Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Swedish Orphan Biovitrum AB (publ), SE-112 76 Stockholm, Sweden
Xiapex is indicated for:
Xiapex must be administered by a physician appropriately trained in the correct administration of the medicinal product and experienced in the diagnosis and management of Dupuytren’s disease.
The recommended dose of Xiapex is 0.58 mg per injection into a palpable Dupuytren’s cord. The volume of solvent required and the volume of reconstituted Xiapex to be administered into the Dupuytren’s cord differs depending on the type of joint being treated (for the reconstitution instructions, see section 6.6, Table 14).
Injections in up to two cords or two affected joints in the same hand can be administered according to the injection procedure during a treatment visit. Two palpable cords affecting two joints may be injected or one palpable cord affecting two joints in the same finger may be injected at two locations during a treatment visit. Each injection contains a 0.58 mg dose. If the disease has resulted in multiple contractures, additional cords may be treated at other treatment visits approximately 4 weeks apart.
Approximately 24-72 hours after injection, a finger extension procedure may be performed, as necessary, to facilitate cord disruption. If a satisfactory response has not been achieved, the injection and finger extension procedures may be repeated after approximately 4 weeks. Injections and finger extension procedures may be administered up to 3 times per cord at approximately 4-week intervals. Clinical study experience with Xiapex is currently limited to up to 3 injections per cord and up to 8 injections in total.
Xiapex must be administered by a physician appropriately trained in the correct administration of the medicinal product and experienced in the diagnosis and treatment of male urological diseases. Patients with penile curvature >90° were not included in the clinical studies. Treatment in this group can therefore not be recommended.
The recommended dose of Xiapex is 0.58 mg per injection administered into a Peyronie’s plaque. The volume of reconstituted Xiapex to be administered into the plaque is 0.25 ml (for reconstitution instructions, see section 6.6, Table 14). If more than one plaque is present, only the plaque causing the curvature deformity should be injected.
A treatment course consists of a maximum of 4 treatment cycles. Each treatment cycle consists of two Xiapex injections and one penile modelling procedure. The second Xiapex injection is administered 1 to 3 days after the first injection. A penile modelling procedure is performed 1 to 3 days after the second injection of each treatment cycle. The interval between treatment cycles is approximately six weeks.
Due to the lack of quantifiable systemic exposure of Xiapex in patients with Dupuytren’s contracture and minimal and short-lived systemic exposure of Xiapex in patients with Peyronie’s disease, no dose adjustment is necessary. No overall differences in safety or effectiveness were observed between elderly and younger patients.
Due to the lack of quantifiable systemic exposure of Xiapex in patients with Dupuytren’s contracture and minimal and short-lived systemic exposure of Xiapex in patients with Peyronie’s disease, no dose adjustment is necessary.
Due to the lack of quantifiable systemic exposure of Xiapex in patients with Dupuytren’s contracture and minimal and short-lived systemic exposure of Xiapex in patients with Peyronie’s disease, no dose adjustment is necessary.
There is no relevant use of Xiapex in the paediatric population aged 0-18 years for the treatment of Dupuytren’s contracture.
Peyronie’s disease occurs exclusively in adult male patients and hence there is no relevant use of Xiapex in the paediatric population aged 0-18 years for the treatment of Peyronie’s disease.
Intralesional use.
Xiapex must be reconstituted with the solvent provided and to the appropriate volume prior to intralesional injection (see section 6.6). A single-use syringe containing 0.01-ml graduations with a permanently fixed 27-gauge 12 or 13 mm needle (not supplied) should be used to withdraw the volume of reconstituted solution. There will be a small amount of reconstituted solution left in the vial.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
Administration of a local anaesthetic medicinal product prior to injection of Xiapex into a Dupuytren’s cord is not recommended, as it may interfere with proper placement of the injection.
The joint to be treated (metacarpophalangeal [MP] or proximal interphalangeal [PIP]) should be confirmed and the volume of solvent required for reconstitution is determined by the type of joint (PIP joint requires a smaller volume for injection). The injection procedure is detailed in the package leaflet and the physician training material and must be followed.
Patients should be instructed:
At the follow-up visit approximately 24-72 hours after injection, it should be determined if the contracture has resolved. If a cord contracture remains, a passive finger extension procedure will be performed in an attempt to disrupt the cord. Local anaesthesia may be used, if needed, during the finger extension procedure.
While the patient’s wrist is in the flexed position, a moderate stretching pressure should be applied to the injected cord by extending the finger for approximately 10 to 20 seconds. For cords affecting the PIP joint, the finger extension procedure should be performed when the MP joint is in the flexed position. If the first finger extension procedure does not result in disruption of the cord, a second and third attempt can be performed at 5- to 10-minute intervals. No more than 3 attempts per affected joint are recommended to disrupt a cord.
If the cord has not disrupted after 3 attempts of extension, a follow-up visit may be scheduled approximately 4 weeks after the injection. If, at that subsequent visit the contracted cord persists, an additional injection and finger extension procedure may be performed.
Following the finger extension procedure(s) and fitting patient with a splint (with treated joint in maximum extension), the patients should be instructed to:
Administration of regional anaesthesia (penile block) or topical anaesthesia could be applied prior to Xiapex injection when desired. In the pivotal clinical studies about 30% of the patients received penile block before injection.
