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BENEFIX(coagulation factor ix (recombinant))kit

2014-06-10 15:41:37 来源: 作者: 【大中小】浏览:332次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use BeneFIX safely and effectively. See full prescribing information for BeneFIX.

BeneFIX [Coagulation Factor IX (Recombinant)] For Intravenous Use, Lyophilized Powder for Reconstitution
Initial U.S. Approval: 1997

INDICATIONS AND USAGE

BeneFIX is an antihemophilic factor (recombinant) indicated for:

Control and prevention of bleeding episodes in adult and pediatric patients with hemophilia B. (1.1)
Peri-operative management in adult and pediatric patients with hemophilia B. (1.2)

DOSAGE AND ADMINISTRATION

For Intravenous Use only

The initial estimated dose may be determined using the following formula: (2)

Required units =

body weight (kg) x desired factor IX increase (IU/dL or % of normal) x reciprocal of observed recovery (IU/kg per IU/dL)

Average Recovery: Adult and Pediatric (<15 years) Patients

In clinical studies with adult and pediatric (<15 years) patients, one IU of BeneFIX per kilogram of body weight increased the circulating activity of factor IX as follows:

Adults: 0.8 ± 0.2 IU/dL [range 0.4 to 1.2 IU/dL]. (2.3)
Pediatric: 0.7 ± 0.3 IU/dL [range 0.2 to 2.1 IU/dL]. (2.3)

Dosing of BeneFIX may differ from that of plasma-derived factor IX products.

Dosage and duration of treatment with BeneFIX depends on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition, age and recovery of factor IX. (2.1)

DOSAGE FORMS AND STRENGTHS

BeneFIX lyophilized powder is available as 250, 500, 1000, or 2000 IU in single-use vials. (3)

CONTRAINDICATIONS

BeneFIX is contraindicated in patients who have manifested life-threatening, immediate hypersensitivity reactions, including anaphylaxis, to the product or its components, including hamster protein. (4)

WARNINGS AND PRECAUTIONS

Anaphylaxis and severe hypersensitivity reactions are possible. Should symptoms occur, treatment with the product should be discontinued, and emergency treatment should be sought. (5.2)
BeneFIX has been associated with the development of thromboembolic complications, including patients receiving continuous infusion through a central venous catheter. (5.3)
Development of activity-neutralizing antibodies has been detected in patients receiving factor IX-containing products. If expected plasma factor IX activity levels are not attained, or if patient presents with allergic reaction, or if bleeding is not controlled with an expected dose, an assay that measures factor IX inhibitor concentration should be performed. (5.5)
Patients may develop hypersensitivity to hamster (CHO) protein as BeneFIX contains trace amounts. (5.2)

ADVERSE REACTIONS

The most common adverse reactions (incidence >5%) from clinical trials were nausea, injection site reaction, injection site pain, headache, dizziness and rash. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Wyeth Pharmaceuticals Inc. at 1-800-934-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

USE IN SPECIFIC POPULATIONS

On average, lower recovery has been observed in pediatric patients (<15 years). A dose adjustment may be needed. (12.3, 14)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling

Revised: 08/2011

Back to Highlights and Tabs

FULL PRESCRIBING INFORMATION: CONTENTS*

* Sections or subsections omitted from the full prescribing information are not listed

1 INDICATIONS AND USAGE

1.1 Control and Prevention of Bleeding Episodes in Hemophilia B

1.2 Peri-operative Management in Patients with Hemophilia B

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations for Administration

2.2 Method of Calculating Initial Estimated Dose

2.3 Dosing Guide for Control and Prevention of Bleeding Episodes and Peri-operative Management

2.4 Instructions for Use

2.5 Preparation and Reconstitution

2.6 Administration (Intravenous Injection)

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 General

5.2 Anaphylaxis and Severe Hypersensitivity Reactions

5.3 Thromboembolic Complications

5.4 Nephrotic Syndrome

5.5 Neutralizing Antibodies (Immunogenicity)

5.6 Monitoring Laboratory Tests

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Post-marketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

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

16.1 How Supplied

16.2 Storage and Handling

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Control and Prevention of Bleeding Episodes in Hemophilia B

BeneFIX®, Coagulation Factor IX (Recombinant), is indicated for the control and prevention of bleeding episodes in adult and pediatric patients with hemophilia B (congenital factor IX deficiency or Christmas disease).

