Source: Health Products Regulatory Authority (IE) Revision Year: 2014 Publisher: Aspen Pharma Trading Limited 3016 Lake Drive Citywest Business Campus Dublin 24 Ireland
Alkeran should not be given to patients who have suffered a previous hypersensitivity reaction to melphalan.
ALKERAN IS AN ACTIVE CYTOTOXIC AGENT FOR USE 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 individuals. Therefore, immunisations with live organism vaccines are not recommended.
Monitoring: Since Alkeran is a potent myelosuppressive 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 leukocyte or platelet counts treatment should be temporarily interrupted.
Alkeran should be used with caution in patients who have undergone recent radiotherapy or chemotherapy in view of increased bone marrow toxicity.
Renal impairment: Alkeran clearance may be reduced in patients with renal impairment, who may also have uraemic bone marrow suppression. Dose reduction may therefore be necessary (see Posology and Method of Administration), and these patients should be closely observed.
Temporary significant elevation of the blood urea has been seen in the early stages of melphalan therapy in myeloma patients with renal damage.
Mutagenicity: Chromosome aberrations have been observed in patients being treated with the drug.
Carcinogenicity: The evidence is growing that melphalan in common with other alkylating agents may be leukaemogenic in man.
Alkeran, 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, multiple myeloma, 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.
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 cyclosporin to prevent graft-versus-host disease.
The teratogenic potential of Alkeran 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.
Alkeran causes suppression of ovarian function in premenopausal women resulting in amenorrhoea in a significant number of patients.
There is evidence from some animal studies that Alkeran can have an adverse effect on spermatogenesis. Therefore, it is possible that Alkeran may cause temporary or permanent sterility in male patients.
As with all cytotoxic chemotherapy, adequate contraceptive precautions should be practised when either partner is receiving Alkeran.
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.
This product should not be used during pregnancy unless considered absolutely essential by the physician.
Mothers receiving Alkeran should not breastfeed.
No data.
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.
Not applicable.
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