STV-40 CAPSULES

(Stavudine Capsules 40mg)

Composition:
Each Capsule contains:
Stavudine 40mg

Presentation:
10x10's

Pharmacology:
Stavudine, a nucleoside analogue of thymidine, inhibits the replication of HIV in human cells in vitro. Stavudine is phosphorylated by cellular kinases to the active metabolite stavudine triphosphate. Stavudine triphosphate inhibits the activity of HIV reverse transcriptase both by competing with the natural substrate deoxythymidine triphosphate (Ki=0.0083 to 0.032 µM), and by its incorporation into viral DNA causing a termination of DNA chain elongation because stavudine lacks the essential 3'-OH group. Stavudine triphos-phate inhibits cellular DNA polymerase beta and gamma, and markedly reduces the synthesis of mitochondrial DNA.

Pharmacokinetics:
The pharmacokinetics of stavudine have been evaluated in HIV-infected adult and pediatric patients. Peak plasma concentrations (Cmax) and area under the plasma concentration-time curve (AUC) increased in proportion to dose after both single and multiple doses ranging from 0.03 to 4 mg/kg. There was no significant accumulation of stavudine with repeated administration every 6, 8, or 12 hours.

Absorption
Following oral administration, stavudine is rapidly absorbed, with peak plasma concentrations occurring within 1 hour after dosing. The systemic exposure to stavudine is the same following administration as capsules or solution.

Distribution
Binding of stavudine to serum proteins was negligible over the concentration range of 0.01 to 11.4 µg/mL. Stavudine distributes equally between red blood cells and plasma.

Metabolism
The metabolic fate of stavudine has not been elucidated in humans. Excretion- Renal elimination accounted for about 40% of the overall clearance regardless of the route of administration. The mean renal clearance was about twice the average endogenous creatinine clearance, indicating active tubular secretion in addition to glomerular filtration.

Indications:
Stavudine is indicated for the treatment of HIV-infected patients who have received prolonged prior zidovudine therapy.

Contra-indications:
Stavudine is contraindicated in patients with clinically significant hypersensitivity to stavudine or to any of the components contained in the formulation. It should not be used in combination with zidovudine.

Dosage and directions for use:

Adults:
The interval between oral doses should be 12 hours. Stavudine may be taken without regard to meals. The recommended starting dose based on body weight is as follows:
40 mg twice daily for patients > 60 kg
30 mg twice daily for patients < 60 kg

Paediatrics:
The recommended starting dose for paediatric patients weighing less than 30 kg is I mg/kg/dose, given every 12 hours. Paediatric patients weighing 30 kg or greater should receive the recommended adult dose.
Dosage adjustment: Patients should be monitored for the development of peripheral neuropathy, which is usually characterised by numbness, tingling or pain in the feet or hands. If these symptoms develop on treatment, stavudine therapy should be interrupted. Symptoms may resolve if therapy is withdrawn promptly. In some cases, symptoms may worsen temporarily following discontinuation of therapy. If symptoms resolve completely, resumption of treatment may be considered using the following dosage schedule.
20 mg twice daily for patients > 60 kg
15 mg twice daily for patients < 60 kg
For paediatric patients, resumption of treatment may be considered at one-half the recommended dose.
Renal Impairment:

Stavudine may be administered to adult patients with impaired renal function. The following schedule is recommended.