RETROVIR Oral solution/syrup Ref.[51356] Active ingredients: Zidovudine

Retrovir should be prescribed by physicians who are experienced in the treatment of HIV infection.

Dosage in adults and adolescents weighing at least 30 kg

The usual recommended dose of Retrovir in combination with other anti-retroviral agents is 250 or 300 mg twice daily.

Dosage in children

Retrovir 100 mg capsules are also available for use in children.

Children weighing at least 9 kg and less than 30 kg

The recommended dose of Retrovir is 0.9 mL/kg (9 mg/kg) twice daily in combination with other antiretroviral agents (e.g. a 15 kg child would require a 13.5 mL dose of oral solution twice daily). The maximum dosage should not exceed 300 mg (30 mL) twice daily.

Children weighing at least 4 kg and less than 9 kg

The recommended dose of Retrovir is 1.2 mL/kg (12 mg/kg) twice daily in combination with other antiretroviral agents (e.g. a 5 kg neonate would require a 6 mL dose of oral solution twice daily).

Available data are insufficient to propose specific dosage recommendations for children weighing less than 4 kg (See below-maternal foetal transmission and section 5.2).

Dosage in the prevention of maternal-foetal transmission

Pregnant women (over 14 weeks of gestation) should be given 500 mg/day orally (100 mg five times per day) until the beginning of labour. During labour and delivery Retrovir should be administered intravenously at 2 mg/kg bodyweight given over one hour followed by a continuous intravenous infusion at 1 mg/kg/h until the umbilical cord is clamped.

Neonates should be given 0.2 mL/kg (2 mg/kg) bodyweight orally every 6 hours starting within 12 hours after birth and continuing until 6 weeks old.

Care should be taken when calculating doses for neonates due to the small volumes of oral solution required. To facilitate dosing precision, an appropriately sized syringe with 0.1 mL graduation should be used to ensure accurate oral dosing of neonates.

Examples of Neonatal Dosing Recommendations for Retrovir Oral Solution for the Prevention of Maternal-Foetal Transmission of HIV in Neonates:

Infants unable to receive oral dosing should be given Retrovir intravenously at 1.5 mg/kg bodyweight infused over 30 minutes every 6 hours.

In case of planned caesarean, the infusion should be started 4 hours before the operation. In the event of a false labour, the Retrovir infusion should be stopped and oral dosing restarted.

Dosage adjustments in patients with haematological adverse reactions

Substitution of zidovudine should be considered in patients whose haemoglobin level or neutrophil count fall to clinically significant levels. Other potential causes of anaemia or neutropenia should be excluded. Retrovir dose reduction or interruption should be considered in the absence of alternative treatments (see sections 4.3 and 4.4).

Dosage in the elderly

Zidovudine pharmacokinetics have not been studied in patients over 65 years of age and no specific data are available. However, since special care is advised in this age group due to age-associated changes such as the decrease in renal function and alterations in haematological parameters, appropriate monitoring of patients before and during use of Retrovir is advised.

Dosage in renal impairment

The recommended dose for patients with severe renal impairment (creatinine clearance - <10 ml/min) and patients with end-stage renal disease maintained on haemodialysis or peritoneal dialysis is 100 mg every 6 to 8 hrs (300-400 mg daily). Haematological parameters and clinical response may influence the need for subsequent dosage adjustment (see section 5.2).

Dosage in hepatic impairment

Data in patients with cirrhosis suggest that accumulation of zidovudine may occur in patients with hepatic impairment because of decreased glucuronidation. Dosage reductions may be necessary but, due to the large variability in zidovudine exposures in patients with moderate to severe liver disease, precise recommendations cannot be made. If monitoring of plasma zidovudine levels is not feasible, physicians will need to monitor for signs of intolerance, such as the development of haematological adverse reactions (anaemia, leucopenia, neutropenia) and reduce the dose and/or increase the interval between doses as appropriate (see section 4.4).

Symptoms and signs

No specific symptoms or signs have been identified following acute overdose with zidovudine apart from those listed as undesirable effects.

Treatment

Patients should be observed closely for evidence of toxicity (see section 4.8) and given the necessary supportive therapy.

Haemodialysis and peritoneal dialysis appear to have a limited effect on elimination of zidovudine but enhance the elimination of the glucuronide metabolite.

Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

2 years.

Discard oral solution 1 month after first opening bottle.

Do not store above 30°C.

Keep the bottle in the outer carton.

Retrovir Oral Solution/Syrup: 200 ml amber glass bottle with a plastic or metal cap and polyethylene wad. A 10 ml oral-dosing syringe is included in the pack, with an adaptor, which should be fitted to the bottle before use.

Retrovir Oral Solution/Syrup (Neonate Pack): 200 ml amber glass bottle with a plastic or metal cap and polyethylene wad. A 1 ml oral-dosing syringe is included in the pack, with an adaptor, which should be fitted to the bottle before use.

Not all pack sizes may be marketed.

No special requirements for disposal.