Collagenase Clostridium Histolyticum

Collagenase Clostridium Histolyticum is a prescription medication used for the treatment of Dupuytren's contracture, Peyronie disease and cellulite.

• Collagenase Clostridium Histolyticum is available under the following different brand names: Xiaflex, Qwo, and Collagenase Clostridium Histolyticum-aaes.

Common side effects of Collagenase Clostridium Histolyticum include:

• Swelling, bruising, bleeding, pain, or tenderness at the injection site,
• Swollen glands in your elbow or underarm,
• Itching, redness, or warmth of the skin,
• Cracked skin,
• Underarm pain,
• Mild pain or tenderness in the treated hand,
• Bruising of the penis or scrotum,
• Erection problems,
• Discoloration of the penis, and
• Bruising or blisters where the medicine was injected.

Serious side effects of Collagenase Clostridium Histolyticum include:

• Hives,
• Difficulty breathing,
• Swelling of your face, lips, tongue, or throat,
• Chest pain,
• Lightheadedness,
• Numbness,
• Tingling,
• Increased pain,
• Trouble bending the finger toward the wrist, and
• New or worsened movement problems in the treated hand,
• Bruising and swelling of the penis,
• Pain when your urine,
• Blood in the urine,
• Sudden erection problems,
• Popping sound or sensation in the penis during an erection,
• Fever,
• Chills,
• Redness or swelling,
• Severe pain,
• Itching,
• Other irritation, and
• Lightheadedness

Rare side effects of Collagenase Clostridium Histolyticum include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Lyophilized powder for injection plus diluent

• 0.9 mg/vial (Xiaflex)
• 0.92 mg/vial (Qwo)
• 1.84 mg/vial (Qwo)

Dupuytren's Contracture

Adult dosage

• Xiaflex only
  • Inject 0.58 mg into palpable Dupuytren's cord with a contracture of the metacarpophalangeal (MP) joint or proximal interphalangeal (PIP) joint.
  • If contracture persists 24-72 hours following injection, perform finger extension procedure.
  • May repeat injection and finger extension procedures up to 3 times per cord at 4-week intervals.
  • Inject only 1 cord at a time; if other cords with contractures exist, inject each cord in sequential order.
  • Each vial of drug and sterile diluent should only be used for a single injection; if 2 joints on the same hand are to be treated during a treatment visit, separate vials and syringes should be used for each reconstitution and injection.
  • Approximately 24-72 hours after injection, perform a finger extension procedure if a contracture persists to facilitate cord disruption.
  • May reinject four weeks after the initial injection if MP or PIP contracture is still present; may reinject with a single dose of collagenase C histolyticum
  • 2 injections on the same hand per treatment visit
  • Perform up to 2 injections in the same hand during a treatment visit.
  • Two palpable cords affecting 2 joints may be injected or 1 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.

Peyronie Disease

Adult dosage

• Xiaflex only
  • Inject 0.58 mg into a Peyronie plaque; if above 1 plaque is present, inject into the plaque causing the curvature deformity
  • Treatment course consists of a maximum of 4 treatment cycles; each treatment cycle consists of 2 injection procedures and 1 penile modeling procedure for a maximum of 8 injection procedures and 4 modeling procedures.
  • Perform 2nd injection procedure 1-3 days after the 1st.
  • Interval between treatment cycles is approximately 6 weeks.
  • Induce a penile erection; to achieve it may use a single intracavernosal injection of 10 or 20 mcg of alprostadil
  • With the penis in the erect state, identify and mark the target area in the Peyronie plaque to be injected.
  • The penis should be in a flaccid state before injecting.
  • Inject 0.58 mg into target plaque once on each of 2 days, 1 to 3 days apart, according to the injection procedure
  • Perform a penile modeling procedure 1 to 3 days after the second injection of each treatment cycle.
  • For each plaque causing the curvature deformity may administer up to four treatment cycles; may repeat each treatment cycle at approximately six-week intervals; if curvature deformity is above 15 degrees after 1st, the 2nd, or 3rd treatment cycle, or if further treatment is not clinically indicated, do not administer subsequent treatment cycles
  • If curvature deformity is below 15 degrees after 1st, the 2nd, or 3rd treatment cycle, or if the healthcare provider determines that further treatment is not clinically indicated, then do not administer subsequent treatment cycles

Cellulite

Adult dosage

• Qwo only
  • Up to twelve 0.07-mg (0.3-mL) Subcutaneous injections totaling 0.84 mg per treatment area (.e, single buttock)
  • Treatment visits may consist of up to 2 treatment areas.
  • Repeat every 21 days for 3 treatment visits.

