Introduction

Anacaulase-bcdb is a mixture of proteolytic enzymes.

Uses for Anacaulase

Anacaulase-bcdb has the following uses:

Anacaulase-bcdb is indicated for eschar removal in adults with deep partial thickness and/or full thickness thermal burns.

The safety and effectiveness of anacaulase-bcdb have not been established for treatment of chemical or electrical burns; burns on the face, perineum, or genitalia; burns on the feet of patients with diabetes mellitus or on the feet of patients with occlusive vascular disease; circumferential burns; and burns in patients with significant cardiopulmonary disease, including inhalation injury.

Anacaulase-bcdb is not recommended for wounds contaminated with radioactive and other hazardous substances to avoid unforeseeable reactions with the product and an increased risk of spreading the noxious substance.

Anacaulase Dosage and Administration

General

Anacaulase-bcdb is available in the following dosage form(s) and strength(s):

• Lyophilized powder containing 0.97 g of anacaulase-bcdb per each g of powder to be mixed with a gel vehicle to provide 8.8% w/w gel for topical use

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• For topical use only.

• Anacaulase-bcdb is only to be administered by a healthcare provider. Healthcare providers should take precautions to avoid exposure to anacaulase-bcdb during preparation and handling.

• The lyophilized powder and gel vehicle must be mixed prior to administration to provide an 8.8% w/w gel for topical use.

• Use 1.94 g of anacaulase-bcdb in 2 g powder mixed with 20 g gel per 1% body surface area (BSA), or 4.85 g of anacaulase-bcdb in 5 g powder mixed with 50 g gel per 2.5% BSA.

• Anacaulase-bcdb may be applied in up to two applications of 4 hours each.

• A first application may be applied to an area of up to 15% BSA. A second application may be applied 24 hours later after the first application to the same or new burn wound area. The total treated area for both applications must not exceed 20% BSA (40 g of anacaulase-bcdb lyophilized powder).

• Prepare anacaulase-bcdb at the patient’s bedside within 15 minutes of intended application. Discard anacaulase-bcdb if not used within 15 minutes of preparation, as the enzymatic activity of the product decreases progressively following mixing.

• Apply anacaulase-bcdb to a clean, moist wound bed free of burned epidermis layer and blisters, and cover with an occlusive film dressing for 4 hours.

• Maintain pain management throughout the application as practiced for an extensive dressing change of burn wounds. At least 15 minutes prior to anacaulase-bcdb application, ensure adequate pain control measures are in place.

• See Full Prescribing Information for additional details on preparation, administration, and removal of anacaulase-bcdb.

Contraindications

• Known hypersensitivity to anacaulase-bcdb, bromelain, pineapples, or to any of the other components.

• Known hypersensitivity to papayas or papain because of the risk of cross-sensitivity.

Warnings/Precautions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, have been reported with postmarketing use of anacaulase-bcdb. If a hypersensitivity reaction occurs, remove anacaulase-bcdb (if applicable) and initiate appropriate therapy.

Anacaulase-bcdb is contraindicated in patients with a known hypersensitivity to anacaulase-bcdb, bromelain, pineapples or to any other component of anacaulase-bcdb. Anacaulase-bcdb is also contraindicated in patients with known hypersensitivity to papayas or papain because of the risk of cross-sensitivity.

Healthcare personnel should take appropriate precautions to avoid exposure when preparing and handling anacaulase-bcdb (e.g., gloves, surgical masks, other protective coverings, as needed). In the event of inadvertent skin exposure, rinse the product off with water to reduce the likelihood of skin sensitization.

Pain Management

Eschar removal with anacaulase-bcdb and treatment-related burn wound procedures are painful and require adequate analgesia and/or anesthesia. Pain management should be appropriate for an extensive dressing change of burn wounds. At least 15 minutes prior to application ensure adequate pain control measures are in place to address anacaulase-related pain.

