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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XIAFLEX (XIAFLEX).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or effects on milk production. Due to lack of systemic absorption after local injection, transfer into breast milk is unlikely. M/P ratio is not applicable. Caution advised; consider importance of drug to mother. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to collagenase clostridium histolyticum or any excipients","Treatment of a ruptured tendon or a condition with a risk of tendon rupture","Injection into the corpus cavernosum in patients with Peyronie's disease who have severe penile vascular disease or severely compromised penile function prior to treatment"]
| 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"] |
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| 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. |