Country: Canada
Language: English
Source: Health Canada
BUSULFAN
PHARMASCIENCE INC
L01AB01
BUSULFAN
6MG
SOLUTION
BUSULFAN 6MG
INTRAVENOUS
8X10ML
Prescription
ANTINEOPLASTIC AGENTS
Active ingredient group (AIG) number: 0103273002; AHFS:
APPROVED
2018-06-15
PRODUCT MONOGRAPH Pr PMS-BUSULFAN Busulfan for injection 6 mg / mL Sterile concentrated solution ANTINEOPLASTIC PHARMASCIENCE INC. 6111 Royalmount Ave., Suite 100 Montréal, Canada H4P 2T4 www.pharmascience.com Date of Preparation: June 14, 2018 Submission Control No: 198231 _pms-BUSULFAN Product Monograph _ _Page 2 of 30 _ PRODUCT MONOGRAPH Pr PMS-BUSULFAN Busulfan for injection 6 mg / mL Sterile concentrated solution PMS-BUSULFAN (BUSULFAN) INJECTION IS A POTENT CYTOTOXIC DRUG THAT RESULTS IN PROFOUND MYELOSUPPRESSION AT THE RECOMMENDED DOSAGE. IT SHOULD BE ADMINISTERED UNDER THE SUPERVISION OF A QUALIFIED PHYSICIAN WHO IS EXPERIENCED IN THE USE OF CANCER CHEMOTHERAPEUTIC AGENTS AND IN THE MANAGEMENT OF PATIENTS WITH SEVERE PANCYTOPENIA. APPROPRIATE MANAGEMENT OF THERAPY AND COMPLICATIONS IS ONLY POSSIBLE WHEN ADEQUATE DIAGNOSTIC AND TREATMENT FACILITIES ARE READILY AVAILABLE. ACTIONS AND CLINICAL PHARMACOLOGY Busulfan is a potent cytotoxic agent and a bifunctional alkylating agent. In aqueous media, release of the methanesulfonate group produces carbonium ions, which can alkylate DNA, thought to be an important biological mechanism for its cytotoxic effect. Current literature suggests that high AUC values (>1,500 mcMol•min) may be associated with an increased risk of developing hepatic veno-occlusive disease and/or seizures. Mean C max , AUC, T 1/2 and plasma clearance are provided below for oral busulfan and IV busulfan (see PHARMACOLOGY). PARAMETER ORAL BUSULFAN IV BUSULFAN C max (ng/mL) (range) (CV %) 870 (30%) 1,167 (12%) AUC (mcMol•min) (CV %) 1,396 (24%) 1,156 (14%) T 1/2 (hr) (CV %) 3.55 (33%) 3.11 (10%) Plasma Clearance (mL/min) (CV %) 195 (27%) 182 (16%) Intravenous busulfan had a more consistent pharmacokinetic profile than oral busulfan among patients. Busulfan achieves concentrations in the cerebrospinal fluid approximately equal to those in plasma. Irreversible binding to plasma elements, primarily albumin, has been estimated to be 32.4 ± 2.2%, which is consistent with the reactive electrophi Read the complete document