1.2 Peri-operative Management in Patients with Hemophilia B

BeneFIX, Coagulation Factor IX (Recombinant), is indicated for peri-operative management in adult and pediatric patients with hemophilia B.

BeneFIX, Coagulation Factor IX (Recombinant), is NOT indicated for:

treatment of other factor deficiencies (e.g., factors II, VII, VIII, and X),
treatment of hemophilia A patients with inhibitors to factor VIII,
reversal of coumarin-induced anticoagulation,
treatment of bleeding due to low levels of liver-dependent coagulation factors.

2 DOSAGE AND ADMINISTRATION

2.1 General Considerations for Administration

For Intravenous Use after Reconstitution

Treatment with BeneFIX, Coagulation Factor IX (Recombinant), should be initiated under the supervision of a physician experienced in the treatment of hemophilia B.
Each vial of BeneFIX has the rFIX potency in the International Units (IU) stated on the vial.
Dosage and duration of treatment for all factor IX products depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition, age and recovery of factor IX.

To ensure that the desired factor IX activity level has been achieved, precise monitoring using the factor IX activity assay is advised. Doses should be titrated using the factor IX activity, pharmacokinetic parameters, such as half-life and recovery, as well as taking the clinical situation into consideration in order to adjust the dose as appropriate.

Dosing of BeneFIX may differ from that of plasma-derived factor IX products [see Clinical Pharmacology (12)]. Subjects at the low end of the observed factor IX recovery may require upward dosage adjustment of BeneFIX to as much as two times (2X) the initial empirically calculated dose in order to achieve the intended rise in circulating factor IX activity.

The safety and efficacy of BeneFIX administration by continuous infusion have not been established [see Warnings and Precautions (5)].

2.2 Method of Calculating Initial Estimated Dose

The method of calculating the factor IX dose is shown in Table 1.

Table 1
number of factor IX IU required (IU)	=	body weight (kg)	x	desired factor IX increase (% or IU/dL)	x	reciprocal of observed recovery (IU/kg per IU/dL)

Average Recovery Adult Patients in Clinical Trial

In adult PTPs, on average, one International Unit (IU) of BeneFIX per kilogram of body weight increased the circulating activity of factor IX by 0.8 ± 0.2 IU/dL (range 0.4 to 1.2 IU/dL). The method of dose estimation is illustrated in Table 2. If you use 0.8 IU/dL average increase of factor IX per IU/kg body weight administered, then:

Table 2
number of factor IX IU required (IU)	=	body weight (kg)	x	desired factor IX increase (% or IU/dL)	x	1.3 (IU/kg per IU/dL)

Average Recovery Pediatric Patients (<15 years) in Clinical Trial

In pediatric patients, on average, one international unit of BeneFIX per kilogram of body weight increased the circulating activity of factor IX by 0.7 ± 0.3 IU/dL (range 0.2 to 2.1 IU/dL; median of 0.6 IU/dL per IU/kg). The method of dose estimation is illustrated in Table 3. If you use 0.7 IU/dL average increase of factor IX per IU/kg body weight administered, then:

Table 3
number of factor IX IU required (IU)	=	body weight (kg)	x	desired factor IX increase (% or IU/dL)	x	1.4 (IU/kg per IU/dL)

Doses administered should be titrated to the patient's clinical response. Patients may vary in their pharmacokinetic (e.g., half-life, in vivo recovery) and clinical responses to BeneFIX. Although the dose can be estimated by the calculations above, it is highly recommended that, whenever possible, appropriate laboratory tests, including serial factor IX activity assays, be performed.

