Melphalan Macure
Powder and solvent for solution for injection/infusion — 50 mg melphalan
Melphalan Macure is a cytotoxic chemotherapy medicine containing melphalan, an alkylating agent of the nitrogen mustard class. It is used primarily for the treatment of multiple myeloma, advanced ovarian cancer, and as a high-dose conditioning regimen before hematopoietic stem cell transplantation. Melphalan works by cross-linking DNA strands in cancer cells, preventing them from dividing and ultimately causing cell death. This medicine is administered intravenously in a hospital setting under the supervision of a specialist oncologist or hematologist experienced in chemotherapy.
Quick Facts
Key Takeaways
- Melphalan Macure is a potent alkylating chemotherapy agent used to treat multiple myeloma, ovarian cancer, and as conditioning before stem cell transplantation.
- It must be administered intravenously in a hospital setting by healthcare professionals experienced in cancer chemotherapy.
- Bone marrow suppression is the most significant side effect — regular blood count monitoring is essential throughout treatment.
- Melphalan is contraindicated in pregnancy and both men and women must use effective contraception during and for 6 months after treatment.
- The reconstituted solution is chemically unstable and must be administered promptly after preparation — typically within 1.5 hours.
What Is Melphalan Macure and What Is It Used For?
Melphalan Macure contains the active substance melphalan, which belongs to a group of anticancer medicines called alkylating agents. Alkylating agents are among the oldest and most widely used classes of chemotherapy drugs. They work by directly damaging the DNA of cancer cells, forming chemical bonds (cross-links) between and within DNA strands that prevent normal cell division and lead to programmed cell death (apoptosis).
Melphalan was first synthesized in the 1950s as a derivative of nitrogen mustard, and it has been a cornerstone of cancer therapy for over six decades. The World Health Organization includes melphalan on its Model List of Essential Medicines, recognizing it as one of the most effective and important medications in the global healthcare system. Melphalan Macure is the branded intravenous formulation manufactured by Macure Pharma ApS.
Approved Indications
Melphalan Macure is indicated for the treatment of the following conditions:
- Multiple myeloma: A cancer of the plasma cells in the bone marrow. Melphalan has been a mainstay of myeloma treatment for decades, both at conventional doses combined with prednisone (the "MP regimen") and at high doses as part of conditioning before autologous stem cell transplantation (ASCT). High-dose melphalan followed by ASCT remains a standard of care for eligible patients with newly diagnosed multiple myeloma, according to international guidelines from the NCCN, ESMO, and the International Myeloma Working Group (IMWG).
- Advanced ovarian cancer (epithelial ovarian carcinoma): When intravenous melphalan may be used as a single agent or in combination chemotherapy regimens, particularly when platinum-based therapies are not suitable or have failed. While platinum-based regimens are now first-line, melphalan retains a role in selected clinical scenarios.
- High-dose conditioning before hematopoietic stem cell transplantation (HSCT): Melphalan at high doses (typically 140–200 mg/m²) is used as a myeloablative conditioning agent before both autologous and allogeneic stem cell transplants. This is one of its most common uses in contemporary oncology practice.
In addition, intravenous melphalan is sometimes used off-label in the treatment of other malignancies including advanced neuroblastoma in children, AL amyloidosis, and other hematological malignancies where myeloablative conditioning is required. These uses are supported by clinical evidence and specialist guidelines, though they may not appear in all product labels.
Mechanism of Action
Melphalan exerts its anticancer effects through a well-characterized mechanism. As a bifunctional alkylating agent, it has two reactive chloroethyl groups that can form covalent bonds with nucleophilic sites on DNA molecules, primarily at the N-7 position of guanine bases. This results in both interstrand cross-links (bonds between the two complementary strands of the DNA double helix) and intrastrand cross-links (bonds between bases on the same strand).
These cross-links are highly cytotoxic because they prevent the DNA strands from being properly separated during cell division (mitosis). When a cell attempts to replicate its damaged DNA, the cross-links trigger DNA damage response pathways, ultimately leading to apoptosis. Because cancer cells generally divide more rapidly than most normal cells, they accumulate more DNA damage and are more susceptible to the effects of melphalan. However, rapidly dividing normal cells — particularly bone marrow progenitor cells, gastrointestinal epithelial cells, and hair follicle cells — are also affected, which accounts for the characteristic side effects of myelosuppression, mucositis, and alopecia.
What Should You Know Before Taking Melphalan Macure?
