Xiaflex (collagenase clostridium histolyticum)

Xiaflex is approved for two uses: Dupuytren’s contracture and Peyronie’s disease. Information is provided separately for each use. Use for treating Dupuytren's contracture is described first, followed by use for treating Peyronie’s disease.

Xiaflex is a prescription medicine used to treat adults with Dupuytren’s contracture when a “cord” can be felt.

Xiaflex is a prescription medicine used to treat adult men with Peyronie’s disease who have a “plaque” that can be felt and a curve in their penis greater than 30 degrees when treatment is started.

It is not known if Xiaflex is safe and effective in children under the age of 18.

Who should not receive Xiaflex?

Do not receive Xiaflex if you:

• are allergic to collagenase clostridium histolyticum, any of the ingredients in Xiaflex, or any other collagenase product.
• have been told by your healthcare provider that the Peyronie’s plaque to be treated involves the “tube” that your urine passes through (urethra).

Talk to your healthcare provider before receiving this medicine if you have any of these conditions.

What should I tell my healthcare provider before receiving Xiaflex?

Before receiving Xiaflex, tell your healthcare provider if you:

• have had an allergic reaction to a Xiaflex injection in the past
• have a bleeding problem
• have received Xiaflex to treat another condition
• have any other medical conditions

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Using Xiaflex with certain other medicines can cause serious side effects.

Especially tell your healthcare provider if you take:

• medicines to thin your blood (anticoagulants). If you are told to stop taking a blood thinner before your Xiaflex injection, your healthcare provider should tell you when to restart the blood thinner.

Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

WARNING

Corporal Rupture (Penile Fracture) or Other Serious Penile Injury in the Treatment of Peyronie’s Disease

Corporal rupture (penile fracture) was reported as an adverse reaction in 5 of 1044 (0.5%) Xiaflex-treated patients in clinical studies. In other Xiaflex-treated patients (9 of 1044; 0.9%), a combination of penile ecchymoses or hematoma, sudden penile detumescence, and/or a penile “popping” sound or sensation was reported, and in these cases, a diagnosis of corporal rupture cannot be excluded. The severe penile hematoma was also reported as an adverse reaction in 39 of 1044 (3.7%) Xiaflex-treated patients.

Signs or symptoms that may reflect serious penile injury should be promptly evaluated to assess for corporal rupture or severe penile hematoma which may require surgical intervention.

Because of the risks of corporal rupture or another serious penile injury, Xiaflex is available for the treatment of Peyronie’s disease only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Xiaflex REMS Program.

Xiaflex may cause serious side effects, including:

increased chance of bleeding. Bleeding or bruising at the injection site can happen in people who receive Xiaflex. Talk to your healthcare provider if you have a problem with your blood clotting. Xiaflex may not be right for you.

What is the most important information I should know about Xiaflex for the treatment of Dupuytren’s contracture?

Xiaflex can cause serious side effects, including:

• Tendon rupture or ligament damage. Receiving an injection of Xiaflex may cause damage to a tendon or ligament in your hand and cause it to break or weaken. This could require surgery to fix the damaged tendon or ligament. Call your healthcare provider right away if you have trouble bending your injected finger (towards the wrist) after the swelling goes down or if you have problems using your treated hand after your follow-up visit.
• Nerve injury or another serious injury of the hand. Call your healthcare provider right away if you get numbness, tingling, increased pain, or tears in the skin (laceration) in your treated finger or hand after your injection or after your follow-up visit.
• Hypersensitivity reactions, including anaphylaxis. Severe allergic reactions can happen in people who receive Xiaflex because it contains foreign proteins.

Call your healthcare provider right away if you have any of these symptoms of an allergic reaction after an injection of Xiaflex:

• hives
• swollen face
• breathing trouble
• chest pain
• low blood pressure
• dizziness or fainting

The most common side effects with Xiaflex for the treatment of Dupuytren’s contracture include:

• swelling of the injection site or the hand
• bruising or bleeding at the injection site
• pain or tenderness of the injection site or the hand
• swelling of the lymph nodes (glands) in the elbow or armpit (axilla)
• itching
• breaks in the skin
• redness or warmth of the skin
• pain in the armpit

What is the most important information I should know about Xiaflex for the treatment of Peyronie’s disease?

