Xiaflex

Dupuytren's Contracture

Xiaflex is used to treat adults with Dupuytren's contracture when a cord can be felt in the palm of the hand. This condition occurs when collagen builds up under the skin, causing one or more fingers to bend toward the palm so they cannot be straightened. The medication is injected directly into the cord to help break it down and improve finger range of motion.

Peyronie's Disease

Xiaflex is also used to treat adult men with Peyronie's disease. This condition involves the development of a scar tissue plaque under the skin of the penis. To be eligible for treatment, the plaque must cause a curvature deformity of at least 30 degrees when the penis is erect. The injection is intended to help reduce the curvature and the associated physical symptoms.

Mechanism of Action

Xiaflex contains two types of enzymes known as collagenases. These enzymes are specifically designed to target and break down collagen, a protein that provides structure to tissues in the body. When collagen builds up excessively, it can form hard cords or plaques that restrict movement or cause physical deformities.

Targeting Collagen Buildup

The medication is injected directly into the area where the collagen has thickened. Once injected, the enzymes work together to dissolve the collagen fibers. This process helps to:

• Soften and weaken the thickened cord in the palm for those with Dupuytren's contracture.
• Break down the hard plaque that causes curvature in those with Peyronie's disease.

By breaking down these structures, Xiaflex allows the affected area to become more flexible. Following the injection, a healthcare provider may perform a manual procedure to help stretch or straighten the area, further improving the range of motion.

Common Side Effects

Most people receiving Xiaflex experience reactions at or near the injection site. Common side effects include:

• Swelling, bruising, or bleeding under the skin
• Pain, tenderness, or itching
• Swollen lymph nodes in the armpit or groin area
• Skin redness or warmth
• Blisters at the injection site

Serious Side Effects

While less common, Xiaflex can cause severe side effects that require immediate medical attention:

• Tendon or ligament damage: In patients treated for Dupuytren's contracture, the medicine may cause a tendon to rupture or ligaments to damage in the hand.
• Penile injury: In patients treated for Peyronie's disease, serious injury to the penis may occur, including corporal rupture (penile fracture), which may require surgery.
• Severe allergic reactions: Symptoms may include hives, swollen face, breathing difficulties, chest pain, or low blood pressure.
• Back pain: Some patients experience sudden back pain, neck pain, or chest stiffness shortly after an injection.
• Fainting: Dizziness or fainting can occur following the procedure.

Contact your healthcare provider immediately if you notice signs of an infection, severe pain, or if you lose the ability to bend your finger after the swelling goes down.

Boxed Warning: Penile Fracture

When used to treat Peyronie's disease, Xiaflex can cause serious injury to the penis, including corporal rupture (penile fracture) or other severe penile tissue damage. These injuries may require surgery to repair. Because of these risks, Xiaflex is only available through a restricted distribution program called the Xiaflex REMS (Risk Evaluation and Mitigation Strategy).

Tendon Rupture and Ligament Damage

Injections for Dupuytren's contracture can cause damage to the tendons or ligaments in the hand. This may result in a tendon rupture, which might require surgical intervention. Healthcare providers typically wait several days after the injection before performing a finger extension procedure to help reduce this risk.

Severe Allergic Reactions

Serious allergic reactions, including anaphylaxis, have occurred after Xiaflex injections because the medication contains foreign proteins. Patients are generally monitored for at least 30 minutes after the procedure. Signs of a severe reaction may include:

• Hives or skin rash
• Swelling of the face, lips, or tongue
• Difficulty breathing or wheezing
• Chest pain, dizziness, or fainting

Bleeding Risks

Xiaflex injections often cause bruising or bleeding at the site of the injection. There is an increased risk of serious bleeding for individuals with underlying bleeding disorders or those taking blood-thinning medications (anticoagulants). These patients require careful monitoring.

Severe Back Pain

Some patients receiving treatment for Peyronie's disease have reported sudden, severe back pain that can spread to the legs or chest. This reaction typically occurs shortly after the injection and generally resolves within a short period.

Contraindications

Xiaflex should not be used in individuals who have a history of severe allergic reactions to collagenase clostridium histolyticum or any other ingredients in the injection. It should also not be used to treat Peyronie's disease if the condition involves the tube that carries urine out of the body (the urethra).

