Evomela 50mg Inj, 1 Vial
WARNING: This drug may lower the ability of the bone marrow to make blood cells that the body needs. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. If you have questions, talk with the doctor.Have blood work checked as you have been told by the doctor. Talk with the doctor.Other types of cancer may rarely happen later in life.Allergic reactions may rarely occur. @ COMMON USES: It is used to treat multiple myeloma. It may be given to you for other reasons. Talk with the doctor.
Drug Class
Antineoplastic Agent
Pharmacologic Class
Alkylating Agent (Nitrogen Mustard Derivative)
Pregnancy Category
Category D
FDA Approved
Mar 2016
DEA Schedule
Not Controlled
Overview
What is this medicine?
Melphalan is a chemotherapy drug used to treat certain types of cancer, such as multiple myeloma and ovarian cancer. It works by stopping the growth of cancer cells.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. It is essential to follow the dosage instructions carefully. This medication is administered as an infusion into a vein over a specified period. In some cases, your doctor may prescribe other medications to be taken before this infusion to minimize potential side effects.
Storing and Disposing of Your Medication
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
Missing a Dose
If you miss a dose, contact your doctor immediately to receive guidance on the next steps to take.
To use this medication correctly, follow your doctor's instructions and read all the information provided. It is essential to follow the dosage instructions carefully. This medication is administered as an infusion into a vein over a specified period. In some cases, your doctor may prescribe other medications to be taken before this infusion to minimize potential side effects.
Storing and Disposing of Your Medication
If you need to store this medication at home, consult with your doctor, nurse, or pharmacist to determine the proper storage procedure.
Missing a Dose
If you miss a dose, contact your doctor immediately to receive guidance on the next steps to take.
Lifestyle & Tips
- Avoid contact with people who are sick or have infections, as your immune system will be weakened.
- Report any signs of infection (fever, chills, sore throat) immediately to your healthcare provider.
- Practice good hand hygiene.
- Avoid activities that could cause cuts or bruises.
- Maintain good oral hygiene to prevent mouth sores.
- Stay well-hydrated unless otherwise instructed by your doctor.
- Do not receive any vaccinations without consulting your doctor, especially live vaccines.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Highly variable based on indication and regimen. For multiple myeloma (high-dose conditioning): 200 mg/m² as a single IV dose or 100 mg/m² daily for 2 consecutive days, followed by autologous stem cell transplantation. For conventional multiple myeloma: 0.25 mg/kg/day for 4 days, repeated every 4-6 weeks.
Dose Range:
0.25 - 200 mg
Condition-Specific Dosing:
multipleMyeloma_highDose:
200 mg/m² IV single dose or 100 mg/m² IV daily for 2 days
multipleMyeloma_conventional:
0.25 mg/kg/day IV for 4 days, repeated every 4-6 weeks
ovarianCancer:
0.2 mg/kg/day IV for 5 days, repeated every 4-5 weeks
Pediatric Dosing
Neonatal:
Not established, but used in specific protocols for certain cancers (e.g., neuroblastoma, retinoblastoma) with highly individualized dosing.
Infant:
Not established, but used in specific protocols for certain cancers (e.g., neuroblastoma, retinoblastoma) with highly individualized dosing.
Child:
Not established, but used in specific protocols for certain cancers (e.g., neuroblastoma, retinoblastoma) with highly individualized dosing.
Adolescent:
Not established, but used in specific protocols for certain cancers (e.g., neuroblastoma, retinoblastoma) with highly individualized dosing.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor closely.
Moderate:
Consider dose reduction (e.g., 50% reduction for high-dose regimens if CrCl < 50 mL/min). Monitor hematologic toxicity closely.
Severe:
Significant dose reduction required (e.g., 75% reduction for high-dose regimens if CrCl < 30 mL/min). Use with extreme caution. Not recommended for conventional dosing if CrCl < 30 mL/min.
Dialysis:
Not dialyzable to a significant extent. Dosing in dialysis patients should be based on residual renal function and close monitoring of toxicity.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended, but monitor for increased toxicity.
Severe:
No specific dose adjustment recommended, but use with caution and monitor for increased toxicity due to potential for impaired drug clearance.
Pharmacology
Mechanism of Action
Melphalan is a bifunctional alkylating agent. It forms covalent bonds with DNA, leading to cross-linking of DNA strands and inhibition of DNA and RNA synthesis. This results in cell cycle arrest and apoptosis, primarily affecting rapidly proliferating cells.
Pharmacokinetics
Absorption:
Bioavailability:
100% (IV administration)
Tmax:
Not applicable (IV administration)
FoodEffect:
Not applicable (IV administration)
Distribution:
Vd:
Approximately 0.5 L/kg
ProteinBinding:
Approximately 50-90% (primarily to albumin)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 1.5 to 2 hours (terminal half-life)
Clearance:
Approximately 7-9 mL/min/kg
ExcretionRoute:
Primarily renal (10-15% unchanged drug), with some biliary excretion.
