Melphalan (Specialist drug)

IMPORTANT SCOPE NOTE: the eMC source fetched is the ORAL product (Melphalan 2 mg Tablets) — this draft covers oral melphalan only. Intravenous melphalan (including high-dose melphalan conditioning before autologous stem-cell transplantation and melphalan flufenamide/regional perfusion products) has entirely separate labelling and a different dose basis; the US label in the bundle is for Melphalan Hydrochloride for Injection (usual IV dose 16 mg/m2 by single infusion over 15-20 minutes, at 2-week intervals for 4 doses then, after adequate recovery from toxicity, at 4-week intervals; dosage reduction of up to 50% considered if BUN >=30 mg/dL). Do NOT apply the oral schedule to an intravenous order — clinician to source the IV SPC separately. eMC §4.2: 'Numerous regimes have been used and the scientific literature should be consulted for details.' The administration of melphalan and prednisone may be more effective than melphalan alone, usually given on an intermittent basis. Prolonging treatment beyond one year in responders does not appear to improve results. OTHER ORAL INDICATIONS: ovarian adenocarcinoma — a typical regimen is 0.2 mg/kg bodyweight/day orally for 5 days, repeated every 4-8 weeks or as soon as the bone marrow has recovered; advanced carcinoma of the breast — 0.15 mg/kg bodyweight or 6 mg/m2 body surface area/day for 5 days, repeated every 6 weeks, with the dose decreased if bone marrow toxicity is observed; polycythaemia vera — for remission induction the usual dose is 6-10 mg daily for 5-7 days, then 2-4 mg daily until satisfactory disease control, maintained with 2-6 mg per week under careful haematological control. MONITORING: melphalan is myelosuppressive, so frequent blood counts are essential and the dose should be delayed or adjusted if necessary; blood counts may continue to fall after treatment is stopped, so at the first sign of an abnormally large fall in leucocyte or platelet counts treatment should be temporarily interrupted. Use with caution after recent radiotherapy or chemotherapy because of increased bone marrow toxicity. THROMBOPROPHYLAXIS: thromboprophylaxis should be given for at least the first 5 months of treatment, especially in patients with additional thrombotic risk factors; if a thromboembolic event occurs, discontinue treatment and start standard anticoagulation — melphalan in combination with lenalidomide and prednisone, or thalidomide and prednisone or dexamethasone, may be restarted at the original dose once the patient is stabilised, on a benefit-risk assessment, continuing anticoagulation throughout. ABSORPTION: absorption of oral melphalan is variable — the dose may need to be cautiously increased until myelosuppression is seen, to ensure potentially therapeutic levels have been reached. LEUKAEMOGENIC RISK: balance the risk of secondary AML and MDS against therapeutic benefit before starting, particularly with thalidomide- or lenalidomide-containing combinations. Live-organism vaccines are not recommended. PAEDIATRIC (no numeric guideline stated, hence paedDose is null): 'Melphalan is very rarely indicated in paediatrics and dosage guidelines cannot be stated.' Verify any paediatric use against a children's formulary and the local protocol. ELDERLY: 'There is no specific information available on the use of Melphalan in older patients.' NOTE: eMC §4.4 was truncated at the source-fetch limit in the fetched bundle — clinician to verify against the full current SPC.