Xiaflex
Encyclopedia
Collagenase clostridium histolyticum is an enzyme
produced by the bacterium Clostridium histolyticum
that dismantles collagen
. It is used as a powder-and-solvent injection kit for the treatment for Dupuytren's contracture
, a condition where the fingers bend towards the palm and cannot be fully straightened. BioSpecifics Technologies developed the preparation, which is manufactured and marketed by Auxilium Pharmaceuticals and Pfizer
as Xiaflex in the US and Xiapex in Europe.
of the United States approved Xiaflex for the treatment of Dupuytren's contracture. It is the first approved nonsurgical treatment for this condition. In a case of Dupuytren's contracture, collagen
accumulates in the tendon sheathes of the hands, so that the fingers cannot be straightened. A similar phenomenon occurs in Peyronie's disease
, a contracture of the penis.
In February 2011, the European Commission's Committee for Medicinal Products for Human Use
approved the product for the treatment of Dupuytren's contracture in adults with a palpable cord by 'properly trained' doctors. Pfizer was reported to be working with Europe's national medicines regulatory bodies to launch the new treatment, hoping doctors could prescribe the treatment by late 2011.
(swollen lymph node
s), itching, pain, oedema, and bleeding (for example in the form of bruise
s or ecchymoses). Allergic reactions are seen in less than 1% of patients.
of C. histolyticum that has been known since 1950.
s.
The two collagenases act synergistically by cleaving tropocollagen (the 'collagen molecule') at different points. AUX-I attacks the C- and N-termini, AUX-II cleaves amino acid bonds within the molecule. Small collagen fragments are broken down by both enzymes.
s, such as tetracyclines, anthracyclines, quinolones and anthraquinone
derivatives, could reduce the efficacy of the collagenases, but no clinical evidence for such an interaction has been observed.
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
produced by the bacterium Clostridium histolyticum
Clostridium histolyticum
Clostridium histolyticum is an anaerobic, motile, gram-positive bacterium that thrives in feces and soil. The ammonia and proteases it produces, including several collagenases, digest proteins outside its body into amino acids, which it eats. When Cl...
that dismantles collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
. It is used as a powder-and-solvent injection kit for the treatment for Dupuytren's contracture
Dupuytren's contracture
Dupuytren's contracture , is a fixed flexion contracture of the hand where the fingers bend towards the palm and cannot be fully extended...
, a condition where the fingers bend towards the palm and cannot be fully straightened. BioSpecifics Technologies developed the preparation, which is manufactured and marketed by Auxilium Pharmaceuticals and Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
as Xiaflex in the US and Xiapex in Europe.
Uses
In February 2010, the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
of the United States approved Xiaflex for the treatment of Dupuytren's contracture. It is the first approved nonsurgical treatment for this condition. In a case of Dupuytren's contracture, collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
accumulates in the tendon sheathes of the hands, so that the fingers cannot be straightened. A similar phenomenon occurs in Peyronie's disease
Peyronie's disease
Peyronie's Disease Peyronie's Disease Peyronie's Disease (also known as "Induratio penis plastica", or more recently Chronic Inflammation of the Tunica Albuginea (CITA), is a connective tissue disorder involving the growth of fibrous plaques in the soft tissue of the penis affecting up to 10% of men...
, a contracture of the penis.
In February 2011, the European Commission's Committee for Medicinal Products for Human Use
Committee for Medicinal Products for Human Use
The Committee for Medicinal Products for Human Use , formerly known as Committee for Proprietary Medicinal Products , is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding medicinal products for human use.E.g.: In June 2007 the CHMP...
approved the product for the treatment of Dupuytren's contracture in adults with a palpable cord by 'properly trained' doctors. Pfizer was reported to be working with Europe's national medicines regulatory bodies to launch the new treatment, hoping doctors could prescribe the treatment by late 2011.
Side effects
The most common side effects include lymphadenopathyLymphadenopathy
Lymphadenopathy is a term meaning "disease of the lymph nodes." It is, however, almost synonymously used with "swollen/enlarged lymph nodes". It could be due to infection, auto-immune disease, or malignancy....
(swollen lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s), itching, pain, oedema, and bleeding (for example in the form of bruise
Bruise
A bruise, also called a contusion, is a type of relatively minor hematoma of tissue in which capillaries and sometimes venules are damaged by trauma, allowing blood to seep into the surrounding interstitial tissues. Bruises can involve capillaries at the level of skin, subcutaneous tissue, muscle,...
s or ecchymoses). Allergic reactions are seen in less than 1% of patients.
Chemical properties
The substance is a constant mixture of two collagenases (AUX-I and AUX-II) with known amino acid sequences and a length of about 1000 amino acids each. It is prepared by anaerobic fermentation from a strainStrain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
of C. histolyticum that has been known since 1950.
Pharmacology
The enzymes do not reach the bloodstream in significant amounts and are presumed to largely stay at the point of injection until they are broken down by proteaseProtease
A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....
s.
The two collagenases act synergistically by cleaving tropocollagen (the 'collagen molecule') at different points. AUX-I attacks the C- and N-termini, AUX-II cleaves amino acid bonds within the molecule. Small collagen fragments are broken down by both enzymes.
Interactions
No interaction studies have been conducted because the drug does not reach the bloodstream and the liver. It is theorised that drugs interfering with matrix metalloproteinaseMatrix metalloproteinase
Matrix metalloproteinases are zinc-dependent endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily....
s, such as tetracyclines, anthracyclines, quinolones and anthraquinone
Anthraquinone
Anthraquinone, also called anthracenedione or dioxoanthracene is an aromatic organic compound with formula . Several isomers are possible, each of which can be viewed as a quinone derivative...
derivatives, could reduce the efficacy of the collagenases, but no clinical evidence for such an interaction has been observed.