collagenase clostridium histolyticum (Rx)

>10%

Dupuytren contracture

• Peripheral edema (ie, swelling of injected hand) (73%)
• Contusion (70%)
• Injection site hemorrhage (38%)
• Injection site reaction (35%)
• Pain in injected extremity (35%)
• Tenderness (24%)
• Injection site swelling (24%)
• Pruritus (15%)
• Lymphadenopathy (13%)

Peyronie Disease

• Penile hematoma (65.5%)
• Penile swelling (55%)
• Penile pain (45.4%)
• Penile ecchymoses (14.5%)

Cellulite

• Bruising (84%)
• Pain (48%)
• Nodule (33%)
• Pruritus (15%)

1-10%

Dupuytren contracture

• Skin laceration (9%)
• Lymph node pain (8%)
• Erythema (6%)
• Axillary pain (6%)

Peyronie Disease

• Blood blister (4.5%)
• Penile blister (3.3%)
• Pruritus genital (3.1%)
• Painful erection (2.9%)
• Erectile dysfunction (1.8%)
• Procedural pain (1.6%)
• Injection site vesicles (1.3%)
• Localized edema (1.3%)
• Dyspareunia (1.1%)
• Injection site pruritus (1.1%)
• Nodule (1.1%)
• Suprapubic pain (1.1%)

Cellulite

• Erythema (9%)
• Discoloration (8%)
• Swelling (8%)
• Warmth (3%)

<1%

Peyronie Disease

• Corporal rupture

Postmarketing Reports

Back pain

Cellulite

• Immune system disorders: serious hypersensitivity reactions including anaphylaxis

Contraindications

Hypersensitivity

Peyronie plaques that involve the penile urethra

Cautions

Do not substitute injectable collagenase products (ie, do not use Xiaflex for cellulite treatment of use Qwo for Dupuytren contracture or Peyronie disease)

Serious hypersensitivity, including anaphylaxis, reported; if hypersensitivity occurs, discontinue and institute appropriate medical therapy

Pruritus experienced especially after more injections

Use with caution in patients with coagulation disorders, including in patients who have received anticoagulant medications other than low- dose aspirin within 7 days of the injection

Administration in patients with abnormal coagulation may result in ecchymosis/contusion or an injection site hemorrhage

Post-injection back pain

• Acute post-injection back pain reactions reported in postmarketing period in patients treated for Peyronie’s disease; these events typically have an onset immediately or within minutes of injection
• The acute lower back pain can be mild to severe in intensity and can radiate to the legs, arms and chest; other systemic symptoms, such as chest pain, headache, and dyspnea, reported along with back pain episodes
• None of the events were reported to occur after the patient’s first injection and a few were reported to occur during a second treatment course
• Reported events typically resolved within 15 minutes, but some lasted up to 30 minutes, and one event lasted 1.5 hours; reported events typically did not require intervention, but some required observation and treatment with analgesics

Dupuytren contracture

• Tendon rupture of other serious injury to the injected extremity reported in clinical trials; avoid injecting into tendons, nerves, blood vessels, or other collagen-containing structure of the hand
• Healthcare providers should be prepared to address hypersensitivity reactions, including anaphylaxis, following injections
• Incidence of skin laceration (22%) was higher when treating 2 concurrent injections compared with up to 3 single injections in the placebo-controlled premarketing trials (9%)

Peyronie Disease

• Advise patients not to have sex between first and second injections of treatment cycle; patients should wait 2 weeks after second injection of treatment cycle before resuming sexual activity, provided pain and swelling have subsided
• May cause corporal rupture (penile fracture) or other serious injury to penis; avoid injecting into urethra, nerves, blood vessels, corpora cavernosa or other collagen-containing structures of the penis since may result in possible permanent injury (eg, corporal rupture)
• If patient experiences severe pain or swelling of the penis, severe purple bruising and swelling of the penis, difficulty urinating or blood in the urine, sudden loss of ability to maintain an erection, should contact health care provider

Cellulite

• Injection site bruising is common; patients with coagulation disorders or using anticoagulants or antiplatelets (except aspirin <150 mg/day) were excluded from clinical trials
• Caution if administered to patients with coagulation disorders or coadministered with anticoagulant or antiplatelet agents

Drug interaction overview

• Safety and efficacy when coadministered with anticoagulants (other than low-dose aspirin up to 150 mg/day) within 7 days of administration is unknown

Pregnancy

Data are not available regarding use in pregnant females to evaluate for a drug- associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal studies

• IV administration to pregnant rats during organogenesis at doses up to 0.13 mg/rat (43x human equivalent dose [HED] on a mg/kg basis) revealed no evidence of fetal harm