Because melphalan is a potent cytotoxic agent, treatment must be initiated and supervised by a physician experienced in the use of cancer chemotherapeutic agents. Before starting treatment, your medical team will conduct a thorough evaluation of your overall health, blood counts, kidney function, and reproductive status to determine whether melphalan is appropriate and safe for you.
Contraindications
Melphalan Macure must not be used if you:
- Are allergic (hypersensitive) to melphalan or any of the other ingredients in this medicine, including propylene glycol in the solvent.
- Are pregnant or may become pregnant, unless the potential benefit clearly outweighs the risk (see Pregnancy section below).
- Are breastfeeding, as it is not known whether melphalan passes into breast milk and harm to the infant cannot be excluded.
Warnings and Precautions
Melphalan causes severe and prolonged bone marrow suppression. Blood counts must be monitored closely. Treatment should not be started, or should be delayed, if blood counts have not recovered sufficiently from previous chemotherapy or radiation therapy. The nadir of blood counts typically occurs 2–3 weeks after administration.
Your doctor will take special care with Melphalan Macure if any of the following apply to you:
- Bone marrow suppression: Melphalan is profoundly myelosuppressive. Leukopenia (low white blood cells), thrombocytopenia (low platelets), and anemia are expected effects. Complete blood counts must be performed frequently — at least weekly during conventional-dose therapy, and daily during high-dose conditioning regimens.
- Kidney impairment: Melphalan is partly cleared by the kidneys, and renal impairment can lead to increased drug exposure and more severe toxicity. Dose adjustments are typically required in patients with reduced kidney function (creatinine clearance <50 mL/min). Your doctor will assess your renal function before each cycle.
- Infections: Because melphalan suppresses the immune system, you are at increased risk of bacterial, viral, and fungal infections. Live vaccines must be avoided during treatment and for a period after treatment ends. Your medical team may prescribe prophylactic antimicrobials.
- Secondary malignancies: Alkylating agents, including melphalan, are known to increase the long-term risk of developing secondary cancers, particularly acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This risk is dose-dependent and cumulative.
- Hepatic veno-occlusive disease (VOD): High-dose melphalan, particularly in the transplant setting, has been associated with hepatic veno-occlusive disease (sinusoidal obstruction syndrome), a potentially fatal complication affecting the liver.
- Extravasation: If the intravenous infusion leaks outside the vein (extravasation), melphalan can cause severe local tissue damage. The infusion site must be monitored carefully throughout administration.
Pregnancy and Breastfeeding
Melphalan is mutagenic and teratogenic. It must not be used during pregnancy unless the clinical condition absolutely requires it and the potential benefit outweighs the significant risk to the fetus. Both male and female patients must use effective contraception during treatment and for at least 6 months after the last dose.
Melphalan has been shown to be teratogenic in animal studies, causing birth defects including malformations of the brain, eyes, and skeletal system. In humans, there are reports of congenital abnormalities in children born to mothers who received melphalan during pregnancy, although the data is limited. The European Medicines Agency (EMA) classifies melphalan as a medicine that should be avoided in pregnancy.
Fertility: Melphalan can cause irreversible damage to the gonads (ovaries and testes). In men, melphalan frequently causes azoospermia (absence of sperm) or severe oligospermia (very low sperm count), which may be permanent. Men should be counseled about sperm cryopreservation before starting treatment. In women, melphalan may cause premature ovarian failure and early menopause, particularly in older patients or those receiving cumulative high doses. Egg or embryo freezing should be discussed where appropriate.
Breastfeeding: It is not known whether melphalan is excreted in human breast milk. Due to the potential for serious adverse effects in the nursing infant, breastfeeding must be discontinued before starting melphalan treatment and should not be resumed during treatment.
How Does Melphalan Macure Interact with Other Drugs?
Drug interactions with melphalan are clinically significant because of its narrow therapeutic index and the severe nature of its toxicity profile. Your oncology team will carefully review all medications you are taking — including prescription drugs, over-the-counter medicines, herbal supplements, and vitamins — before starting treatment.