Unchanged:
10-15% (renal)
Pharmacodynamics
OnsetOfAction:
Rapid (within minutes of administration)
PeakEffect:
Cellular effects are cumulative and manifest over days to weeks (e.g., nadir of blood counts typically occurs 10-14 days post-dose).
DurationOfAction:
Effects on bone marrow are prolonged, leading to myelosuppression lasting several weeks.
Safety & Warnings
BLACK BOX WARNING
Melphalan can cause severe bone marrow suppression, leading to infection, bleeding, or death. Secondary malignancies, including acute nonlymphocytic leukemia, have been reported. Hypersensitivity reactions, including anaphylaxis, have occurred.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction: rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises or bruising that worsens, or uncontrollable bleeding.
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellowing of the skin or eyes.
Signs of electrolyte problems: mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance disturbances, abnormal heartbeat, seizures, loss of appetite, or severe stomach upset or vomiting.
Pale skin
Chest pain or pressure, or a rapid heartbeat
Dizziness or fainting
Shortness of breath
Swelling
Missed menstrual period
Skin lump or growth
Blurred vision
Serious Lung or Breathing Problems
This medication can cause severe and potentially life-threatening lung or breathing problems. If you experience any of the following symptoms, contact your doctor immediately: trouble breathing, shortness of breath, or a new or worsening cough.
Tissue Damage
If the medication leaks from the vein, it can cause tissue damage. Inform your nurse if you notice any redness, burning, pain, swelling, blisters, skin sores, or fluid leakage at the injection site.
Other Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Mouth irritation or mouth sores
Fatigue or weakness
Constipation
Stomach pain
Diarrhea, vomiting, stomach upset, or decreased appetite (common side effects; discuss ways to manage them with your doctor)
Change in taste
Weight loss
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction: rash, hives, itching, redness, swelling, blistering, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, bleeding gums, abnormal vaginal bleeding, unexplained bruises or bruising that worsens, or uncontrollable bleeding.
Signs of liver problems: dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellowing of the skin or eyes.
Signs of electrolyte problems: mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance disturbances, abnormal heartbeat, seizures, loss of appetite, or severe stomach upset or vomiting.
Pale skin
Chest pain or pressure, or a rapid heartbeat
Dizziness or fainting
Shortness of breath
Swelling
Missed menstrual period
Skin lump or growth
Blurred vision
Serious Lung or Breathing Problems
This medication can cause severe and potentially life-threatening lung or breathing problems. If you experience any of the following symptoms, contact your doctor immediately: trouble breathing, shortness of breath, or a new or worsening cough.
Tissue Damage
If the medication leaks from the vein, it can cause tissue damage. Inform your nurse if you notice any redness, burning, pain, swelling, blisters, skin sores, or fluid leakage at the injection site.
Other Side Effects
Like all medications, this drug can cause side effects. Many people may not experience any side effects or only minor ones. If you're bothered by any of the following side effects or if they persist, contact your doctor:
Mouth irritation or mouth sores
Fatigue or weakness
Constipation
Stomach pain
Diarrhea, vomiting, stomach upset, or decreased appetite (common side effects; discuss ways to manage them with your doctor)
Change in taste
Weight loss
Reporting Side Effects
If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Fever (100.4°F or 38°C or higher) or chills
- Unusual bleeding or bruising (e.g., nosebleeds, bleeding gums, petechiae)
- Severe nausea, vomiting, or diarrhea that does not improve
- Severe mouth sores or difficulty swallowing
- Extreme fatigue or weakness
- Yellowing of skin or eyes (jaundice)
- Swelling in ankles or feet
- Shortness of breath or persistent cough
- Any signs of an allergic reaction (rash, itching, hives, swelling of face/lips/tongue, difficulty breathing)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 1 week after your last dose.
To ensure safe treatment, it is crucial to discuss the following with your doctor and pharmacist:
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins.
Any existing health problems, as this medication may interact with other drugs or health conditions.
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm it is safe to do so. This will help prevent potential interactions and ensure your treatment plan is optimized.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 1 week after your last dose.
To ensure safe treatment, it is crucial to discuss the following with your doctor and pharmacist:
All medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins.
Any existing health problems, as this medication may interact with other drugs or health conditions.
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm it is safe to do so. This will help prevent potential interactions and ensure your treatment plan is optimized.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
While taking this drug, you may be more susceptible to infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Be aware that this medication may increase your risk of bleeding easily. To reduce this risk, be cautious and avoid injuries. Use a soft-bristled toothbrush and an electric razor for shaving. Before receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication.
