EVOMELA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVOMELA (EVOMELA).
EVOMELA (melphalan) is a bifunctional alkylating agent that forms cross-links between DNA strands, inhibiting DNA replication and transcription, leading to cell death.
| Metabolism | Melphalan is primarily hydrolyzed to inactive monohydroxymelphalan and dihydroxymelphalan. Minor metabolism via CYP450 enzymes is not clinically significant. |
| Excretion | Primarily renal: approximately 10-30% of unchanged drug excreted in urine within 24 hours; extensive hepatic metabolism; fecal excretion accounts for <5% |
| Half-life | Terminal elimination half-life is approximately 75 minutes (range 40-120 minutes) in patients with normal renal function; prolonged to 180-300 minutes in renal impairment |
| Protein binding | Approximately 60-90% bound to albumin and alpha1-acid glycoprotein; binding is concentration-dependent and non-linear |
| Volume of Distribution | Total volume of distribution at steady state (Vdss) is approximately 0.5-0.8 L/kg (25-60 L in adults), indicating extensive tissue binding |
| Bioavailability | Melphalan oral bioavailability is variable, ranging from 25% to 89% (mean approximately 60%) due to incomplete absorption and first-pass metabolism; IV dosing results in 100% bioavailability |
| Onset of Action | Intravenous: clinical response (myelosuppression) observed within 4-7 days; maximal effect on blood counts occurs around 9-14 days |
| Duration of Action | Myelosuppressive effects persist for 3-5 weeks; recovery of neutrophil nadir typically by 21-28 days post-dose |
140-200 mg/m² IV over 30 minutes for conditioning prior to ASCT; off-label: 16 mg/m² IV over 15-20 minutes every 4 weeks for MM.
| Dosage form | POWDER |
| Renal impairment | CrCl >60: no adjustment; CrCl 30-60: reduce dose by 25%; CrCl <30: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 25-50%; Child-Pugh C: contraindicated. |
| Pediatric use | Safety and efficacy not established; limited data: 140-200 mg/m² IV for conditioning in clinical trials. |
| Geriatric use | No specific dose adjustment; monitor renal function and hematologic toxicity closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVOMELA (EVOMELA).
| Breastfeeding | It is unknown whether melphalan is excreted in human breast milk. The M/P ratio has not been determined. Due to the potential for serious adverse reactions (e.g., myelosuppression, carcinogenesis) in nursing infants, breastfeeding is contraindicated during treatment and for at least 2 weeks after the last dose. |
| Teratogenic Risk | Evomela (melphalan) is a pregnancy category D drug. In the first trimester, there is a high risk of teratogenicity, including structural malformations (e.g., skeletal, central nervous system) and fetal death. In the second and third trimesters, it can cause fetal growth restriction, myelosuppression, and potential carcinogenesis. Use during pregnancy is contraindicated unless no safer alternative exists. |
■ FDA Black Box Warning
EVOMELA causes severe bone marrow suppression (neutropenia, thrombocytopenia, anemia), which can be fatal. Do not use in patients with inadequate bone marrow reserve. Monitor blood counts frequently.
| Serious Effects |
["Hypersensitivity to melphalan or any component of EVOMELA","Severe bone marrow suppression","Concurrent therapy with other myelosuppressive drugs (unless carefully controlled)"]
| Precautions | ["Bone marrow suppression","Secondary malignancies (e.g., myelodysplastic syndrome, acute leukemia)","Hypersensitivity reactions","Veno-occlusive disease (hepatic)","Renal toxicity"," Embryo-fetal toxicity"] |
| Food/Dietary | No specific food interactions reported; maintain adequate hydration. Avoid grapefruit and grapefruit juice during treatment as it may alter liver metabolism. |
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| Fetal Monitoring | Maternal monitoring: Complete blood count (CBC) with differential, platelet count, renal function (serum creatinine, BUN), and hepatic function (AST, ALT, bilirubin) prior to each cycle. Fetal monitoring: Perform high-resolution ultrasound to assess fetal growth and anatomy every 4 weeks during pregnancy. |
| Fertility Effects | Melphalan can cause ovarian toxicity in females, leading to amenorrhea and premature ovarian failure. In males, it may cause azoospermia or oligospermia, potentially permanent. Pre-treatment fertility preservation (e.g., oocyte or sperm cryopreservation) should be discussed. |
| Clinical Pearls | EVOMELA (melphalan) is an alkylating agent used in high-dose conditioning regimens for multiple myeloma prior to autologous stem cell transplant. It requires dose adjustment in renal impairment (CrCl < 45 mL/min). Premedicate with antiemetics due to high emetogenic potential. Monitor for myelosuppression, mucositis, and hepatic veno-occlusive disease. Avoid live vaccines during treatment. |
| Patient Advice | Take exactly as prescribed; do not adjust dose without consulting your doctor. · Avoid pregnancy and breastfeeding during treatment; use effective contraception. · Report any signs of infection (fever, chills), unusual bleeding or bruising, mouth sores, or jaundice immediately. · Avoid live vaccines (e.g., MMR, varicella) during and after treatment. · Stay hydrated and report nausea/vomiting that prevents eating or drinking. · Do not take aspirin, NSAIDs, or any other OTC medications without approval. |