|| DRUGS INDEX | MANUFACTURERS INDEX | HEALTH | ANATOMY | GEOGRAPHY | USA STATISTICS | CHINA STATISTICS | JOBS ||
Xiaflex (Collagenase clostridium histolyticum) for injection, for intralesional use (Auxilium)
- Drugs index
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use XIAFLEX safely and effectively. See full prescribing information for XIAFLEX.
----------------------------- INDICATIONS AND USAGE ---------------------------
XIAFLEX is indicated for the treatment of adult patients with Dupuytren’s contracture with a palpable cord.
--------------------------- DOSAGE AND ADMINISTRATION -----------------------
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.
FULL PRESCRIBING INFORMATION
FULL PRESCRIBING INFORMATION: CONTENTS*
2.2 Reconstitution of the Lyophilized Powder
2.3 Preparation Prior to Injection
2.4 Injection Procedure
2.5 Finger Extension Procedure
5 WARNINGS AND PRECAUTIONS
5.2 Patients with Abnormal Coagulation
5.3 Allergic Reactions
6.2 Postmarketing Experience
8 USE IN SPECIFIC POPULATIONS
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
10.2 Management of Overdose11
12 CLINICAL PHARMACOLOGY
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING
* Sections or subsections omitted from the full prescribing information are not listed.
FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE
XIAFLEX is indicated for the treatment of adult patients with Dupuytren’s contracture with a palpable cord.
DOSAGE AND ADMINISTRATION
f) The reconstituted XIAFLEX solution can be kept at room temperature (20º to 25ºC/68º to 77ºF) for up to one hour or refrigerated at 2º to 8°C (36º to 46°F) for up to 4 hours prior to administration. If the reconstituted XIAFLEX solution is refrigerated, allow this solution to return to room temperature for approximately 15 minutes before use.
g) Discard the syringe and needle used for reconstitution and the diluent vial.
Preparation Prior to Injection
a) The reconstituted XIAFLEX solution should be clear. Inspect the solution visually for particulate matter and discoloration prior to administration. If the solution contains particulates, is cloudy, or is discolored, do not inject the reconstituted solution.
b) Administration of a local anesthetic agent prior to injection is not recommended, as it may interfere with proper placement of the XIAFLEX injection.
c) If injecting into a cord affecting the PIP joint of the fifth finger, care should be taken to inject as close to the palmar digital crease as possible (as far proximal to the digital PIP joint crease), and the needle insertion should not be more than 2 to 3 mm in depth. Tendon ruptures occurred after XIAFLEX injections near the digital PIP joint crease [see Warnings and Precautions (5.1)].
d) Reconfirm the cord to be injected. The site chosen for injection should be the area where the contracting cord is maximally separated from the underlying flexor tendons and where the skin is not intimately adhered to the cord.
e) Apply an antiseptic at the site of the injection and allow the skin to dry.
a) Using a new 1 mL hubless syringe that contains 0.01 mL graduations with a permanently fixed, 27-gauge ½-inch needle (not supplied), withdraw a volume of reconstituted solution (containing 0.58 mg of XIAFLEX) as follows:
c) If the needle is in the proper location, there will be some resistance noted during the injection procedure. After confirming that the needle is correctly placed in the cord, inject approximately one-third of the dose.
d) Next, withdraw the needle tip from the cord and reposition it in a slightly more distal location (approximately 2 to 3 mm) to the initial injection in the cord and inject another one-third of the dose.
e) Again withdraw the needle tip from the cord and reposition it a third time proximal to the initial injection (approximately 2 to 3 mm) and inject the final portion of the dose into the cord.
f) Wrap the patient’s treated hand with a soft, bulky, gauze dressing.
g) Instruct the patient to limit motion of the treated finger and to keep the injected hand elevated until bedtime.
h) Instruct the patient not to attempt to disrupt the injected cord by self-manipulation and to return to the provider’s office the next day for follow-up and a finger extension procedure, if needed.
i) Discard the unused portion of the reconstituted solution and diluent after injection. Do not store, pool, or use any vials containing unused reconstituted solution or diluent.
Finger Extension Procedure
a) At the follow-up visit the day after the injection, if a contracture remains, perform a passive finger extension procedure (as described below) to facilitate cord disruption.
b) Local anesthesia may be used. Avoid direct pressure on the injection site as it will likely be tender.
c) While the patient’s wrist is in the flexed position, apply moderate stretching pressure to the injected cord by extending the finger for approximately 10 to 20 seconds. For cords affecting the PIP joint, perform the finger extension procedure when the MP joint is in the flexed position.
d) If the first finger extension procedure does not result in disruption of the cord, a second and third attempt can be performed at 5- to 10-minute intervals. However, no more than 3 attempts are recommended to disrupt a cord.
e) If the cord has not been disrupted after 3 attempts, a follow-up visit may be scheduled in approximately 4 weeks. If, at that subsequent visit, the contracted cord persists, an additional XIAFLEX injection with finger extension procedures may be performed [see Dosage and Administration (2.1)].
f) Following the finger extension procedure(s), fit patient with a splint and provide instructions for use at bedtime for up to 4 months to maintain finger extension. Also, instruct the patient to perform finger extension and flexion exercises several times a day for several months.
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.
WARNINGS AND PRECAUTIONS
Tendon Rupture or Other Serious Injury to the Injected Extremity
Patients with Abnormal Coagulation
The following serious adverse reactions are discussed in greater detail elsewhere in the labeling:
Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Out of 1082 patients who received 0.58 mg of XIAFLEX in the controlled and uncontrolled portions of the XIAFLEX studies (2630 XIAFLEX injections), 3 (0.3%) patients had a flexor tendon rupture of the treated finger within 7 days of the injection.
