|
Drug Information
Pharmacokinetics
| Indication
& Dosage | Action
| Interactions Precautions
|
Brands available in Market
Pharmacokinetics
Absorption of melphalan from the gastrointestinal tract is variable; the mean bioavailability is reported to be 56% but it may range from 25 to 89%. Absorption is reduced by the presence of food. Following absorption it is rapidly distributed throughout body water with a volume of distribution of about 0.5 litres per kg body-weight, and has been reported to be inactivated mainly by spontaneous hydrolysis. The terminal plasma half-life of melphalan has been reported to be of the order of 40 to 140 minutes. Melphalan is excreted in the urine, about 10% as unchanged drug. About 50 to 60% of an absorbed dose has been stated to be protein bound initially, increasing to 80 to 90% after 12 hours.
Oral
MULTIPLE MYELOMA: Several regimens have been recommended. One regimen is start 6mg/day as a single dose daily, adjusted according to weekly blood counts. After 2-3 weeks discontinue for 4 weeks and start maintenance dose at 2mg/kg
ADVANCED OVARIAN CANCER: 0.2mg/kg daily for 5 days. This course can be repeated every 4-5 weeks.
IV
MYELOMAS, SOLID TUMORS, LYMPHOMAS: 16mg/m2 as an IV infusion over 15-20 mins. Repeat at 2 week intervals for 4 doses followed by 4-week intervals.
An alkylating agent active against some malignancies. It is active against both resting and rapidly dividing cells.
Concomitant administration of nalidixic acid with high-dose intravenous melphalan in children has resulted in fatal haemorrhagic enterocolitis.
With Food
The bioavailability of oral melphalan is significantly reduced, by up to 45%, by concomitant administration with food. Some recommend that melphalan should not be taken with food, and that if administration is switched from after to before food patients should be monitored for increased toxicity.
The onset of neutropenia and thrombocytopenia is variable; bone-marrow depression has been reported 2 to 3 weeks after starting treatment with melphalan, with a nadir at 3 to 5 weeks, but has also occurred after only 5 days. Recovery may be prolonged.
Skin rashes and hypersensitivity reactions, including anaphylaxis, may occur. Cardiac arrest has been reported in association with such effects. Gastrointestinal disturbances may sometimes occur, particularly at high doses where diarrhoea, vomiting, and stomatitis may become dose-limiting. Haemolytic anaemia, vasculitis, and pulmonary fibrosis have been reported. Suppression of ovarian function is common in premenopausal women; temporary or permanent sterility may occur in male patients. As with other alkylating agents, melphalan also has carcinogenic, mutagenic, and teratogenic potential.
Care is required in patients with impaired renal function. The dose of the intravenous preparation should be reduced by 50% in patients with moderate to severe renal impairment and dosage reduction should be considered when administering melphalan by mouth. High dose regimens are not recommended in patients with severe renal impairment.