Major Interactions
| Interacting Drug | Effect | Clinical Significance |
|---|---|---|
| Cyclosporine | Increased risk of severe nephrotoxicity (kidney damage) | Avoid combination or monitor renal function very closely; dose adjustments may be required |
| Live vaccines (e.g., MMR, varicella, oral polio) | Risk of disseminated vaccine-strain infection, potentially fatal | Contraindicated during treatment and for at least 3–6 months after last dose |
| Busulfan | Increased risk of hepatic veno-occlusive disease (VOD) and pulmonary toxicity when used in combination conditioning regimens | Requires careful timing and dose sequencing; specialist management essential |
| Nalidixic acid | Reports of fatal hemorrhagic enterocolitis in children when combined with IV melphalan | This combination must be avoided |
| Other myelosuppressive agents | Additive bone marrow suppression | Blood counts require more frequent monitoring; dose adjustments may be necessary |
Minor Interactions
The following interactions are generally less severe but should still be communicated to your healthcare team:
- Cimetidine: May reduce oral melphalan bioavailability, though this is not relevant for the intravenous formulation (Melphalan Macure).
- Interferon alfa: May reduce the plasma levels of melphalan, though the clinical significance is uncertain.
- Carmustine (BCNU): When used in combination conditioning regimens, may increase pulmonary toxicity.
- Amphotericin B: Concurrent use may increase the risk of nephrotoxicity, requiring careful renal monitoring.
Because melphalan suppresses the immune system, the effectiveness of inactivated vaccines may also be reduced during treatment. Your doctor may recommend checking antibody levels (titers) after vaccination to ensure adequate protection. Seasonal influenza vaccination and COVID-19 vaccination (with inactivated or mRNA vaccines) may still be recommended despite potentially reduced efficacy, as partial protection is better than none.
What Is the Correct Dosage of Melphalan Macure?
Melphalan Macure is always administered by healthcare professionals in a hospital or specialized clinic setting. The dose is calculated individually for each patient based on their condition, body measurements, kidney function, and response to previous treatment. You should never attempt to self-administer this medication.
Adults
Multiple Myeloma — Conventional Dose
The typical intravenous dose is 0.4 mg/kg body weight (approximately 16 mg/m² body surface area), administered as an intermittent infusion over 15–20 minutes. This is usually repeated at intervals of 4 weeks, often combined with oral prednisone (the "MP regimen"). The exact interval between courses depends on the recovery of blood counts — treatment should not be repeated until white blood cells and platelet counts have returned to acceptable levels.
Multiple Myeloma — High-Dose Conditioning for ASCT
For autologous stem cell transplantation (ASCT), the standard high-dose conditioning regimen is 200 mg/m², typically given as a single dose or divided into two doses of 100 mg/m² on consecutive days (day −3 and day −2, or day −2 and day −1 before transplant). In patients over 65–70 years or those with significant comorbidities, a reduced dose of 140 mg/m² may be used. The infusion is given over 30–60 minutes. Stem cell infusion follows 24–48 hours after the last melphalan dose.
Advanced Ovarian Cancer
When used intravenously for ovarian cancer, the dose is typically 1 mg/kg body weight (approximately 18 mg/m²) given at intervals of 4 weeks, provided blood counts have adequately recovered.
Children
Melphalan is used in pediatric patients primarily for high-dose conditioning before stem cell transplantation in conditions such as neuroblastoma and certain other childhood cancers. Dosing in children follows weight-based or body surface area-based protocols established by pediatric oncology guidelines (e.g., COG — Children's Oncology Group). High-dose regimens typically use 100–200 mg/m², similar to adult conditioning doses, but carefully adjusted for the child's size, organ function, and specific protocol requirements.
Elderly
Older patients are more susceptible to the myelosuppressive effects of melphalan, and age-related decline in renal function is common. The European Society for Medical Oncology (ESMO) and IMWG guidelines recommend that patients over 65–70 years, or those with significant comorbidities, who are undergoing high-dose therapy should receive a reduced conditioning dose of 140 mg/m² rather than the standard 200 mg/m². For conventional-dose therapy, the standard dose is used but with careful monitoring and readiness to dose-reduce or extend intervals based on blood count recovery.
Dose Adjustment in Renal Impairment
| Creatinine Clearance | Conventional Dose | High-Dose Conditioning |
|---|---|---|
| >50 mL/min (normal) | Full dose | 200 mg/m² |
| 30–50 mL/min (moderate) | Reduce by 25–50% | 140 mg/m² |
| <30 mL/min (severe) | Consider alternative agents | 100–140 mg/m² (specialist decision) |
Missed Dose
Since Melphalan Macure is administered by healthcare professionals in a clinical setting, missed doses are unlikely. If an appointment for treatment is missed, the medical team will reschedule based on your blood count results and overall condition. The timing of the next dose is not fixed but depends on recovery of bone marrow function. Do not attempt to compensate for a missed dose by receiving a larger amount.
