Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2014 Publisher: Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland
Melphalan should not be given to patients who have suffered a previous hypersensitivity reaction to melphalan.
Melphalan is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.
Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.
See 6.6 Instructions for use/handling
Since Melphalan is a potent myelosuppresive agent, it is essential that careful attention should be paid to the monitoring of blood counts to avoid the possibility of excessive myelosuppression and the risk of irreversible bone marrow aplasia. 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. Melphalan should be used with caution in patients who have undergone recent radiotherapy or chemotherapy in view of increased bone marrow toxicity.
Patients with renal impairment should be closely observed as they may have uraemic marrow suppression. (See undesirable effects for elevation of blood urea Section 4.8)
Melphalan is mutagenic in animals and chromosome aberrations have been observed in patients being treated with the drug.
The evidence is growing that melphalan in common with other alkylating agents has been reported to be leukaemogenic. There have been reports of acute leukaemia occurring after melphalan treatment for diseases such as amyloid, malignant melanoma, macroglobulinaemia, cold agglutinin syndrome and ovarian cancer.
A comparison of patients with ovarian cancer who received alkylating agents with those who did not, showed that the use of alkylating agents, including melphalan, significantly increased the incidence of acute leukaemia. The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of melphalan.
Melphalan causes suppression of ovarian function in premenopausal women resulting in amenorrhoea in a significant number of patients.
Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Warnings and Precautions).
Nalidixic acid together with high-dose intravenous melphalan has caused deaths in children due to haemorrhagic enterocolitis.
Impaired renal function has been described in bone marrow transplant patients who were pre-conditioned with high dose intravenous melphalan and who subsequently received ciclosporin to prevent graft-versus-host disease.
As with all cytotoxic chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving Melphalan.
The teratogenic potential of Melphalan has not been studied. In view of its mutagenic properties and structural similarity to known teratogenic compounds, it is possible that melphalan could cause congenital defects in the offspring of patients treated with the drug.
The use of melphalan should be avoided whenever possible during pregnancy, particularly during the first trimester. In any individual case the potential hazard to the foetus must be balanced against the expected benefit to the mother.
Mother receiving Melphalan should not breast-feed.
Not known.
For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the indication and dose received and also when given in combination with other therapeutic agents.
The following convention has been utilised for the classification of frequency:- Very common ≥1/10, common ≥1/100, <1/10, uncommon ≥1/1000 and <1/100, rare ≥1/10,000 and <1/1000, very rare <1/10,000.
Very common: bone marrow depression leading to leucopenia, thrombocytopenia and anaemia
Rare: haemolytic anaemia
Rare: allergic reactions (see Skin and Subcutaneous Tissue Disorders)
Allergic reactions to melphalan such as urticaria, oedema, skin rashes and anaphylactic shock have been reported uncommonly following initial or subsequent dosing, particularly after intravenous administration. Cardiac arrest has also been reported rarely in association with such events.
Rare: interstitial pneumonitis and pulmonary fibrosis (including fatal reports)
Very common: nausea, vomiting and diarrhoea; stomatitis at high dose
Rare: stomatitis at conventional dose
Gastrointestinal effects such as nausea and vomiting have been reported in up to 30% of patients receiving conventional oral doses of melphalan.
Rare: hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice
Very common: alopecia at high dose
Common: alopecia at conventional dose
Rare: maculopapular rashes and pruritus (see Immune System Disorders)
Common: temporary significant elevation of the blood urea has been seen in the early stages of melphalan therapy in myeloma patients with renal damage
None known.
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