To manage mouth sores, use a soft toothbrush or cotton swabs to clean your mouth, and rinse with a non-alcoholic mouthwash. Avoid using mouth rinses that contain alcohol.
If you are 65 years or older, use this medication with caution, as you may be more prone to experiencing side effects.
This drug may affect ovarian function, potentially leading to the cessation of menstrual periods. Discuss this with your doctor.
Additionally, this medication may impact fertility, making it more challenging to conceive or father a child. Although fertility may return to normal after treatment, it is essential to discuss any concerns with your doctor.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you may become pregnant, use effective birth control methods while taking this medication and for 6 months after your last dose. If you become pregnant, notify your doctor immediately.
If your partner may become pregnant, take measures to prevent pregnancy during treatment and for a specified period after your last dose. Consult with your doctor to determine the recommended duration of birth control after stopping this medication.
While taking this drug, you may be more susceptible to infections. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Be aware that this medication may increase your risk of bleeding easily. To reduce this risk, be cautious and avoid injuries. Use a soft-bristled toothbrush and an electric razor for shaving. Before receiving any vaccinations, consult with your doctor, as certain vaccines may not be effective or may increase the risk of infection when taken with this medication.
To manage mouth sores, use a soft toothbrush or cotton swabs to clean your mouth, and rinse with a non-alcoholic mouthwash. Avoid using mouth rinses that contain alcohol.
If you are 65 years or older, use this medication with caution, as you may be more prone to experiencing side effects.
This drug may affect ovarian function, potentially leading to the cessation of menstrual periods. Discuss this with your doctor.
Additionally, this medication may impact fertility, making it more challenging to conceive or father a child. Although fertility may return to normal after treatment, it is essential to discuss any concerns with your doctor.
This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you may become pregnant, use effective birth control methods while taking this medication and for 6 months after your last dose. If you become pregnant, notify your doctor immediately.
If your partner may become pregnant, take measures to prevent pregnancy during treatment and for a specified period after your last dose. Consult with your doctor to determine the recommended duration of birth control after stopping this medication.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (profound leukopenia, thrombocytopenia, anemia)
- Severe mucositis (mouth sores, gastrointestinal inflammation)
- Nausea, vomiting, diarrhea
- Alopecia
- Pulmonary fibrosis (rare, with chronic use)
- Hepatotoxicity
What to Do:
There is no specific antidote for melphalan overdose. Management is supportive and includes frequent monitoring of blood counts, administration of blood products (platelets, red blood cells) as needed, antiemetics, aggressive hydration, and management of infections with appropriate antibiotics. Granulocyte colony-stimulating factors (G-CSFs) may be used to promote neutrophil recovery. Bone marrow transplantation may be considered in severe cases of irreversible bone marrow aplasia.
Drug Interactions
Contraindicated Interactions
- Live vaccines (due to immunosuppression)
Major Interactions
- Nalidixic acid (increased risk of severe hemorrhagic enterocolitis in pediatric patients)
- Cyclosporine (increased risk of nephrotoxicity and myelosuppression)
- Other myelosuppressive agents (additive bone marrow suppression)
- Radiation therapy (additive myelosuppression)
Moderate Interactions
- Cimetidine (may reduce melphalan clearance, increasing toxicity)
- Busulfan (increased risk of veno-occlusive disease of the liver when used in conditioning regimens)
- Phenytoin (reduced phenytoin levels)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential and platelets
Rationale: To establish baseline hematologic status before initiating myelosuppressive therapy.
Timing: Prior to first dose
Renal function tests (serum creatinine, BUN, creatinine clearance)
Rationale: To assess kidney function for dose adjustment and risk assessment.
Timing: Prior to first dose
Liver function tests (ALT, AST, bilirubin, alkaline phosphatase)
Rationale: To assess liver function and identify potential risk for hepatotoxicity.
Timing: Prior to first dose
Routine Monitoring
Complete Blood Count (CBC) with differential and platelets
Frequency: At least weekly, or more frequently during periods of expected nadir (e.g., twice weekly after high-dose therapy) until recovery.
Target: Maintain ANC > 1500 cells/mm³, platelets > 100,000 cells/mm³ (for conventional dosing); specific recovery targets for transplant.
Action Threshold: Hold or reduce dose for severe myelosuppression (e.g., ANC < 500 cells/mm³, platelets < 25,000 cells/mm³).
Renal function tests
Frequency: Periodically, especially if renal impairment is present or suspected.
Target: Maintain within acceptable limits for patient.
Action Threshold: Significant decline in CrCl may necessitate dose adjustment or discontinuation.
Liver function tests
Frequency: Periodically, especially if liver impairment is present or suspected.
