MELPHALAN Film-coated tablets Ref.[8200] Active ingredients: Melphalan

Since Melphalan is myelosuppressive, frequent blood counts are essential during therapy and the dosage should be delayed or adjusted if necessary (see Special Warnings and Precautions for Use).

Oral administration in Adults

The absorption of Melphalan after oral administration is variable. Dosage may need to be cautiously increased until myelosuppresion is seen, in order to ensure that potentially therapeutic levels have been reached.

Multiple Myleloma

Numerous regimes have been used and the scientific literature should be consulted for details. The administration of Melphalan and prednisone is more effective than Melphalan alone. The combination is usually given on an intermittent basis, although the superiority of this technique over continuous therapy is not established. A typical oral dosage schedule is 0.15 mg/kg bodyweight/day in divided doses for 4 days repeated at intervals of six weeks. Prolonging treatment beyond one year in responders does not appear to improve results.

Ovarian adenocarcinoma

A typical regimen is 0.2 mg/kg bodyweight/day orally for 5 days. This is repeated every 4-8 weeks, or as soon as the bone marrow has recovered. Melphalan has also been used intravenously in the treatment of ovarian carcinoma.

Advanced carcinoma of the breast

Melphalan has been given orally at a dose of 0.15 mg/kg bodyweight or 6 mg/m2 body surface area/day for 5 days and repeated every 6 weeks. The dose was decreased if bone marrow toxicity was observed.

Polycythaemia vera

For remission induction the usual dose is 6-10 mg daily for 5-7 days, after which 2-4 mg daily is given until satisfactory disease control is achieved. Therapy is maintained with a dose of 2-6 mg per week. During maintenance therapy, careful haematological control is essential with dosage adjustment according to the results of frequent blood counts.

Children

Melphalan is very rarely indicated in children and dosage guidelines cannot be stated.

Use in the elderly

There is no specific information available on the use of Melphalan in elderly patients.

Dosage in renal impairment

In patients with moderate to severe renal impairment currently available pharmacokinetic data do not justify an absolute recommendation on dosage reduction when administering the oral preparation to these patients, but it may be prudent to use a reduced dose initially.

Symptoms and signs

Gastro-intestinal effects, including nausea, vomiting and diarrhoea are the most likely signs of acute oral overdosage. Diarrhoea, sometimes haemorrhagic, has been reported after intravenous overdosage. The principal toxic effect is bone marrow aplasia, leading to leucopoenia, thrombocytopenia and anaemia.

Treatment

There is no specific antidote. The blood picture should be closely monitored for at least four weeks following overdosage until there is evidence of recovery.

General supportive measures, together with appropriate blood transfusion, should be instituted if necessary.

Shelf life: 24 months.

Store at 2°C to 8°C.

Supplied in amber glass bottles with a child resistant closure containing 25 or 50 tablets.

Safe handling of MELPHALAN tablets

The handling of Melphalan tablets should follow guidelines for the handling of cytotoxic drugs according to prevailing local recommendations and/or regulations (for example Royal Pharmaceutical Society of Great Britain Working Party on the Handling of Cytotoxic Drugs).

Provided the outer coating of the tablet is intact, there is no risk in handling Melphalan tablets.

Melphalan tablets should not be divided.

Disposal

Melphalan tablets should be destroyed in accordance with relevant local regulatory requirements concerning the disposal of cytotoxic drugs.