Stavudine (Zerit®, d4T) (PDF Version)
Stavudine is a thymidine analogue.
Nucleoside reverse transcriptase inhibitor (NRTI).
Stavudine is converted to stavudine 5'-triphosphate which competes with thymidine 5'-triphosphate for incorporation into viral DNA. Stavudine 5'-triphosphate lacks a 3'-hydroxyl group and leads to chain termination.
Resistance to NRTIs occurs through two mechanisms; decreased incorporation of NRTIs into the viral DNA and increased excision of NRTIs from the viral DNA
Stavudine bioavailability is 99% in adults and 78% in children. The volume of distribution ranges from 0.54 to 0.69 L/kg in adults and is 9.3 L/mm3 in children. Approximately 40% of a dose of stavudine can be recovered as parent drug in the urine.
The most common adverse effect is peripheral neuropathy. Bone marrow suppression may also occur.
Capsule 15mg, 20mg, 30mg, 40mg
Powder for Oral Solution 1mg/ml
Adults:
≥ 60kg – 40 mg twice daily
< 60kg – 30 mg twice daily
Pediatric:
2 mg/kg/day in two divided doses
Disease state based dosing:
Renal Impairment:
≥ 60kg:
CrCl > 50ml/min – 40mg twice daily
CrCl 26-50ml/min – 20mg twice daily
CrCl 10-25ml/min – 20mg once daily
CrCl < 10ml/min – 20mg every other day
Hemodialysis – 20mg once daily after hemodialysis
< 60mg:
CrCl > 50ml/min – 30mg twice daily
CrCl 26-50ml/min – 15mg twice daily
CrCl 10-25ml/min – 15mg once daily
CrCl < 10ml/min – 15mg every other day
Hemodialysis – 15mg once daily after hemodialysis
Hepatic Impairment: no dose adjustment necessary
Contraindications/Warnings/ Precautions:
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of NRTIs. Fatal and nonfatal pancreatitis has occurred during therapy with stavudine.
Stavudine should not be administered with zidovudine due to antagonism.
Category C: Risk unknown. Human studies inadequate.
Monitoring Requirements:
CBC with differential, LFTs, platelet count, serum amylase, serum creatinine, serum lipase
Brand names/Manufacturer:
Zerit®/ER Squibb and Sons Inc