"The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
Dotarem is a gadolinium-based"...
Factor VIII:C is the coagulant portion of the Factor VIII complex circulating in plasma. It is noncovalently associated with the von Willebrand protein responsible for von Willebrand factor activity. These two proteins have distinct biochemical and immunological properties and are under separate genetic control. Factor VIII:C acts as a cofactor for Factor IX to activate Factor X in the intrinsic pathway of blood coagulation.8 Hemophilia A, a hereditary disorder of blood coagulation due to decreased levels of Factor VIII:C, results in profuse bleeding into joints, muscles or internal organs as a result of a trauma. Monoclate-P® (antihemophilic factor) provides an increase in plasma levels of AHF, thereby enabling temporary correction of Hemophilia A bleeding.
Clinical evaluation of Monoclate-P® (antihemophilic factor) concentrate for its half-life characteristics in hemophilic patients showed it to be comparable to other commercially available Antihemophilic Factor (Human) concentrates. The mean half-life obtained from six patients was 17.5 hours with a mean recovery of 1.9 units/dl rise/U/kg.
The pasteurization process used in the manufacture of this concentrate has demonstrated in vitro inactivation of human immunodeficiency virus (HIV) and several model viruses. In two separate studies, HIV was reduced by ≥ 7.0 log10 to an undetectable level and by 10.5 log10, respectively. In addition to HIV, studies were also performed using three lipid containing model viruses and one non-lipid, encapsulated model virus. Vesicular stomatitis (VSV) was reduced by ≥ 6.79 log10 to undetectable, Sindbis was reduced by ≥ 6.48 log10 to undetectable and Vaccinia was reduced by ≥ 5.36 log10 to undetectable. Murine encephalomyocarditis (EMC), a non-lipid, encapsulated model virus, was reduced by ≥ 7.1 log10 to undetectable.
Evidence of the capability of the purification and preparative steps used in the production of Monoclate-P® (antihemophilic factor) to reduce viral bioburden was obtained in studies involving the addition of known quantities of virus to cryoprecipitate. These studies were conducted using an earlier form of the concentrate which had not undergone liquid pasteurization (Monoclate®, Antihemophilic Factor (Human), Monoclonal Antibody Purified, Factor VIII:C, Heat-Treated). These studies provide evidence of the viral removal potential of the purification and preparative steps of the manufacturing process (exclusive of heat treatment) which are common to both concentrates. In one study, the viruses used were human immunodeficiency virus (HIV), Sindbis virus, vesicular stomatitis virus (VSV) and pseudorabies virus (PsRV). A comparison of the cumulative mean reductions for all viruses tested with the individual values obtained in each experiment indicates that the combined effects of the manufacturing steps, which purify the Factor VIII:C and prepare the concentrate in a final sterile container as a lyophilized powder, contribute viral reduction capabilities of approximately 5 to 6 logs. In a separate study, aluminum hydroxide treatment followed by antibody affinity chromatography reduced vaccinia virus infectivity by 4.81 logs. These studies indicate that the purification and preparative steps of the manufacturing process are capable of providing a non-specific, viral reduction of approximately 5 to 6 logs, independent of the pasteurization process.
Monoclate-P® (antihemophilic factor) contains trace amounts of mouse protein9 ( ≤ 50 ng per 100 I.U. of AHF). In a study using an earlier form of the concentrate which had not undergone pasteurization (Monoclate®), a number of patients seronegative for Anti-HIV-1 were monitored to determine whether they would develop antibody or experience adverse reactions as a result of repeated exposure. These patients were treated on multiple occasions. Pre-study serum measurements of 27 patients for human anti-mouse IgG showed that, prior to treatment, 6 of them had either detectable antibody to mouse proteins or cross-reactive proteins. These patients continued to demonstrate similar or lower antibody levels during the study. Of the remaining 21 patients, 6 were shown to have low antibody levels on one or more occasions. In no case was observance of low antibody level associated with an anamnestic response or with any clinical adverse reaction. Patients were observed for time periods ranging from 2 to 30 months.
The viral safety of Monoclate-P® (antihemophilic factor) has been evaluated in two open-label studies using patients (aged 1 day to 20 years) with moderate to severe hemophilia A previously unexposed to blood or blood products. Thirty patients received Monoclate-P® (antihemophilic factor) therapy for 5 to 34 months as necessary according to the normal practices of the treatment center. These patients were followed for serum ALT elevations and a range of viral serologies. Six patients received another blood product prior to or during the study. Twenty-four patients were evaluable for assessment of viral safety of Monoclate-P® (antihemophilic factor) . No patients seroconverted to HIV, hepatitis nonA/nonB, or hepatitis B. Factor VIII:C inhibitors developed in 7 patients (23%) with 3 being high ( > 10 BU) titer.
8. L.W. Hoyer, The Factor VIII Complex: Structure and Function, Blood 58 (1981), p.1.
9. F. Feldman, S. Chandra, R. Kleszynski, C.C. Huang and R.L. Weeks, Measurement of Murine Protein Levels in Monoclonal Antibody Purified Coagulation Factor, from the XVIII International Congress of the World Federation of Hemophilia, May 1988.
Last reviewed on RxList: 2/24/2009
This monograph has been modified to include the generic and brand name in many instances.
Additional Monoclate-P Information
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