea and respiratory infections is low, the Health and Human Services perinatal HIV guidelines do not recommend breastfeeding for patients with HIV when safer infant feeding options are available. Persons with HIV who maintain an undetectable viral load while taking antiretroviral therapy (ART) should evaluate infant feeding options (formula, banked donor milk, or breastfeeding) as part of a shared decision-making process (if breastfeeding is being considered, see guidelines for measures to reduce the risk of HIV transmission). When the HIV status at delivery is not known, breast milk may be expressed and stored until a negative test is available. If HIV infection is diagnosed after breastfeeding has been initiated, breastfeeding should be discontinued immediately. Breastfeeding is not recommended for persons with HIV who are not taking ART and/or who do not have sustained viral suppression.
Information is available for counseling and managing patients with HIV who are considering breastfeeding (1-888-448-8765). In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender diverse people assigned female sex at birth (HHS [perinatal] 2023).
May be taken without regard to meals. Some products may contain sucrose.
Monitor liver function tests and renal function tests; signs and symptoms of peripheral neuropathy; monitor viral load and CD4 count
Stavudine is a thymidine analog which interferes with HIV viral DNA dependent DNA polymerase resulting in inhibition of viral replication; nucleoside reverse transcriptase inhibitor
Absorption: Rapid
Distribution: 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
Protein binding: Negligible
Metabolism: 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
Bioavailability: Capsule and solution are bioequivalent; Children: 76.9%; Adults: 86.4%
Half-life elimination: 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
Time to peak, serum: 1 hour
Excretion: Urine 95% (74% as unchanged drug); feces 3% (62% as unchanged drug)
Altered kidney function: 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.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
