† Identified in postmarketing experience

Rarely, alpha interferons including Roferon-A used alone or in combination with ribavirin, may be associated with pancytopenia, and very rarely, aplastic anaemia has been reported.

Neutralising antibodies to interferons may form in some patients. In certain clinical conditions (cancer, systemic lupus erythematosus, herpes zoster) antibodies to human leucocyte interferon may also occur spontaneously in patients who have never received exogenous interferons. The clinical significance of the development of antibodies has not been fully clarified.

In clinical trials where lyophilised Roferon-A which had been stored at 25°C was used, neutralising antibodies to Roferon-A have been detected in approximately one fifth of patients. In patients with hepatitis C, a trend for responding patients who develop neutralising antibodies to lose response while still on treatment and to lose it earlier than patients who do not develop such antibodies, has been seen. No other clinical sequelae of the presence of antibodies to Roferon-A have been documented. The clinical significance of the development of antibodies has not been fully clarified.
No data on neutralizing antibodies yet exist from clinical trials in which lyophilised Roferon-A or Roferon-A solution for injection which is stored at 4°C has been used. In a mouse model, the relative immunogenicity of lyophilised Roferon-A increases with time when the material is stored at 25°C - no such increase in immunogenicity is observed when lyophilised Roferon-A is stored at 4°C, the recommended storage conditions.
4.9 Overdose

 There are no reports of overdosage but repeated large doses of interferon can be associated with profound lethargy, fatigue, prostration and coma. Such patients should be hospitalised for observation and appropriate supportive treatment given.

Patients who experience severe reactions to Roferon-A will usually recover within days after discontinuation of therapy, given appropriate supportive care. Coma has been observed in 0.4% of cancer patients in clinical trials.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group:
 Antineoplastic and immunomodulating agents, Interferons

ATC Code L03AB04

Roferon-A has been shown to possess many of the activities of the so-called natural human alpha-interferon preparations. Roferon-A exerts its antiviral effects by inducing a state of resistance to viral infections in cells and by modulating the effector arm of the immune system to neutralise viruses or eliminate virus infected cells. The essential mechanism for the antitumour action of Roferon-A is not yet known. However, several changes are described in human tumoural cells treated with Roferon-A: HT 29 cells show a significant reduction of DNA, RNA and protein synthesis. Roferon-A has been shown to exert antiproliferative activity against a variety of human tumours in vitro and to inhibit the growth of some human tumour xenografts in nude mice. A limited number of human tumour cell lines grown in vivo in immunocompromised nude mice has been tested for the susceptibility to Roferon-A. In vivo antiproliferative activity of Roferon-A has been studied on tumours including breast mucoid carcinoma, adenocarcinoma of the caecum, colon carcinoma and prostatic carcinoma. The degree of antiproliferative activity is variable.