Melphalan


Full Prescribing Info
Dosage/Direction for Use

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: Dose reduction may be required.

Oral

Breast cancer
Adult: 150 mcg/kg daily or 6 mg/m2 daily for 5 days, repeated every 6 wk.
Renal impairment: Dose reduction may be required.

Oral

Ovarian carcinoma
Adult: 200 mcg/kg daily for 5 days every 4-8 wk.
Renal impairment: Dose reduction may be required.

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.
Renal impairment: Dose reduction may be required.

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.
Renal impairment: Reduce dose by 50%.
Reconstitution:
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: Dextrose 5% in water, Lactated Ringer's; variable stability in normal saline.

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.
Renal impairment: Conventional dose: Reduce dose by 50%. High-dose regimen: Not recommended in moderate to severe impairment.
Reconstitution:
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: Dextrose 5% in water, Lactated Ringer's; variable stability in normal saline.

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.
Renal impairment: High-dose regimen: Not recommended in moderate to severe impairment.
Reconstitution:
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: Dextrose 5% in water, Lactated Ringer's; variable stability in normal saline.

Intra-arterial
Melanoma
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).
Renal impairment: Reduce dose by 50%.

Intra-arterial

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).
Renal impairment: Reduce dose by 50%.
Administration
Should be taken on an empty stomach. Take on an empty stomach 1 hr before or 2 hr after meals.
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.
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.
Food Interaction
Food significantly reduces oral absorption. Avoid excessive alcohol intake.
Lab Interference
False-positive Coombs' test.
Action
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.
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.
ATC Classification
L01AA03 - melphalan ; Belongs to the class of alkylating agents, nitrogen mustard analogues. Used in the treatment of cancer.
Disclaimer: This information is independently developed by CIMS 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 CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS 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 CIMS. All rights reserved. Powered by CIMSAsia.com
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