Proteolytic Injury to Non-target Tissues

Anacaulase-bcdb is not recommended for treatment of burn wounds where medical devices (e.g., implants, pacemakers, shunts) or vital structures (e.g., large vessels) could become exposed during eschar removal.

Protect any open wounds (e.g., laceration, abraded skin and escharotomy incision) with skin protectant ointments or ointment gauze to prevent possible exposure to anacaulase-bcdb.

Coagulopathy

A reduction of platelet aggregation and plasma fibrinogen levels and a moderate increase in partial thromboplastin and prothrombin times have been reported in the literature as possible effects following oral administration of bromelain, a component of anacaulase-bcdb. In vitro and animal data suggest that bromelain can also promote fibrinolysis.

Avoid use of anacaulase-bcdb in patients with uncontrolled disorders of coagulation. Use anacaulase-bcdb with caution in patients on anticoagulant therapy or other drugs affecting coagulation, and in patients with low platelet counts and increased risk of bleeding from other causes (e.g., peptic ulcers and sepsis). Patients should be monitored for possible signs of coagulation abnormalities and signs of bleeding.

Specific Populations

Pregnancy

There are no available data on anacaulase-bcdb use in pregnant women to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% an 15 to 20%, respectively.

In embryofetal developmental studies in rats and rabbits, intravenous doses up to 4 and 0.1 mg/kg/day of anacaulase-bcdb were administered to pregnant rats and rabbits, respectively, during organogenesis. No significant developmental toxicities were observed in these studies. However, severe maternal toxicities were noted and the tolerable maternal exposure levels were much lower compared with the maximum human exposure in clinical setting.

Lactation

There are no data on the presence of anacaulase-bcdb in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for anacaulase-bcdb and any potential adverse effects on the breastfed infant from anacaulase-bcdb or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of anacaulase-bcdb in pediatric patients have not been established.

Geriatric Use

Of the 177 subjects exposed to anacaulase-bcdb for eschar removal in deep partial thickness (DPT) and/or full thickness (FT) thermal burns, 6 (3%) subjects were 65 years or older, and 1 (<1%) subject was 75 years or older. Clinical studies of anacaulase-bcdb did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects.

Common Adverse Effects

The most common adverse reactions (>10%) were pruritus and pyrexia.

General

Anacaulase-bcdb is available in the following dosage form(s) and strength(s):

• Lyophilized powder containing 0.97 g of anacaulase-bcdb per each g of powder to be mixed with a gel vehicle to provide 8.8% w/w gel for topical use

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• For topical use only.

• Anacaulase-bcdb is only to be administered by a healthcare provider. Healthcare providers should take precautions to avoid exposure to anacaulase-bcdb during preparation and handling.

• The lyophilized powder and gel vehicle must be mixed prior to administration to provide an 8.8% w/w gel for topical use.

• Use 1.94 g of anacaulase-bcdb in 2 g powder mixed with 20 g gel per 1% body surface area (BSA), or 4.85 g of anacaulase-bcdb in 5 g powder mixed with 50 g gel per 2.5% BSA.

• Anacaulase-bcdb may be applied in up to two applications of 4 hours each.

• A first application may be applied to an area of up to 15% BSA. A second application may be applied 24 hours later after the first application to the same or new burn wound area. The total treated area for both applications must not exceed 20% BSA (40 g of anacaulase-bcdb lyophilized powder).

• Prepare anacaulase-bcdb at the patient’s bedside within 15 minutes of intended application. Discard anacaulase-bcdb if not used within 15 minutes of preparation, as the enzymatic activity of the product decreases progressively following mixing.

• Apply anacaulase-bcdb to a clean, moist wound bed free of burned epidermis layer and blisters, and cover with an occlusive film dressing for 4 hours.

• Maintain pain management throughout the application as practiced for an extensive dressing change of burn wounds. At least 15 minutes prior to anacaulase-bcdb application, ensure adequate pain control measures are in place.

• See Full Prescribing Information for additional details on preparation, administration, and removal of anacaulase-bcdb.

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.