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Collagenase Clostridium Histolyticum has no noted severe interactions with any other drugs.
• Collagenase Clostridium Histolyticum has no noted serious interactions with any other drugs.
• Collagenase Clostridium Histolyticum has moderate interactions with the following drugs:
  • antithrombin alfa
  • antithrombin III
  • argatroban
  • aspirin
  • bivalirudin
  • dabigatran
  • dalteparin
  • desirudin
  • enoxaparin
  • fondaparinux
  • heparin
  • protein C concentrate
  • rivaroxaban
• Collagenase Clostridium Histolyticum has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice or health questions or concerns.

Contraindications

• Hypersensitivity
• Peyronie plaques that involve the penile urethra.

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Collagenase Clostridium Histolyticum?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Collagenase Clostridium Histolyticum?”

Cautions

• Do not substitute injectable collagenase products (. e, do not use Xiaflex for cellulite treatment or use Qwo for Dupuytren's contracture or Peyronie disease)
• Serious hypersensitivity, including anaphylaxis, reported; if hypersensitivity occurs, discontinue and institute appropriate medical therapy
• Pruritus is 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 the postmarketing period in patients treated for Peyronie’s disease; these events typically have an onset immediately or within minutes of injection.
  • 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's contracture
  • Tendon rupture of another serious injury to the injected extremity reported in clinical trials; avoid injecting into tendons, nerves, blood vessels, or other collagen-containing structures 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%)
  • Postmarketing cases of skin laceration requiring skin graft after finger extension procedures and local skin and soft-tissue necrosis, some requiring skin grafting or, other surgical interventions including finger amputation reported; signs or symptoms that may reflect serious injury to injected finger/hand should be promptly evaluated because surgical intervention may be required.
• Peyronie Disease
  • Advise patients not to have sex between the first and second injections of the treatment cycle; patients should wait 2 weeks after the second injection of the treatment cycle before resuming sexual activity, provided pain and swelling have subsided.
  • May cause corporal rupture (penile fracture) or another serious injury to the penis; avoid injecting into the urethra, nerves, blood vessels, corpora cavernosa, or other collagen-containing structures of the penis since may result in possible permanent injury (. g, corporal rupture)
  • If a patient experiences severe pain or swelling of the penis, severe purple bruising and swelling of the penis, difficulty urinating or blood in the urine, or sudden loss of ability to maintain an erection, should contact the health care provider.
  • In the postmarketing setting, cases of localized skin and soft tissue necrosis occurring as sequelae of penile hematoma were reported; some cases required surgical intervention.
• Syncope and Presyncope
  • Cases of syncope and presyncope were reported in the postmarketing period in patients treated with this medication.
  • Most, but not all, cases in patients with Peyronie’s disease, occurred in association with post-injection penile pain and hematoma, penile pain with spontaneous erections, and pain during micturition; these potential triggers for the syncopal events suggest a vasovagal mechanism. Make Peyronie’s disease patients aware of the potential for penile pain and painful penile hematoma that could trigger syncope and presyncope after treatment with this drug.
  • In most cases in patients with Dupuytren's’s Contracture, the injection procedure, finger extension procedure, or pain following the procedures were reported as potential triggers for the events, suggesting a vasovagal mechanism; most, but not all cases in patients with Dupuytren's’s contracture occurred in the immediate treatment period (injection or finger extension procedure) or within 1-2 days following injection or finger extension procedure.
  • If presyncope symptoms occur, patients should remain recumbent until symptoms resolve.
  • Syncope may be associated with bodily injuries, including concussion, head abrasion, and other accidental injuries.
• Cellulite
  • Injection site bruising is common; patients with coagulation disorders or using anticoagulants or antiplatelets (except aspirin below 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 the administration, is unknown.

Pregnancy and Lactation

• 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.
• Lactation
  • Data are not available regarding the presence in human milk, its effects on breastfed children, or milk production.
  • Following subcutaneous injection, systemic concentrations were below the bioanalytical assay limit of quantification.