Pregnancy

It is not known whether Xiaflex can cause harm to an unborn baby or affect reproductive capacity. There are no adequate and well-controlled studies of Xiaflex in pregnant women, and animal reproduction studies have not been performed.

While Xiaflex is injected locally and typically does not reach significant levels in the bloodstream, patients should discuss the potential risks and benefits with their healthcare provider if they are pregnant or planning to become pregnant.

Breastfeeding

It is unknown if Xiaflex passes into breast milk or if it could affect a nursing child. Because many drugs are excreted in human milk, caution is recommended when administering this medication to a person who is breastfeeding.

Individuals should consult with their doctor to determine if the benefits of treatment outweigh any potential risks to the infant while nursing.

Dosage Forms

Xiaflex is supplied as a sterile, preservative-free powder in a vial. It is intended for reconstitution, which means it must be mixed with a liquid before it can be used.

Packaging and Preparation

The medication is typically provided in a kit that includes:

• Lyophilized Powder: A concentrated, freeze-dried form of the medication.
• Sterile Diluent: A specific liquid used to dissolve the powder for injection.

Xiaflex is administered as an intralesional injection, meaning it is injected directly into the target tissue by a trained healthcare professional in a clinical setting. Each vial of powder and diluent is intended for a single use only, and any unused portion must be discarded after the procedure.

FDA Approval History

Xiaflex (collagenase clostridium histolyticum) was first approved by the U.S. Food and Drug Administration (FDA) in February 2010 for the treatment of Dupuytren's contracture in adults with a palpable cord. In December 2013, the FDA expanded its approval to include the treatment of adult men with Peyronie's disease who have a palpable plaque and a curvature deformity of at least 30 degrees at the start of therapy.

Boxed Warning

The FDA has issued a boxed warning for Xiaflex regarding the risk of corporal rupture (penile fracture) or other serious penile injuries when the drug is used to treat Peyronie's disease. These injuries can occur if the medication is injected into certain structures of the penis other than the target plaque.

REMS Program

Because of the risks of serious injury, Xiaflex is only available through a restricted distribution program called the Xiaflex Risk Evaluation and Mitigation Strategy (REMS). The requirements of this program include:

• Healthcare providers must be certified with the REMS program by completing training on the administration of the drug.
• Healthcare facilities must be certified and ensure that the drug is only dispensed for use by certified providers.
• The drug must only be administered by healthcare professionals trained in the management of the specific conditions it treats.

Other Regulatory Considerations

Xiaflex is a biological product. There are currently no approved generic or biosimilar versions of this medication. The FDA continues to monitor the safety of the product through post-marketing reports, which have included warnings about the risk of hypersensitivity reactions, including anaphylaxis, and the risk of tendon rupture when used for Dupuytren's contracture.

Factors Influencing Cost

The overall expense for Xiaflex treatment involves several components beyond the price of the medication itself:

• Medication Price: The cost of the vial is a primary factor. Because Xiaflex is a specialized biologic, it typically has a high list price.
• Administration Fees: Xiaflex must be administered by a healthcare professional who has been specifically trained in the injection technique. Patients will incur costs for the office visit and the medical procedure.
• Treatment Cycles: The number of injections needed varies by patient. For Dupuytren's contracture, multiple injections may be needed if the cord persists. For Peyronie's disease, a full treatment course typically involves multiple injection cycles.

Insurance and Prior Authorization

Most private insurance plans and Medicare cover Xiaflex for its FDA-approved uses. However, insurance companies often require prior authorization, which means the healthcare provider must prove the treatment is medically necessary before the insurer agrees to pay. Patients should check their specific plan details to understand their deductibles, copayments, or coinsurance responsibilities.

Financial Assistance

Financial assistance programs may be available to help eligible patients manage out-of-pocket costs. These often include:

• Copay Cards: For patients with commercial insurance, the manufacturer may offer programs to reduce the cost of the medication.
• Patient Assistance Programs: Patients who are uninsured or meet certain income requirements may be eligible for assistance to receive the medication at a lower cost or for free.

It is recommended that patients contact their insurance provider and the healthcare facility's billing department for a comprehensive cost estimate before starting treatment.