Alkeran Special Precautions

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: Bone marrow depression, with leucopenia and thrombocytopenia, is the main side effect. The time of maximum depression is variable, and 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.
Venous thromboembolic events: Patients treated with ALKERAN in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone, have an increased risk of deep vein thrombosis and pulmonary embolism (see Adverse Reactions). The risk appears to be greatest during the first 5 months of therapy, especially in patients with additional thrombotic risk factors (e.g. smoking, hypertension, hyperlipidaemia and history of thrombosis). These patients should be closely monitored and actions to minimize all modifiable risk factors should be undertaken. Thromboprophylaxis and dosing/anticoagulation therapy recommendations are provided in Dosage & Administration.
Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, arm or leg swelling. If a patient experiences any thromboembolic events, discontinue the treatment immediately and initiate the standard anticoagulation therapy. Once the patient has been stabilised on the anticoagulation treatment and any complications of the thromboembolic event have been managed, ALKERAN in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone may be restarted at the original dose dependent upon a benefit-risk assessment. The patient should continue anticoagulation therapy throughout the course of treatment.
Neutropenia and thrombocytopenia: Increased rate of haematological toxicities, particularly, neutropenia and thrombocytopenia, was observed in newly diagnosed elderly multiple myeloma in patients treated with ALKERAN in combination with lenalidomide and prednisone or thalidomide and prednisone or dexamethasone. Patients and physicians are advised to be observant for signs and symptoms of bleeding, including petechiae and epistaxes, especially in patients receiving combination drug regimens described (Adverse Reactions).
Mutagenicity: ALKERAN has been shown to be mutagenic and carcinogenic in animals and chromosome aberrations have been observed in patients being treated with the drug. ALKERAN has also been shown to be carcinogenic in animals (Pharmacology: Toxicology: Preclinical safety data under Actions), and the possibility of a similar effect should be borne in mind when designing the long-term management of the patient.
Carcinogenicity (Second primary malignancy): Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS): ALKERAN, in common with other alkylating agents has been reported to be leukaemogenic, especially in older patients after long combination therapy and radiotherapy.
There have been reports of acute leukaemia occurring after ALKERAN treatment for diseases such as amyloidosis, malignant melanoma, multiple myeloma, macroglobulinaemia, cold agglutinin syndrome and there has been a significant increase in patients with 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 ALKERAN, significantly increased the incidence of acute leukaemia.
Before the start of the treatment, the leukaemogenic risk (AML and MDS) must be balanced against the potential therapeutic benefit, especially if the use of ALKERAN in combination with thalidomide or lenalidomide and prednisone is considered, as it has been shown that these combinations may increase the leukaemogenic risk. Before, during and after treatment doctors must therefore examine the patient at all times by usual measurements to ensure the early detection of cancer and initiate treatment if necessary.
Solid tumours: Use of alkylating agents has been linked with the development of second primary malignancy (SPM). In particular, ALKERAN 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 (e.g. 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 ALKERAN administration.
Contraception: Due to an increased risk of venous thromboembolism in patients undergoing treatment with ALKERAN 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. ovulation inhibitory progesterone-only pills such as desogestrel, barriermethod, etc). The risk of venous thromboembolism continues for 4–6 weeks afterdiscontinuing combined oral contraception.
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 Dosage & Administration), and these patients should be closely observed.
Effects on ability to drive and use machines: Effects on the ability to drive and operate machinery in patients taking this medicine have not been studied.