Stavudine

Indications

Stavudine is used for: HIV infection

Adult Dose

Oral HIV infection Adult: <60 kg: 30 mg 12 hrly; >60 kg: 40 mg 12 hrly.

Child Dose

Oral HIV infection Child: Birth to 13 days 0.5 mg/kg 12 hrly; >14 days <30 kg: 1 mg/kg 12 hrly; >30 kg: Same as adult dose.

Renal Dose

CrCl (mL/min) Dosage <26 <60 kg: 15 mg 24 hrly; ?60 kg: 20 mg 24 hrly. 26-50 <60 kg: 15 mg 12 hrly; ?60 kg: 20 mg 12 hrly.

Administration

May be taken with or without food. Oral soln: Reconstitute w/ purified water to provide a soln containing 1 mg/mL.

Contra Indications

Hypersensitivity to stavudine. Lactation.

Precautions

Patient w/ hepatomegaly, hepatitis or other risk factors for liver disease (esp obese women); pre-existing bone marrow suppression; history of peripheral neuropathy; history of or risk factors for pancreatitis. Renal or hepatic impairment. Pregnancy. Monitor LFTs, renal function tests, viral load, CD4 count.

Pregnancy-Lactation

Pregnancy Fatal lactic acidosis reported in pregnant individuals who received combination of stavudine and didanosine with other antiretroviral agents; unclear if pregnancy augments risk of lactic acidosis/hepatic steatosis syndrome reported in non-pregnant individuals receiving nucleoside analogues; combination of with didanosine is contraindicated Prospective pregnancy data from APR not sufficient to adequately assess risk of major birth defects, miscarriage or adverse developmental outcomes Animal data In animal reproduction studies, no adverse developmental effects observed with oral administration of stavudine at clinically relevant exposures; no developmental toxicities observed in rats and rabbits at systemic exposures 112 (AUC) and 183 (Cmax) times, respectively, exposures in humans at recommended human dose Lactation The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV; based on limited data, the drug has been detected in human milk; no data are available regarding effects of stavudine on breastfed infant, or effects on milk production Because of potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV-positive infants) and adverse reactions in breastfed infants similar to those seen in adults, instruct mothers not to breastfeed if they are receiving therapy

Interactions

Increased risk of pancreatitis, peripheral neuropathy and hepatotoxicity in combination w/ didanosine and hydroxycarbamide. Risk of hepatic decompensation w/ interferon and ribavirin. Risk of peripheral neuropathy w/ isoniazid. Zidovudine may decrease the phosphorylation of stavudine to its active triphosphate form. Doxorubicin and ribavirin may inhibit stavudine activation.

Adverse Effects

Side effects of Stavudine : >10% Headache Chills/fever Malaise Insomnia Anxiety Depression Pain Rash Nausea Vomiting Diarrhea Pancreatitis Abdominal pain Peripheral neuropathy 1-10% Neutropenia Thrombocytopenia Incr hepatic transaminases Incr bilirubin Myalgia Back pain Weakness

Mechanism of Action

Stavudine, a thymidine analogue, is converted intracellularly to the active metabolite stavudine triphosphate which inhibits HIV reverse transcriptase by competing w/ the natural substrate, thymidine triphosphate. It also inhibits viral DNA synthesis by causing DNA chain termination.