Xiapex

Dupuytren’s contracture 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. 58 mg per injection into a palpable Dupuytren’s cord.

6, Table 14). 25 ml. 20 ml. 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 locationsMedicinal product no longer authorised 3 during a treatment visit.

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. Peyronie’s disease 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. 58 mg per injection administered into a Peyronie’s plaque. 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. Special population Elderly 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.

Dupuytren’s contracture Summary of the safety profile The most frequently reported adverse reactions during the Xiapex clinical studies (272 of 409 patients received up to three single injections of Xiapex and 775 patients received two concurrent injections in the same hand) were local injection site reactions such as oedema peripheral (local to the injection site), contusion (including ecchymosis), injection site haemorrhage and injection site pain.

Injection site reactions were very common, occurring in the vast majority of patients, were mostly mild to moderate in severity and generally subsided within 1-2 weeks post injection. Serious adverse reactions of tendon rupture (6 cases), tendonitis (1 case), other ligament injury (2 cases) and complex regional pain syndrome (1 case) related to the medicinal product were reported.

Anaphylactic reaction was reported in a patient previously treated with Xiapex (1 case). Tabulated list of adverse reactions Table 1 presents adverse reactions listed by system organ class and frequency categories, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), and uncommon (≥1/1,000 to <1/100), and not known: cannot be estimated from the available data.

Within each frequency group, adverse reactions are presented in order of decreasing seriousness. Adverse reactions reported from the clinical programme are those that occurred in the Phase 3 double blind placebo-controlled studies for the treatment of Dupuytren’s contracture in adult patients with a palpable cord (AUX-CC-857, AUX-CC-859) and the post-marketing clinical studies (AUX-CC-864, AUX-CC-867) for two concurrent injections in the same hand.

Table 1:

Tabulated list of adverse reactions. System organ class Very common Common Uncommon Not known Infections and infestations Injection site cellulitis Lymphangitis Blood and lymphatic system disorders Lymphadenopathy Lymph node pain Thrombocytopenia Lymphadenitis Immune system disorders Hypersensitivity Anaphylactic reactionMedicinal product no longer authorised 10 System organ class Very common Common Uncommon Not known Psychiatric disorders Disorientation Agitation Insomnia Irritability Restlessness Nervous system disorders Paresthesia Hypoesthesia Burning sensation Dizziness Headache Complex regional pain syndrome Monoplegia Syncope vasovagal Tremor Hyperaesthesia Eye disorders Eyelid oedema Vascular disorders Haematoma Hypotension Respiratory, thoracic and mediastinal disorders Dyspnoea Hyperventilation Gastrointestinal disorders Nausea Diarrhoea Vomiting Abdominal pain upper Skin and subcutaneous tissue disorders Pruritus Ecchymosis Blood blistera Blister Rash Erythema Hyperhidrosis Erythematous or macular rash Eczema Swelling face Skin disorders, like exfoliation, lesions, pain, tightness, discoloration or scab Musculoskeletal and connective tissue disorders Pain in extremity Arthralgia Axillary mass Joint swelling Myalgia Pain in chest wall, groin, neck or shoulder Musculoskeletal discomfort or stiffness, joint stiffness or crepitation Limb discomfort Tendonitis Muscle spasms or weakness Reproductive system and breast disorders Breast tenderness Hypertrophy breastMedicinal product no longer authorised 11 System organ class Very common Common Uncommon Not known General disorders and administration site conditions Oedema peripheralc Injection site haemorrhage, pain or swelling Tenderness Axillary pain Inflammation Injection site warmth, erythema, inflammation, vesicles or pruritus Swelling Local swelling Pyrexia Pain Discomfort Fatigue Feeling hot Influenza like illness Injection site reaction, malaise, irritation, anaesthesia, desquamation, nodule or discoloration Cold intolerance of the treated fingers Investigations Lymph node palpable Alanine aminotransferase increased Aspartate aminotransferase increased Body temperature increased Injury, poisoning and procedural complications Contusion Skin lacerationa,b Tendon rupture Ligament injury Limb injury Open wound Wound dehiscence Digital necrosisd Digital fractured a reported with a higher incidence (very common) in patients who received two concurrent injections of Xiapex in the same hand compared with subjects treated with up to three single injections in the Phase 3 placebo-controlled pivotal studies in Dupuytren’s contracture.

g. wide spread redness or rash, swelling, tightness in the throat or difficulty breathing. Patients should be instructed to consult a doctor immediately if they experience any of these signs or symptoms. Emergency medication for treatment of potential allergic reactions should be available.

An anaphylactic reaction was reported in a post-marketing clinical study in a patient who had previous exposure to Xiapex for the treatment of Dupuytren’s contracture, demonstrating that severe reactions including anaphylaxis can occur following Xiapex injections.

Some patients with Dupuytren’s contracture developed IgE-anti-drug antibodies in greater proportions and higher titers with successive Xiapex injections. e. pruritus) after up to 3 injections. Medicinal product no longer authorised 6 In the double-blind portion of the two phase 3 placebo-controlled clinical trials in Peyronie’s disease, a greater proportion of Xiapex-treated patients (4%) compared to placebo-treated patients (1%) had localized pruritus after up to 4 treatment cycles (involving up to 8 Xiapex injections).

The incidence of Xiapex-associated pruritus was similar after each injection regardless of the number of injections administered. Tendon rupture or other serious injury to the injected finger/hand in the treatment of Dupuytren’s contracture Xiapex must only be injected into the Dupuytren’s cord.

Because Xiapex lyses collagen, care must be taken to avoid injecting into tendons, nerves, blood vessels, or other collagen-containing structures of the hand. Injection of Xiapex into collagen containing structures may result in damage to those structures, and possible permanent injury such as tendon rupture or ligament damage.

Care should be taken when injecting Xiapex into cords contracting the PIP joints as clinical studies indicate an increased risk of tendon rupture and ligament injury associated with treatment of PIP contractures with Xiapex. This is particularly important for cords situated at the PIP joint of the fifth finger.

1. Treatment of Peyronie’s plaques that involve the penile urethra due to potential risk to this structure.