Version May 2024
Corporal rupture (penile fracture) was reported as an adverse reaction in 5 of 1044 (0.5%) collagenase-treated patients in clinical studies. In other collagenase-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%) collagenase-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, collagenase is available for the treatment of Peyronie disease only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the Xiaflex REMS program.
Cellulite (QWO): SUBQ: Females: Inject 0.84 mg per treatment area; a treatment area consists of a single buttock receiving up to 12 injections (0.3 mL/injection up to maximum of 3.6 mL); may treat up to 2 treatment areas per visit. Treatment may be repeated every 21 days for a total of 3 treatment visits.
Dupuytren contracture (Xiaflex): Intralesional: Inject 0.58 mg per cord affecting a metacarpophalangeal (MP) joint or a proximal interphalangeal (PIP) joint. If contracture persists, finger extension procedure should be performed 24 to 72 hours following injection to facilitate cord disruption. If MP or PIP contracture remains, may reinject cord with a single dose of 0.58 mg 4 weeks following initial injection; injections and finger extension procedures may be administered up to 3 times per cord separated by ~4-week intervals. Note: Up to 2 injections per hand may be used during a treatment; 2 palpable cords affecting 2 joints or 1 palpable cord affecting 2 joints in the same finger may be injected at 2 locations during a treatment. Other palpable cords with contractures of MP or PIP joints may be injected at other treatment visits ~4 weeks apart.
Peyronie disease (Xiaflex): Intralesional: Inject 0.58 mg into a Peyronie plaque; repeat injection 1 to 3 days later. A penile modeling procedure should be performed 1 to 3 days after the second injection. Administer a second treatment cycle (two 0.58 mg injections and a penile modeling procedure) in ~6 weeks if needed (maximum, 4 treatment cycles [a total of 8 injection procedures and 4 penile modeling procedures]); subsequent treatment cycles should not be administered if the curvature deformity is <15 degrees after a treatment cycle or health care provider determines further treatment is not indicated. The safety of more than 1 treatment course (ie, 4 treatment cycles) is not known. Note: If more than 1 plaque is present, inject into the plaque causing the curvature deformity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.
There are no dosage adjustments provided in the manufacturer's labeling. However, dosage adjustment unlikely due to low systemic absorption.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
Cellulite, moderate to severe:
>10%:
Immunologic: Antibody development (≥26%; neutralizing antibodies: AUX-I: 68%; AUX-II: 83%)
Local: Injection-site reaction (including bruising at injection site [84%], erythema at injection site [9%], injection-site nodule [33%], injection-site pruritus [15%], pain at injection site [48%], skin discoloration at injection site [8%], swelling at injection site [8%], warm sensation at injection site [3%])
Dupuytren's contracture:
>10%:
Cardiovascular: Peripheral edema (primarily as swelling of injected hand: 73% to 77%)
Dermatologic: Hemorrhagic blister (12%), pruritus (15%)
Hematologic & oncologic: Bruise (59% to 70%), lymphadenopathy (13%)
Immunologic: Antibody development (≥86%; neutralizing antibodies: AUX-I: 10%; AUX-II: 21%)
Local: Injection-site reaction (including bleeding at injection site [6% to 38%], erythema at injection site [≤35%], hematoma at injection site [8%], inflammation at injection site [≤35%], irritation at injection site [≤35%], pain at injection site [14%], swelling at injection site [5% to 24%], tenderness at injection site [24%], warm sensation at injection site [≤35%])
Neuromuscular & skeletal: Limb pain (35% to 51%)
Miscellaneous: Laceration (skin: 9% to 22%)
1% to 10%:
Dermatologic: Ecchymoses (5%), erythema of skin (6%)
Immunologic: Lymph node pain (8%)
Neuromuscular & skeletal: Axillary pain (6% to 7%)
<1%: Neuromuscular & skeletal: Rupture of tendon
Peyronie disease:
>10%:
Genitourinary: Penile ecchymoses (15%), penile hematoma (66%; severe: 4% to 6%), penile pain (45%), penile popping sensation (13%), penile swelling (55%)
Immunologic: Antibody development (55% to 99%; neutralizing antibodies: AUX-I: 60%; AUX-II: 52%; no correlation to clinical response or adverse reaction)
1% to 10%:
Dermatologic: Hemorrhagic blister (5%), skin discoloration (2%)
Genitourinary: Blisters on penis (3%), dyspareunia (1%), erectile dysfunction (2%), genital pruritus (3%), painful erection (3%)
Local: Injection-site pruritus (1% to 4%), localized edema (1%), localized vesiculation (injection site: 1%)
Nervous system: Procedural pain (2%), suprapubic pain (1%)
Miscellaneous: Nodule (1%)
<1%: Genitourinary: Penile fracture, sudden penile detumescence
Frequency not defined (any indication):
Nervous system: Abnormal sensory symptoms (hand), complex regional pain syndrome
Neuromuscular & skeletal: Ligament disorder, pulley rupture
Postmarketing (any indication):
Cardiovascular: Syncope (including presyncope and vasodepressor syncope)
Dermatologic: Skin or other soft tissue necrosis
Hypersensitivity: Severe hypersensitivity reaction (including anaphylaxis)
Nervous system: Abnormal gait, paresthesia
Neuromuscular & skeletal: Lower back pain (acute), muscle spasm
Respiratory: Dyspnea
QWO: History of hypersensitivity to collagenase or any components of the formulation; infection at the injection sites.
