Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. Ribavirin therapy is contraindicated in women who are pregnant. Extreme care must be taken to avoid pregnancy in female patients or in partners of male patients taking Roferon-A in combination with ribavirin. Female patients of childbearing potential and their partners must each use an effective contraceptive during treatment and for 4 months after treatment has been concluded. Male patients and their female partners must each use an effective contraception during treatment and for 7 months after treatment has been concluded. Please refer to the ribavirin SPC.

4.7 Effects on ability to drive and use machines

 No studies on the effects on the ability to drive and use machines have been performed. However depending on dose and schedule as well as the sensitivity of the individual patient, Roferon-A may have an effect on the speed of reaction which could impair certain operations, e.g., driving, operation of machinery etc.

4.8 Undesirable effects

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

The following data on adverse reactions are based on information derived from the treatment of cancer patients with a wide variety of malignancies and often refractory to previous therapy and suffering from advanced disease, patients with chronic hepatitis B, and patients with chronic hepatitis C.

Approximately two thirds of cancer patients experienced anorexia and one half nausea. Cardiovascular and pulmonary disorders were seen in about one fifth of cancer patients and consisted of transient hypotension, hypertension, oedema, cyanosis, arrhythmias, palpitations and chest pain. Most cancer patients received doses that were significantly higher than the dose now recommended and may explain the higher frequency and severity of adverse reactions in this patient group compared with patients with hepatitis B where adverse reactions are usually transient, and patients return to pre-treatment status within 1 to 2 weeks after the end of therapy. Cardiovascular disorders were very rarely seen in patients with hepatitis B. In hepatitis B patients, changes in transaminases usually signal an improvement in the clinical state of the patient.

The majority of the patients experienced flu-like symptoms such as fatigue, pyrexia, rigors, decreased appetite, myalgia, headache, arthralgia and diaphoresis. These acute side-effects can usually be reduced or eliminated by concurrent administration of paracetamol and tend to diminish with continued therapy or dose modification although continuing therapy can lead to lethargy, asthenia and fatigue.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness:

Body System
 Very common

(1/10)
 Common

(1/100 to <1/10)
 Uncommon

(1/1 000 to <1/100)
 Rare

(1/10 000 to
<1/1 000)
 Very rare

(<1/10 000)
 Not known

(can not be estimated from the available data)
 
Infections and infestations
 
 
 
 - Pneumonia

- Herpes simplex1
 
 
 
Blood and lymphatic system disorders2
 - L