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MYLERAN is a brand name for Busulfan, supplied as a tablet. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: MYLERAN® (busulfan) is indicated for: Chronic granulocytic (myelocytic, myeloid) leukemia for the production of remissions. May be used with extreme caution in patients with prior radiation or P32 therapy and in those untreated by any other means. 1.1 Pediatrics Pediatrics (0-18 years): No data are available to Health…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Health Canada has not authorized an indication for pediatric use. 2 Recommended Dose and Dosage Adjustment Induction in adults:. 8 mg/m2 body surface area) to a total maximum dose of 4 mg daily, until maximum hematological and clinical improvement is obtained or symptoms of toxicity supervene.
During remission, the patient is examined at monthly intervals and the treatment is resumed when the white cell count reaches 50,000/mm3. When remission is shorter than 3 months, maintenance therapy of 1 to 3 mg daily may be advisable in order to keep the hematological status under control and prevent rapid relapse.
Discontinue drug or reduce dosage at the first sign of abnormal depression of platelets, hemoglobin, or low white blood cell count.
1 Adverse Reaction Overview The following table of adverse reactions originated from the use of MYLERAN® or busulfan in combination with other therapeutic agents. Table 2. System Organ Class Frequency Side Effects Neoplasms benign, malignant and unspecified (including cysts and polyps) Common Leukaemia secondary to oncology chemotherapy (see Warnings and Precautions; Carcinogenicity) Blood and lymphatic system disorders * Very common Dose-related bone marrow failure, manifesting as leukopenia and particularly thrombocytopenia Rare Aplastic anaemia Unknown Pancytopenia Immune System Disorders Rare Sjögren’s syndrome Nervous system disorders * Rare At high-dose: seizure (see Interactions and Warnings and Precautions) Very rare Myasthenia gravis Eye disorders * Rare Lens disorder and cataract (which may be bilateral) corneal thinning (reported after bone marrow transplantation preceded by high-dose MYLERAN® treatment) Cardiac disorders * Common At high-dose: cardiac tamponade in patients with thalassaemia Unknown Endocardial fibrosis Respiratory, thoracic and mediastinal disorders * Very common At high-dose: idiopathic pneumonia syndrome Common Interstitial lung disease following long term conventional dose use Rare Interstitial pulmonary fibrosis Myleran® Product Monograph Page 13 of 33 System Organ Class Frequency Side Effects Metabolism and nutritional disorders * Common Hyperuricemia and/or hyperuricosuria, uric acid nephropathy Gastrointestinal disorders * Very common At high-dose: nausea, vomiting, diarrhoea, mouth ulceration Rare At conventional dose: nausea, vomiting, diarrhoea, mouth ulceration, which may possibly be ameliorated by using divided doses.
Dry mouth Unknown Glossitis Not known Tooth hypoplasia (paediatric)* (see Gastrointestinal disorders Dental anomalies (paediatric) Hepatobiliary disorders * Very common At high-dose: hyperbilirubinaemia, jaundice, veno occlusive liver disease (see Warnings and Precautions and Interactions) and biliary fibrosis with hepatic atrophy and hepatic necrosis Rare Cholestatic jaundice and hepatic function abnormal, at conventional dose.
Please see the Serious Warnings and Precautions Box at the beginning of Part I:
Health Professional Information. Carcinogenesis and Mutagenesis MYLERAN® may cause cellular dysplasia in many organs in addition to the lung. Cytologic abnormalities characterized by giant, hyperchromatic nuclei have been reported in lymph nodes, pancreas, thyroid, adrenal glands, liver, and bone marrow.
This cytologic dysplasia may be Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Tablets 2 mg Tablet core: anhydrous lactose, magnesium stearate, and pregelatinized starch.
Tablet coating:
The film coat contains hypromellose (hydroxypropyl methylcellulose), titanium dioxide and triacetin. Myleran® Product Monograph Page 6 of 33 severe enough to cause difficulty in interpretation of exfoliative cytologic examinations from the lung, bladder, breast and the uterine cervix.
