Included as part of the PRECAUTIONS section.

Tendon Rupture or Other Serious Injury to the Injected Extremity

In the controlled and uncontrolled portions of the clinical trials, flexor tendon ruptures occurred after XIAFLEX injection [see ADVERSE REACTIONS]. Injection of XIAFLEX into collagen-containing structures such as tendons or ligaments of the hand may result in damage to those structures and possible permanent injury such as tendon rupture or ligament damage. Therefore, XIAFLEX should be injected only into the collagen cord with a MP or PIP joint contracture, and care should be taken to avoid injecting into tendons, nerves, blood vessels, or other collagen-containing structures of the hand. When injecting a cord affecting a PIP joint of the fifth finger, the needle insertion should not be more than 2 to 3 mm in depth and avoid injecting more than 4 mm distal to the palmar digital crease [see DOSAGE AND ADMINISTRATION].

Other XIAFLEX-associated serious local adverse reactions in the controlled and uncontrolled portions of the studies included pulley rupture, ligament injury, complex regional pain syndrome (CRPS), and sensory abnormality of the hand.

Allergic Reactions

In the controlled portions of the clinical trials (Studies 1 and 2), a greater proportion of XIAFLEX-treated patients (15%) compared to placebo-treated patients (1%) had mild allergic reactions (pruritus) after up to 3 injections. The incidence of XIAFLEX-associated pruritus increased after more XIAFLEX injections.

Although there were no severe allergic reactions observed in the XIAFLEX studies (e.g., those associated with respiratory compromise, hypotension, or end-organ dysfunction), severe reactions including anaphylaxis could occur following XIAFLEX injections. XIAFLEX contains foreign proteins and patients developed IgE-anti-drug antibodies in greater proportions and higher titers with successive XIAFLEX injections. Healthcare providers should be prepared to address severe allergic reactions following XIAFLEX injections.

Patients with Abnormal Coagulation

In the XIAFLEX trials (Studies 1 and 2), 70% and 38% of XIAFLEX-treated patients developed an ecchymosis/contusion or an injection site hemorrhage, respectively. The efficacy and safety of XIAFLEX in patients receiving anticoagulant medications (other than low-dose aspirin, e.g., up to 150 mg per day) within 7 days prior to XIAFLEX administration is not known. Therefore, XIAFLEX should be used with caution in patients with coagulation disorders including patients receiving concomitant anticoagulants (except for low-dose aspirin).

Patient Counseling Information

See Medication Guide

Advise patients of the following:

• Serious complications of XIAFLEX injection include tendon rupture or serious ligament damage that may result in the inability to fully bend the finger and may require surgery to correct the complication.
• XIAFLEX injection is likely to result in swelling, bruising, bleeding, and/or pain of the injected site and surrounding tissue.

After the XIAFLEX injections, instruct patients:

• Not to flex or extend the fingers of the injected hand to reduce extravasation of XIAFLEX out of the cord.
• Not to attempt to disrupt the injected cord by self manipulation.
• To elevate the injected hand until bedtime.
• To promptly contact their physician if there is evidence of infection (e.g., fever, chills, increasing redness or edema), sensory changes in the treated finger, or trouble bending the finger after the swelling goes down (symptoms of tendon rupture).
• To return to their healthcare provider's office the next day for an examination of the injected hand and for a possible finger extension procedure to disrupt the cord.

Following the finger extension procedure(s) and fitting patient with a splint, instruct patients:

• Not to perform strenuous activity with the injected hand until advised to do so.
• To wear the splint at bedtime for up to 4 months.
• To perform a series of finger flexion and extension exercises each day.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term animal studies to evaluate the carcinogenic potential of collagenase clostridium histolyticum have not been conducted.

Purified collagenase clostridium histolyticum was not mutagenic in Salmonella typhimurium (AMES test) and was not clastogenic in both an in vivo mouse micronucleus assay and an in vitro chromosomal aberration assay in human lymphocytes.

Collagenase clostridium histolyticum did not impair fertility and early embryonic development when administered intravenously in rats at doses up to 0.13 mg/dose (approximately 45 times the human dose on a mg/kg basis).

Use In Specific Populations

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies of XIAFLEX in pregnant women. Human pharmacokinetic studies showed that XIAFLEX levels were not quantifiable in the systemic circulation following injection into a Dupuytren's cord [see CLINICAL PHARMACOLOGY]. Reproduction studies have been performed in rats with intravenous doses up to 0.13 mg (approximately 45 times the human dose of XIAFLEX on a mg/kg basis, if administered intravenously) and have revealed no evidence of impaired fertility or harm to the fetus due to collagenase clostridium histolyticum. Almost all patients develop anti-product antibodies (anti-AUX-I and anti-AUX-II) after treatment with XIAFLEX, and the clinical significance of anti-product antibody formation on a developing fetus is not known [see ADVERSE REACTIONS]. Because animal reproduction studies are not always predictive of human response, XIAFLEX should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether collagenase clostridium histolyticum is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when XIAFLEX is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of XIAFLEX in pediatric patients less than 18 years old have not been established.

Geriatric Use

Of the 249 XIAFLEX-treated patients in the double-blind, placebo-controlled, clinical trials (Studies 1 and 2), 104 (42%) were 65 years of age or older and 9% were 75 years of age or older. No overall differences in safety or effectiveness of XIAFLEX were observed between these patients and younger patients.

Last reviewed on RxList: 3/13/2012
This monograph has been modified to include the generic and brand name in many instances.