XIAFLEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XIAFLEX (XIAFLEX).
XIAFLEX (collagenase clostridium histolyticum) is a combination of two collagenases (AUX-I and AUX-II) that hydrolyze collagen in the extracellular matrix. It targets type I and type III collagen, leading to enzymatic disruption of collagen-rich structures such as Dupuytren's cords and Peyronie's plaques.
| Metabolism | XIAFLEX is a protein; metabolism is expected to involve proteolytic degradation via endogenous proteinases into small peptides and amino acids. No specific hepatic cytochrome P450 metabolism. |
| Excretion | Primarily metabolized locally; systemic absorption minimal. No renal or biliary excretion data available; eliminated via local degradation. |
| Half-life | Systemic half-life not applicable due to minimal systemic absorption. Locally, collagenase activity declines within 1-2 days post-injection. |
| Protein binding | Not extensively studied; anticipated to bind to alpha2-macroglobulin and other serum proteins, but systemic levels are negligible. |
| Volume of Distribution | Not applicable due to local administration and negligible systemic absorption; Vd cannot be determined. |
| Bioavailability | Intralesional injection: Bioavailability is 100% at the site of action; systemic bioavailability is negligible (<1% of total dose). |
| Onset of Action | Intralesional injection: Clinical effect (cord softening) typically observed within 24-48 hours. |
| Duration of Action | Duration of effect: Single injection provides cord rupture within 7 days; full effect may require up to 30 days. Repeat injections may be needed. |
| Molecular Weight | 110000 |
0.58 mg injected directly into the palpable cord, up to 3 injections per treatment session (one per affected cord) at intervals of 1–2 days apart; repeated every 4 weeks as needed, up to 3 treatment sessions per cord.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required based on renal function; not studied in severe renal impairment. |
| Liver impairment | No specific guidelines; caution in moderate to severe hepatic impairment (Child-Pugh B or C) due to lack of data. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; clinical studies included patients aged 65 years and older, but no overall differences in safety or efficacy observed. |
| 1st trimester | XIAFLEX (collagenase clostridium histolyticum) is not recommended during pregnancy. Animal studies have shown embryotoxicity and fetal abnormalities at doses below the human dose. |
| 2nd trimester | Not recommended. Avoid use due to potential fetal harm based on animal studies. |
| 3rd trimester | Not recommended. Avoid use, especially near term, due to risk of uterine contractions or bleeding. |
Clinical note
Comprehensive clinical and safety monograph for XIAFLEX (XIAFLEX).
| Placental transfer | Unknown in humans. Animal studies demonstrate placental transfer; embryotoxicity and fetal malformations observed. |
| Breastfeeding | Unknown if XIAFLEX is excreted in human milk. Due to potential for adverse reactions in nursing infants, breastfeeding should be discontinued during treatment and for 14 days after the last dose. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to collagenase clostridium histolyticum or any excipientPeyronie's disease with a penile deformity due to non-plaque causes (e.g., curvature due to congenital or acquired causes)Use in patients with bleeding disorders or those receiving anticoagulant therapy (except antiplatelet agents) within 7 days of treatmentUse in patients with a history of severe allergic reaction to XIAFLEX
| Precautions | Corporal rupture (penile fracture) or other serious penile injury in Peyronie's disease patients, Tendon rupture or other serious injury to the injected finger in Dupuytren's contracture patients, Hypersensitivity reactions including anaphylaxis have been reported, Injection site reactions including hematoma, contusion, and swelling |
| Food/Dietary | No specific food interactions require restrictions. Avoid alcohol for at least 24 hours post-injection to minimize bleeding risk. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | XIAFLEX (collagenase clostridium histolyticum) is not systemically absorbed following local injection; therefore, minimal fetal exposure is expected. No adequate and well-controlled studies in pregnant women. Animal reproduction studies have not been conducted due to lack of systemic absorption. Risk cannot be ruled out; however, based on mechanism and local administration, teratogenic risk is considered low across all trimesters. |
| Fetal Monitoring | No specific maternal or fetal monitoring required beyond standard obstetric care. Monitor injection site for local reactions. Systemic effects are rare due to minimal absorption. |
| Fertility Effects | No studies on fertility in humans. Animal studies have not been conducted. Based on local administration and lack of systemic exposure, significant effects on fertility are not expected. |
| Clinical Pearls | XIAFLEX (collagenase clostridium histolyticum) is indicated for adult patients with Dupuytren's contracture with a palpable cord. Do not inject into the palm or near tendons/nerves/vessels; ensure proper cord palpation. Reconstitute with supplied diluent only; use within 1 hour. Post-injection finger extension with local anesthesia is critical. Avoid concomitant anticoagulants (except low-dose aspirin). Monitor for tendon rupture, nerve injury, or immunogenicity with repeated doses. |
| Patient Advice | This medication breaks down the collagen cord causing your finger to bend, allowing your doctor to straighten it. · You will receive an injection into the cord, followed by a finger extension procedure the next day. · Common side effects include swelling, bruising, pain, and bleeding at the injection site. · Seek immediate medical attention if you experience severe pain, numbness, or inability to move fingers. · Avoid anticoagulant medications (except low-dose aspirin) for 7 days before injection. · Do not receive a second injection in the same cord within 30 days. |