Dermatologic Agent
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of collagenase Clostridium histolycticum in human pregnancy have been located. Reproduction studies in rats revealed no evidence of harm to the fetus, but the comparison to the human dose was based on body weight and may not be interpretable. However, in humans, quantifiable levels of the drug did not occur in the systemic circulation after injection into a Dupuytren cord. Almost all patients treated with collagenase C. histolyticum develop antiproduct antibodies after treatment. The clinical significance of antiproduct antibody formation on a developing fetus is not known.
FETAL RISK SUMMARY
Collagenase Clostridium histolyticum is a polypeptide consisting of two microbial collagenases (proteinases), collagenase AUX-I and collagenase AUX-II, isolated from the fermentation of C. histolyticumbacteria. It is indicated for the treatment of adult patients with Dupyutren contracture with a palpable cord. The drug is given by local injection into the hand. After injection into a Dupuytren cord, neither of the collagenases had quantifiable levels in the systemic circulation (the lower limit of quantification for AUX I and AUX II in human plasma is 5 and 25 ng/mL, respectively).
Reproduction studies have been performed in rats. No evidence of fetal harm was observed in pregnant rats given IV doses up to about 45 times the IV human dose based on body weight (HD) (1).
Carcinogenicity studies with collagenase C. histolyticum have not been conducted. Various assays for mutagenic and clastogenic effects were negative. The polypeptide did not impair fertility or early embryonic development when administered IV to rats at doses up to about 45 times the HD (1).
It is not known if the two collagenases cross the human placenta. The molecular weights of collagenase AUX-1 and collagenase AUX-II are 114,000 and 113,000, respectively, and nonquantifiable systemic levels suggest that clinically significant exposure of the embryo or fetus is unlikely.
BREASTFEEDING SUMMARY
No reports on the use of collagenase C. histolyticum during lactation have been located. The molecular weights of collagenase AUX-1 and collagenase AUX-II are 114,000 and 113,000, respectively, and, combined with the nonquantifiable systemic levels, suggest that the presence in milk of clinically significant amounts is unlikely.
Reference
1.Product information. Xiaflex. Auxilium Pharmaceuticals, 2010.