Recombinant Factor VIIA in the Treatment of Bleeding

Madhu V. Midathada, MD; Paulette Mehta, MD; Milton Waner, MD; Louis M. Fink, MD

Disclosures

Am J Clin Pathol. 2004;121(1) 

In This Article

Pharmacokinetics and Dosing of rFVIIa

The pharmacokinetic profiles of rFVIIa have been evaluated in healthy adult volunteers who were pretreated with acenocoumarol, in adults and children with hemophilia A or B, and in adults with cirrhosis and a prolonged PT. The clearance and half-life values of rFVIIa after bolus injections were in the same range in the adult populations studied. The volume of distribution at steady state was slightly smaller in healthy volunteers than in patients with hemophilia. The pharmacokinetic profile of rFVIIa seems to be independent of bleeding or nonbleeding conditions in adults with hemophilia. The values of clearance also were dose-independent in adults with hemophilia and in patients with cirrhosis, whereas in the pediatric patients, the half-life was shorter and clearance was higher than in adults with hemophilia.[118]

A double-blinded, placebo-controlled, randomized, dose-escalation trial was conducted to investigate 8 single intravenous doses of FFR-rFVIIa (inactivated rFVIIa) in 62 healthy male volunteers. Safety, pharmacokinetics, and pharmacodynamics of FFR-rFVIIa were assessed. The mean elimination half-life ranged from 3.8 to 5.8 hours. The mean area under the curve increased with increasing dose levels. The maximum concentration seemed to be proportional to the dose level, with the exception of the lowest dose level. A dose-dependent prolongation of the PT was found, demonstrating that FFR-rFVIIa inhibited coagulation via the TF-dependent pathway. FFR-rFVIIa was well tolerated at all dose levels studied.[119] The standard dosing has been 90 to 120 µg/kg every 2 to 3 hours until bleeding stops.[120]

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