Bufacord

Followed by cyclophosphamide as conditioning treatment prior to conventional haematopoietic progenitor cell transplantation (HPCT) in adult patients when combination is considered the best available option. Following fludarabine as conditioning treatment prior to HPCT in adult patients who are candidates for reduced-intensity conditioning regimen. Followed by cyclophosphamide or melphalan as conditioning treatment prior to conventional HCPT in paed patients.

Administered prior to HPCT. Premedicate w/ anticonvulsants (eg, phenytoin or benzodiazepines) 12 hr prior to 24 hr after last high dose of busulfan. Administer antiemetics prior to 1st dose & continue on fixed schedule. In combination w/ cyclophosphamide or melphalan Adult 0.8 mg/kg as 2-hr infusion every 6 hr over 4 consecutive days for total of 16 doses, followed by cyclophosphamide at 60 mg/kg/day over 2 days initiated for at least 24 hr following the 16th dose of busulfan. Childn 0-7 yr, >34 kg 0.8 mg/kg, >23-34 kg 0.95 mg/kg, 16-23 kg 1.1 mg/kg, 9-<16 kg 1.2 mg/kg, <9 kg 1 mg/kg, followed by 4 cycles of cyclophosphamide 50 mg/kg or 1 administration of melphalan 140 mg/m² initiated for at least 24 hr following the 16th dose of busulfan. Administer as 2-hr infusion every 6 hr over 4 consecutive days for total of 16 doses prior to cyclophosphamide or melphalan & HPCT. In combination w/ fludarabine Adult Administer fludarabine 30 mg/m² as single daily 1-hr infusion for 5 consecutive days or 40 mg/m² for 4 consecutive days. Then, administer busulfan 3.2 mg/kg as single daily 3-hr infusion immediately after fludarabine for 2-3 consecutive days. Obese adult patient Consider dosing based on adjusted ideal body wt.

Hypersensitivity. Pregnancy.

Not to be given by rapid IV, bolus or peripheral inj. Profound myelosuppression. Monitor CBC, including differential WBC & platelet counts during treatment & until recovery is achieved. Consider prophylactic or empiric use of anti-infectives (bacterial, fungal, viral) for prevention & management of infections during neutropenic period. Employ platelet & RBC support, as well as use of growth factors eg, granulocyte colony stimulating agent, as medically indicated. Therapeutic drug monitoring may be justified on case by case basis in childn <9 kg, in particular in extremely young childn & neonates. Limited clinical experience of use as component of conditioning regimen prior to HSCT in childn w/ Fanconi's anaemia. Caution in patients w/ pre-existing impairment of liver function, especially in those w/ severe hepatic impairment. Regularly monitor serum transaminase, alkaline phosphatase, & bilirubin 28 days following transplant for early detection of hepatotoxicity. Increased risk of hepatic veno-occlusive disease in patients who have received prior RT, ≥3 cycles of chemotherapy, or prior progenitor cell transplant. Caution when using paracetamol prior to (<72 hr) or concurrently w/ busulfan due to possible decrease in metabolism of busulfan. Regularly monitor cardiac function. May induce pulmonary toxicity that may be additive to effects produced by other cytotoxic agents. Acute resp distress syndrome w/ subsequent resp failure associated w/ interstitial pulmonary fibrosis in patients w/ prior history of mediastinal or pulmonary radiation. Periodic monitoring of renal function during therapy. Adequate anticonvulsant prophylaxis in patients w/ history of seizures. Increased risk of 2nd malignancy. May impair fertility. Advise men not to father child during & up to 6 mth after treatment & to seek advice on cryo-conservation of sperm prior to treatment. Advise women of childbearing potential to use effective contraception during & up to 6 mth after treatment. Discontinue breast-feeding during treatment. Safety & efficacy of treatment in combination w/ fludarabine in paed population (0-17 yr) has not been established. Not recommended in obese childn & adolescents w/ BMI >30 kg/m².

Hyperglycaemia; stomatitis, diarrhoea; mucositis; increased transaminases, bilirubin & alkaline phosphatases. In combination w/ cyclophosphamide or melphalan: Rhinitis, pharyngitis; neutropenia, thrombocytopenia, febrile neutropenia, anaemia, pancytopenia; allergic reaction; anorexia, hypocalcaemia, hypokalaemia, hypomagnesaemia, hypophosphatemia; anxiety, depression, insomnia; headache, dizziness; tachycardia; HTN, hypotension, thrombosis, vasodilation; dyspnoea, epistaxis, cough, hiccup; abdominal pain, nausea, vomiting, dyspepsia, ascites, constipation, anus discomfort; hepatomegaly, jaundice; rash, pruritus, alopecia; myalgia, back pain, arthralgia; dysuria, oligurea; asthenia, chills, fever, chest pain, oedema, general oedema, pain, pain or inflammation at inj site; increased GGT. Hyponatraemia; confusion; arrhythmia, atrial fibrillation, cardiomegaly, pericardial effusion, pericarditis; hyperventilation, resp failure, alveolar haemorrhages, asthma, atelectasis, pleural effusion; haematemesis, ileus, oesophagitis; veno occlusive liver disease; skin desquamation, erythema, pigmentation disorder; haematuria, moderate renal insufficiency; increased BUN, decreased ejection fraction. In combination w/ fludarabine: Viral infection, CMV & EBV reactivation, bacterial infection; hypoalbuminaemia, electrolyte disturbance; nausea, vomiting; veno occlusive liver disease; haemorrhagic cystitis. Invasive fungal & pulmonary infection; headache, nervous system disorders; HTN; pulmonary haemorrhage; rash; renal disorder; elevated creatinine.

Reduced/decreased clearance w/ itraconazole & paracetamol. High levels of plasma w/ ketobemidone (analgesic). Time interval between last oral busulfan administration & 1st cyclophosphamide administration may influence development of toxicities in adults. Administration of melphalan <24 hr after last oral busulfan administration may influence development of toxicities in paed population. Increased clearance w/ concomitant systemic administration of phenytoin in patients receiving high-dose oral busulfan.

Cytotoxic Chemotherapy

L01AB01 - busulfan ; Belongs to the class of alkylating agents, alkyl sulfonates. Used in the treatment of cancer.

Rx