g by enzymatic degradation is probably only important in patients with severely compromised renal function.
Excretion
The primary route of elimination is via the kidneys. About 65% of the administered intravenous dose is excreted in urine within 24 hours. In patients with normal renal function, plasma concentrations of bleomycin decline biexponentially with a mean terminal half-life of 2 hours following intravenous bolus administration. Total body clearance and renal clearance averaged 51 mL/min/m2 and 23 mL/min/m2, respectively.
Following intrapleural administration to patients with normal renal function, a lower percentage of drug (40%) is recovered in the urine, as compared to that found in the urine after intravenous administration.
Special Populations
Age, Gender, and Race
The effects of age, gender, and race on the pharmacokinetics of BLENOXANE have not been eva luated.
Pediatric
Children of less than 3 years of age have higher total body clearance than in adults, 71 mL/min/m2 versus 51 mL/min/m2, respectively, following intravenous bolus administration. Children of more than 8 years of age have comparable clearance as in adults.
In children with normal renal function, plasma concentrations of bleomycin decline biexponentially as in adults. The volume of distribution and terminal half-life of bleomycin in children appears comparable to that in adults.
Renal Insufficiency
Renal insufficiency markedly alters bleomycin elimination. The terminal elimination half-life increases exponentially as the creatinine clearance decreases. Dosing reductions were proposed for patients with creatinine clearance values of <50 mL/min (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Hepatic Insufficiency
The effect of hepatic insufficiency on the pharmacokinetics of BLENOXANE has not been eva luated.
Drug Interactions
Drugs that Can Affect Renal Clearance
Because bleomycin is eliminated predominantly through renal excretion, the administration of nephrotoxic drugs with bleomycin may affect its renal clearance. Specifically, in one report of 2 children receiving concomitant cisplatin with bleomycin, total body clearance of bleomycin decreased from 39 to 18 mL/min/m2 as the cumulative dose of cisplatin exceeded 300 mg/m2. Terminal half-life of bleomycin also increased from 4.4 to 6.0 hours. Fatal bleomycin pulmonary toxicity has been reported in a patient with unrecognized cisplatin-induced oliguric renal failure.
Clinical Studies
Malignant Pleural Effusion
The safety and efficacy of BLENOXANE 60 units and tetracycline (1 g) as treatment for malignant pleural effusion were eva luated in a multicenter, randomized trial. Patients were required to have cytologically positive pleural effusion, good performance status (0,1,2), lung re-expansion following tube thoracostomy with drainage rates of 100 mL/24 hours or less, no prior intrapleural therapy, no prior systemic BLENOXANE therapy, no chest irradiation, and no recent change in systemic therapy. Overall survival did not differ between the BLENOXANE (n=44) and tetracycline treatment (n=41) groups. Of patients eva luated within 30 days of instillation, the recurrence rate was 36% (10/28) with BLENOXANE and 67% (18/27) with tetracycline (p=0.023). Toxicity was similar between groups.
INDICATIONS AND USAGE
BLENOXANE should be considered a palliative treatment. It has been shown to be useful in the management of the following neoplasms either as a single ag |
