Krajina: Kanada
Jazyk: angličtina
Zdroj: Health Canada
BUSULFAN
STERIMAX INC
L01AB01
BUSULFAN
60MG
SOLUTION
BUSULFAN 60MG
INTRAVENOUS
10ML
Prescription
ANTINEOPLASTIC AGENTS
Active ingredient group (AIG) number: 0103273002; AHFS:
APPROVED
2017-05-05
_ _ _Busulfan for Injection _ _Page 1 of 31 _ PRODUCT MONOGRAPH PR BUSULFAN FOR INJECTION 6 mg/mL Sterile solution for injection Antineoplastic SteriMax Inc. 2770 Portland Drive Oakville, ON L6H 6R4 Date of Preparation: May 4, 2017 Submission Control No: 193322 _ _ _Busulfan for Injection _ _Page 2 of 31 _ PRODUCT MONOGRAPH PR BUSULFAN FOR INJECTION 6 mg/mL BUSULFAN FOR 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 μMol•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 intravenous (IV) busulfan (See PHARMACOLOGY). PARAMETER ORAL BUSULFAN IV BUSULFAN Cmax (ng/mL) (range) (CV%) 870 (30%) 1,167 (12%) AUC (μMol•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 electrophilic properties of this alkylator. Busulfan is predominately meta Prečítajte si celý dokument