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 hosts. Therefore, immunisations with live organism vaccines are not recommended.
Inj: ALKERAN Injection solution may cause local tissue damage should extravasation occur and consequently, it should not be administered by direct injection into a peripheral vein. It is recommended that ALKERAN Injection solution is administered by injecting slowly into a fast-running intravenous infusion via a swabbed injection port or via a central venous line.
In view of the hazards involved and the level of supportive care required, the administration of high-dose ALKERAN Injection should be confined to specialist centres, with the appropriate facilities and only be conducted by experienced clinicians.
In patients receiving high-dose ALKERAN Injection, consideration should be given to the prophylactic administration of anti-infective agents and the administration of blood products as required.
Consideration should be given to ensure adequate performance status and organ function before using high-dose ALKERAN Injection.
Safe Handling of ALKERAN: Safe handling of ALKERAN (see Instructions for Use/Handling under Cautions for Usage).
The handling of ALKERAN formulations should follow guidelines for the handling of cytotoxic drugs according to prevailing local recommendations and/or regulations (for example, Royal Pharmaceutical Society of Great Britain Working Party on the Handling of Cytotoxic Drugs).
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 leucocyte 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.
Tab: Contraception: Due to an increased risk of venous thromboembolism in patients undergoing treatment with melphalan in combination with lenalidomide and prednisone or in combination with thalidomide and prednisone or dexamethasone, combined oral contraceptive pills are not recommended. If a patient is currently using combined oral contraception, she should switch to another reliable contraceptive method (i.e. barrier method etc). The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception.
It is recommended that men who are receiving treatment with melphalan not father a child during treatment and up to 6 months afterwards and that they have a consultation on sperm preservation before treatment due to the possibility of irreversible infertility as a result of melphalan treatment.
Effects on Ability to Drive and Use Machines: No data.
Renal Impairment: ALKERAN clearance may be reduced in patients with renal impairment, who may also have uraemic bone marrow suppression. Dosage reduction may therefore be necessary (see Dosage & Administration), and these patients should be closely observed.
Carcinogenicity: ALKERAN, in common with other alkylating agents, has been reported to be leukaemogenic. There have been reports of acute leukaemia occurring after ALKERAN 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 show that the use of alkylating agents, including ALKERAN, significantly increased the incidence of acute leukaemia.
The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of ALKERAN.
Tab: Solid tumours: Use of alkylating agents has been linked with the development of second primary malignancy (SPM). In particular, melphalan in combination with lenalidomide and prednisone and, to a lesser extent, thalidomide and prednisone has been associated with the increased risk of solid SPM in elderly newly diagnosed multiple myeloma patients.
Patient characteristics (eg. age, ethnicity), primary indication and treatment modalities (e.g. radiation therapy, transplantation), as well as environmental risk factors (e.g. tobacco use) should be evaluated prior to melphalan administration.
Mutagenicity: Chromosome aberrations have been observed in patients being treated with the drug.