The location of the target treatment area in the Peyronie’s plaque is identified at the point of maximum concavity (or focal point) in the erect penis state and marked with a surgical marker. Xiapex should be injected into the target plaque when the penis is in a flaccid state. The injection procedure is detailed in the package leaflet and the physician training material and must be followed.
Penile modelling helps relieve curvature deformity and straighten the penile shaft. At the follow-up visit 1 to 3 days after the second injection of each treatment cycle, the trained physician should perform a penile modelling procedure on the flaccid penis to stretch and elongate the treated plaque that Xiapex has disrupted. Local anaesthesia may be applied before the modelling if desired. Wearing gloves the physician should grasp the plaque or indurated portion of the flaccid penis about 1 cm proximal and distal to the injection site. Direct pressure on the injection site should be avoided. The target plaque is used as a fulcrum point with both hands, to firmly apply a steady pressure to elongate and stretch the plaque. The goal is to gradually create bending opposite to the patient’s penile curvature, with stretching to the point of moderate resistance. The penile pressure should be hold for 30 seconds, thereafter released with a resting period for 30 seconds before repeating the penile modelling technique for a total of 3 modelling attempts at 30 seconds for each attempt.
In addition to the in-office penile modelling procedure, patients should be provided instructions on the appropriate technique to self-perform penile modelling activities at home each day for the 6-week period following the physician penile plaque modelling visit of each treatment cycle, according to the detailed instructions provided in the package leaflet.
If the curvature deformity is less than 15 degrees after the first, second or third treatment cycle, or if the physician determines that further treatment is not clinically indicated, then the subsequent treatment cycles should not be administered.
The safety of more than one treatment course of Xiapex for Peyronie’s disease is not known.
Administration of Xiapex at greater than recommended doses is expected to be associated with increased local reactions at the site of injection. Routine supportive care and symptomatic treatment must be provided in the case of overdose.
3 years.
After reconstitution, immediate use is recommended. Reconstituted Xiapex can be kept at ambient room temperature (20ºC-25ºC) for up to one hour or refrigerated 2ºC-8˚C for up to 4 hours prior to administration. If refrigerated, the reconstituted solution must be allowed to return to ambient room temperature (20ºC-25ºC) for approximately 15 minutes before use.
Store in a refrigerator (2ºC-8ºC).
Do not freeze.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
Xiapex powder is supplied in a clear glass vial (3 ml, type I glass) with rubber stopper, aluminium seal and flip-off cap (polypropylene).
Solvent: 3 ml solution supplied in a clear glass vial (5 ml, type I glass) with rubber stopper, aluminium seal and flip-off cap (polypropylene).
Pack of 1 vial of powder and 1 vial of solvent.
The vial containing Xiapex and the vial containing the solvent for solution for injection for reconstitution must be refrigerated. Prior to use, the vial containing Xiapex and the vial containing the solvent for solution for reconstitution must be removed from the refrigerator and allowed to stand at room temperature for at least 15 minutes and no longer than 60 minutes. Each vial of Xiapex and sterile solvent for reconstitution should only be used for a single injection. If two cords of affected joints on the same hand are to be treated during a treatment visit, separate vials and syringes should be used for each reconstitution and injection.
Using an aseptic technique, the following procedure for reconstitution must be followed:
1. Dupuytren’s contracture: The joint to be treated (MP or PIP) should be confirmed as the volume of solvent required for reconstitution is determined by the type of joint (PIP joint requires a smaller volume for injection). Peyronie’s disease: The treatment area should be identified and marked with a surgical marker on the erected penis.
2. The flip-off plastic caps should be removed from both vials. The rubber stopper and surrounding surface of the vial containing Xiapex and the vial containing the solvent for reconstitution should be swabbed with sterile alcohol (no other antiseptics must be used).
3. Only the supplied solvent must be used for reconstitution; it contains calcium which is required for the activity of Xiapex. Using a sterile syringe calibrated with 0.01 ml graduations, the appropriate amount of solvent supplied should be withdrawn in order to deliver as follows:
Table 14. Volumes needed for administration:
| Treatment area | Solvent required for reconstitution | Injection volume to deliver Xiapex 0.58 mg dose† |
|---|---|---|
| Dupuytren’s MP joints | 0.39 ml | 0.25 ml |
| Dupuytren’s PIP joints | 0.31 ml | 0.20 ml |
| Peyronie’s plaque | 0.39 ml | 0.25 ml |
† Note that injection volume for delivery of a 0.58 mg dose is less than the total volume of solvent used for reconstitution.
4. The solvent should slowly be injected into the sides of the vial containing the lyophilised powder of Xiapex. The vial containing the solution should not be inverted or shaken. The solution should slowly be swirled to ensure that all of the lyophilised powder has gone into solution. The syringe and needle used for reconstitution are thereafter removed and discarded.
5. The solution should visually be inspected for particulate matter and discoloration prior to administration. The reconstituted solution of Xiapex must be clear. If the solution contains particles, is cloudy or discoloured, it should not be injected.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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