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ELOCTATE™ [Antihemophilic Factor (Recombinant), Fc Fusion Protein]

2015-04-13 10:52:51 来源: 作者: 【大中小】浏览:314次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ELOCTATE™ safely and effectively. See full prescribing information for ELOCTATE.
ELOCTATE™ [Antihemophilic Factor (Recombinant), Fc Fusion Protein]
Lyophilized Powder for Solution For Intravenous Injection.
Initial U.S. Approval: [2014]
INDICATIONS AND USAGE
ELOCTATE, Antihemophilic Factor (Recombinant), Fc Fusion Protein, is a recombinant DNA derived, antihemophilic factor indicated in adults and children with Hemophilia A (congenital Factor VIII deficiency) for:
•Control and prevention of bleeding episodes
•Perioperative management
•Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
ELOCTATE is not indicated for the treatment of von Willebrand disease. (1)
DOSAGE AND ADMINISTRATION
For intravenous use after reconstitution only.
One unit per kilogram body weight will raise the Factor VIII level by 2% international units per deciliter [IU/dL]. Each vial of ELOCTATE is labeled with the amount of recombinant factor VIII in IU. (2)
Dosing formula for bleeding episodes and perioperative management:
Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg)
OR
Required Dose (IU) = Body Weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Dosing for routine prophylaxis is: 50 IU/kg every 4 days; it may be adjusted based on patient response with dosing in the range of 25-65 IU/kg at 3-5 day intervals. More frequent or higher doses up to 80 IU/kg may be required in children less than 6 years of age. (2)
DOSAGE FORMS AND STRENGTHS
ELOCTATE is available as a lyophilized powder in single use vials containing nominally 250, 500, 750, 1000, 1500, 2000, or 3000 international units (IU) of Factor VIII potency. Each vial of ELOCTATE is labeled with the actual content in IU. (3)
CONTRAINDICATIONS
Do not use in patients who have had life-threatening hypersensitivity reactions, including anaphylaxis, to ELOCTATE. (4)
WARNINGS AND PRECAUTIONS
•Hypersensitivity reactions, including anaphylaxis, are possible. (5.1)
•Development of Factor VIII neutralizing antibodies (inhibitors) may occur. If expected plasma Factor VIII activity levels are not attained, or if bleeding is not controlled with an appropriate dose, perform an assay that measures Factor VIII inhibitor concentration. (5.2, 5.3)
ADVERSE REACTIONS
Common adverse reactions (incidence ≥1%) observed in clinical trials were arthralgia and malaise. (6)
To report SUSPECTED ADVERSE REACTIONS, contact BIOGEN IDEC at 1-855-693-5628 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
•Pregnancy: No human or animal data. Use only if clearly needed. (8.1)
•Pediatric: Clearance (based on per kg body weight) is higher in pediatric patients 2 to 5 years of age. Higher or more frequent dosing may be needed. (8.4)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 6/2014
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Dosing Guidelines
2.2 Preparation and Reconstitution
2.3 Administration
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
5.2 Neutralizing Antibodies
5.3 Monitoring Laboratory Tests
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Immunogenicity
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy
8.3 Nursing Mothers
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
15 REFERENCES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*
Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

ELOCTATE, Antihemophilic Factor (Recombinant), Fc Fusion Protein, is a recombinant DNA derived, antihemophilic factor indicated in adults and children with Hemophilia A (congenital Factor VIII deficiency) for:

Control and prevention of bleeding episodes,
Perioperative management (surgical prophylaxis),
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.

ELOCTATE is not indicated for the treatment of von Willebrand disease.

2 DOSAGE AND ADMINISTRATION

For intravenous use after reconstitution only.

2.1 Dosing Guidelines

Dose 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 monitoring of replacement therapy is necessary in cases of major surgery or life-threatening bleeding episodes.
Each vial label of ELOCTATE states the Factor VIII potency in international units (IU). One IU corresponds to the activity of Factor VIII contained in one milliliter of normal human plasma.
Potency assignment is determined using a chromogenic substrate assay. A field study1 has indicated that plasma Factor VIII levels can be monitored using either a chromogenic substrate assay or a one stage clotting assay routinely used in US clinical laboratories.
Calculation of the required dose of Factor VIII is based on the empirical finding that 1 IU of Factor VIII per kg body weight raises the plasma Factor VIII level by 2 IU/dL. The expected in vivo peak increase in Factor VIII level expressed as IU/dL (or % of normal) is estimated using the following formula:

Estimated Increment of Factor VIII (IU/dL or % of normal) = [Total Dose (IU)/body weight (kg)] x 2 (IU/dL per IU/kg)

The dose to achieve a desired in vivo peak increase in Factor VIII level may be calculated using the following formula:

Dose (IU) = body weight (kg) x Desired Factor VIII Rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL)
Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses. Base the dose and frequency of ELOCTATE on the individual clinical response.
Dose adjustment may be necessary in pediatric patients under six years of age [see Use in Specific Populations (8.4)]. For patients six years of age or older, dose adjustment is not usually required.

Control and Prevention of Bleeding Episodes

A guide for dosing ELOCTATE for the control and prevention of bleeding episodes is provided in Table 1. Consideration should be given to maintaining a Factor VIII activity at or above the target range.

Table 1: Dosing for Control and Prevention of Bleeding Episodes
Type of Bleeding	Factor VIII Level Required (IU/dL or % of normal)	Dose (IU/kg)	Frequency of Dosing (hours)	Duration of Therapy (days)
Minor and Moderate Joint, superficial muscle/no neurovascular compromise (except iliopsoas), deep laceration and renal, superficial soft tissue, mucous membranes	40-60	20-30	Repeat every 24-48 hours (12 to 24 hours for patients less than 6 years of age)	Until the bleeding episode is resolved
Major Life or limb threatening hemorrhage, iliopsoas and deep muscle with neurovascular injury, retroperitoneum, intracranial, or gastrointestinal	80-100	40-50	Repeat every 12-24 hours (8 to 24 hours for patients less than 6 years of age)	Until bleeding is resolved (approximately 7-10 days)

Perioperative Management

A guide for dosing ELOCTATE during surgery (perioperative management) is provided in Table 2. Consideration should be given to maintaining a Factor VIII activity at or above the target range.