The use of Roferon-A in children is not recommended as the safety and effectiveness of Roferon-A in children have not been established.

Efficacy in patients with chronic hepatitis B or C who are on haemodialysis or have haemophilia or are coinfected with human immunodeficiency virus has not been demonstrated.

This product contains less than 1 mmol sodium (23 mg) per 0.5 ml, i.e. essentially 'sodium-free'.

Combination therapy with ribavirin: Also see ribavirin labelling if interferon alfa-2a is to be administered in combination with ribavirin in patients with chronic hepatitis C.

Patients co-infected with HIV and receiving Highly Active Anti-Retroviral Therapy (HAART) may be at increased risk of developing lactic acidosis. Caution should be used when adding Roferon-A and ribavirin to HAART therapy (see ribavirin SPC).

Co-infected patients with advanced cirrhosis receiving HAART may be at increased risk of hepatic decompensation and death. Adding treatment with alfa interferons alone or in combination with ribavirin may increase the risk in this patient subset.

4.5 Interaction with other medicinal products and other forms of interaction

 Since alpha-interferons alter cellular metabolism, the potential to modify the activity of other drugs exists. In a small study, Roferon-A was shown to have an effect on specific microsomal enzyme systems. The clinical relevance of these findings is unknown.

Alpha-interferons may affect the oxidative metabolic process; this should be borne in mind when prescribing concomitant therapy with drugs metabolised by this route. However, as yet no specific information is available.

Roferon-A has been reported to reduce the clearance of theophylline.

As Roferon-A may affect central nervous system functions, interactions could occur following concurrent administration of centrally-acting drugs. The neurotoxic, haematotoxic or cardiotoxic effects of previously or concurrently administered drugs may be increased by interferons.

Combination therapy with ribavirin: Also see ribavirin labelling if interferon alfa-2a is to be administered in combination with ribavirin in patients with chronic hepatitis C.

Results from a controlled clinical study in renal cancer patients demonstrated no significant effect of bevacizumab (Avastin) on the pharmacokinetics of interferon alfa-2a (Roferon-A).

4.6 Pregnancy and lactation

 Men and women receiving Roferon-A should practise effective contraception. There are no adequate data on the use of Roferon-A in pregnant women. When doses greatly in excess of the recommended clinical dose were administered to pregnant rhesus monkeys in the early to mid-foetal period, an abortifacient effect was observed (see section 5.3). Although animal tests do not indicate that Roferon-A is a teratogen, harm to the foetus from use during pregnancy cannot be excluded. In pregnancy, Roferon-A should be administered only if the benefit to the woman justifies the potential risk to the foetus.

It is not known whether this drug is excreted in human milk. A decision must be taken whether to suspend breast feeding or to discontinue the drug, taking into account the importance of the drug to the mother.

Use with ribavirin in patients with chronic hepatiti