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XYNTHA SOLOFUSE(antihemophilic factor [recombinant]) lyophilized powder

2016-03-25 10:24:16 来源: 作者: 【大中小】浏览:541次评论:0条

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use XYNTHA safely and effectively. See full prescribing information for XYNTHA.
XYNTHA ® SOLOFUSE™ (antihemophilic factor [recombinant]) lyophilized powder for solution in prefilled dual-chamber syringe, for intravenous injection
Initial U.S. Approval: 2008
RECENT MAJOR CHANGES

Indications and Usage (1)

10/2014

INDICATIONS AND USAGE

XYNTHA is a recombinant antihemophilic factor indicated in adults and children with hemophilia A for control and prevention of bleeding episodes and for perioperative management. (1)
XYNTHA is not indicated in patients with von Willebrand's disease. (1)

DOSAGE AND ADMINISTRATION
For intravenous use after reconstitution only (2)

The required dose is determined using the following formula:
Required units = body weight (kg) × desired factor VIII rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL), where IU = International Unit.
Frequency of XYNTHA administration is determined by the type of bleeding episode and the recommendation of the treating physician. (2.1, 2.2)

DOSAGE FORMS AND STRENGTHS
XYNTHA SOLOFUSE is available as lyophilized powder in single-use prefilled dual-chamber syringes containing nominally 250, 500, 1000, 2000, or 3000 IU. (3)
CONTRAINDICATIONS
Do not use in patients who have manifested life-threatening immediate hypersensitivity reactions, including anaphylaxis, to the product or its components, including hamster proteins. (4)
WARNINGS AND PRECAUTIONS

Anaphylaxis and severe hypersensitivity reactions are possible. Patients may develop hypersensitivity to hamster protein, which is present in trace amounts in XYNTHA. Should such reactions occur, discontinue treatment with the product, and administer appropriate treatment. (5.1)
Development of activity-neutralizing antibodies has been detected in patients receiving factor VIII-containing products, including XYNTHA. 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, 6.2)

ADVERSE REACTIONS

The most common adverse reactions (≥ 10%) with XYNTHA in adult and pediatric PTPs were headache, arthralgia, pyrexia, and cough. (6)
Across all studies, 3 subjects developed factor VIII inhibitors (2.1%). (6.2)

To report SUSPECTED ADVERSE REACTIONS, contact Wyeth Pharmaceuticals Inc. at 1-800-438-1985 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)
Pediatrics: Half-lives are shorter, volumes of distribution are larger, and recovery is lower after XYNTHA administration in children. Higher or more frequent dosing may be needed. (8.4)

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

Revised: 10/2014

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Dose

2.2 Preparation and Reconstitution

2.3 Administration

2.4 Use of a XYNTHA Vial Kit with a XYNTHA SOLOFUSE Kit

2.5 Use of Multiple XYNTHA SOLOFUSE Kits

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

6.3 Postmarketing Experience

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

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

13.2 Animal Toxicology and/or Pharmacology

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.

1 INDICATIONS AND USAGE

XYNTHA, Antihemophilic Factor (Recombinant), is indicated for use in adults and children with hemophilia A (congenital factor VIII deficiency) for:

Control and prevention of bleeding episodes
Perioperative management

XYNTHA does not contain von Willebrand factor, and therefore is not indicated in patients with von Willebrand's disease.

2 DOSAGE AND ADMINISTRATION

For intravenous use after reconstitution only.

2.1 Dose

Initiate treatment with XYNTHA under the supervision of a physician experienced in the treatment of hemophilia A.
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. Titrate the administered doses to the patient's clinical response.
One International Unit (IU) of factor VIII activity corresponds approximately to the quantity of factor VIII in one milliliter of normal human plasma. The calculation of the required dosage of factor VIII is based upon the empirical finding that, on average, 1 IU of factor VIII per kg body weight raises the plasma factor VIII activity by approximately 2 IU/dL.2

The expected in vivo peak increase in factor VIII level expressed as IU/dL (or % normal) can be estimated using the following formulas:

Dosage (International Units) = body weight (kg) × desired factor VIII rise (IU/dL or % of normal) × 0.5 (IU/kg per IU/dL)

IU/dL (or % normal) = Total Dose (IU)/body weight (kg) × 2 [IU/dL]/[IU/kg]

Control and Prevention of Bleeding Episodes

A guide for dosing XYNTHA for the control and prevention of bleeding episodes is provided in Table 1. Maintain the plasma factor VIII activity at or above the levels (in % of normal or in IU/dL) outlined in Table 1 for the indicated period.

Table 1: Dosing for Control and Prevention of Bleeding Episodes
Type of Bleeding Episode	Factor VIII Level Required (IU/dL or % of normal)	Frequency of Doses (hours)	Duration of Therapy
Minor
Early hemarthrosis, minor muscle or oral bleeds.	20–40	12–24	At least 1 day, depending upon the severity of the bleeding episode.
Moderate
Bleeding into muscles. Mild head trauma. Bleeding into the oral cavity.	30–60	12–24	3–4 days or until adequate local hemostasis is achieved.
Major
Gastrointestinal bleeding. Intracranial, intra-abdominal or intrathoracic bleeding. Fractures.	60–100	8–24	Until bleeding is resolved.

Perioperative Management

A guide for dosing XYNTHA during surgery (perioperative management) is provided in Table 2. Maintain the plasma factor VIII activity level at or above the level (in % of normal or in IU/dL) outlined in Table 2 for the indicated period. Monitor the replacement therapy by means of plasma factor VIII activity.