Collagenase (Systemic)

Treatment of Peyronie plaques that involve the penile urethra; history of hypersensitivity to collagenase or to collagenase used in any other therapeutic application or application method.

Dupuytren contracture: Intralesional: Inject 0.58 mg per cord affecting a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint. If contracture persists, finger extension procedure should be performed 24 to 72 hours following injection to facilitate cord disruption. If MP or PIP contracture remains, may reinject cord with a single dose of 0.58 mg 4 weeks following initial injection; injections and finger extension procedures may be administered up to 3 times per cord separated by ~4 week intervals. Note: Up to 2 injections per hand may be used during a treatment; 2 palpable cords affecting 2 joints or 1 palpable cord affecting 2 joints in the same finger may be injected at 2 locations during a treatment. Other palpable cords with contractures of MP or PIP joints may be injected at other treatment visits ~4 weeks apart.

Peyronie disease: Intralesional: Males: Inject 0.58 mg into a Peyronie plaque; repeat injection 1 to 3 days later. A penile modeling procedure should be performed 1 to 3 days after the second injection. Administer a second treatment cycle (two 0.58 mg injections and a penile modeling procedure) in ~6 weeks if needed (maximum, 4 treatment cycles [a total of 8 injection procedures and 4 penile modeling procedures]); subsequent treatment cycles should not be administered if the curvature deformity is <15 degrees after a treatment cycle or health care provider determines further treatment is not indicated. The safety of more than 1 treatment course (ie, 4 treatment cycles) is not known. Note: If more than 1 plaque is present, inject into the plaque causing the curvature deformity.

Refer to adult dosing.

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Anticoagulants: May enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dupuytren's contracture:

>10%:

Cardiovascular: Peripheral edema (primarily as swelling of injected hand: 73% to 77%)

Dermatologic: Pruritus (4% to 15%), hemorrhagic blister (12%)

Hematologic & oncologic: Bruise (59% to 70%), lymphadenopathy (13%)

Immunologic: Antibody development (≥86%; neutralizing antibodies: AUX-I: 10%; AUX-II: 21%)

Local: Bleeding at injection site (6% to 38%), injection site reaction (35%; includes erythema, inflammation, irritation), swelling at injection site (5% to 24%), tenderness at injection site (24%), pain at injection site (14%)

Neuromuscular & skeletal: Limb pain (35% to 51%)

Miscellaneous: Laceration (9% to 22%)

1% to 10%:

Central nervous system: Lymph node pain (8%), axillary pain (6% to 7%)

Dermatologic: Erythema (6%), ecchymoses (5%)

Local: Hematoma at injection site (8%)

<1% (Limited to important or life-threatening): Anaphylaxis, antibody development (IgE; increased with successive injections), causalgia, ligament disorder, rupture of tendon, sensory disturbance, vasodepressor syncope

Peyronie disease:

>10%:

Genitourinary: Penile hematoma (66%; severe: 4% to 6%), penile swelling (55%), penile pain (45%), penile ecchymoses (15%), penile popping sensation (13%)

Immunologic: Antibody development (55% to >99%; neutralizing antibodies: AUX-I: 60%; AUX-II: 52%; no correlation to clinical response or adverse reaction)

1% to 10%:

Central nervous system: Procedural pain (2%), suprapubic pain (1%)

Dermatologic: Hemorrhagic blister (5%), genital pruritus (3%), skin discoloration (2%), localized vesiculation (injection site, 1%)

Genitourinary: Blisters on penis (3%), painful erection (3%), erectile dysfunction (2%), dyspareunia (1%)

Local: Itching at injection site (1% to 4%), localized edema (1%)

Miscellaneous: Nodule (1%)

<1% (Limited to important or life-threatening): Penile fracture, sudden penile detumescence

Applies to collagenase clostridium histolyticum: injection powder for solution

Along with its needed effects, collagenase clostridium histolyticum may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking collagenase clostridium histolyticum:

• Bruising or bleeding at the injection site
• swelling of the hands
• tearing of the skin

• Itching, pain, redness, swelling, or bruise of the penis
• popping sound or sensation in an erect penis

• Decreased interest in sexual intercourse
• inability to have or keep an erection
• loss in sexual ability, desire, drive, or performance
• painful sexual intercourse

• Bone pain
• lower back or side pain
• painful, swollen joints

Some side effects of collagenase clostridium histolyticum may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, lumps, numbness, rash, scarring, stinging, tingling, or ulceration at the injection site
• bruise
• flushing, redness of the skin or unusually warm skin at the injection site
• itching, pain, swelling, or tenderness at the injection site
• swollen, painful, or tender lymph glands in the neck or armpit

Applies to collagenase clostridium histolyticum: injectable powder for injection

Musculoskeletal

Very common (10% or more): Pain in extremity (35%), arthralgia (11%)
Common (1% to 10%): Shoulder pain
Uncommon (0.1% to 1%): Axillary mass, chest wall pain, groin pain, joint crepitation, joint stiffness, limb discomfort, muscle spasms, muscular weakness, musculoskeletal stiffness, neck pain, tendon rupture[Ref]

