MELPHALAN HYDROCHLORIDE
Clinical safety rating: avoid
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and secondary malignancies.
Melphalan is a bifunctional alkylating agent that forms cross-links between DNA strands, inhibiting DNA replication and transcription. It is cell cycle phase-nonspecific.
| Metabolism | Melphalan undergoes rapid hydrolysis in plasma to mono- and dihydroxy metabolites. Minor hepatic metabolism via cytochrome P450 (CYP2B6, CYP2C8, CYP3A4) but hydrolysis is the primary pathway. |
| Excretion | Renal: 10-30% unchanged; fecal: 20-30% as metabolites; biliary: minor. |
| Half-life | 1.5-2.5 h (terminal) in normal renal function; may be prolonged in renal impairment. |
| Protein binding | 60-90% bound, primarily to albumin. |
| Volume of Distribution | 0.5-0.6 L/kg; distributes to total body water with some tissue binding. |
| Bioavailability | Oral: 25-30% with high interpatient variability; IV: 100%. |
| Onset of Action | IV: 2-4 weeks for multiple myeloma; oral: 4-6 weeks. |
| Duration of Action | 3-6 weeks; myelosuppression nadir at 4-6 weeks, recovery at 6-8 weeks. |
16 mg/m² intravenously over 15-20 minutes every 2 weeks for 4 doses, then every 4 weeks
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: 100% dose; CrCl 10-50 mL/min: 75% dose; CrCl <10 mL/min: 50% dose |
| Liver impairment | Child-Pugh A: 100% dose; Child-Pugh B: 75% dose; Child-Pugh C: 50% dose |
| Pediatric use | 10-25 mg/m² orally once daily for 4-7 days every 4-6 weeks; adjust based on toxicity |
| Geriatric use | Reduce initial dose by 25% due to increased toxicity; monitor renal function and hematologic parameters |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other bone marrow suppressants may have additive effects Can cause severe myelosuppression and secondary malignancies.
| FDA category | Contraindicated |
| Breastfeeding | No data are available on melphalan excretion into human breast milk. However, due to the drug's molecular weight (about 289 Da) and low oral bioavailability, transfer to infants via breastfeeding is expected to be minimal. The M/P ratio is unknown. Because of potential serious adverse reactions in the breastfed infant (e.g., myelosuppression, carcinogenicity), breastfeeding is not recommended during melphalan therapy and for at least 2 weeks after the last dose. |
■ FDA Black Box Warning
WARNING: Melphalan should be administered under the supervision of a qualified physician experienced in cancer chemotherapy. Severe bone marrow suppression with resulting infection or bleeding may occur. Melphalan is leukemogenic in humans. Monitor blood counts frequently.
| Common Effects | other cancers |
| Serious Effects |
["Hypersensitivity to melphalan or any component of the formulation","Severe bone marrow suppression (unless benefit outweighs risk)","Breastfeeding (due to potential carcinogenicity)"]
| Precautions | ["Bone marrow suppression (dose-limiting toxicity)","Hypersensitivity reactions (including anaphylaxis)","Secondary malignancies (especially acute leukemia)","Myelosuppression exacerbated by renal impairment","Carcinogenicity and mutagenicity","Embryo-fetal toxicity","Vaccination risks with live vaccines"] |
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| Teratogenic Risk |
| Melphalan is a DNA alkylating agent with known teratogenic potential. Exposure during the first trimester is associated with major congenital malformations, including neural tube defects, skeletal anomalies, and growth restriction. During the second and third trimesters, it may cause fetal myelosuppression, intrauterine growth restriction, and low birth weight. Use during pregnancy is contraindicated unless maternal benefit justifies fetal risk. |
| Fetal Monitoring | Baseline and serial complete blood counts (CBC) with differential to monitor myelosuppression. Liver function tests (LFTs) and renal function tests (serum creatinine, BUN) prior to each cycle. Fetal monitoring includes serial ultrasound for growth assessment and anatomy survey in the second trimester. Assess for signs of intrauterine growth restriction, oligohydramnios, or hydrops. |
| Fertility Effects | Melphalan is gonadotoxic. It can cause amenorrhea, ovarian failure, and premature ovarian insufficiency in women. In men, it may cause azoospermia or oligospermia with potential for permanent infertility. Effects are dose- and age-dependent. Pre-treatment fertility preservation counseling is strongly recommended for patients of reproductive potential. |