What to Know About Xiaflex (Collagenase Clostridium Histolyticum)

Xiaflex (collagenase clostridium histolyticum) is a prescription injection used to treat Dupuytren's contracture and Peyronie's disease. Approved in 2010, it is made up of several types of collagenase that come from bacteria. Collagenase is an enzyme that digests, or breaks down, collagen proteins. Symptoms of both Dupuytren's contracture and Peyronie's disease include abnormal collagen growth in affected areas.

Uses

Xiaflex is approved by the U.S. Food and Drug Administration (FDA) for treatment of adults with Dupuytren's contracture and for adult men with Peyronie's diseases with a palpable plaque and curvature deformity. It does not have any off-label uses.

Before Taking

Indications for Xiaflex depend on what condition you are being treated for.

Patients with Peyronie's Disease

Xiaflex is the only FDA-approved, non-surgical treatment for Peyronie's disease.

This drug, which is injected into penile plaques, is approved for the treatment of men with stable penile curvature. This means that men with active Peyronie's disease are not generally considered to be appropriate for Xiaflex treatment.

Treatment with Xiaflex in patients with acute-phase disease is considered to be off-label.

In addition, treatment with Xiaflex has not been shown to be as effective for men with the following types of Peyronie's symptoms:

• Hourglass deformity (indentation rather than curvature of the penis)
• Calcified, or hardened, plaques

Patients with Dupuytren's Contracture

As with Peyronie's disease, Xiaflex is the only FDA-approved, non-surgical option for treating Dupuytren's contracture. It is indicated for use only in individuals over 18 years of age.

Injections should only be given to people who have contractures of between 20 and 100 degrees for the metacarpophalangeal joint⁠—this is the joint between the hand and the finger. It can also be used for people with contractures of between 20 and 90 degrees of the proximal interphalangeal joint (first finger joint, not thumb).

In order for this treatment to be used, patients must have some flexion contracture. This is because the finger must be extended after treatment to disrupt the contracted cord.

Precautions and Contraindications

Xiaflex should not be used by anyone who has had an allergic reaction to any collagenase product. It should also not be used by anyone who is allergic to any of the following ingredients that are present in the medication:

• Hydrochloric acid
• Sucrose
• Tromethamine
• Calcium chloride dihydrate
• Sodium chloride  

Patients whose Peyronie's disease involve the urethra should not use Xiaflex.

Xiaflex is contraindicated in people who:

• Have a history of bleeding problems
• Use anti-coagulation therapy within the week prior to injection (low dose aspirin is acceptable)
• Have had previous treatment with Xiaflex for another condition

The impact of Xiaflex on pregnancy and newborns has not been studied.

Dosage

All listed dosages are according to the drug manufacturer. Check your prescription and talk to your healthcare provider to make sure you are taking the right dose for you.

Xiaflex is injected into the affected tissue by a healthcare provider.

Xiaflex Treatment for Dupuytren's Contracture

According to the manufacturer, treatment for Dupuytren's contracture involves injecting 0.58 milligrams (mg) of Xiaflex into each palpable, contracted cord. Up to two joints in the same hand can be treated during a single visit, however, any more should be treated at separate visits. Higher numbers of cords requiring treatment can be an indication for surgery.

Approximately 24 to 72 hours after injection, a finger extension procedure is performed. This extension can help break down the injected cords.

The process of injection and finger extension can be repeated up to three times for each cord. This should be done at approximately four-week intervals, as needed.

Xiaflex Treatment for Peyronie's Disease

According to the manufacturer, treatment for Peyronie's disease involves injecting 0.58 mg of Xiaflex into an identified plaque. In order to identify the plaque to be treated, an erection is first induced (either naturally or by injection.) The plaque is then marked.

Once the penis is again flaccid, and only when the penis is flaccid, the Xiaflex is injected. This injection is then repeated a second time⁠—one to three days after the first injection.

Approximately one to three days after the second injection, the healthcare provider will perform a penile modeling procedure. This involves stretching and reshaping the penis to try and increase length and reduce curvature. The healthcare provider will also teach you how to gently stretch and straighten your penis.

The manufacturer recommends stretching the flaccid penis three times a day, and straightening the penis up to once a day, for the six weeks after each treatment cycle. However, the penis should only be straightened if you have a spontaneous erection.

Treatment can be repeated up to four times for each plaque. Re-treatment is recommended by the manufacturer to occur at approximately six-week intervals. Treatment should stop if curvature decreases to less than 15 degrees or it is otherwise not clinically indicated.

Side Effects

Again, side effects will differ depending on which condition you're being treated for.

Common Side Effects of Treatment for Dupuytren's Contracture

A quarter or more of patients being injected with Xiaflex for Dupuytren's contracture will experience one or more of the following side effects:

• Swelling of the injected hand
• Bruising
• Hemorrhage (excessive bleeding) at the injection site
• Other injection site reactions
• Pain

Severe Side Effects of Treatment for Dupuytren's Contracture

In rare cases, Dupuytren's contracture treatment with Xiaflex can lead to rupture of the flexor tendon. If the drug is injected incorrectly into tendons or ligaments, they can be temporarily or permanently damaged. Therefore proper training and injection technique is critical to safety.

Other severe reactions reported include:

• Pulley rupture
• Ligament injury
• Complex regional pain syndrome (CRPS)
• Sensory abnormalities of the hand
• Skin tears

The risk of skin tears is highest in patients treated with multiple injections at the same time.

Common Side Effects of Treatment for Peyronie's Disease

Side effects affecting more than one in four patients with Peyronie's disease include:

• Bruising of the penis
• Swelling of the penis
• Pain

Severe Side Effects of Treatment for Peyronie's Disease

Serious side effects have occurred in people being injected with Xiaflex for Peyronie's treatment. These include:

• Penile fracture, which the manufacture reports occurring in 0.5% of patients in clinical trials
• Combinations of severe penile swelling or bruising with a sudden loss of erection and/or a penile "popping sound" that cannot be ruled out as penile fracture. The manufacturer reports this occurring in 0.9% of patients in clinical trials.
• Severe penile bruising

These side effects may require surgical treatment. Therefore any symptoms that might reflect a serious penile injury should be reported to your healthcare provider immediately.

Concerns about Xiaflex treatment effects are significant enough that healthcare providers can only use it to treat Peyronie's disease if they are certified by the medication's REMS program. REMS stands for "risk evaluation and mitigation strategies."

In order to join the REMS program for Peyronie's treatment, healthcare providers must undergo training in Xiaflex administration. Healthcare sites where the drug is available must also be certified and agree to make certain that the medication is only used by certified prescribers.

Warnings and Interactions

The manufacturer warns about the risk of serious injury after injection, as described above. Penile fracture, and potential penile fracture, are a high enough risk that the drug has a boxed warning for treatment of Peyronie's disease.

The manufacturer reports that there is a risk of hypersensitivity reactions and anaphylaxis (allergic reaction) for people being injected with Xiaflex. Such reactions can occur after up to three injections in Dupuytren's patients and four injections in Peyronie's patients. Severe allergic reactions to Xiaflex are extremely rare, but healthcare providers injecting the medication should be prepared to treat anaphylaxis.

There is also a significant risk of bleeding in patients who have a history of bleeding problems and are treated with Xiaflex. The manufacturer recommends caution in using Xiaflex with any patient who has a diagnosed clotting problem or who is taking anti-coagulation therapy. In general, treatment with Xiaflex is not recommended for patients taking anticoagulants. The sole exception to this is individuals receiving low dose aspirin (up to 150 mg/day).