Local

Very common (10% or more): Injection site hemorrhage (38%), injection site reaction (erythema, inflammation, irritation, pain, warmth) (35%), injection site swelling and edema (24%), pruritus (15%), blood blister (13%)
Common (1% to 10%): Ecchymosis, hyperhidrosis, rash, skin laceration
Uncommon (0.1% to 1%): Eczema, swelling face, pain of skin, skin exfoliation, skin lesion, scab, skin discoloration, skin tightness[Ref]

Cardiovascular

Very common (10% or more): Peripheral edema (most cases were swelling of the injected hand) (73%)
Frequency not reported: Vasovagal syncope (after finger extension procedures)[Ref]

Other

Very common (10% or more): Contusion (any body system) and ecchymosis (70%), tenderness (24%)
Common (1% to 10%): Axillary pain
Uncommon (0.1% to 1%): Breast tenderness, hypertrophy breast[Ref]

Dermatologic

Common (1% to 10%): Lymphadenopathy, lymph node pain
Uncommon (0.1% to 1%): Thrombocytopenia[Ref]

Gastrointestinal

Common (1% to 10%): Nausea
Uncommon (0.1% to 1%): Diarrhea, vomiting, abdominal pain upper[Ref]

Genitourinary

Patients with Peyronie's disease:
Very common (10% or more): Penile hematoma (65.5%), penile swelling (55%), penile pain (45.4%), penile ecchymoses (14.5%), a popping noise or popping sensation in the penis, sometimes described as "snapping" or "cracking", and sometimes accompanied by detumescence, hematoma, and/or pain (13.2%)
Common (1% to 10%): blood blister (4.5%), penile blister (3.3%), genital pruritus (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%)
Uncommon (0.1% to 1%): Corporal rupture (penile fracture) (0.5%)[Ref]

Hematologic

Very common (10% or more): Lymphadenopathy (13%)
Common (1% to 10%): Lymph node pain
Uncommon (0.1% to 1%): Thrombocytopenia[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity[Ref]

Immunologic

Uncommon (0.1% to 1%): Injection site cellulitis, lymphangitis[Ref]

Nervous system

Common (1% to 10%): Burning sensation, dizziness, headache, hypoesthesia, paresthesia
Uncommon (0.1% to 1%): Disorientation, agitation, insomnia, irritability,
restlessness[Ref]

Ocular

Uncommon (0.1% to 1%): Eyelid edema[Ref]

Respiratory

Uncommon (0.1% to 1%): Dyspnea, hyperventilation[Ref]

Some side effects of collagenase clostridium histolyticum may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

0.58 mg injected into a palpable cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint

Comments:
-This drug should be administered by a healthcare provider experienced in injection procedures of the hand and in the treatment of patients with Dupuytren's contracture.
-Up to 2 joints in the same hand may be treated during a treatment visit. Two palpable cords affecting 2 joints may be injected or one palpable cord affecting 2 joints in the same finger may be injected at 2 locations during a treatment visit. If a patient has other palpable cords with contractures of MP or PIP joints, these cords may be injected at other treatment visits approximately 4 weeks apart.
-Approximately 24 to 72 hours following an injection, a finger extension procedure should be performed if a contracture persists. Consult manufacturer product information or local protocol for information on the finger extension procedure.
-Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals.
-Up to 2 cords in the same hand may be injected at a treatment visit. If a patient has other cords with contractures, those cords should be injected at another treatment visit.
-Vital signs should be monitored and appropriate equipment should be available to address any severe local or systemic reactions including the potential for anaphylaxis that may occur following injection.

Use: The treatment of adult patients with Dupuytren's contracture with a palpable cord

US REMS: The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for collagenase clostridium histolyticum. It includes elements to assure safe use, and implementation system. For additional information: htmhttp://www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:
-This drug can cause corporal rupture (penile fracture) or other serious penile injury in the treatment of Peyronie's disease. Corporal rupture (penile fracture) has been reported in 0.5% of patients in clinical studies. In 0.9% of treated patients, a combination of penile ecchymoses or hematoma, sudden penile detumescence, and/or a penile "popping" sound or sensation has been reported, and in these cases, a diagnosis of corporal rupture cannot be excluded. Severe penile hematoma has also been reported in 3.7% of treated patients. Signs of serious penile injury should be promptly evaluated to assess for corporal rupture or severe penile hematoma which may require surgical intervention.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Administration advice:
-Consult the manufacturer product information or local protocol.

Reconstitution/preparation advice:
-Consult the manufacturer product information.

Storage requirements:
-The reconstituted solution can be kept at room temperature 20C to 25C (68F to 77F) for up to one hour or refrigerated at 2C to 8C (36F to 46F) for up to 4 hours prior to administration. If the reconstituted solution is refrigerated, this solution should be allowed to return to room temperature for approximately 15 minutes before use.