ed 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.
4.6 Pregnancy and lactation
Teratogenicity:-
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.
Effects on fertility:
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.
Pregnancy:-
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 be not used during pregnancy unless absolutely considered absolutely essential by the physician.
Lactation:-
Mothers receiving Alkeran should not breastfeed.
4.7 Effects on ability to drive and use machines
No data.
4.8 Undesirable effects
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.
Blood and Lymphatic System Disorders
Very common: bone marrow depression leading to leucopenia, thrombocytopenia and anaemia
Rare: haemolytic anaemia
Immune System Disorders
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.
Respiratory, Thoracic and Mediastinal Disorders
Rare: interstitial pneumonitis and pulmonary fibrosis (including fatal reports)
Gastrointestinal Disorders
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 m |
