How does XIAFLEX® work?

XIAFLEX® helps disrupt 2 collagen types within a Peyronie's plaque1

  • At higher doses and longer incubation times, nonfibrillar type IV collagen was affected causing collagen lysis in small veins1
  • Did not cause structural damage to arteries, nerves, or large veins that contain type IV collagen in in vitro or in vivo studies1
  • There are no clinical data regarding the relative contributions of the individual collagenases to the efficacy of XIAFLEX® in the treatment of Peyronie’s disease1

Injection of XIAFLEX® into collagen-containing structures such as the corpora cavernosa of the penis may result in damage to those structures and possible injury such as corporal rupture (penile fracture). Therefore, XIAFLEX® should be injected only into the Peyronie’s plaque and care should be taken to avoid injecting into the urethra, nerves, blood vessels, corpora cavernosa, or other collagen-containing structures of the penis.1

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AUA Peyronie's disease treatment guideline for XIAFLEX®

In 2015, the American Urological Association (AUA) published a guideline that provides a clinical framework for the diagnosis and treatment of Peyronie's disease. The following guideline statements are specific to XIAFLEX®.

Clinicians may administer intralesional collagenase clostridium histolyticum in combination with modeling by the clinician and by the patient for the reduction of penile curvature in patients with stable Peyronie's disease, penile curvature >30° and <90°, and intact erectile function (with or without the use of medications). (Moderate Recommendation; Evidence Strength Grade B)2

Clinicians should counsel patients with Peyronie's disease prior to beginning treatment with intralesional collagenase regarding potential occurrence of adverse events, including penile ecchymosis, swelling, pain, and corporal rupture. (Clinical Principle)2

  • Moderate Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is moderate2
  • Body of Evidence Strength Grade B in support of a Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances but that better evidence could change confidence2

A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature.2

What does treatment with XIAFLEX® consist of?

A treatment course of XIAFLEX® takes ~24 weeks and consists of up to 4 treatment cycles approximately 6 weeks apart1

HCP=healthcare professional.

If the curvature deformity is less than 15 degrees after the first, second, or third treatment cycle, or if further treatment is not clinically indicated, then subsequent treatment cycles should not be administered.1

The safety of more than one treatment course of XIAFLEX® is not known.1

Each treatment cycle involves1:

  • 3 office visits over the course of 3–7 days
  • Each cycle begins with the injection of XIAFLEX® into the palpable Peyronie's plaque
  • The second injection is performed 1–3 days later after the first injection
    • Based on patient's penile swelling, you can assess if he is ready for the second injection
  • In-office modeling is performed 1–3 days after the second injection
  • The patient then performs at-home daily penile modeling for approximately 6 weeks

See the XIAFLEX® treatment procedure

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Penile modeling: Helps reduce erectile curvature and straighten the penile shaft1

Offer patients a guide for treatment and at-home modeling

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Storage & preparation of XIAFLEX®

1
Rest & Check
A vial of XIAFLEX® and a vial of sterile diluent, side-by-side
1

Let Stand at room temperature (68°F to 77°F; 20°C to 25°C).
At least 15 minutes, but no longer than 60 minutes.1

Note: Images of vials shown are not actual size.

2
Rest & Check
An example of what intact powder looks like versus eroded powder for XIAFLEX®
2

Visually Inspect the cake of XIAFLEX® powder–it should be intact and white in color.

If eroded, call Endo at 1-800-462-3636.1

3
Reconstitution
A physician swabbing the full surface of the vial
3

Swab rubber stopper and surrounding surface of each vial using aseptic technique with sterile alcohol after removal of the flip-off cap from each vial. No other antiseptics should be used.1

4
Reconstitution
Use a 1 milliliter syringe, with 0.01 milliliter graduations, and a 27 guage 0.5 inch needle, which is not supplied
4

Withdraw 0.39 mL of sterile diluent. Use only the diluent supplied—it contains calcium, which is required for the activity of XIAFLEX®.1

5
Reconstitution
A physician holding a syringe fully inserted into a vial of XIAFLEX®
5

Aim syringe toward the side of the vial of XIAFLEX® powder and slowly inject diluent. Do not invert the vial or shake the solution. Slowly swirl the solution to ensure that all of the lyophilized powder has gone into the solution. Do not use if opaque particles, discoloration, or other foreign particles are present.1

6
Dose Prep
Identify treatment area, then use a new hubless syringe containing 0.01 milliliter graduations with a permanently fixed 27 guage 0.5 inch needle (1)
6

Withdraw 0.25 mL reconstituted solution (0.58 mg of XIAFLEX®) using the hubless syringe.1

Prior to withdrawal, if solution contains particulates or is cloudy or discolored, do not use. The entire reconstituted XIAFLEX® solution contains 0.9 mg of XIAFLEX® and is for single use. Discard unused portion.1

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Storage

Before Reconstitution1

Vial of XIAFLEX® and vial of the supplied diluent

Store in refrigerator (36°F to 46°F; 2°C to 8°C).

Do not freeze. Ensure both vials are upright prior to refrigerating.

