Medical Editor: John P. Cunha, DO, FACOEP
What Is Evomela?
Evomela (melphalan) for injection is an alkylating drug indicated for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation in patients with multiple myeloma, and for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.
What Are Side Effects of Evomela?
Common side effects of Evomela include diarrhea, nausea, fatigue, anemia, vomiting, loss of appetite, fever, constipation, sinus inflammation, dizziness, swelling of the hands or feet, mouth or lip sores, abdominal pain, changes in taste, indigestion, low blood potassium (hypokalemia), neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, and low blood phosphates.
Dosage for Evomela
The recommended dose of Evomela for conditioning treatment is 100 mg/m2/day administered over 30 minutes by intravenous infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplantation (ASCT, Day 0).
What Drugs, Substances, or Supplements Interact with Evomela?
The recommended dose of Evomela for palliative treatment is 16 mg/m2 administered as a single intravenous infusion over 15-20 minutes at 2-week intervals for 4 doses, then, after adequate recovery from toxicity, at 4-week intervals.
Evomela During Pregnancy and Breastfeeding
Evomela may interact with other drugs. Tell your doctor all medications and supplements you use. Evomela is not recommended for use during pregnancy; it may harm a fetus. Women should discuss use of contraception with their doctor during and after treatment with Evomela. Males with female partners of childbearing age should use contraception during and after treatment with Evomela. Breastfeeding is not recommended during treatment with Evomela.
Our Evomela (melphalan) for injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
The following serious adverse reactions are described in more detail in other sections of the prescribing information.
- Bone Marrow Suppression [see WARNINGS AND PRECAUTIONS]
- Gastrointestinal Toxicity [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Hypersensitivity [see WARNINGS AND PRECAUTIONS]
- Secondary Malignancies [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of Evomela 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 Evomela were neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting.
Myeloablative Conditioning In Multiple Myeloma Patients Undergoing ASCT
The safety of Evomela was evaluated in 61 patients with multiple myeloma in a single arm clinical trial in which patients were administered Evomela at a dosage of 100 mg/m2/day administered over ~30 minutes (range: 24-48 minutes) by intravenous (IV) infusion for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplant (ASCT, Day 0).
Table 1 summarizes the adverse reactions from the single-arm trial in patients with multiple myeloma. Severe myelosuppression is expected and these adverse reactions are not listed below.
Table 1 Non-hematologic Adverse Reactions in ≥ 25% of Patients with Multiple Myeloma Who Received Evomela Conditioning for ASCT
|Adverse Reactions||Number (%) of Patients|
|All Grades||Grade 3or 4|
|All Adverse Reactions||61||61|
|Diarrhea||57 (93%)||2 (3%)|
|Nausea||55 (90%)||1 (2%)|
|Fatigue||47 (77%)||1 (2%)|
|Hypokalemia||45 (74%)||17 (28%)|
|Vomiting||39 (64%)||0 (0%)|
|Hypophosphatemia||30 (49%)||29 (48%)|
|Decreased Appetite||30 (49%)||0 (0%)|
|Pyrexia||29 (48%)||2 (3%)|
|Constipation||29 (48%)||0 (0%)|
|Febrile Neutropenia||25 (41%)||17 (28%)|
|Mucosal Inflammation||23 (38%)||6 (10%)|
|Dizziness||23 (38%)||0 (0%)|
|Edema Peripheral||20 (33%)||0 (0%)|
|Stomatitis||17 (28%)||3 (5%)|
|Abdominal Pain||17 (28%)||0 (0%)|
|Dysgeusia||17 (28%)||0 (0%)|
|Dyspepsia||16 (26%)||0 (0%)|
Serious Adverse Reactions
Twelve (20%) patients experienced a treatment emergent serious adverse reaction while on study. The most common serious adverse reactions (>1 patient, 1.6%) were pyrexia, hematochezia, febrile neutropenia, and renal failure. Treatment-related serious adverse reactions reported in >1 patient were pyrexia (n=2, 3%), febrile neutropenia (n=2, 3%), and hematochezia (n=2, 3%).
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 IV melphalan at a dosage of 16 mg/m2 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 IV melphalan arm (28%) than in the oral melphalan arm (11%).
An association was noted between poor renal function and myelosuppression; consequently, an amendment to the protocol required a 50% reduction in IV melphalan dose if the BUN was ≥30 mg/dL. The rate of severe leukopenia in the IV arm in the patients with BUN over 30 mg/dL decreased from 50% (8/16) before protocol amendment to 11% (3/28) after the amendment.
Before the dosing amendment, there was a 10% (8/77) incidence of drug-related death in the IV arm. After the dosing amendment, this incidence was 3% (3/108). This compares to an overall 1% (1/100) incidence of drugrelated death in the oral melphalan arm.
Read the entire FDA prescribing information for Evomela (Melphalan for Injection, for Intravenous Use)
© Evomela Patient Information is supplied by Cerner Multum, Inc. and Evomela Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.