Stavudine

Registered South African indications:

• HIV infection

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Coadministration with didanosine

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• History of severe hyperlactatemia with a nucleotide reverse transcriptase inhibitor
• Co-infection with hepatitis B or C
• History of or risk factors for neuropathy
• History of or risk factors for pancreatitis  
• Long term  exposure to combination antiretroviral therapy
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption 2

Forms avail in SA and covered in this monograph: cap

HIV infection

• Oral (cap): 30mg, 12hrly

Paed. forms avail. in SA and covered in this monograph: cap

HIV infection

Younger than 3 months and < 30kg

• Not established for children below 3 months or 30kg

Older than 3 months and < 30kg

• Oral (cap): 1mg/kg, 12hrly

> 30kg

• See adult dosages

Consult HIV/infectious disease specialists prior to any decisions related to ARV regimen termination/switch

Pregnancy 

• Caution
• Stavudine should not be used during pregnancy unless clearly necessary
• Clinical experience in pregnant women is limited, but congenital anomalies and abortions have been reported
• In study AI455-094, performed in South-Africa, 362 mother-infant pairs were included in a prevention of mother-to-child-transmission study. Treatment naive pregnant women were enrolled into the study at gestation week 34-36 and given antiretroviral treatment until delivery. Antiretroviral prophylaxis, the same medications as given to the mother, was given to the new-born infant within 36 hours of delivery and continued for 6 weeks. In the stavudine containing arms, the neonates were treated for 6 weeks with stavudine 1 mg/kg BID. The follow-up time was up to 24 weeks of age
• The mother-infant pairs were randomised to receive either stavudine (N= 91), didanosine (N= 94), stavudine + didanosine (N= 88) or zidovudine (N= 89)
• 95% Confidence intervals for the mother-to-child-transmission rates were 5.4-19.3% (stavudine), 5.2-18.7% (didanosine); 1.3-11.2% (stavudine + didanosine); and 1.9-12.6% for zidovudine
• Preliminary safety data from this study, showed an increased infant mortality in the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group. Data on lactic acid in serum were not collected in this study
• However lactic acidosis, sometimes fatal, has been reported in pregnant women who received the combination of didanosine and stavudine with or without other anti-retroviral treatment. Embryo-foetal toxicities were seen only at high exposure levels in animals. Preclinical studies showed placental transfer of stavudine. Until additional data become available, stavudine should be given during pregnancy only after special consideration; there is insufficient information to recommend stavudine for prevention of mother-to-child transmission of HIV

Breastfeeding

• Caution; not recommended 
• It is recommended that HIV infected women should not breastfeed under any circumstances in order to avoid transmission of HIV
• The data available on stavudine excretion into human breast milk are insufficient to assess the risk to the infant. Studies in lactating rats showed that stavudine is excreted in breast milk. Therefore, mothers should be instructed to discontinue breastfeeding prior to receiving stavudine

Renal Impairment

• Caution; dose adjustment recommended
• 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

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; no information available

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Permitted - No warning

Central Nervous System Disorders

• Depression
• Anxiety
• Emotional lability
• Peripheral neuropathy
• Paresthesia
• Peripheral neuritis
• Dizziness
• Abnormal dreams
• Headache
• Insomnia
• Abnormal thinking
• Somnolence
• Motor weakness

Gastrointestinal Disorders

• Diarrhoea
• Abdominal pain
• Nausea and vomiting
• Dyspepsia
• Pancreatitis

Hepatobiliary Disorders

• Hepatitis
• Jaundice
• Hepatic steatosis
• Hepatic failure

Endocrine and Metabolic Disorders

• Gynaecomastia 
• Lipoatrophy
• Asymptomatic hyperlactatemia
• Lactic acidosis 
• Anorexia
• Hyperglycaemia
• Diabetes mellitus
• Increase in blood lipid levels 
• Increase in blood glucose levels 
• Mitochondrial dysfunction

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash 
• Prutitis
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Anaemia 
• Neutropenia
• Thrombocytopenia 

Others

• Fatigue 
• Asthenia

• Didanosine
• Medicinal products which are actively secreted by the renal tubules  
• Zidovudine
• Doxorubicin
• Ribavirin
• Drugs known to cause pancreatitis or peripheral neuropathy

• Hepatic function

Specific cases may require

• Renal function
• Lipid profile
• Blood glucose

Stavudine is a synthetic thymidine nucleoside analogue. It enters cells by diffusion and is phosphorylated by cellular kinases to the active metabolite stavudine triphosphate. It inhibits HIV reverse transcriptase by competing with the natural substrate, thymidine triphosphate. It also inhibits viral DNA synthesis by causing DNA chain termination due to a lack of the 3'-hydroxyl group necessary for DNA elongation. It further inhibits cellular DNA polymerase and gamma, and markedly reduces the synthesis of mitochondrial DNA.

Capsule 15mg

• Aspen Stavudine (Pharmacare)

Capsule 20mg

• Aspen Stavudine (Pharmacare)

Capsule 30mg

• Aspen Stavudine (Pharmacare)
• Sonke Stavudine (Ranbaxy)
• Vanra (Aurobindo)
• Vari-Stavudine (LeBassi)

Capsule 40mg

• Aspen Stavudine (Pharmacare)

COMBINATION PREPARATIONS

Stavudine/ Lamivudine/ Nevirapine

Tablet 30mg/150mg/200mg

• Nevasta (Emcure)
• Sonke-Laminevstav 30 (Ranbaxy)
• Triomune (Cipla)
• Virtrium 30mg/150mg/200mg (Pharmacare)