The data described below are based on two pooled randomized, double-blind, placebo-controlled trials through Day 90 in patients with Dupuytren’s contracture (Studies 1 and 2). In these trials, patients were treated with up to 3 injections of 0.58 mg of XIAFLEX or placebo with approximately 4-week intervals between injections and the patients had finger extension procedures the day after injection, if needed, to facilitate disruption of the cord [see Clinical Studies (14)]. These trials were comprised of 374 patients of whom 249 and 125 received 0.58 mg of XIAFLEX and placebo, respectively. The mean age was 63 years, 80% were male and 20% were female, and 100% were white.
In the placebo-controlled portions of Studies 1 and 2 through Day 90, 98% and 51% of XIAFLEX-treated and placebo-treated patients had an adverse reaction after up to 3 injections, respectively. Over 95% of XIAFLEX-treated patients had an adverse reaction of the injected extremity after up to 3 injections. Approximately 81% of these local reactions resolved without intervention within 4 weeks of XIAFLEX injections. The adverse reaction profile was similar for each injection, regardless of the number of injections administered. However, the incidence of pruritus increased with more injections [see Warnings and Precautions (5.3)].
Table 2 shows the incidence of adverse reactions that were reported in greater than or equal to 5% of XIAFLEX-treated patients and at a frequency greater than placebo-treated patients after up to 3 injections in the pooled placebo-controlled trials through Day 90 (Studies 1 and 2).
Some patients developed vasovagal syncope after finger extension procedures.
During clinical studies, patients with Dupuytren’s contracture were tested at multiple time points for antibodies to the protein components of XIAFLEX (AUX-I and AUX-II). At 30 days post the first injection of XIAFLEX 0.58 mg, 92% of patients had antibodies detected against AUX-I and 86% of patients had antibodies detected against AUX-II. After the fourth injection of XIAFLEX, every XIAFLEX-treated patient developed high titers of antibodies to both AUX-I and AUX-II. Neutralizing antibodies to AUX-I or AUX-II, were detected in 10% and 21%, respectively, of patients treated with XIAFLEX. However, there was no apparent correlation of antibody frequency, antibody titers, or neutralizing status to clinical response or adverse reactions.
Since the protein components in XIAFLEX (AUX-I and AUX-II) have some sequence homology with human matrix metalloproteinases (MMPs), anti-product antibodies could theoretically interfere with human MMPs.
Immunogenicity assay results are highly dependent on the sensitivity and specificity of the assay used in detection and may be influenced by several factors, including sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to collagenase clostridium histolyticum with the incidence of antibodies to other products may be misleading.
Anticoagulant drugs: XIAFLEX should be used with caution in patients receiving concomitant anticoagulants (except for low-dose aspirin) [see Warnings and Precautions].
USE IN SPECIFIC POPULATIONS
The effects of overdose of XIAFLEX are unknown. It is possible that multiple simultaneous or excessive doses of XIAFLEX may cause more severe local effects including serious adverse reactions (e.g., tendon ruptures) than the recommended doses. Supportive care and symptomatic treatment are recommended in these circumstances.
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.
Mechanism of Action
Carcinogenesis, Mutagenesis, Impairment of Fertility
The efficacy of 0.58 mg of XIAFLEX was evaluated in two randomized, double-blind, placebo-controlled, multi-centered trials in 374 adult patients with Dupuytren’s contracture (Studies 1 and 2). At study entry, patients must have had: (1) a finger flexion contracture with a palpable cord of at least one finger (other than the thumb) of 20° to 100° in a metacarpophalangeal (MP) joint or 20 ° to 80° in a proximal interphalangeal (PIP) joint and (2) a positive “table top test” defined as the inability to simultaneously place the affected finger(s) and palm flat against a table top. Patients could not have received a surgical treatment (e.g., fasciectomy, fasciotomy) on the selected primary joint within 90 days before the first injection of study medication and patients could not have received anticoagulation medication (except for up to 150 mg of aspirin per day) within 7 days before the first injection of study medication.
The cord affecting the selected primary joint received up to 3 injections of 0.58 mg of XIAFLEX or placebo on Days 0, 30, and 60. About 24 hours after each injection of study medication, if needed, the investigator manipulated (extended) the treated finger in an attempt to facilitate rupture of the cord (finger extension procedure). Following manipulation, patients were fitted with a splint, instructed to wear the splint at bedtime for up to 4 months, and instructed to perform a series of finger flexion and extension exercises each day.
Each single-use vial of XIAFLEX is packaged with a single-use vial of sterile diluent in an outer carton. The National Drug Code is:
Sterile diluent for reconstitution is available in single-use, glass vials containing 3 mL of 0.3 mg/mL calcium chloride dihydrate in 0.9% sodium chloride.
STORAGE AND STABILITYPrior to reconstitution, the vials of XIAFLEX and diluent should be stored in a refrigerator at 2º to 8ºC (36º to 46ºF) [see Dosage and Administration (2.2)]. Do not freeze.
The reconstituted XIAFLEX solution can be kept at room temperature (20º to 25ºC/68º to 77ºF) for up to one hour or refrigerated at 2º to 8˚C (36º to 46°F) for up to 4 hours prior to administration [see Dosage and Administration].
PATIENT COUNSELING INFORMATION
See Medication Guide
Manufactured and distributed by: