counts are taken throughout therapy, with dosage adjustment or breaks in treatment, as appropriate, to maintain careful haematological control.
Use in children: Alkeran is only rarely indicated in children and absolute dosage guidelines cannot be provided.
Use in the elderly: Although Alkeran is frequently used at conventional dosage in the elderly, there is no specific information available relating to its administration to this patient sub-group. However, caution should be taken where there is renal impairment.
Dosage in renal impairment: (see also Special Warnings and Special Precautions for Use). Alkeran clearance, though variable, is decreased in renal impairment.
Currently available pharmacokinetic data do not justify an absolute recommendation on dosage reduction when administering Alkeran Tablets to patients with renal impairment, but it may be prudent to use a reduced dosage initially until tolerance is established.
4.3 Contraindications
Alkeran should not be given to patients who have suffered a previous hypersensitivity reaction to melphalan.
4.4 Special warnings and precautions for use
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.
4.5 Interaction with other medicinal products and other forms of interaction
Vaccinations with live organism vaccines are not recommended in immunocompromis |
