RETROVIR ORAL SOLUTION 10 mg/ml

SYRUP

**Dosage and Administration** **Pharmaceutical form:** Oral solution. _RETROVIR_ therapy should be initiated by a physician experienced in the management of HIV infection. - **Adults and adolescents weighing at least 30 kg** The recommended dose of _RETROVIR_ in combination with other antiretroviral agents is 250 or 300 mg twice daily. - **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 – Pregnancy and Lactation and Pharmacokinetics_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). - **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. - **Renal impairment** In patients with severe renal impairment, daily dosages of 300 to 400 mg should be appropriate. Haematological parameters and clinical response may influence the need for subsequent dosage adjustment. Haemodialysis and peritoneal dialysis have no significant effect on _RETROVIR_ elimination whereas elimination of the glucuronide metabolite is increased. For patients with end-stage renal disease maintained on haemodialysis or peritoneal dialysis, the recommended dose is 100 mg every 6 to 8 h ( _see Pharmacokinetics_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). - **Hepatic impairment** Limited data in patients with cirrhosis suggest that accumulation of zidovudine may occur in patients with hepatic impairment because of decreased glucuronidation. Dosage adjustments may be necessary but precise recommendations cannot be made at present. If monitoring of plasma zidovudine levels is not feasible, physicians will need to pay particular attention to signs of intolerance and increase the interval between doses as appropriate. - **Patients with haematological adverse reactions** Dosage adjustments may be necessary in patients with haematological adverse reactions. This is more likely in patients with poor bone marrow reserve prior to treatment, particularly in patients with advanced HIV disease. If the haemoglobin level falls to between 7.5 g/dl (4.65 mmol/l) and 9 g/dl (5.59 mmol/l) or the neutrophil count falls to between 0.75 x 109/l and 1.0 x 109/l, the daily dosage may be reduced until there is evidence of marrow recovery; alternatively, recovery may be enhanced by a brief (2–4 weeks) interruption of _RETROVIR_ therapy. If dosage reduction is considered, the daily dosage may, for example, be halved and subsequently increased, depending on patient tolerance, up to the original dosage. Therapy with _RETROVIR_ should be interrupted if the haemoglobin level falls below 7.5 g/dl (4.65 mmol/l) or the neutrophil count falls to less than 0.75 x 109/l ( _see Contraindications, Warnings and Precautions_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Marrow recovery is usually observed within 2 weeks after which time _RETROVIR_ therapy at a reduced dosage may be reinstituted. After a further 2–4 weeks the dosage may be gradually increased, depending on patient tolerance, up to the original dosage.