Overdose
Overdose of intravenous melphalan can cause life-threatening bone marrow failure, severe mucositis, and multi-organ toxicity. There is no specific antidote for melphalan overdose. Treatment is supportive: blood transfusions, growth factor support (G-CSF), broad-spectrum antibiotics, and intensive care monitoring. In extreme cases, rescue stem cell infusion may be considered.
Immediate effects of overdose may include severe nausea, vomiting, and diarrhea. The primary delayed toxicity is profound and prolonged pancytopenia (suppression of all blood cell lines), which typically develops over the following 1–3 weeks. Mucositis (inflammation and ulceration of the mouth and gastrointestinal tract) can be severe and lead to difficulty eating and secondary infections. Patients who have received an accidental overdose require intensive monitoring in a specialized hematology or oncology unit with full supportive care capabilities.
What Are the Side Effects of Melphalan Macure?
Like all chemotherapy medicines, melphalan can cause side effects, although not everybody experiences all of them. The type and severity of side effects depend on the dose administered — high-dose conditioning regimens cause more severe toxicity than conventional doses. Your medical team will closely monitor you for side effects and provide supportive treatments as needed.
The following side effects are classified according to their approximate frequency, based on data from clinical trials and post-marketing surveillance reported by the EMA and international pharmacovigilance databases:
Very Common
Affects more than 1 in 10 patients
- Bone marrow suppression (myelosuppression): Low white blood cells (leukopenia, neutropenia), low platelets (thrombocytopenia), and low red blood cells (anemia) — this is the dose-limiting toxicity
- Nausea and vomiting: Particularly common with high-dose IV administration; antiemetic prophylaxis is routinely given
- Diarrhea: Especially with high-dose regimens, can be severe and require fluid replacement
- Stomatitis and mucositis: Inflammation and ulceration of the mouth and gastrointestinal tract, most common after high-dose therapy
- Alopecia (hair loss): Very common with high-dose regimens; typically reversible after treatment completion
- Infections: Due to immunosuppression — bacterial, viral, and fungal infections can occur
Common
Affects 1 in 10 to 1 in 100 patients
- Elevated liver enzymes: Transient increases in transaminases (ALT, AST)
- Febrile neutropenia: Fever occurring during the period of low white blood cells, a medical emergency requiring immediate treatment
- Hemorrhage: Bleeding related to low platelet counts, including nosebleeds, bruising, and gastrointestinal bleeding
- Fatigue and malaise: Generalized tiredness and weakness
- Loss of appetite (anorexia)
Uncommon
Affects 1 in 100 to 1 in 1,000 patients
- Skin rash: Including maculopapular eruptions
- Interstitial pneumonitis and pulmonary fibrosis: Inflammation or scarring of lung tissue
- Peripheral neuropathy: Numbness, tingling, or pain in hands and feet (more common with prolonged use)
- Cardiac toxicity: Including atrial fibrillation (particularly with high-dose regimens)
Rare
Affects fewer than 1 in 1,000 patients
- Secondary malignancies: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) — typically occurring years after treatment; risk is dose-dependent
- Hepatic veno-occlusive disease (VOD/SOS): Sinusoidal obstruction syndrome, mainly with high-dose therapy; potentially fatal
- Anaphylaxis: Severe allergic reactions including hypotension, urticaria, angioedema, and bronchospasm — can occur with first or subsequent doses
- Hemolytic anemia: Destruction of red blood cells, typically autoimmune-mediated
- Irreversible infertility: Particularly in males (azoospermia); may also affect female fertility
Contact your medical team immediately or go to the nearest emergency department if you experience: fever ≥38°C or chills during treatment (signs of infection), unusual bleeding or bruising, severe difficulty breathing, swelling of the face or throat, rapid heartbeat or dizziness, or severe abdominal pain.
How Should You Store Melphalan Macure?
Melphalan Macure is a hospital-only medicine handled by trained pharmacy staff and healthcare professionals. Patients do not store or prepare this medicine at home. However, understanding the storage requirements helps appreciate why the medicine must be freshly prepared before each administration.
- Unopened vials: Store below 25°C. Keep in the original packaging to protect from light.
