• Xiaflex is a brand (trade) name for collagenase clostridium histolyticum, which may be used to treat Dupuytren's contracture in adults and Peyronie's disease in adult men.
• Xiaflex (collagenase clostridium histolyticum) contains a mixture of two enzymes (AUXI and AUXII) derived from the fermentation of Clostridium histolyticum bacteria. These enzymes are proteinases that are highly specific for collagen and can break it down. Because the cord of a Dupuytren's contracture is mainly composed of collagen, administration of Xiaflex can result in a disruption of this cord and an easing of symptoms. In Peyronie's disease, the plaque is mainly composed of collagen that can harden to the thickness of bone. Xiaflex actively targets the Peyronie's plaque to break it down and together with manual stretching and straightening this can help reduce the degree of curvature of the penis.
• Xiaflex belongs to the class of medicines known as collagen-specific enzymes.

• Xiaflex may be used to treat adults with Dupuytren’s contracture and a palpable cord.
• Xiaflex is a nonsurgical treatment for Peyronie's disease in adult men who have a palpable plaque and curvature deformity of at least 30 degrees at the start of treatment.
• Nonsurgical option.
• At recommended dosages, Xiaflex does not damage arteries, nerves, or large veins because these contain type 4 collagen. Xiaflex only acts on type 1 and 3 collagen.
• Successfully resolves Dupuytren’s contracture to within 0 to 5 degrees of normal after up to 3 injections (by day 90) in 44% to 64% of people.
• May work better for people who have Dupuytren's contracture in their metacarpophalangeal (MP) joint as the studies report that the contracture resolved to within 0 to 5 degrees of normal in 77% of people with an MP contracture compared to only 40% of people with PIP contracture. Only 7% (study 1) and 5% (study 2) of people reported an improvement with a placebo treatment (which was a saline treatment).
• A 33% to 35% improvement in penile curvature was reported in two studies that investigated treatment with Xiaflex for 832 men with Peyronie's disease. These trials excluded men with a penile curvature deformity of less than 30 degrees and those with a ventral curvature deformity, an isolated hourglass deformity, or a calcified plaque that could have interfered with the injection technique.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Bruising and pain at and around the site of injection. This is caused by small blood vessels leaking because their support is affected by collagen and when this breaks down they leak which causes the appearance of bruising. 3.7% of patients reported severe bruising.
• Other common side effects include swelling, bruising, bleeding, pain, and tenderness. Skin tears, redness, and lymph node pain and swelling have also been reported. In men receiving Xiaflex for Peyronie's disease, painful erections, scrotal swelling, skin discoloration, and pain when urinating have also been reported.
• Intense lower back pain that sometimes radiates to the legs, arms, or chest has been reported after the administration of Xiaflex for Peyronie's disease. These events tend to last 15 to 30 minutes and most resolved without any intervention.
• Fainting or dizziness has been reported following Xiaflex injection, most commonly in people reporting pain following injection for Peyronie's disease or Dupuytren's contracture. If this occurs, keep the person lying down until the symptoms resolve.
• The risk of Xiaflex-associated pruritus increased the more injections given (15% reported pruritus after 3 Xiaflex injections) for Dupuytren's contracture, but not with Peyronie's disease (4% risk of pruritus).
• Serious side effects such as corporal rupture (penile fracture) were reported in 5 of 1044 (0.5%) men treated with Xiaflex for Peyronie's disease. 9 out of 1044 (0.9%) of men treated with Xiaflex for Peyronie's disease reported a sudden loss of erection and/or a penile “popping” sound or sensation which could also indicate a corporal rupture. Because of these serious risks, Xiaflex is only available through a Risk Evaluation and Mitigation Strategy (REMS) program, called the Xiaflex REMS.
• Flexor tendon ruptures have occurred after a Xiaflex injection. Accidental injections into tendons or ligaments may result in potentially permanent damage to these structures. Take care to avoid injecting into tendons, nerves, blood vessels, or other collagen-containing structures of the hand.
• Pulley ruptures, complex regional pain syndrome, sensory abnormalities, and skin lacerations have also been reported. Some skin lacerations have required skin grafting or, rarely, amputation.
• Injection into collagen-containing structures such as the corpora cavernosa of the penis may result in damage to these structures and possible injury. Take care to avoid injecting into the urethra, nerves, blood vessels, corpora cavernosa, or other collagen containing structures.
• Must be administered by a healthcare professional experienced in administering hand injections for the treatment of Dupuytren's contracture or one experienced in the treatment of male urological diseases who has completed training in the use of Xiaflex for Peyronie's disease.
• Should not be given to men with Peyronie's plaque that involve the penile urethra because Xiaflex may cause damage to this structure, or to men with a history of hypersensitivity to Xiaflex or collagenases.
• Xiaflex should be stored in the refrigerator prior to reconstitution. Once reconstituted, Xiaflex can be kept at room temperature for up to 1 hour or refrigerated and used within 4 hours.
• May not be suitable for people taking anticoagulants or aspirin because of the increased risk of bleeding.
• Xiaflex has not been studied in children and should not be used in people under the age of 18 years.
• There are no studies regarding the use of Xiaflex in women who are pregnant or breastfeeding. Use only if the benefits outweigh the risks.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