In addition to the widespread epithelial dysplasia that has been observed during MYLERAN® therapy, chromosome aberrations have been reported in cells from patients receiving MYLERAN®. MYLERAN® is mutagenic in mice and, possibly in man.
A number of malignant tumours have been reported in patients on MYLERAN® therapy and this drug may be a human carcinogen. Four cases of acute leukemia occurred among 243 patients treated with MYLERAN® as adjuvant chemotherapy following surgical resection of bronchogenic carcinoma.
All four cases were from a subgroup of 19 of these 243 patients who developed pancytopenia while taking MYLERAN® five to eight years before leukemia became clinically apparent. These findings suggest that MYLERAN® is leukemogenic, although its mode of action is uncertain.
Cardiovascular Cardiac tamponade has been reported in a small number of patients with thalassemia (2% in one series) who received high doses of MYLERAN® and cyclophosphamide as the preparatory regimen for bone marrow transplantation.
MYLERAN® is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Dosage Forms, Strengths, Composition and Packaging.
MYLERAN® should not be given if neutrophil or platelet counts are depressed. MYLERAN® should not be used in patients whose disease has demonstrated resistance to busulfan.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Biliary fibrosis Unknown Centrilobular sinusoidal fibrosis Skin and subcutaneous tissue disorders * Common Alopecia at high-dose. Skin hyperpigmentation (see also General disorders and administration site conditions) Rare Alopecia at conventional dose, skin reactions including urticaria, erythema multiforme, erythema nodosum, porphyria non-acute, rash, dry skin and skin fragility with complete anhydrosis cheilosis Unknown Esophageal varices Injury, poisoning and procedural complications Rare Radiation skin injury is increased in patients receiving radiotherapy soon after high- dose MYLERAN® Renal and urinary disorders * Common At high-dose1)2): cystitis haemorrhagic in combination with cyclophosphamide Reproductive system and breast disorders * Very common Ovarian disorder and amenorrhoea with menopausal symptoms in pre-menopausal patients at high-dose; severe and persistent ovarian failure, including pubertal failure after administration to young girls and pre-adolescents at high-dose.
Myleran® Product Monograph Page 14 of 33 System Organ Class Frequency Side Effects Male sterility, azoospermia and testicular atrophy in male patients receiving MYLERAN® Uncommon Ovarian disorder and amenorrhoea with menopausal symptoms in pre-menopausal patients at conventional dose.
06 mg/kg/day w ith an initial daily maximum of 4 mg. 5 to 2 mg daily. *Description of selected adverse events Blood and lymphatic system disorders The chief toxic effect is a dosage-related myelosuppression which may cause leucopenia and thrombocytopenia (hemorrhage) and eventually lead to pancytopenia.
Aplastic anemia (sometimes irreversible) has been reported rarely, often following long-term conventional doses and also high doses of MYLERAN®. Events of irreversible bone marrow aplasia have been reported. Nervous system disorders Seizures have been observed in patients receiving higher than recommended doses of MYLERAN®.
Other complications of therapy include myasthenia gravis Respiratory, thoracic and mediastinal disorders Pulmonary toxicity after either high or conventional dose treatment typically presents with non-specific non-productive cough, dyspnoea and hypoxia with evidence of abnormal pulmonary physiology.
Other cytotoxic agents and radiotherapy may cause additive lung toxicity (see Interactions). It is possible that subsequent radiotherapy can augment subclinical lung injury caused by busulphan. Once pulmonary toxicity is established the prognosis is poor despite busulphan withdrawal and there is little evidence that corticosteroids are helpful.
Idiopathic pneumonia syndrome is a non-infectious diffuse pneumonia which usually occurs within three months of high dose busulphan conditioning prior to allogeneic or autologous Myleran® Product Monograph Page 15 of 33 haemopoietic transplant.
Diffuse alveolar haemorrhage may also be detected in some cases after broncholavage. Chest X-rays or CT scans show diffuse or non- specific focal infiltrates and biopsy shows interstitial pneumonitis and diffase alveolar damage and sometimes fibrosis.
