Melphalan


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Multiple myeloma 150 mcg/kg/day in divided doses for 4-7 days, followed by rest period (for haematologic recovery) up to 6 wk, then repeat the course or start maintenance w/ 1-3 mg/day. Breast cancer 150 mcg/kg/day, repeat 6 wkly. Ovarian carcinoma 200 mcg/kg/day for 5 days 4-8 wkly. Polycythaemia vera 6-10 mg/day for 5-7 days; 2-4 mg/day for remission induction. Maintenance: 2-6 mg/wk. IV Ovarian adenocarcinoma 1 mg/kg as a single dose, repeat in 4 wk if platelet and neutrophil counts permit. Multiple myeloma 400 mcg/kg /m2 via infusion, 1st 4 doses may be given 2 wkly; further doses given 4 wkly depending on toxicity. Neuroblastoma 100-240 mg/m2 followed by autologous stem cell rescue if doses are >140 mg/m2. Intra-arterial Melanoma; Soft tissue sarcoma Upper extremity perfusions: 0.6-1 mg/kg. Lower extremity perfusions: 0.8-1.5 mg/kg (melanoma) or 1-1.4 mg/kg (sarcoma).
Dosage Details
Intra-arterial
Melanoma, Soft tissue sarcoma
Adult: 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).

Intravenous
Multiple myeloma
Adult: 400 mcg/kg or 16 mg/m2 infused over 15-20 min. First 4 doses may be given every 2 wk and further doses given every 4 wk depending on toxicity. High-dose regimen: 100-200 mg/m2 followed by autologous stem cell rescue which is essential if doses exceed 140 mg/m2, to be given through a central venous catheter.

Intravenous
Ovarian adenocarcinoma
Adult: 1 mg/kg as a single dose repeated in 4 wk if platelet and neutrophil counts permit. May be infused in sodium chloride 0.9% or inj into the tubing of a fast-running drip.

Intravenous
Neuroblastoma
Adult: High-dose regimen: 100-240 mg/m2 followed by autologous stem cell rescue which is essential if doses are >140 mg/m2. Give through a central venous catheter.

Oral
Ovarian carcinoma
Adult: 200 mcg/kg daily for 5 days every 4-8 wk.

Oral
Breast cancer
Adult: 150 mcg/kg daily or 6 mg/m2 daily for 5 days, repeated every 6 wk.

Oral
Polycythemia vera
Adult: 6-10 mg daily for 5-7 days; 2-4 mg daily for remission induction. Maintenance dose: 2-6 mg wkly.

Oral
Multiple myeloma
Adult: 150 mcg/kg daily in divided doses for 4-7 days or 250 mcg/kg daily for 4 days or 6 mg daily for 2-3 wk. Usually combined with corticosteroids. Follow treatment course by a rest period of up to 6 wk to allow haematologic recovery. Then repeat the course or start maintenance treatment with 1-3 mg or up to 50 mcg/kg daily. For optimal effect, adjust therapy to produce moderate leucopenia (WBC counts of 3,000-3,500 cells/mm3).
Renal Impairment
Intra-arterial:
Reduce dose by 50%.
Intravenous:
Multiple myeloma: Conventional dose: Reduce dose by 50%. High-dose regimen: Not recommended in moderate to severe impairment.
Ovarian adenocarcinoma: Reduce dose by 50%.
Neuroblastoma: High-dose regimen: Not recommended in moderate to severe impairment.
Oral:
Dose reduction may be required.
Administration
Should be taken on an empty stomach. Take 1 hr before or 2 hr after meals.
Reconstitution
Intravenous:
Inj must be prepared fresh. Keep to a minimum (<60 min) the time between reconstitution/dilution and admin. Dissolve powder initially with diluent 10 ml to a concentration of 5 mg/ml. Shake vigorously to dissolve. Immediately dilute in 250-500 ml normal saline to a concentration of 0.1-0.45 mg/ml.
Incompatibility
Intravenous:
Dextrose 5% in water, Lactated Ringer's; variable stability in normal saline.
Contraindications
Hypersensitivity. Severe bone marrow suppression. Pregnancy.
Special Precautions
Renal impairment. Lactation. Prior bone marrow suppression, prior chemotherapy or irradiation. May mask signs of infection e.g. fever and increased WBC. Elderly.
Adverse Reactions
Diarrhoea, stomatitis, vomiting; haemolytic anaemia, vasculitis, pulmonary fibrosis, hepatic disorders, suppression of ovarian function in premenopausal women, temporary or permanent sterility in male patients. Allergic reactions.
Potentially Fatal: Bone marrow suppression. Secondary malignancy, cardiac arrest. Anaphylaxis.
IV/Parenteral/PO: D
Overdosage
Symptoms: Hypocalcaemia, hyponatraemia, pulmonary fibrosis, severe nausea and vomiting, diarrhoea, GI haemorrhage, mucositis, stomatitis, bone marrow suppression. Deaths have been reported (IV). Management: Symptomatic and supportive. Closely monitor haematologic function for 3-6 wk. Growth factor support, transfusions and antibiotics may be considered. Not removed by haemodialysis.
Drug Interactions
Potentially Fatal: Fatal haemorrhagic enterocolitis with concurrent nalidixic acid in children. Potentiates risk of renal damage with ciclosporin.
Food Interaction
Food significantly reduces oral absorption. Avoid excessive alcohol intake.
Lab Interference
False-positive Coombs' test.
Action
Description: Melphalan, a mechlorethamine derivative, is an alkylating antineoplastic agent. It forms carbonium ions, resulting in DNA and RNA synthesis inhibition. It cross-links DNA strands and acts on both resting and rapidly dividing tumour cells.
Pharmacokinetics:
Absorption: Variable absorption from the GI tract; absorption reduced by food (oral).
Distribution: Rapid throughout body water. Protein-binding: 50-60%, mainly to albumin.
Metabolism: Inactivated by hydrolysis.
Excretion: Via urine (10%, as unchanged drug); 30-150 min (terminal half-life).
Storage
Intravenous:
Store at room temperature (15-30°C). Protect from light.
Oral:
Store in a refrigerator at 2-8°C (36-46°F). Protect from light.
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 © 2020 MIMS. All rights reserved. Powered by MIMS.com
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