Intramuscular administration of Roferon-A one or more times daily for up to 28 days to some patients with disseminated cancer resulted in peak plasma concentrations of two to four times greater than those seen after single doses. However, multiple dosing caused no changes in its distribution or elimination parameters during several dosage regimens studied.

For other information on pharmacokinetic properties please refer to the SmPC for Ribavirin.

5.3 Preclinical safety data

 Because of species specificity of human interferon, only limited toxicological studies have been carried out with Roferon-A. The acute parenteral toxicity of Roferon-A has been studied in mice rats, rabbits and ferrets at doses up to 30 million IU/kg intravenously, and 500 million IU/kg intramuscularly. No treatment-related mortality was noted in any species studied given Roferon-A by any of the routes of administration. With doses greatly exceeding the recommended clinical dose no significant adverse effects were observed except for an abortifacient effect when administered to pregnant rhesus monkeys in the early to mid-foetal period and transient menstrual cycle irregularities including prolonged menstrual periods in non-pregnant monkeys. The relevance of these findings in man has not been established.

Mutagenic effects of Roferon-A have not been observed experimentally.

For other information on preclinical safety data please refer to the SmPC for Ribavirin.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

 Ammonium acetate

Sodium Chloride

Benzyl alcohol (10mg/1ml)

Polysorbate 80

Glacial Acetic acid

Sodium Hydroxide

Water for Injections

6.2 Incompatibilities

 In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

2 years

Chemical and physical in use stability has been demonstrated for 28 days at 25°C.

From a microbiological point of view, once opened, the product may be stored for a maximum of 28 days at 25°C. Other in-use storage times and conditions are the responsibility of the user.

However, it is recommended that the Roferon-Pen/cartridge combination be returned to the fridge after each injection.

6.4 Special precautions for storage

 Store in a refrigerator (2 °C - 8°C). Do not freeze. Keep cartridge in the outer carton in order to protect from light.

The 18 MIU/0.6 ml solution for injection is suitable for multiple-dose use.

For storage conditions of the reconstituted medicinal product, see section 6.3.

6.5 Nature and contents of container

 0.6 ml of solution in cartridge (type I glass), with a plunger stopper (PTFE laminated), aluminium crimp cap with PTFE laminated butyl rubber stopper inner seal. Pack sizes of 1, 3 and 6. Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

 Roferon®-A cartridges are for multi-dose and single patient use only and should be used exclusively with the Roferon®-Pen. A new, sterile needle must be used for every injection.

Each Roferon®