Target: Maintain within acceptable limits for patient.
Action Threshold: Significant elevation may necessitate dose adjustment or discontinuation.
Symptom Monitoring
- Fever (sign of infection due to myelosuppression)
- Unusual bleeding or bruising (sign of thrombocytopenia)
- Severe nausea, vomiting, diarrhea
- Mouth sores or mucositis
- Fatigue, weakness
- Skin rash or itching (hypersensitivity reaction)
- Shortness of breath, cough (pulmonary toxicity)
- Signs of veno-occlusive disease (right upper quadrant pain, ascites, weight gain, jaundice)
Special Patient Groups
Pregnancy
Melphalan is classified as Pregnancy Category D. It can cause fetal harm when administered to a pregnant woman. It is a known teratogen and mutagen. Women of childbearing potential should be advised to avoid becoming pregnant during treatment and for a period after treatment. Effective contraception should be used by both male and female patients.
Trimester-Specific Risks:
First Trimester:
Highest risk of major congenital malformations and spontaneous abortion due to organogenesis.
Second Trimester:
Risk of fetal growth restriction, myelosuppression, and other adverse effects.
Third Trimester:
Risk of fetal myelosuppression and other adverse effects.
Lactation
It is not known whether melphalan is excreted in human milk. However, due to the potential for serious adverse reactions in breastfed infants, including carcinogenicity and myelosuppression, breastfeeding is contraindicated during treatment with melphalan and for a period after the last dose.
Infant Risk:
High risk of serious adverse effects, including myelosuppression, immunosuppression, and potential carcinogenicity.
Pediatric Use
Melphalan has been used in pediatric oncology for various indications (e.g., neuroblastoma, retinoblastoma, conditioning for stem cell transplant). Dosing is highly individualized based on body surface area or weight, and specific protocols. Pediatric patients may be more susceptible to certain toxicities, and long-term effects (e.g., secondary malignancies, infertility) are a concern.
Geriatric Use
Elderly patients may have reduced renal function, which can lead to decreased melphalan clearance and increased risk of toxicity, particularly myelosuppression. Dose adjustments based on renal function are often necessary. Close monitoring for adverse effects is crucial in this population.
Clinical Information
Clinical Pearls
- Melphalan is a vesicant; ensure proper IV access and monitor for extravasation. If extravasation occurs, discontinue infusion immediately and manage according to institutional guidelines.
- Administer melphalan injection slowly over 15-30 minutes to minimize the risk of nausea, vomiting, and hypersensitivity reactions.
- Pre-medication with antiemetics is highly recommended to manage severe nausea and vomiting.
- Hydration is important to prevent renal toxicity, especially with high-dose regimens.
- Monitor for hypersensitivity reactions, which can range from rash to anaphylaxis. Have resuscitation equipment readily available.
- Oral mucositis is a common and dose-limiting toxicity, especially with high-dose regimens. Prophylactic oral care is essential.
- Patients should be educated on the signs and symptoms of myelosuppression and instructed to report them immediately.
Alternative Therapies
- Other chemotherapy regimens for multiple myeloma (e.g., VRd, KRd, Dara-Rd)
- Other chemotherapy regimens for ovarian cancer (e.g., carboplatin/paclitaxel)
- Radiation therapy
- Targeted therapies
- Immunotherapy
Cost & Coverage
Average Cost:
Highly variable, typically several thousand dollars per vial. per 50mg vial
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization, often covered under medical benefit for oncology indications)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further guidance. To ensure your safety and the safety of others, never share your medication with anyone, and do not take medication prescribed to someone else.
Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Properly dispose of any unused or expired medication. Unless instructed to do so by a healthcare professional or pharmacist, avoid flushing medications down the toilet or pouring them down the drain. If you are unsure about the correct disposal method, consult your pharmacist, as they can provide guidance on the best approach. Additionally, you may want to inquire about potential drug take-back programs available in your area.
Some medications may come with an additional patient information leaflet, so it is a good idea to check with your pharmacist to see if this is the case. If you have any questions or concerns about your medication, do not hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider for clarification.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the type of medication taken, the amount, and the time it occurred, to ensure you receive appropriate care.
Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Properly dispose of any unused or expired medication. Unless instructed to do so by a healthcare professional or pharmacist, avoid flushing medications down the toilet or pouring them down the drain. If you are unsure about the correct disposal method, consult your pharmacist, as they can provide guidance on the best approach. Additionally, you may want to inquire about potential drug take-back programs available in your area.
Some medications may come with an additional patient information leaflet, so it is a good idea to check with your pharmacist to see if this is the case. If you have any questions or concerns about your medication, do not hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider for clarification.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide detailed information about the overdose, including the type of medication taken, the amount, and the time it occurred, to ensure you receive appropriate care.