Xiaflex (collagenase clostridium histolyticum) is indicated for Dupuytren's contracture and Peyronie's disease. For Dupuytren's, it is injected into palpable cords to release contractures, followed by finger extension procedures. For Peyronie's, it is injected into plaques and accompanied by penile modeling activities. Side effects include swelling, pain and bruising. There is a black box warning for corporal rupture with Peyronie's treatment. Proper training and counseling of providers and patients is required through a REMS program due to risks.

1. XIAFLEXCOLLAGENASE CLOSTRIDIUM HISTOLYTICUM
Charles Ng PharmD/MBA Candidate 2017

2. INDICATIONS
• Dupuytren’s contracture with a palpable cord
• Peyronie’s disease with a palpable plaque and curvature deformity of at least 30
degrees at the start of therapy

3. DUPUYTREN’S CONTRACTURE
• Inherited proliferative connective tissue disorder
• Flexion contracture of the hand due to a palmar fibromatosis
• Fingers bend towards the palm and cannot be fully extended
• Ring finger  middle and little fingers  thumb and index finger
• Progresses slowly and is often accompanied by some aching and
itching
• Incidence increases after 40 years old (M>W)
• Beyond 80 years old, the gender distribution is about even

4. PEYRONIE’S DISEASE
• Curved or bent penis
• Connective tissue disorder involving the growth of fibrous plaques in the soft
tissue of the penis
• Affects 5% of men
• Pain, abnormal curvature, erectile dysfunction, indentation, loss of girth, shortening

5. MECHANISM OF ACTION
• Collagenase clostridium histolyticum
• An enzyme produced by the bacterium Clostridium histolyticum that dismantles
collagen

6. DOSAGE FORMS & STORAGE
• Single-use glass vials containing 0.9 mg of collagenase clostridium
histolyticum as a sterile, lyophilized powder for reconstitution
• Sterile diluent for reconstitution is also
provided in a single-use glass vial
• Store in refrigerator prior to reconstitution
• Reconstituted solution can be kept at
room temperature for 1 hour or
refrigerated for 4 hours

7. DUPUYTREN’S CONTRACTURE DOSING &
ADMINISTRATION
• Reconstitute XIAFLEX lyophilized powder with the diluent
• Metacarpophalangeal (MCP) joint: 0.39 mL
• Proximal interphalangeal (PIP) joint: 0.31 mL
• Inject 0.58 mg into each palpable Dupuytren’s cord with a contracture
• Metacarpophalangeal (MCP) joint: 0.25 mL
• Proximal interphalangeal (PIP) joint: 0.20 mL

9. DUPUYTREN’S CONTRACTURE DOSING &
ADMINISTRATION
• ~24-72 hours following an injection, perform a finger extension procedure if a
contracture persists
• Injections and finger extension procedures may be administered up to 3 times per
cord at approximately 4-week intervals
• Inject up to 2 cords in the same hand per treatment visit
• Following the finger extension procedures, fit patient with a splint for use at
bedtime for up to 4 months to maintain finger extension
• Instruct patient to perform finger extension and flexion exercises several times a day
for several months

10. FINGER EXTENSION
• While the patient’s wrist is in the flexed position, apply moderate stretching pressure to
the injected cord by extending the finger for approximately 10-20 seconds.
• For cords affecting the PIP joint, perform the
finger extension procedure when the
MCP joint is in the flexed position

11. PEYRONIE’S DISEASE DOSING &
ADMINISTRATION
• Induce an erection and mark the target area in the Peyronie’s plaque to be injected
• Reconstitute XIAFLEX lyophilized powder with 0.39 mL of sterile diluent
• A treatment cycle = 2 XIAFLEX injections and a penile modeling procedure
• Inject 0.58 mg (0.25 mL) into the target plaque of a flaccid penis once, 1-3 days apart
• Perform a penile modeling procedure 1-3 days after the 2nd injection of each treatment cycle
• For each plaque causing the curvature deformity, up to 4 treatment cycles may be administered at ~ 6-
week intervals
• If the curvature deformity is less than 15 degrees then subsequent treatment cycles should not be
administered

12. PENILE MODELING ACTIVITIES
• Stretching
• Grasp the tip of the penis with the fingers of one hand and hold the base of the penis
with the fingers of the other
• Gently pull the penis away from the body to its full length
• Hold the stretch for 30 seconds
• Let go and allow the penis to return to its normal, unstretched length

13. PENILE MODELING ACTIVITIES
• Straightening
• Gently attempt to bend the shaft of the erect penis in the opposite direction of the
curve, but not so forcefully as to produce significant pain or discomfort
• Hold the penis in this more straightened position for 30 seconds, then let go
• Perform this no more than once per day, if a spontaneous erection unrelated to sexual
activity occurs

14. EFFICACY
• Dupuytren’s contracture
• In 2 clinical trials, 64% and 44% of the XIAFLEX treated patients,
compared to 7% and 5% of the placebo treated patients,
achieved reduction in contracture of the primary joint (MCP or
PIP) to 0°-5° after up to 3 injections
• Peyronie’s Disease
• 30% curvature change vs placebo

15. CONTRAINDICATIONS
• Peyronie’s plaques that involve the penile urethra due to potential risk to this
structure
• History of hypersensitivity to XIAFLEX or to collagenase used in any other
therapeutic application or application method
• Anticoagulants  increased bleeding risk
• < 18 years old?

16. DUPUYTREN’S CONTRACTURE: SIDE EFFECTS
• Peripheral edema: mostly swelling of injected hand
• Contusion
• Injection site hemorrhage/reaction
• Pain in extremity
• Tenderness
• Injection site swelling
• Pruritus
• Lymphadenopathy
• Skin laceration
• Lymph node pain
• Erythema
• Axillary pain

17. PEYRONIE’S DISEASE: SIDE EFFECTS
• Penile hematoma/swelling/pain/ecchymoses
• Blood blister
• Penile blister
• Genital pruritus
• Painful erection
• Skin discoloration
• Procedural pain
• Injection site vesicles
• Localized edema
• Dyspareunia
• Injection site pruritus
• Nodule
• Suprapubic pain

18. BLACK BOX WARNING
• Corporal rupture (penile fracture) and severe penile
hematoma
• Signs and symptoms
• 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

19. REMS
• Training for healthcare providers on the risks of corporal rupture and other serious
injuries to the penis, and how to properly administer XIAFLEX
• Certification in the XIAFLEX REMS Program by completing training and enrollment
in the program
• Patient Counseling about the risks of corporal rupture and other serious injuries to
the penis and the importance of patient adherence to post-injection instructions.
Healthcare Providers must give patients the Patient Counseling Tool, "What You
Need to Know About XIAFLEX Treatment for Peyronie's Disease: A Patient Guide",
after each XIAFLEX injection.
• Restricted distribution through specially certified healthcare settings (e.g.,
pharmacies, practitioners, hospitals or outpatient settings)

20. PATIENT EDUCATION
• Finger extension exercises  several months
• Penile modeling exercises  6 weeks
• Do not have sex or have any other sexual activity for at least 2 weeks after the
second injection of a treatment cycle with XIAFLEX and after any pain and swelling
has gone away

21. COST SAVINGS
• XIAFLEX Copay Program for eligible patients can cover up to $1200 for each vial of
XIAFLEX
• $2650 (2 vials)  $250

22. QUESTIONS????