Lactation

Data are not available regarding presence in human milk, effects on breastfed children, or on milk production

Following SC injection, systemic concentrations were below the bioanalytical assay limit of quantification

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Proteinase that hydrolyzes collagen in its native triple-helical conformation, resulting in lysis of collagen deposits

Injection of into a Dupuytren’s cord, which is comprised mostly of collagen, may result in enzymatic disruption of the cord

Believed to work for Peyronie’s disease by breaking down the buildup of collagen (a structural protein in connective tissue) that causes the curvature deformity

Mechanism for treatment of moderate-to-severe cellulite is unknown

Pharmacokinetics

Absorption: Not absorbed

Xiaflex Preparation

Reconstitution of lyophilized powder

• Must reconstitute lyophilized powder with provided diluent prior to use
• Remove lyophilized powder and diluent from refrigerator and allow to stand at room temperature for at least 15 min (not to exceed 60 min)
• Remove flip off cap from each vial, utilize aseptic technique and swab rubber stoppers of each vial with sterile alcohol
• Use only the supplied diluent for reconstitution (contains calcium required for activity of collagenase clostridium histolyticum
• Use 1-mL syringe with 0.01 mL gradations and 27-ga 0.5-in needle to withdraw diluent
• Inject diluent slowly into side of lyophilized powder vial, then slowly swirl solution to ensure al powder has gone into solution
• Do not invert vial or shake the solution

Sterile diluent volume for specific indication

• Dupuytren contracture

  • MP joints: Reconstitute with 0.39 mL diluent (resulting concentration 0.58 mg/0.25 mL)
  • PIP joints: Reconstitute with 0.31 mL diluent (resulting concentration 0.58 mg/0.2 mL)

• Peyronie disease

  • Reconstitute with 0.39 mL diluent (resulting concentration 0.58 mg/0.25 mL)

Qwo Preparation

Before reconstitution, remove vials from refrigerator and let stand at room temperature for at least 15 minutes

Inspect vials; lyophilized powder cake should be white in color and intact, showing no signs of erosion; diluent solution should appear colorless and free of particulate matter

After removal of the flip-off cap from the vial(s), using aseptic technique swab the rubber stopper and surrounding surface of the vial(s) with sterile alcohol (no other antiseptics should be used)

Use only the supplied diluent for reconstitution

Using appropriate sized syringe and needle (not supplied), withdraw the amount of supplied diluent based on the number of injection sites

Inject diluent slowly into the sides of vial containing lyophilized powder

Do not invert or shake solution; slowly swirl solution to ensure that all of the lyophilized powder has gone into solution

Sterile diluent volume

• 1 treatment area: Reconstitute 0.92-mg vial with 4 mL diluent
• 2 treatment areas: Reconstitute 1.84-mg vial with 8 mL diluent
• Resulting concentration is 0.23 mg/mL

Xiaflex Administration

See prescribing information for specific injection techniques for Dupuytren contracture or Peyronie disease

Dupuytren contracture: Follow-up visit needed 24-72 hr following injection for finger extension procedure

Peyronie disease: Follow-up visit needed 24-72 hr following injection for penile modeling procedure

Qwo SC Administration

Using 1-mL syringes with removable needles (not supplied), draw up 0.9 mL of the reconstituted solution into each syringe (0.21 mg/0.9 mL)

Single treatment visit: Four syringes totaling 0.84 mg

Two treatment visit: Eight syringes totaling 1.68 mg

Mark injection sites while the patient is standing

Inject SC while patient is in prone position

Each injection should be administered as three 0.1-mL aliquots to 3 different positions (see prescribing information image for angle and direction of each injection); for a total injection volume of 0.3 mL

Injection depth is 0.5 inches (corresponding to the length of the needle) without downward pressure

Each treatment area may receive up 12 injections

Patient should remain prone for at least 5 minutes after completion

Storage

Xiaflex

• Before reconstitution: Refrigerate lyophilized powder for injection and diluent at 2-8ºC (36-46ºF); do not freeze
• Reconstituted solution: May store at room temperature (20-25ºC [68-77ºF]) up to 1 hr, or refrigerate (2-8ºC [36-46ºF) up to 4 h before administration

Qwo

• Before reconstitution: Refrigerate lyophilized powder and diluent at 2-8ºC (36-46ºF); do not freeze
• Reconstituted solution: May store at room temperature (20-25ºC [68-77ºF]) up to 8 hr, or refrigerated (2-8ºC [36-46ºF) up to 72 hr before administration