Melphalan Hcl Drug Information

Multiple Myeloma-Palliative Treatment IVRA is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate. IVRA is an alkylating drug indicated for palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of melphalan may not reflect the rates observed in practice. The most common adverse reactions observed in at least 50% of patients with multiple myeloma treated with melphalan were neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting. Palliative Treatment of Patients with Multiple Myeloma The safety of melphalan was evaluated in 295 patients with multiple myeloma in the randomized clinical trial.

One hundred and ninety-five patients were administered intravenous melphalan at a dosage of 16 mg/m 2 q 2 weeks x 4 (over 6 weeks) followed by the same dose every 4 weeks. One hundred patients were administered oral melphalan at a dosage of 0.15 mg/kg/day x 7 followed by 0.05 mg/kg/day when WBC counts began to rise. Severe myelotoxicity (WBC ≤1,000 and/or platelets ≤25,000) was more common in the intravenous melphalan arm (28%) than in the oral melphalan arm (11%).

Effect of Other Drugs on

IVRA Cisplatin Concomitant use with cisplatin may alter melphalan clearance by inducing renal dysfunction. Consider intravenous IVRA dosage reduction in patients with renal insufficiency following concomitant use with cisplatin .

Effect of

IVRA on Other Drugs BCNU Concomitant use with BCNU may reduce the threshold for lung toxicity. Monitor for increased lung toxicity.

Cyclosporine

Concomitant use with cyclosporine may increase the risk of developing severe renal failure. Consider intravenous IVRA dosage reduction in patients with renal insufficiency following concomitant use with cyclosporine .

Pregnancy Risk Summary Based on its mechanism of action and findings from animal studies, IVRA can cause fetal harm when administered to a pregnant woman. There are no available data on IVRA use in pregnant women to evaluate for a drug-associated risk. In rats, melphalan was embryolethal and teratogenic at doses lower than the highest recommended clinical dose (see Data). If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus.

The background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Data Animal Data Adequate animal studies have not been conducted with intravenous melphalan. Melphalan was embryolethal and teratogenic in rats following oral administration of 6 to 18 mg/m 2 /day for 10 days (0.06 to 0.18 times the highest recommended clinical dose of 100 mg/m 2 /day) and intraperitoneal administration of 18 mg/m 2 (0.18 times the highest recommended clinical dose). Malformations resulting from melphalan administration included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, and hepatocele (exomphaly).

Pediatric Use The safety and effectiveness of IVRA in pediatric patients have not been established.

is contraindicated in patients with a history of severe hypersensitivity to melphalan. Reactions have included anaphylaxis. History of severe hypersensitivity to melphalan.

Overdoses resulting in death have been reported. Overdoses, including doses up to 290 mg/m 2 (18 times the recommended dose), have produced the following symptoms: severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis, and cholinomimetic effects. Severe mucositis, stomatitis, colitis, diarrhea, and hemorrhage of the gastrointestinal tract occur at high doses (greater than 100 mg/m 2 6 times the recommended dose). Elevations in liver enzymes and veno-occlusive disease have occurred.

Significant hyponatremia caused by an associated inappropriate secretion of ADH syndrome has been observed. Nephrotoxicity and adult respiratory distress syndrome have been reported. The principal toxic effect is bone marrow suppression.

In the event of an overdosage, monitor hematologic parameters for 3 to 6 weeks. General supportive measures together with appropriate blood transfusions and antibiotics should be instituted as deemed necessary by the physician. This drug is not removed from plasma to any significant degree by hemodialysis or hemoperfusion.