- Arthritis
 
 
 
Renal and urinary disorders
 
 
 - Proteinuria

- Increased cell count in urine
 - Acute renal failure7

- Renal impairment
 
 
 
General disorders and administration site conditions
 -Flu like illness

-Appetite decreased

-Pyrexia

-Rigors

-Fatigue
 - Chest pain

- Oedema
 
 
 -Injection site necrosis

-Injection site reaction
 
 
Investigations
 
 - weight loss
 -Increased ALT

-Increased transaminase

-Increased blood alkaline phosphatase
 - Increased blood creatinine

-Increased blood urea

- Increased blood bilirubin

- Increased blood uric acid

-Increased blood LDH

1(including exacerbations of herpes labialis)

2In myelosuppressed patients, thrombocytopenia and decreased haemoglobin occurred more frequently. Recovery of severe haematological deviations to pre-treatment levels usually occurred within seven to ten days after discontinuing Roferon-A treatment.

3(e.g. urticaria, angioedema, bronchospasm and anaphylaxis)

4including atrioventricular block

5(reversible upon discontinuation; increased hair loss may continue for several weeks after end of treatment)

6exacerbation of, or provocation of psoriasis

7(mainly in cancer patients with renal disease)

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 neutralising 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.