Melphalan dosage

F. Malecki and J. C. Crawhall, Determination of melphalan and chlorambucil in tablet dosage form using high-performance liquid chromatography and amperometric detection, Anal. Lett., 23 1685— 1693 (1990). 

Peripheral neuropathy, mainly mild and infrequent, has been observed after conventional dosages of etoposide and teniposide. However, during combination therapy with etoposide and vinca alkaloids, more serious forms of peripheral neuropathy have been reported. Of 142 patients with autologous bone marrow transplantation given high-dose etoposide (for example 60 mg/kg combined with melphalan), six developed grade 2-3 polyneuropathy starting 2-8 weeks after transplantation. 

Melphalan (Alkeran) for multiple myeloma is used in doses of 6 to 8 mg daily for a period of 4 days, in combination with other agents. A rest period of up to 4 weeks should then intervene. The usual intravenous dose is 15 mg/m infused over 15 to 20 minutes. Doses are repeated at 2-week intervals for four doses and then at 4-week intervals based on response and tolerance. Dosage adjustments should be considered based on blood cell counts and in patients with renal impairment. 

Melphalan is orally active, but absorption can be erratic. Absorption is decreased with food, but dosing regimens do not demand an empty stomach. The drug can be formulated for IV administration, but the risk of serious side effects is higher. Melphalan distributes into body water, so toxicity can be pronounced in dehydrated patients or in those with renal dysfunction. Dehydration can be corrected, but dosage adjustments should be considered in patients with renal disease. 

A man well stabilised on warfarin had a marked reduction in his anticoagulant response on two occasions while taking mercaptopurine, but no changes occurred when he took busulfan, cyclophosphamide, cytarab-ine, hydroxycarbamide, mitobronitol, demecolcine or melphalan. A woman needed a marked increase in her dosage of acenocoumarol, from 21 to 70 mg weekly, when she was given mercaptopurine 100 mg daily. Another patient required about a 25% increase in warfarin dose while taking mercaptopurine 1(X) mg daily. 

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