Interstitial pneumonitis may occur following conventional dose use and lead to pulmonary fibrosis. This usually occurs after prolonged treatment over a number of years. The onset is usually insidious but may also be acute. Histological features include atypical changes of the alveolar and bronchiolar epithelium and the presence of giant cells with large hyperchromatic nuclei.
The lung pathology may be complicated by superimposed infections. Pulmonary ossification and dystrophic calcification have also been reported. Metabolism and nutrition disorders Hyperuricemia and/or hyperuricosuria are not uncommon in patients with chronic myelogenous […]
In this series, the cardiac tamponade was often fatal. Abdominal pain and vomiting preceded the tamponade in most patients. If high-dose MYLERAN® is prescribed, patients should be given prophylactic anticonvulsant therapy preferably with a benzodiazepine rather than enzyme inducing anticonvulsants (eg.
phenytoin) (see Drug Interactions). Patients co-prescribed systemic itraconazole with MYLERAN® should be monitored for signs of busulfan toxicity (see Drug Interactions).
Gastrointestinal Dental anomalies (paediatric):
In paediatric transplant recipients, dental development anomalies (such as tooth hypoplasia, microdontia, and absence of permanent teeth) have been observed with busulfan-based conditioning regimens. (see ADVERSE REACTIONS and NON-CLINICAL TOXICOLOGY sections).
Myleran® Product Monograph Page 7 of 33 Hematologic Use of MYLERAN® should be restricted to patients for whom complete blood counts are available at intervals of at least 1 week. The most careful hematological control is essential since large doses may produce irreversible depression of the bone marrow which may not be obvious for 4 to 6 months.
Events of irreversible bone marrow aplasia have been reported. The most consistent, dose-related toxicity is bone marrow suppression. This may be manifested by anemia, leukopenia, thrombocytopenia or any combination of these. It is imperative that patients be instructed to report promptly the development of fever, s ore throat, signs of local infection, bleeding from any site or symptoms suggestive of anemia.
Any one of these findings may indicate busulfan toxicity; however, they may also indicate transformation of the disease to an acute “blastic” form. Since MYLERAN® may have a delayed effect on the bone marrow, it is important to withdraw the medication temporarily at the first sign of an abnormally large or exceptionally rapid fall in any of the formed elements of the blood.
The most frequent, serious side effect of treatment with MYLERAN® is the induction of bone marrow failure (which may or may not be anatomically hypoplastic) resulting in severe pancytopenia. The pancytopenia caused by MYLERAN® may be more prolonged than that induced with other alkylating agents.
It is generally felt that the usual cause of busulfan-induced pancytopenia is the failure to stop administration of the drug soon enough; individual idiosyncrasy to the drug does not seem to be an important factor. MYLERAN® should be used with extreme caution and exceptional vigilance in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy, or whose marrow function is recovering from previous cytotoxic therapy.
Although recovery from busulfan- induced pancytopenia may take from 1 month to 2 years, this complication is potentially reversible and the patient should be vigorously supported through any period of severe pancytopenia. Hepatic/Biliary/Pancreatic MYLERAN® has not been studied in patients with hepatic impairment.
Since busulfan is mainly metabolized through the liver, caution should be observed when MYLERAN® is used in patients with pre-existing impairment of liver function, especially in those with severe h epatic impairment. Hepatic veno-occlusive disease, which may be life-threatening, has been reported following the investigational use of very high doses of MYLERAN® in combination with cyclophosphamide or other chemotherapeutic agents prior to bone marrow transplantation.
Possible risk factors for Myleran® Product Monograph Page 8 of 33 the development of hepatic veno-occlusive disease include: total MYLERAN® dose exceeding 16 mg/kg based on the ideal body weight, and concurrent use of multiple alkylating agents.
Hepatic veno-occlusive disease is a major complication that can occur during treatment with MYLERAN® Patients who have received prior radiation therapy, greater than or equal to three cycles of chemotherapy, or prior progenitor cell transplant may be at an increased ri sk (see Adverse Reactions section).
A clear cause and effect relationship with MYLERAN® […]