Melphalan


Generic Medicine Info
Indications and Dosage
Intra-arterial
Malignant melanoma, Soft tissue sarcoma
Adult: As melphalan hydrochloride: Upper extremity perfusions: 0.6-1 mg/kg. Lower extremity perfusions: 0.8-1.5 mg/kg (in melanoma) or 1-1.4 mg/kg (in sarcoma).
Elderly: Initiate treatment at the lower end of the dosing range.

Intravenous
Multiple myeloma
Adult: As melphalan hydrochloride: 0.4 mg/kg (16 mg/m2) repeated at appropriate intervals (e.g. once every 4 weeks) provided there has been recovery of the peripheral blood count during this period. As high-dose regimen: 100-200 mg/m2, to be followed by haematopoietic stem cell rescue if doses are >140 mg/m2. As melphalan flufenamide: In patients with relapsed or refractory multiple myeloma who have received ≥4 prior lines of therapy and whose disease is refractory to ≥1 proteasome inhibitor, 1 immunomodulatory agent, and 1 CD38-directed monoclonal antibody: 40 mg over 30 minutes on Day 1 of each 28-day treatment cycle, in combination with dexamethasone. Continue until disease progression or unacceptable toxicity. Dose reduction or modifications may be required according to individual safety or tolerability (refer to detailed product guideline).
Elderly: Initiate treatment at the lower end of the dosing range.

Intravenous
Ovarian adenocarcinoma
Adult: As melphalan hydrochloride: Monotherapy: 1 mg/kg (approx 40 mg/m2) given at intervals of 4 weeks. In combination with other cytotoxic drugs: 0.3-0.4 mg/kg (12-16 mg/m2) at intervals of 4-6 weeks.
Elderly: Initiate treatment at the lower end of the dosing range.

Intravenous
Advanced neuroblastoma
Child: As melphalan hydrochloride: High-dose regimen: 100-240 mg/m2 (may be divided equally over 3 consecutive days) followed by haematopoietic stem cell rescue if doses are >140 mg/m2.

Oral
Ovarian adenocarcinoma
Adult: 0.2 mg/kg daily for 5 days, repeated every 4-8 weeks, or as soon as the bone marrow has recovered.
Elderly: Initiate treatment at the lower end of the dosing range.

Oral
Breast cancer
Adult: 0.15 mg/kg or 6 mg/m2 daily for 5 days, repeated every 6 weeks. Dose reduction may be needed if bone marrow toxicity was observed.
Elderly: Initiate treatment at the lower end of the dosing range.

Oral
Polycythemia vera
Adult: Remission induction: 6-10 mg daily for 5-7 days, then 2-4 mg daily until satisfactory disease control is achieved. Maintenance: 2-6 mg once weekly, with careful haematological control and dosage adjustment based on blood counts.
Elderly: Initiate treatment at the lower end of the dosing range.