• Your doctor will usually administer a local anesthetic before giving you a Xiaflex injection, so receiving the actual injection is not uncomfortable. However, some people report significant injection site pain and discomfort, swelling, and bruising for up to 48 hours after receiving the injection. In some, the pain persists for longer.
• It takes at least a week for your hand to recover after a Xiaflex injection for Dupuytren's contracture, in some people it may take 2 to 4 weeks before they can fully use their hand again, especially if you have skin tears which will need daily wound care.
• Immediately after being given Xiaflex for Dupuytren's contracture, your hand will be wrapped in a soft dressing and will be bruised and swollen but you should be able to drive yourself home (if you drive). You should avoid flexing the fingers of the injected hand or any kind of heavy lifting or pushing or pulling with the affected hand for at least a week, but you can use your hand for gentle everyday activities such as eating, writing, brushing your teeth, writing, typing, or preparing food. Elevate the injected hand until bedtime on the day of the injection. After 1 week you can return to playing golf, tennis, and other recreational activities, but if you have skin tears you will need to wait until the wound heals before you do any recreational activities. You may need to wear a splint at bedtime for up to 4 months and perform a series of finger flexion and extension exercises each day.
• Call your doctor immediately if you have any signs of infection (such as fever, chills, increasing redness, or swelling), or difficulty bending the fingers after the swelling goes down.
• Your doctor should ask you to come back for an examination and possible finger extension procedures 1 to 3 days after the injection.
• If you have had a Xiaflex injection for Peyronie’s disease, the recovery time varies depending on how much pain or swelling is present but generally takes 2 to 4 weeks. You should not have sex or have any other sexual activity between the 2 injections of a treatment cycle and for at least 4 weeks after the second injection of a treatment cycle. During this time you should also avoid activities and situations that may cause you to strain your abdominal muscles (such as sit-ups or straining during a bowel movement) and vacuum erection devices. Immediately after the procedure, your penis may appear bruised or swollen, and you may have mild to moderate pain in your penis that can be relieved with over-the-counter pain medications such as acetaminophen or ibuprofen. Some men may also experience sudden back pain following the procedure that can radiate to the legs, chest, and arms that typically last only 15 minutes. If you experience this or any other serious side effect then talk to your healthcare provider.
• Call your doctor immediately if you experience severe pain or swelling in your penis, difficulty urinating or blood in the urine, or sudden loss of the ability to maintain an erection. These symptoms may be accompanied by a popping or cracking sound from the penis. Do not have sex between the first and second injections of a treatment cycle, and then wait 4 weeks after the second injection before resuming sexual activity. Perform gentle penile modeling activities at home as recommended by your doctor. Avoid abdominal straining, for example, with constipation (treat with laxatives).
• Xiaflex for Peyronie's disease can only be administered by healthcare providers that have completed training in the administration of Xiaflex.
• Tell your healthcare provider immediately if you experience any severe side effects, such as an allergic reaction (symptoms include significant swelling, a rash, or significant itch), significant bleeding or bruising, intense lower back pain, chest pain, or shortness of breath.

• Xiaflex starts to work within 30 days for some people with Dupuytren’s Contracture, but some people may have to wait up to 90 days to see a result. Up to 39% report an improvement after 30 days which increases to up to 64% by 90 days.
• For Dupuytren’s contracture, two trials (total number =374 adults) investigated the effectiveness of Xiaflex at reducing the contracture of the selected primary joint (metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint) to within 0 to 5 degrees of normal, 30 days after the last injection of that joint. Injections were given on days 0, 30, and 60, and results were measured on days 30, 60, or 90. Up to 3 injections were given.
• After the endpoint of the study (after 90 days), the MP or PIP joints of 64% of people in study 1 and 44% of people in study 2 had improved to within 0 to 5 degrees of normal.
• 39% of people had improved to within 0 to 5 degrees of normal after 1 injection (at day 30) in study 1 and 27% had improved to within 0 to 5 degrees of normal by day 30 in study 2.
• When Xiaflex is used to treat Peyronie’s Disease, it may take several months for it to start working although some improvements may be noticed within the first month or two. Maximal effects may not be seen for at least 24 weeks. Trials reported on outcomes at 52 weeks.
• The two trials that investigated the effectiveness of Xiaflex for Peyronie’s disease reported on two outcomes after 52 weeks: percentage change in abnormal curvature and reduction in patient-reported bother regarding Peyronies disease and its effects on the man’s quality of life.
• In Study 1 there was a significant change in the baseline deformity of -35.0% which compared with -17.8% for those administered placebo (an inactive treatment), making an overall difference of 17.2%. There was also a significant improvement of 2.8 points in the patient-reported bother score, which was 1.2 points higher than that observed with a placebo.
• In study 2, there was a significant change in the baseline deformity of -33.2% with Xiaflex compared to -21.8% with placebo making an overall difference of 11.4%. There was also a significant change in patient-reported bother score of 2.6 points, with an overall improvement of 1.1 compared with placebo.
• These trials used 4 treatment cycles of Xiaflex or placebo, each given 6 weeks apart (weeks 0, 6, 12, 18) with a follow-up at 24 and 52 weeks. Patients were also asked to perform penile modeling at home which consisted of gently stretching the penis 3 times a day for 6 weeks after each treatment cycle, and straightening the penis daily if an erection occurred without any sexual activity.

Medicines that interact with Xiaflex may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Xiaflex. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Xiaflex include:

• aspirin
• anticoagulants, such as apixaban, dabigatran, clopidogrel, rivaroxaban, and warfarin
• heparin
• streptokinase
• tetracycline
• urokinase.

Note that this list is not all-inclusive and includes only common medications that may interact with Xiaflex. You should refer to the prescribing information for Xiaflex for a complete list of interactions.