Xiaflex can cause serious side effects, including:

• Penile fracture (corporal rupture) or another serious injury to the penis. Receiving an injection of Xiaflex may cause damage to the tubes in your penis called the corpora. After treatment with Xiaflex, one of these tubes may break during an erection. This is called a corporal rupture or penile fracture. This could require surgery to fix the damaged area. Damage to your penis might not get better after a corporal rupture.
  • After treatment with Xiaflex, blood vessels in your penis may also break, causing blood to collect under the skin (hematoma). This could require a procedure to drain the blood from under the skin.
    • Symptoms of corporal rupture or another serious injury to your penis may include:
      • a popping sound or sensation in an erect penis
      • sudden loss of the ability to maintain an erection
      • pain in your penis
      • purple bruising and swelling of your penis
      • difficulty urinating or blood in the urine

Call your healthcare provider right away if you have any of the symptoms of corporal rupture or serious injury to the penis listed above.

Do not have sex or any other sexual activity between the first and second injections of a treatment cycle.

Do not have sex or have any other sexual activity for at least 4 weeks after the second injection of a treatment cycle with Xiaflex and after any pain and swelling have gone away.

Xiaflex for the treatment of Peyronie’s disease is only available through a restricted program called the Xiaflex Risk Evaluation and Mitigation Strategy (REMS) Program. For more information about the Xiaflex REMS Program go to www.XiaflexREMS.com or call 1-877-942-3539.

• Hypersensitivity reactions, including anaphylaxis. Severe allergic reactions can happen in people who receive Xiaflex because it contains foreign proteins.

Call your healthcare provider right away if you have any of these symptoms of an allergic reaction after an injection of Xiaflex:

• hives
• swollen face
• breathing trouble
• chest pain
• low blood pressure
• dizziness or fainting

The most common side effects with Xiaflex for the treatment of Peyronie’s disease include:

• a small collection of blood under the skin at the injection site (hematoma)
• swelling at the injection site or along your penis
• pain or tenderness at the injection site, along your penis, and above your penis
• penis bruising
• itching of your penis or scrotum (genitals)
• painful erection
• erection problems (erectile dysfunction)
• changes in the color of the skin of your penis
• blisters at the injection site
• pain with sex
• a lump at the injection site (nodule)

Tell your healthcare provider if you have any side effect that bothers you or does not go away.

These are not all of the possible side effects of Xiaflex. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dosing Overview for Dupuytren's Contracture

Xiaflex should be administered by a healthcare provider experienced in injection procedures of the hand and the treatment of patients with Dupuytren's contracture.

Xiaflex, supplied as a lyophilized powder, must be reconstituted with the provided diluent before use. The dose of Xiaflex is 0.58 mg per injection into a palpable cord with a contracture of a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint. Each vial of Xiaflex and sterile diluent should only be used for a single injection. If two 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.

Table 1 displays an overview of the volumes of sterile diluent for reconstitution and the reconstituted Xiaflex solution to be used in the intralesional injection. Approximately 24 to 72 hours after injection, perform a finger extension procedure if a contracture persists to facilitate cord disruption.

Table 1. Volumes Needed for Reconstitution and Administration for Dupuytren's Contracture

Dosing Overview of Peyronie's Disease

Xiaflex should be administered by a healthcare provider experienced in the treatment of male urological diseases, who has completed the required training for use of Xiaflex in the treatment of Peyronie's disease.

Xiaflex, supplied as a lyophilized powder, must be reconstituted with the provided diluent before use. The dose of Xiaflex is 0.58 mg per injection administered into a Peyronie's plaque. If more than one plaque is present, inject it into the plaque causing the curvature deformity.

A treatment course consists of a maximum of 4 treatment cycles. Each treatment cycle consists of two Xiaflex injection procedures and one penile modeling procedure. The second Xiaflex injection procedure is performed 1 to 3 days after the first. The penile modeling procedure is performed 1 to 3 days after the second injection of the treatment cycle. The interval between treatment cycles is approximately six weeks. The treatment course, therefore, consists of a maximum of 8 injection procedures and 4 modeling procedures.

If the curvature deformity is less than 15 degrees after the first, second or third treatment cycle, or if the healthcare provider determines that further treatment is not clinically indicated, then the subsequent treatment cycles should not be administered.

The safety of more than one treatment course of Xiaflex is not known.

Table 2 displays an overview of the volume of sterile diluent for reconstitution and the reconstituted Xiaflex solution to be used in the intralesional injection.

Table 2. Volumes Needed for Reconstitution and Administration

Anticoagulant drugs: Xiaflex should be used with caution in patients receiving concomitant anticoagulants (except for low-dose aspirin). 

Before receiving Xiaflex, tell your healthcare provider if you:

• are pregnant or plan to become pregnant. It is not known if Xiaflex will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if Xiaflex passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you receive Xiaflex.