Xiaflex: Treatment of Peyronie plaques that involve the penile urethra; history of hypersensitivity to collagenase or to collagenase used in any other therapeutic application or application method.
Concerns related to adverse effects:
F• Hypersensitivity reactions: Severe allergic reactions, including anaphylaxis, may occur in response to administration of foreign proteins (ie, collagenase). Health care providers should be prepared for the immediate treatment with epinephrine for any possible severe allergic reaction.
Disease-related concerns:
• Bleeding disorders: Avoid use in patients with coagulation disorders, including patients receiving concomitant anticoagulants (except low-dose aspirin).
• Corporal rupture: Peyronie disease: [US Boxed Warning]: Corporal rupture (penile fracture) was reported in 0.5% of patients in clinical studies; severe penile hematoma and a combination of penile ecchymoses or hematoma, sudden penile detumescence, and/or a penile “popping” sound or sensation was also reported. Signs or symptoms that may reflect serious penile injury should be promptly evaluated. Localized skin and soft tissue necrosis due to penile hematoma has been reported, including some cases requiring surgical intervention. Careful injection technique of collagenase into the Peyronie plaque is required to avoid inadvertent injection into the urethra, nerves, blood vessels, corpora cavernosa, or other collagen-containing structures of the penis.
• Postinjection back-pain reactions: Peyronie disease: Acute postinjection back-pain reactions may occur; pain ranges from mild to severe and may radiate to the arms, chest, and legs; chest pain, dyspnea, and headache were also reported. Reactions usually happened immediately or within minutes of injection and have only been reported after the second or subsequent injections; reported reactions usually resolved within 15 minutes but have lasted up to 1.5 hours. Observation and treatment with analgesics may be needed.
• Presyncope/Syncope: Dupuytren contracture, Peyronie disease: Cases of presyncope and syncope have been reported. Most cases in patients with Peyronie disease were associated with postinjection penile pain, postinjection hematoma, penile pain with spontaneous erection, or pain during micturition suggesting a vasovagal mechanism. In patients with Dupuytren contracture, the injection procedure, finger extension procedure, or pain following the procedures were the most common causes and suggestive of a vasovagal mechanism; usually occurred during the procedure or within 1 to 2 days after the procedure. Ensure patients remain recumbent if presyncopal symptoms occur.
• Tendon rupture: Dupuytren contracture: Administration may result in tendon rupture, ligament damage, or other serious injury (eg, pulley rupture, sensory and pain abnormalities, and skin lacerations); careful injection technique of collagenase into the Dupuytren cord is required to avoid inadvertent injection into tendons, nerves, blood vessels, or other collagen-containing structures of the hand. Skin laceration requiring skin graft after finger extension procedures and local skin and soft-tissue necrosis, including some requiring skin grafting or other surgical interventions (eg, finger amputation), have been reported. Signs or symptoms of serious injury to the injected hand or finger should be immediately evaluated; surgical intervention may be necessary.
Dosage form specific issues:
• Product interchangeability: QWO and Xiaflex are not interchangeable. QWO is not intended for the treatment of Dupuytren contracture or Peyronie disease.
Other warnings/precautions:
• Antibody formation: IgE-anti-drug antibodies commonly developed in treated patients, with higher frequencies and titers seen in patients treated with successive injections.
• Appropriate use: Only health care providers skilled in the treatment of Dupuytren contractures or Peyronie disease and appropriate injection procedures should administer treatment. Local anesthetic is not recommended prior to Dupuytren contracture treatment due to possible interference with proper needle placement.