2.3 Dosing Guide for Control and Prevention of Bleeding Episodes and Peri-operative Management

Table 4
Type of Hemorrhage	Circulating Factor IX Activity Required [% or (IU/dL)]	Dosing Interval [hours]	Duration of Therapy [days]
Adapted from: Roberts and Eberst1
Minor
Uncomplicated hemarthroses, superficial muscle, or soft tissue	20-30	12-24	1-2
Moderate
Intramuscle or soft tissue with dissection, mucous membranes, dental extractions, or hematuria	25-50	12-24	Treat until bleeding stops and healing begins, about 2 to 7 days
Major
Pharynx, retropharynx, retroperitoneum, CNS, surgery	50-100	12-24	7-10

2.4 Instructions for Use

BeneFIX is administered by intravenous (IV) infusion after reconstitution of the lyophilized powder with the supplied pre-filled diluent (0.234% sodium chloride solution) syringe.

Patients should follow the specific reconstitution and administration procedures provided by their physicians.

For instructions, patients should follow the recommendations in the FDA-Approved Patient Labeling [see Patient Counseling Information (17.3)].

Reconstitution, product administration, and handling of the administration set must be done with caution. Discard all equipment, including any reconstituted BeneFIX product, in an appropriate container. Place needles used for venipuncture in a sharps container after single use. Percutaneous puncture with a needle contaminated with blood from an infected patient can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs.

2.5 Preparation and Reconstitution

The procedures below are provided as general guidelines for the reconstitution and administration of BeneFIX.

Preparation

Always wash your hands before performing the following procedures.
Aseptic technique (meaning clean and germ-free) should be used during the reconstitution procedure.
Use all components in the reconstitution and administration of this product as soon as possible after opening their sterile containers to minimize unnecessary exposure to the atmosphere.
Note: If you use more than one vial of BeneFIX per infusion, each vial should be reconstituted according to the following instructions. The diluent syringe should be removed leaving the vial adapter in place, and a separate large luer lock syringe may be used to draw back the reconstituted contents of each vial. Do not detach the diluent syringes or the large luer lock syringe until you are ready to attach the large luer lock syringe to the next vial adapter.

Reconstitution

If refrigerated allow the vial of lyophilized BeneFIX and the pre-filled diluent syringe to reach room temperature.

Remove the plastic flip-top cap from the BeneFIX vial to expose the central portions of the rubber stopper.

Wipe the top of the vial with the alcohol swab provided, or use another antiseptic solution, and allow to dry. After cleaning, do not touch the rubber stopper with your hand or allow it to touch any surface.

Peel back the cover from the clear plastic vial adapter package. Do not remove the adapter from the package.

Place the vial on a flat surface. While holding the adapter in the package, place the vial adapter over the vial and press down firmly on the package until the adapter spike penetrates the vial stopper.

Grasp the plunger rod as shown in the diagram. Avoid contact with the shaft of the plunger rod. Attach the threaded end of the plunger rod to the diluent syringe plunger by pushing and turning firmly.

Break off the tamper-resistant plastic-tip cap from the diluent syringe by snapping the perforation of the cap. Do not touch the inside of the cap or the syringe tip. The diluent syringe may need to be recapped (if not administering reconstituted BeneFIX immediately), so place the cap on its top on a clean surface in a spot where it would be least likely to become environmentally contaminated.

Lift the package away from the adapter and discard the package.

Place the vial on a flat surface. Connect the diluent syringe to the vial adapter by inserting the tip into the adapter opening while firmly pushing and turning the syringe clockwise until secured.

Slowly depress the plunger rod to inject all the diluent into the BeneFIX vial.

Without removing the syringe, gently swirl the contents of the vial until the powder is dissolved.
Note: The final solution should be inspected visually for particulate

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