COMBIVIR Film-coated tablet Ref.[10508] Active ingredients: Lamivudine Zidovudine Zidovudine and Lamivudine

Therapy should be initiated by a physician experienced in the management of HIV infection.

Combivir may be administered with or without food.

To ensure administration of the entire dose, the tablet(s) should ideally be swallowed without crushing. For patients who are unable to swallow tablets, tablets may be crushed and added to a small amount of semi-solid food or liquid, all of which should be consumed immediately (see section 5.2).

Adults and adolescents weighing at least 30 kg: The recommended dose of Combivir is one tablet twice daily.

Children weighing between 21 kg and 30 kg: The recommended oral dose of Combivir is one-half tablet taken in the morning and one whole tablet taken in the evening.

Children weighing from 14 kg to 21 kg: The recommended oral dose of Combivir is one-half tablet taken twice daily.

The dosing regimen for paediatric patients weighing 14-30 kg is based primarily on pharmacokinetic modelling and supported by data from clinical studies using the individual components lamivudine and zidovudine. A pharmacokinetic overexposure of zidovudine can occur, therefore close safety monitoring is warranted in these patients. If gastrointestinal intolerance occurs in patients weighing 21-30 kg, an alternative dosing schedule with one-half tablet taken thrice daily can be applied in attempt to improve tolerability.

Combivir tablets should not be used for children weighing less than 14 kg, since doses cannot be appropriately adjusted for the weight of the child. In these patients, lamivudine and zidovudine should be taken as separate formulations according to the prescribed dosing recommendations for these products. For these patients and for patients, who are unable to swallow tablets, oral solutions of lamivudine and zidovudine are available.

For situations where discontinuation of therapy with one of the active substances of Combivir, or dose reduction is necessary separate preparations of lamivudine and zidovudine are available in tablets/capsules and oral solution.

Renal impairment

Lamivudine and zidovudine concentrations are increased in patients with renal impairment due to decreased clearance (see section 4.4). Therefore as dosage adjustment of these may be necessary it is recommended that separate preparations of lamivudine and zidovudine be administered to patients with severe renal impairment (creatinine clearance ≤30 mL/min). Physicians should refer to the individual prescribing information for these medicinal products.

Hepatic impairment

Limited data in patients with cirrhosis suggest that accumulation of zidovudine may occur in patients with hepatic impairment because of decreased glucuronidation. Data obtained in patients with moderate to severe hepatic impairment show that lamivudine pharmacokinetics are not significantly affected by hepatic dysfunction. However, as dosage adjustments for zidovudine may be necessary, it is recommended that separate preparations of lamivudine and zidovudine be administered to patients with severe hepatic impairment. Physicians should refer to the individual prescribing information for these medicinal products.

Dosage adjustments in patients with haematological adverse reactions

Dosage adjustment of zidovudine may be necessary if the haemoglobin level falls below 9 g/dl or 5.59 mmol/l or the neutrophil count falls below 1.0 × 10⁹/l (see sections 4.3 and 4.4). As dosage adjustment of Combivir is not possible, separate preparations of zidovudine and lamivudine should be used. Physicians should refer to the individual prescribing information for these medicinal products.

Dosage in the elderly

No specific data are available, however special care is advised in this age group due to age associated changes such as the decrease in renal function and alteration of haematological parameters.

There is limited experience of overdosage with Combivir. No specific symptoms or signs have been identified following acute overdose with zidovudine or lamivudine apart from those listed as undesirable effects. No fatalities occurred, and all patients recovered.

If overdosage occurs the patient should be monitored for evidence of toxicity (see section 4.8), and standard supportive treatment applied as necessary. Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdosage, although this has not been studied. Haemodialysis and peritoneal dialysis appear to have a limited effect on elimination of zidovudine, but enhance the elimination of the glucuronide metabolite. For more details physicians should refer to the individual prescribing information for lamivudine and zidovudine.

2 years.

Do not store above 30°C.

Cartons containing opaque polyvinyl chloride/foil blister packs. Cartons containing white high density polyethylene (HDPE) bottle with a child-resistant closure. Each pack type contains 60 film-coated tablets.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.