KOVALTRY [ Antihemophilic Factor ( Recombinant )]
Lyophilized Powder for Solution for Intravenous Injection – Reconstitution with Vial Adapter
Initial U . S . Approval : 2016
BRIEF SUMMARY CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION
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 .
4 CONTRAINDICATIONS KOVALTRY is contraindicated in patients who have a history of hypersensitivity reactions to the active substance , to any of the excipients , or to mouse or hamster proteins [ see Description ( 11 )].
5 WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Reactions Hypersensitivity reactions , including anaphylaxis , are possible with KOVALTRY . Early signs of hypersensitivity reactions , which can progress to anaphylaxis , may include chest or throat tightness , dizziness , mild hypotension and nausea . Discontinue KOVALTRY if symptoms occur and seek immediate emergency treatment .
KOVALTRY may contain trace amounts of mouse and hamster proteins [ see Description ( 11 )]. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins .
5.2 Neutralizing Antibodies Neutralizing antibody ( inhibitor ) formation can occur following administration of KOVALTRY . Previously untreated patients ( PUPs ) are at greatest risk for inhibitor development with all Factor VIII products [ see Adverse Reactions ( 6.1 )]. Carefully monitor patients for the development of Factor VIII inhibitors , using appropriate clinical observations and laboratory tests . If expected plasma Factor VIII activity levels are not attained or if bleeding is not controlled as expected with administered dose , suspect the presence of an inhibitor ( neutralizing antibody ) [ see Warnings and Precautions ( 5.5 )].
5.3 Cardiovascular Risk Factors Hemophilic patients with cardiovascular risk factors or diseases may be at the same risk to develop cardiovascular events as non-hemophilic patients when clotting has been normalized by treatment with Factor VIII .
5.4 Catheter-related Infections Catheter-related infections may be observed when KOVALTRY is administered via central venous access devices ( CVADs ). These infections have not been associated with the product itself .
5.5 Monitoring Laboratory Tests
• Monitor plasma Factor VIII activity levels using a validated test to confirm that adequate Factor VIII levels have been achieved and maintained [ see Dosage and Administration ( 2.1 )].
• Monitor for development of Factor VIII inhibitors . Perform a Bethesda inhibitor assay if expected Factor VIII plasma levels are not attained or if bleeding is not controlled with the expected dose of KOVALTRY . Use Bethesda Units ( BU ) to report inhibitor titers .
6 ADVERSE REACTIONS The most frequently reported adverse reactions in clinical trials ( ≥3 %) were headache , pyrexia , and pruritus ( see Table 3 ).
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice . The safety profile of KOVALTRY was evaluated in 193 previously treated patients ( PTPs ) ( inclusive of 51 pediatric patients < 12 years of age ) with at least three months of exposure to KOVALTRY . The safety analysis was done using a pooled database from three multi-center , prospective , open-label clinical studies . The median time on study for patients ≥12 years of age was 372 days with a median of 159 exposure days ( EDs ). The median time on study for patients < 12 years of age was 182 days with a median of 73 EDs . Subjects who received KOVALTRY for perioperative management ( n = 5 ) with treatment period of 2 to 3 weeks and those who received single doses of KOVALTRY for PK studies ( n = 6 ) were excluded from safety analysis . Table 3 lists the adverse reactions reported during clinical studies . The frequency , type , and severity of adverse reactions in children are similar to those in adults .
Table 3 : Adverse Reactions in PTPs ( N = 193 )
MedDRA Primary System Organ Class Preferred term
Frequency N (%)
Blood and the Lymphatic System Disorders Lymphadenopathy 2 ( 1.0 %)
Cardiac Disorders Palpitation Sinus tachycardia
Gastrointestinal Disorders Abdominal pain Abdominal discomfort Dyspepsia
General Disorders and Administration Site Conditions Pyrexia Chest discomfort Injection site reactions a
2 ( 1.0 %) 2 ( 1.0 %)
4 ( 2.1 %) 3 ( 1.6 %) 4 ( 2.1 %)
8 ( 4.1 %) 2 ( 1.0 %) 5 ( 2.6 %)
Immune System Disorders Hypersensitivity 1 ( 0.5 %)
Nervous System Disorders Dizziness Dysgeusia Headache
2 ( 1.0 %) 1 ( 0.5 %) 14 ( 7.3 %)
Psychiatric Disorders Insomnia 5 ( 2.6 %) Skin and Subcutaneous Tissue Disorders Dermatitis allergic Pruritus
Rash b
Urticaria
2 ( 1.0 %) 6 ( 3.1 %) 5 ( 2.6 %) 1 ( 0.5 %)
Vascular disorders Flushing 1 ( 0.5 %)
a
Includes injection site extravasation and hematoma , infusion site pain , pruritus , and swelling b
Includes rash , rash erythematous , and rash pruritic