- After reconstitution: The reconstituted solution is chemically and physically unstable. Significant degradation of melphalan occurs rapidly in solution. The manufacturer recommends using the reconstituted solution within 1.5 hours at room temperature. Some guidelines permit refrigerated storage (2–8°C) for slightly longer, but this varies by formulation.
- Further dilution: If the reconstituted solution is further diluted in sodium chloride 0.9% infusion solution, administration should begin as promptly as possible due to ongoing degradation. The solution should not be refrigerated after dilution as crystallization may occur.
- Visual inspection: The reconstituted solution should be clear and colorless to pale yellow. Do not use if the solution is discolored, turbid, or contains visible particles.
- Disposal: Any unused product or waste material must be disposed of as cytotoxic waste in accordance with local hospital protocols and regulations for hazardous pharmaceutical waste.
Melphalan is a cytotoxic substance. Healthcare professionals who prepare and administer Melphalan Macure must follow strict safe handling procedures including the use of protective gloves, gowns, and if appropriate, eye protection and masks. Preparation should ideally be performed in a biological safety cabinet or isolator. Accidental skin or eye contact with the solution requires immediate and thorough washing.
What Does Melphalan Macure Contain?
Active Ingredient
The active substance is melphalan. Each vial of powder contains 50 mg of melphalan (as melphalan hydrochloride). After reconstitution with the provided solvent, the resulting solution contains approximately 5 mg/mL of melphalan.
Other Ingredients
Powder: The lyophilized (freeze-dried) powder contains melphalan hydrochloride, povidone, and hydrochloric acid (for pH adjustment).
Solvent: The solvent provided for reconstitution contains:
- Propylene glycol — used as a co-solvent to keep melphalan in solution. Note: propylene glycol may cause alcohol-like symptoms and can be problematic in patients with liver disease, kidney disease, or in young children.
- Ethanol (alcohol) — also used as a co-solvent. The reconstituted solution contains a small amount of alcohol. This should be considered in pregnant women, patients with liver disease, those with epilepsy, and children.
- Water for injections
Product Appearance
Melphalan Macure is supplied as a white to off-white lyophilized powder in a glass vial, together with a separate vial of clear, colorless solvent. After reconstitution, the solution should appear clear and colorless to pale yellow. The product is supplied in packs containing 1 vial of powder and 1 vial of solvent.
Marketing Authorization Holder
Melphalan Macure is manufactured and marketed by Macure Pharma ApS, based in Denmark. The product is authorized for use in multiple countries across Europe and internationally through the relevant regulatory authorities.
Frequently Asked Questions About Melphalan Macure
References
This article is based on the following peer-reviewed sources and international medical guidelines:
- European Medicines Agency (EMA). Melphalan — Summary of Product Characteristics. European Medicines Agency. Available at: www.ema.europa.eu
- World Health Organization (WHO). WHO Model List of Essential Medicines — 23rd List (2023). World Health Organization. Geneva, 2023.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 2.2025. NCCN Guidelines.
- Dimopoulos MA, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2021;32(3):309–322. doi:10.1016/j.annonc.2020.11.014
- Palumbo A, et al. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014;371(10):895–905. doi:10.1056/NEJMoa1402888
- European Society for Blood and Marrow Transplantation (EBMT). Guidelines for Hematopoietic Stem Cell Transplantation Conditioning Regimens. EBMT Handbook. 2024 revision.
- British National Formulary (BNF). Melphalan — Drug Monograph. National Institute for Health and Care Excellence (NICE). Available at: bnf.nice.org.uk
- Cavo M, et al. Role of melphalan dose in the conditioning regimen for autologous stem cell transplantation in multiple myeloma. Blood. 2020;136(Supplement 1):35–36. doi:10.1182/blood-2020-140768
- Drugs@FDA. Melphalan Hydrochloride for Injection — Prescribing Information. U.S. Food and Drug Administration. Available at: www.accessdata.fda.gov
- International Agency for Research on Cancer (IARC). Melphalan — IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 100A. World Health Organization. 2012.
Medical Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in oncology, hematology, and clinical pharmacology. Our content follows the GRADE evidence framework and adheres to guidelines from the WHO, EMA, FDA, NCCN, and EBMT.
Prepared by medical professionals with expertise in oncology pharmacology and evidence-based medicine. All clinical claims are supported by Level 1A evidence from systematic reviews and randomized controlled trials where available.
Independently reviewed by the iMedic Medical Review Board, which includes board-certified oncologists and hematologists. The review ensures accuracy, clinical relevance, and alignment with current international guidelines.
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