| XIAFLEX™ (collagenase clostridium histolyticum)
for injection, for intralesional use
Initial U.S. Approval: 2010
XIAFLEX contains purified collagenase clostridium histolyticum, consisting of two microbial collagenases in a defined mass ratio, Collagenase AUX-I and Collagenase AUX-II, which are isolated and purified from the fermentation of Clostridium histolyticum bacteria.
Collagenase AUX-I is a single polypeptide chain consisting of approximately 1000 amino acids of known sequence. It has an observed molecular weight of 114 kiloDaltons (kDa). It belongs to the class I Clostridium histolyticum collagenases.
Collagenase AUX-II is a single polypeptide chain consisting of approximately 1000 amino acids of deduced sequence. It has an observed molecular weight of 113 kDa. It belongs to the class II Clostridium histolyticum collagenases.
XIAFLEX is supplied as a sterile lyophilized powder (white cake) intended for reconstitution with 0.39 mL (for a MP joint) or 0.31 mL (for a PIP joint) of the supplied sterile diluent (0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride) prior to intralesional injection into a Dupuytren’s cord.
XIAFLEX is available in single-use, glass vials containing 0.9 mg of collagenase clostridium histolyticum. Each vial also contains 0.5 mg of hydrochloric acid, 18.5 mg of sucrose, and 1.1 mg of tromethamine.
| CLINICAL PHARMACOLOGY
Mechanism of Action
Collagenases are proteinases that hydrolyze collagen in its native triple helical conformation under physiological conditions, resulting in lysis of collagen deposits. Injection of XIAFLEX into a Dupuytren’s cord, which is comprised mostly of collagen, may result in enzymatic disruption of the cord.
Results of in vitro studies suggest that the collagenases (AUX-I and AUX-II) worked synergistically to provide hydrolyzing activity towards collagen. However, there are no clinical data regarding the relative contributions of the individual collagenases (AUX-I or AUX-II) to the efficacy of XIAFLEX in the treatment of Dupuytren’s contracture.
| INDICATIONS AND USAGE
XIAFLEX is indicated for the treatment of adult patients with Dupuytren’s contracture with a palpable cord.
| WARNINGS AND PRECAUTIONS
| ADVERSE REACTIONS
The most common adverse reactions reported in 25% of patients treated with XIAFLEX and at an incidence greater than placebo were edema peripheral (e.g., swelling of the injected hand), contusion, injection site reaction, injection site hemorrhage, and pain in the injected extremity.
To report SUSPECTED ADVERSE REACTIONS, contact Auxilium Pharmaceuticals, Inc. at 1-877-663-0412 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
| DOSAGE AND ADMINISTRATION
XIAFLEX should be administered by a healthcare provider experienced in injection procedures of the hand and in the treatment of patients with Dupuytren’s contracture.
XIAFLEX, supplied as a lyophilized powder, must be reconstituted with the provided diluent prior to use. The dose of XIAFLEX is 0.58 mg per injection into a palpable cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint. Table 1 displays an overview of the volumes of sterile diluent for reconstitution and the reconstituted XIAFLEX solution to be used in the intralesional injection. Approximately 24 hours after injection, perform a finger extension procedure if a contracture persists to facilitate cord disruption.
Table 1. Volumes Needed for Reconstitution and Administration
Four weeks after the XIAFLEX injection and finger extension procedure, if a MP or PIP contracture remains, the cord may be re-injected with a single dose of 0.58 mg of XIAFLEX and the finger extension procedure may be repeated (approximately 24 hours after injection). Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals.
Inject only one cord at a time. If a patient has other palpable cords with contractures of MP or PIP joints, these cords may be injected with XIAFLEX in a sequential order.
Reconstitution of the Lyophilized Powder:
Preparation Prior to Injection:
Finger Extension Procedure:
| DOSAGE FORMS AND STRENGTHS
XIAFLEX is supplied in single-use glass vials containing 0.9 mg of collagenase clostridium histolyticum as a sterile, lyophilized powder for reconstitution. Sterile diluent for reconstitution is provided in the package in a single-use glass vial containing 3 mL of 0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride.
Storage and Stability
The reconstituted XIAFLEX solution can be kept at room temperature (20° to 25°C/68° to 77°F) for up to one hour or refrigerated at 2° to 8°C (36° to 46°F) for up to 4 hours prior to administration
National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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