AHFS Class:

• Basic Ointments and Protectants 84:24.12

Generic Name(s):

• Collagenase

Collagenase is an enzymatic debriding agent.

Wound Debridement

Collagenase is used to promote debridement of necrotic tissue in the treatment of severe burns and dermal ulcers including decubitus ulcers.

When applied daily to experimental third-degree burns in animals, collagenase ointment or powder produced total separation of the burn eschar within 7 days. Similar burns treated with trypsin or fibrinolysin and desoxyribonuclease (no longer commercially available in the US) required 14 days of enzyme application before eschar separation occurred. In one comparative study in patients 5-60 years of age with partial-thickness burn wounds, therapy with collagenase ointment and Polysporin^® powder (polymyxin B sulfate and bacitracin zinc) was at least as effective (as measured by the time to a clean wound bed and the time to healing [complete epithelialization]) as silver sulfadiazine 1% cream. In one group of patients, debridement of decubiti occurred within 10 days when daily application of collagenase ointment was used. Another group of patients with stasis ulcers of the lower extremities received topical application of collagenase ointment once or twice daily; debridement occurred within 6 days in about half of the patients.

Other Uses

For other uses of collagenase, see Collagenase Clostridium Histolyticum 44.00.

Collagenase is applied topically as an ointment once daily. If the dressing becomes soiled (e.g., due to incontinence), collagenase may be applied more frequently. Strict aseptic conditions should be maintained.

If the lesion to be treated with collagenase has been exposed to detergents or heavy metal ions incompatible with collagenase, the site should be carefully cleansed by repeated washings with 0.9% sodium chloride solution. Prior to each collagenase application, the lesion should be gently cleansed with a gauze pad saturated with 0.9% sodium chloride solution or another cleaning solution that is compatible with collagenase ointment to remove necrotic material. As much loosened detritus should be removed as can be done readily with forceps and scissors. Thick eschar may be cross-hatched with a #10 scalpel blade.

When infection is present, a topical antibiotic can be used concomitantly. An appropriate antibiotic compatible with collagenase may be applied to the lesion as a powder prior to application of collagenase. If the infection does not respond to this combined therapy, collagenase should be discontinued until the infection has resolved.

Collagenase ointment may be applied directly to the wound or to a sterile gauze pad which is then applied to the wound and properly secured. Caution should be used to restrict application of the enzyme ointment to the lesion, avoiding application to healthy surrounding skin. A sterile gauze pad should be placed over the wound.

Application of collagenase should be discontinued when debridement of necrotic tissue is well established.

Adverse Effects

Pain and burning may occur at the site of collagenase application. Slight erythema may develop in surrounding tissue, especially if the ointment is not confined to the lesion being treated. The ointment should be applied carefully within the affected area.

A systemic hypersensitivity reaction to collagenase has been reported following prolonged use (more than one year) of collagenase in conjunction with cortisone.

Precautions and Contraindications

Because of the theoretical possibility that debridement may increase the risk of bacteremia, debilitated patients receiving treatment with collagenase should be observed for evidence of systemic bacterial infection.

Collagenase probably should not be introduced into major body cavities, such as pleural or peritoneal cavities. Collagenase is contraindicated in patients who show local or systemic hypersensitivity to the enzyme.

Although systemic or local reactions attributable to overdosage have not been observed in collagenase-treated patients, if inactivation of collagenase is deemed necessary, the area may be washed with povidone iodine.

Safety and efficacy of collagenase ointment in pediatric patients have not been established.

Pharmacology

Collagenase is an enzymatic debriding agent capable of specifically hydrolyzing peptide bonds of undenatured and denatured collagen. The enzyme liquefies necrotic tissue without damaging granulation tissue. In vitro, collagenase does not degrade fat, keratin, fibrin, hemoglobin, or elastin. In general, proteolytic enzymes have no anti-infective properties, but the action of the drug may remove substrates necessary for bacterial proliferation or may permit antibodies, leukocytes, and antibiotics better access to the infected area.

Chemistry and Stability

Chemistry

Collagenase is an enzyme concentrate derived from Clostridium histolyticum. Collagenase occurs as a fine, brown amorphous powder and is soluble in water. The potency of collagenase is expressed in N-units which are based on the amount of enzyme required to degrade a standard undenatured collagen substrate under specified conditions.

Stability

Collagenase is stable at physiologic pH and has optimal activity at pH 6-8. The enzyme is inactive below pH 5 and may be irreversibly inactivated by such pH conditions. Collagenase is reversibly inactivated at pH 8.5 or greater; activity can be restored by return of pH to 7.4.

Collagenase can be destroyed by other proteolytic enzymes or by exposure to temperatures exceeding 56°C. The commercially available collagenase ointments should be stored at temperatures not exceeding 25°C.

The enzymatic activity of collagenase is adversely affected by detergents, heavy metal ions such as mercury or silver contained in some antiseptic products, and povidone iodine. Solutions containing metal ions and those with a low pH can inhibit the activity of collagenase. Calcium ions, however, are thought to be necessary for optimal collagenase activity. It has not yet been determined if collagenase activity is inhibited by serum. Hydrogen peroxide, Dakin's solution, 0.9% sodium chloride solution, polymyxin B, and bacitracin do not interfere with collagenase activity.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.