Oral
Multiple myeloma
Adult: Usual dosage regimens: Regimen 1: 0.15 mg/kg daily in divided doses for 4 days, repeated at 6-week intervals, usually in combination with a corticosteroid. Regimen 2: 6 mg once daily for 2-3 weeks, followed by up to 4 weeks rest with careful monitoring of blood counts. A maintenance dose of 2 mg daily may be given if WBC and platelet counts are rising. Several regimens have been used; refer to detailed product-specific guidelines. Delay or adjust dose if necessary. Dosage may need to be cautiously increased until myelosuppression is observed, to ensure that potentially therapeutic levels have been reached.
Elderly: Initiate treatment at the lower end of the dosing range.
Renal Impairment
Dose reduction may be required.
Administration
Should be taken on an empty stomach. Take 1 hr before or 2 hr after meals.
Reconstitution
Product preparations differ between formulations, refer to detailed product-specific guidelines.
Incompatibility
Infusion solutions containing dextrose.
Contraindications
Hypersensitivity. Pregnancy and lactation.
Special Precautions
Patients with compromised bone marrow reserve due to prior irradiation or chemotherapy, or whose marrow function is recovering from previous cytotoxic therapy. Renal impairment. Elderly.
Adverse Reactions
Significant: Bone marrow depression leading to leucopenia, thrombocytopenia and anaemia; secondary malignancies (e.g. myeloproliferative syndrome, acute myeloid leukaemia), gastrointestinal toxicity (including nausea, vomiting, diarrhoea, stomatitis), hepatitis, jaundice, hypersensitivity reactions (including anaphylaxis), interstitial pneumonitis, suppression of ovarian function (in premenopausal women), testicular suppression, extravasation causing local tissue damage.
General disorders and administration site conditions: Fatigue, pyrexia, transient warm and tingling sensation at inj site (IV).
Investigations: Abnormal LFTs, increased blood urea and blood creatine phosphokinase.
Metabolism and nutrition disorders: Hypokalaemia (IV).
Musculoskeletal and connective tissue disorders: Myalgia, muscle atrophy or fibrosis, compartment syndrome.
Skin and subcutaneous tissue disorders: Alopecia.
Potentially Fatal: Pulmonary fibrosis.
IV/Parenteral/PO: D
Monitoring Parameters
Monitor CBC with differential, platelet count, serum electrolytes, renal/liver function tests, serum uric acid; signs and symptoms of hypersensitivity reaction, pulmonary or gastrointestinal toxicity.
Overdosage
Symptoms: Bone marrow suppression, leading to leucopenia, thrombocytopenia and anaemia; nausea, vomiting, diarrhoea, stomatitis, colitis, gastrointestinal bleeding. Elevations in liver enzymes, veno-occlusive disease, hyponatraemia, nephrotoxicity and respiratory distress syndrome may also occur. Management: General supportive measures with appropriate blood transfusion and administration of antibiotics as necessary.
Drug Interactions
May enhance the adverse/toxic effect of live vaccines, cisplatin, and carmustine. May enhance the nephrotoxic effect of ciclosporin. May enhance the adverse/toxic effect (e.g. necrotic enterocolitis in paediatric patients) with nalidixic acid.
Food Interaction
Reduced exposure with high-fat meals.
Lab Interference
False-positive Coombs' test.
Action
Description: Melphalan is a bifunctional alkylating antineoplastic agent. It forms carbonium ions, enabling alkylation through covalent binding with the 7-nitrogen of guanine on DNA, cross-linking DNA strands, thereby preventing cell replication. It acts on both resting and rapidly dividing tumour cells.
Pharmacokinetics:
Absorption: Variable absorption from the gastrointestinal tract. Reduced exposure with high-fat meal. Absolute bioavailability: 56-93%. Time to peak plasma concentration: Approx 0.5-2 hours.
Distribution: Limited penetration into CSF. Enters breast milk. Volume of distribution: Approx 35.5-185.7 L/m2. Plasma protein binding: Approx 50-92% (40-60% to albumin; approx 20% to α1-acid glycoprotein).
Metabolism: Metabolised in the liver via hydrolysis to monohydroxymelphalan and dihydroxymelphalan.
Excretion: Oral: Via faeces (20-50%); urine (approx 10%, as unchanged drug). IV: Via urine: (6-21%). Terminal elimination half-life: 1.5 ± 0.83 hours (oral); approx 75 minutes (IV).
Chemical Structure

Chemical Structure Image
Melphalan

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 460612, Melphalan. https://pubchem.ncbi.nlm.nih.gov/compound/Melphalan. Accessed Nov. 24, 2021.

Storage
Tab: Store between 2-8°C. Melphalan hydrochloride inj: Store below 30°C. Melphalan flufenamide inj: Store between 2-8°C. Protect from light. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
MIMS Class
Cytotoxic Chemotherapy
ATC Classification
L01AA03 - melphalan ; Belongs to the class of alkylating agents, nitrogen mustard analogues. Used in the treatment of cancer.
References
Alkeran Tablet, Film Coated (ApoPharma USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 20/09/2021.

Alkeran Tablets (Aspen Medical Products Malaysia Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 20/09/2021.

Anon. Melphalan. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 20/09/2021.

Buckingham R (ed). Melphalan. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/09/2021.

Evomela Injection, Powder, Lyophilized, for Solution (Acrotech Biopharma LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 20/09/2021.

Joint Formulary Committee. Melphalan. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 20/09/2021.

Melphalan 2 mg Tablets (Aspen Pharma Trading Limited). MHRA. https://products.mhra.gov.uk. Accessed 20/09/2021.

Melphalan 50 mg Powder and Solvent for Solution for Injection/Infusion (Teva UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 20/09/2021.

Pepaxto Injection, Powder, Lyophilized, for Solution (Oncopeptides, AB). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 20/09/2021.

Pharmacy Retailing Pty Ltd. Alkeran Injection 50 mg data sheet 17 March 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 20/09/2021.

Pharmacy Retailing Pty Ltd. Alkeran Tablets 2 mg data sheet 18 March 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 20/09/2021.

Disclaimer: This information is independently developed by MIMS based on Melphalan from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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