6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
14.1 On-demand Treatment and Control of Bleeding Episodes
14.2 Perioperative Management
14.3 Routine Prophylaxis
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
* Sections or subsections omitted from the full prescribing information are not listed. CLOSE
1 INDICATIONS AND USAGE
KOVALTRY, Antihemophilic Factor (Recombinant), is a recombinant, human DNA sequence derived, full length Factor VIII concentrate indicated for use in adults and children with hemophilia A (congenital Factor VIII deficiency) for:.
•On-demand treatment and control of bleeding episodes
•Perioperative management of bleeding
•Routine prophylaxis to reduce the frequency of bleeding episodes
KOVALTRY is not indicated for the treatment of von Willebrand disease.
2 DOSAGE AND ADMINISTRATION
For intravenous use after reconstitution only.
2.1 Dose
•Dosage and duration of treatment depend on the severity of the Factor VIII deficiency, the location and extent of bleeding, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life-threatening bleeding episodes.
•Each vial label of KOVALTRY states the Factor VIII potency in international units (IU). One IU is defined by the current WHO (World Health Organization) international standard (IS) for Factor VIII concentrate.
•
Potency assignment for KOVALTRY is determined using a chromogenic substrate assay. A field study involving 41 clinical laboratories from around the world measured recoveries of KOVALTRY spiked into hemophilic plasma. The results of the field study indicated that the Factor VIII activity of KOVALTRY can be accurately measured in plasma using either a one-stage clotting or chromogenic substrate assay according to routine methods of the testing laboratory.
•The required dose for a desired Factor VIII level expressed as IU/dL (or % of normal) can be estimated using the following formula:
Required dose (IU) = body weight (kg) × desired Factor VIII rise (% of normal or IU/dL)
× reciprocal of expected/observed recovery (e.g., 0.5 for a recovery of 2 IU/dL per IU/kg)
The expected in vivo peak increase of Factor VIII level expressed as IU/dL (or % of normal) can be estimated using the following formula:
Estimated increment of Factor VIII (IU/dL or % of normal) = [Total dose (IU)/body weight (kg)]
× 2 (IU/dL per IU/kg)
Examples (assuming patient’s baseline Factor VIII is <1%):
1.A peak of 50% is required in a 20 kg child. In this situation, the required dose of KOVALTRY would be 20 kg x 50 IU/dL x 0.5% (for recovery of 2 IU/dL per IU/kg) = 500 IU
2.A dose of 2000 IU of KOVALTRY administered to a 50 kg patient should be expected to result in post-infusion Factor VIII increase of 2000 IU / 50 kg (body weight) x 2 IU/dL per IU/kg = 80 IU/dL (80% of normal)
3.Adjust dose to the patient’s clinical response. Patients may vary in their pharmacokinetic (e.g., half-life, incremental recover |
