Refacto

ReFacto® Antihemophilic Factor (Recombinant) is a purified protein produced by recombinant DNA technology for use in therapy of factor VIII deficiency. ReFacto (antihemophilic factor) is a glycoprotein with an approximate molecular mass of 170 kDa consisting of 1438 amino acids. It has an amino acid sequence that is comparable to the 90 + 80 kDa form of factor VIII, and post-translational modifications that are similar to those of the plasma-derived molecule. ReFacto (antihemophilic factor) has in vitro functional characteristics comparable to those of endogenous factor VIII.

ReFacto (antihemophilic factor) is produced by a genetically engineered Chinese hamster ovary (CHO) cell line. The CHO cell line secretes B-domain deleted recombinant factor VIII into a defined cell culture medium that contains human serum albumin and recombinant insulin, but does not contain any proteins derived from animal sources. The protein is purified by a chromatography purification process that yields a high-purity, active product. The potency expressed in international units (IU) is determined using the European Pharmacopoeial chromogenic assay against the WHO standard. The specific activity of ReFacto (antihemophilic factor) is 9110-13700 IU per milligram of protein. ReFacto (antihemophilic factor) is not purified from human blood and contains no preservatives or added human or animal components in the final formulation.

ReFacto (antihemophilic factor) is formulated as a sterile, nonpyrogenic, lyophilized powder preparation for intravenous (IV) injection. It is available in single-use vials containing the labeled amount of factor VIII activity (IU). Each vial contains nominally 250, 500, 1000 or 2000 IU of ReFacto (antihemophilic factor) per vial. The formulated product is a clear colorless solution upon reconstitution and contains sodium chloride, sucrose, L-histidine, calcium chloride, and polysorbate 80.

ReFacto® Antihemophilic Factor (Recombinant) is supplied in kits that include single-use (4 mL size, dried) vials which contain nominally 250, 500, 1000 or 2000 IU per vial:

250 IU Kit: NDC 58394–007–04
500 IU Kit: NDC 58394–006–04
1000 IU Kit: NDC 58394–005–04
2000 IU Kit: NDC 58394–011–04

Actual factor VIII activity in IU is stated on the label of each ReFacto® Antihemophilic Factor (Recombinant) vial.

In addition, each ReFacto® Antihemophilic Factor (Recombinant) kit contains: one pre-filled diluent syringe containing 4 mL 0.9% Sodium Chloride with plunger rod for assembly, one vial adapter, one sterile infusion set, two alcohol swabs, one bandage, one gauze, and one package insert.

REFERENCES

11. Kessler CM. An Introduction to Factor VIII Inhibitors: The Detection and Quantitation. American Journal of Medicine. 1991;91(Supplement 5A):1S-5S.

This product's label may have been updated. For current package insert and further product information, please visit www.wyeth.com or call our medical communications department toll-free at 1-800-934-5556. Manufactured and Distributed by: Wyeth Pharmaceuticals Inc. Philadelphia, PA 19101. Rev 12/07.

In phase 3 clinical studies of ReFacto (antihemophilic factor) involving a total of 218 study subjects (113 PTPs, 101 PUPs, and 4 PTPs who participated in the surgery study only), more than 138 million IU were administered during a total of 75,757 exposure days. The 113 PTPs in the long-term PTP study were given a median of 327 injections (range 4-1769 injections) over a median of 313 exposure days (range 4-1312 days). The 101 PUPs in the long-term PUP study were given a median of 218 injections (range 1-1476 injections) over a median of 197 exposure days (range 1-1466 days).

As with the intravenous administration of any protein product, the following reactions may be observed after administration: headache, fever, chills, flushing, nausea, vomiting, lethargy, or manifestations of allergic reactions. During phase 3 clinical studies with ReFacto® Antihemophilic Factor (Recombinant), 278 adverse reactions were probably or possibly related or of unknown relation to therapy with 80,370 infusions (0.35% of infusions) in 109 of 218 study subjects (50%).

Adverse reactions reported by ≥ 1% of study subjects are presented in Tables 2 and 3 for PTPs and PUPs, respectively. One of 218 subjects experienced hypotension that was mild in severity and considered probably related to the administration of ReFacto (antihemophilic factor) as noted in Table 3.

TABLE 2. SUMMARY OF STUDY-DRUG RELATED ADVERSE EVENTS IN ≥ 1% OF PTPS

TABLE 3. SUMMARY OF STUDY-DRUG RELATED ADVERSE EVENTS IN ≥ 1% OF PUPS

If any adverse reaction takes place that is thought to be related to administration of ReFacto (antihemophilic factor) , the rate of infusion should be decreased or stopped.

Inhibitor development is a known adverse event associated with the treatment of patients with hemophilia A. In addition to the one report of a high-titer inhibitor in the clinical study of PTPs (see CLINICAL PHARMACOLOGY), there have been reports of high-titer inhibitors in PTPs in the post-marketing setting. High- and low-titer inhibitors have been reported in PUPs in both clinical trials and the post-marketing setting (see PRECAUTIONS, General).

Other adverse experiences that were reported during the clinical trials, but which were assessed by both the investigator and the sponsor as “unlikely” to be related to ReFacto (antihemophilic factor) administration included: dyspnea (3), rash (2), pruritus (1), neuropathy (1), arm weakness (1), and thrombophlebitis of upper arm (1).

Recombinant antihemophilic factor is sometimes used only as needed, so you may not be on a dosing schedule. If you are taking the medication regularly, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Your pharmacist can provide more information about recombinant antihemophilic factor.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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