- SURGICALLY RESECTED MALIGNANT MELANOMA.

Adjuvant therapy with a low dose of Roferon-A prolongs disease-free interval in patients with no nodal or distant metastases following resection of a melanoma (tumour thickness > 1.5 mm).

Dosage recommendation:

Roferon-A should be administered subcutaneously at a dose of 3 million IU three times a week for 18 months, starting no later than six weeks post surgery. If intolerance develops, the dose should be lowered to 1.5 million IU three times a week.

4.3 Contraindications

 Roferon-A is contraindicated in patients with:

1) A history of hypersensitivity to recombinant interferon alfa-2a or to any of the excipients,

2) Patients with severe pre-existing cardiac disease or with any history of cardiac illness. No direct cardiotoxic effect has been demonstrated, but it is likely that acute, self-limiting toxicities (i.e., fever, chills) frequently associated with administration of Roferon-A may exacerbate pre-existing cardiac conditions,

3) Severe renal, hepatic or myeloid dysfunction,

4) Uncontrolled seizure disorders and/or compromised central nervous system function (see section 4.4.),

5) Chronic hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver,

6) Chronic hepatitis who are being or have recently been treated with immunosuppressive agents,

7) Benzyl alcohol, which is an excipient in Roferon-A solution for injection has on rare occasions been associated with potentially fatal toxicities and anaphylactoid reactions in children up to 3 years old. Therefore, Roferon-A solution for injection should not be used in premature babies, neonates, infants or children up to 3 years old Roferon-A solution contains 10 mg / ml Benzyl alcohol.

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.

4.4 Special warnings and precautions for use

 Roferon-A should be administered under the supervision of a qualified physician experienced in the management of the respective indication. Appropriate management of the therapy and its complications is possible only when adequate diagnostic and treatment facilities are readily available.

Patients should be informed not only of the benefits of therapy but also that they will probably experience adverse reactions.

Hypersensitivity: If a hypersensitivity reaction occurs during treatment with Roferon-A or in the combination therapy with ribavirin, treatment has to be discontinued and appropriate medical therapy has to be instituted immediately. Transient rashes do not necessitate interruption of treatment.

In transplant patients (e.g., kidney or bone marrow transplant) therapeutic immunosuppression may be weakened because interferons also exert an immunostimulatory action. As with other alpha interferons, graft rejections have been reported in patients taking Roferon-A.

Fever/Infections: While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, other causes of persistent fever, particularly serious infections (bacterial, viral, fungal) must be ruled out, especially in patients with neutro