After Reconstitution1

Vial of XIAFLEX® solution

Can be kept at room temperature (68°F to 77°F; 20°C to 25°C) for up to 1 hour or refrigerate (36°F to 46°F; 2°C to 8°C) for up to 4 hours prior to administration.

If refrigerated, let stand at room temperature for approximately 15 minutes before use.

See how an experienced injector reconstitutes XIAFLEX®

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INDICATION

XIAFLEX® is indicated for the treatment of adult men with Peyronie's disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.


Important Safety
Information for XIAFLEX

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. 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 other 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.

INDICATION

XIAFLEX® is indicated for the treatment of adult men with Peyronie's disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.


Important Safety
Information for XIAFLEX

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. 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 other 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.

  • Contraindications: XIAFLEX is contraindicated in the treatment of Peyronie's plaques that involve the penile urethra due to potential risk to this structure and in patients with a history of hypersensitivity to XIAFLEX or to collagenase used in any other therapeutic application or application method
  • Corporal Rupture or Other Serious Injury to the Penis: Injection of XIAFLEX into collagen‑containing structures such as the corpora cavernosa of the penis may result in damage to those structures and possible injury such as corporal rupture (penile fracture). Therefore, XIAFLEX should be injected only into the Peyronie's plaque and care should be taken to avoid injecting into the urethra, nerves, blood vessels, corpora cavernosa or other collagen‑containing structures of the penis. Cases of localized skin and soft tissue necrosis occurring as sequelae of penile hematoma, some requiring surgical intervention, have been reported post-marketing
  • Hypersensitivity Reactions, Including Anaphylaxis: In the double‑blind, placebo‑controlled portions of the clinical trials in Peyronie's disease, a greater proportion of XIAFLEX‑treated patients (4%) compared to placebo‑treated patients (1%) had localized pruritus after up to 4 treatment cycles (involving up to 8 XIAFLEX injection procedures). The incidence of XIAFLEX‑associated pruritus was similar after each injection regardless of the number of injections administered
  • Because XIAFLEX contains foreign proteins, severe allergic reactions to XIAFLEX can occur. Anaphylaxis was reported in a post‑marketing clinical trial in one patient who had previous exposure to XIAFLEX for the treatment of Dupuytren's contracture. Healthcare providers should be prepared to address severe allergic reactions following XIAFLEX injections. The safety of more than one treatment course of XIAFLEX is not known
  • Risk of Bleeding in Patients with Abnormal Coagulation: In the XIAFLEX controlled trials in Peyronie’s disease, 65.5% of XIAFLEX‑treated patients developed penile hematoma, and 14.5% developed penile ecchymosis. Patients with abnormal coagulation (except for patients taking low‑dose aspirin, eg, up to 150 mg per day) were excluded from participating in these studies. Therefore, the efficacy and safety of XIAFLEX in patients receiving anticoagulant medications (other than low‑dose aspirin, eg, up to 150 mg per day) within 7 days prior to XIAFLEX administration is not known. In addition, it is recommended to avoid use of XIAFLEX in patients with coagulation disorders, including patients receiving concomitant anticoagulants (except for low‑dose aspirin)
  • Acute Post-Injection Back Pain Reactions: Post-marketing reports of acute lower back pain reactions, sometimes accompanied by radiation to the lower extremities, chest and arms, muscle spasms, chest pain, paresthesias, headache, and dyspnea, have been received by patients treated with XIAFLEX for Peyronie's disease. These events can be mild to severe in intensity. The events typically lasted for 15 minutes and typically did not require intervention. Administer the smallest number of treatment cycles necessary to treat the patient's curvature deformity
  • Syncope and Presyncope: Most, but not all cases of syncope and presyncope 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 suggest a vasovagal mechanism. Make patients aware of the potential symptoms that could trigger syncope and presyncope after treatment with XIAFLEX.
    If presyncopal symptoms occur, patients should remain recumbent until symptoms resolve. Syncope may be associated with bodily injuries, including concussion, head abrasion, and other accidental injuries

Adverse Reactions

Clinical trials

  • In the XIAFLEX clinical trials for Peyronie's disease, the most frequently reported adverse drug reactions (≥25%) and at an incidence greater than placebo included: penile hematoma, penile swelling, and penile pain.

Post-marketing experience

  • Acute post-injection lower back pain reactions have occurred in close temporal proximity to XIAFLEX treatments
  • Cases of localized skin and soft tissue necrosis events as sequelae of penile hematoma, some of which required surgical intervention
  • Syncope and presyncope have been reported in men treated with XIAFLEX for Peyronie’s disease. Most, but not all cases occurred in the immediate treatment period or within 1-2 days following injection. Bodily injuries associated with the syncopal events have been reported

Click for full Prescribing Information, including BOXED WARNING and Medication Guide.

References:

1.  XIAFLEX® [package insert]. Malvern, PA: Endo Pharmaceuticals Inc.
2.  Nehra A, Alterowitz R, Culkin DJ, et al. Peyronie’s disease: AUA guideline. J Urol. 2015;194(3):745-753.
3.  Data on file. DOF-XPD-03. Endo Pharmaceuticals Inc; January 7, 2016.
4.  Data on file. DOF-XPD-04. Endo Pharmaceuticals Inc; January 7, 2016.