• REMS program: Peyronie disease: [US Boxed Warning]: Because of the risks of corporal rupture or other serious penile injury, collagenase is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the XIAFLEX REMS Program. Prescribers and healthcare sites must be certified with the program. Call 1-877-313-1235 or visit www.Xiaflexrems.com for more information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Xiaflex: 0.9 mg (1 ea)
No
Solution (reconstituted) (Xiaflex Injection)
0.9 mg (per each): $7,604.72
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Injection:
Xiaflex: 0.9 mg ([DSC])
SUBQ: QWO: Mark injection sites while patient is standing. Inject SUBQ into buttocks while patient is in a prone position using a 1 mL syringe with a 30-gauge ½-inch needle. If reconstituted solution is refrigerated, warm to room temperature for ≥15 minutes before use; do not store reconstituted solution in 1 mL syringes. Refer to product labeling for additional administration details.
Intralesional: Xiaflex: Inject intralesionally into a palpable cord or plaque using a 1 mL syringe with 0.01 mL graduations with a 27-gauge ½-inch needle. If reconstituted solution is refrigerated, warm to room temperature for ~15 to 60 minutes before use. Refer to product labeling for additional administration details.
Dupuytren contracture: Divide dose into 3 injections; after correct needle placement, inject 1/3 of the dose, then reposition the needle in a distal location ~2 to 3 mm from the initial injection for the second injection (1/3 of the dose), followed by the final injection (1/3 of the dose) positioned ~2 to 3 mm proximal to the initial injection. To avoid tendon rupture when injecting a cord affecting a PIP joint of the fifth finger, needle insertion should not be >2 to 3 mm in depth or >4 mm distal to the palmar digital crease. Do not administer local anesthetic agent prior to administration due to possible interference with proper needle placement. When administering two injections in the same hand during a treatment, begin with the affected finger in the most medial aspect of the hand and continue toward the lateral aspect (eg, fifth finger to index finger). When administering two injections in a cord affecting two joints in the same finger, begin with the affected joint in the most proximal aspect of the finger and continue toward the distal aspect (eg, MP to PIP).
Peyronie disease: Local anesthetic may be administered prior to injection. The penis should be in a flaccid state before injection. The first injection should be into the plaque at the point of maximum concavity (or focal point) in the bend of the penis; second injection of each treatment cycle should be made ~2 to 3 mm apart from the first injection. Inject only into the plaque; avoid injection into the urethra, nerves, blood vessels, corpora cavernosa, or other collagen-containing structures of the penis to avoid damage to these structures and possible corporal rupture. Do not advance the needle beneath the plaque or perpendicularly towards the corpora cavernosum. Withdraw the needle slowly to deposit the full dose along the needle track within the plaque.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125338s111lbl.pdf#page=33, must be dispensed with this medication.
Cellulite, moderate to severe (QWO): Treatment of moderate to severe cellulite in the buttocks of adult females.
Dupuytren contracture (Xiaflex): Treatment of adults with Dupuytren contracture with a palpable cord.
Peyronie disease (Xiaflex): Treatment of adults with Peyronie disease with a palpable plaque and curvature deformity of at least 30 degrees at the start of therapy.
Collagenase clostridium histolyticum (Xiaflex) may be confused with topical collagenase formulation (ie, Santyl)
Xiaflex may be confused with Zanaflex
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Anticoagulants: May enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy
Aspirin: May enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Pharmacokinetic studies in humans did not show quantifiable systemic levels following SUBQ injection or intralesional injection into a Dupuytren cord.
It is not known if collagenase is present in breast milk.
According to the manufacturer, the decision to breastfeed following injection into a Dupuytren cord should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Range of motion (Dupuytren contracture); curvature deformity (Peyronie disease).
Collagenase clostridium histolyticum contains two forms of microbial collagenase (Collagenase AUX-I and Collagenase AUX-II) isolated and purified from the fermentation of Clostridium histolyticum bacteria; collagenase lyses collagen, leading to enzymatic disruption of contracted Dupuytren cord or Peyronie plaque (both comprised primarily of collagen); enzymatic disruption of the fibrous septae creating a skin-smoothing effect (Kaufman-Janette 2021).
Absorption: Systemic plasma concentrations of collagenase AUX-I or collagenase AUX-II were undetectable for up to 30 days following intralesional injection into a Dupuytren cord. Low levels of collagenase AUX-I and AUX-II were quantifiable for up to 30 minutes following intralesional injection into a Peyronie plaque; systemic plasma concentrations of collagenase AUX-I or collagenase AUX-II were below the lower limit of quantitation following SUBQ injection in patients being treated for cellulite.
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