anacaulase (Rx)

>10%

Pruritus (15%)

Pyrexia (12%)

1-10%

Wound complication (9%)

Anemia (6%)

Vomiting (5%)

Insomnia (5%)

Urinary tract infection (4%)

Tachycardia (3%)

Rash (3%)

Infection (2%)

Sepsis (2%)

Leukocytosis (2%)

Hypotension (2%)

Hepatic function abnormal (1%)

Drug hypersensitivity (1%)

Bacteremia (1%)

Scar (1%)

Subcutaneous hematoma (1%)

Decubitus ulcer (1%)

Postmarketing Reports

Immune system disorders: Hypersensitivity, including anaphylaxis and urticaria

Contraindications

Hypersensitivity to anacaulase, bromelain, pineapples, or to any other components

Hypersensitivity to papayas or papain because of the risk of cross-sensitivity

Cautions

Eschar removal with anacaulase and treatment-related burn wound procedures are painful and require adequate analgesia and/or anesthesia; apply appropriate pain management for an extensive dressing change of burn wounds; ensure adequate pain control is in place at least 15 minutes before application

Not recommended for treatment of burn wounds where medical devices (eg, implants, pacemakers, shunts) or vital structures (eg, large vessels); protect any open wounds (eg, laceration, abraded skin and escharotomy incision) with skin protectant ointments or ointment gauze

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
• Avoid use in patients with uncontrolled disorders of coagulation
• Use 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 (eg, septic ulcers, sepsis)
• Monitor for possible signs of coagulation abnormalities and signs of bleeding

Hypersensitivity reactions

• Serious hypersensitivity reactions, including anaphylaxis, reported
• If a hypersensitivity reaction occurs, remove anacaulase (if applicable) and initiate appropriate therapy
• When preparing and handling drug, take appropriate precautions (eg, gloves, surgical masks, other coverings) as needed
• If inadvertent skin exposure occurs, rinse drug off with water to reduce the likelihood of skin sensitization

Drug interaction overview

• No drug interaction studies conducted
• Bromelain, a component of anacaulase, exhibited CYP2C8 time-dependent inhibition in human hepatocytes and inhibited human microsomal CYP2C9

Pregnancy

Data are not available on use in pregnant females to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

Animal studies

• IV doses up to 4 and 0.1 mg/kg/day were administered to pregnant rats and rabbits, respectively, during organogenesis
• No significant developmental toxicities were observed
• 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 presence in either human or animal milk, effects on breastfed infants, or effects on milk production

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Mixture of proteolytic enzymes extracted from the stems of pineapple plants (Ananas comosus) that has been sterile filtered and lyophilized

Composed mainly (80-95% w/w) of the proteins: stem bromelain, ananain, jacalin-like lectin, bromelain inhibitors, and phytocystatin inhibitor; and saccharides, as both free monosaccharides and the N-linked glycan of stem bromelain, and small molecule metabolites

The enzyme mixture dissolves burn wound eschar; specific components responsible for this effect have not been identified

Absorption

Peak plasma time: 4 hr

AUC

• Systemic exposure (ie, AUC) of the component bromelain correlates with size of the treated area and dose, but not burn wound depth

Elimination

Half-life (bromelain): 4.4 hr

Topical Preparation

Gather sterile supplies

• Instrument for mixing (eg, spatula or tongue depressor)
• Tongue depressor for application
• 0.9% NaCl irrigation
• Occlusive film dressing
• Loose, thick fluffy dressing and bandage

Anacaulase gel preparation

• Pour lyophilized powder into gel vehicle jar
• Thoroughly mix using sterile instrument (eg, tongue depressor or spatula) until the mixture is uniform
• Mixed product final concentration is 8.8% w/w
• Discard mixture if not used within 15 minutes of preparation, as the enzymatic activity of the product decreases progressively following mixing

Topical Administration

For topical use only

Patient preparation

• Use pain management as practiced for an extensive dressing change of burn wounds 15 minutes before all anacaulase-related procedures and maintain throughout application as practiced for an extensive dressing change of burn wounds

• Prepare wound area as follows

  • Thoroughly clean wound to remove any charred tissue, blisters, and any topical products
  • Apply dressing soaked with an antibacterial solution to treatment area for at least 2 hr
  • Ensure wound bed is clear of any remnants of topical agents (eg silver sulfadiazine or povidone iodine)
  • Apply an ointment skin protectant (eg, petrolatum) 2-3 cm outside of treatment area to create an ointment barrier
  • Protect any open wounds (eg, laceration, abraded ski, escharotomy incision) with skin protectant ointments or ointment gauze to prevent possible exposure to anacaulase
  • Avoid applying ointment to the treatment area itself, as this would impede direct contact of anacaulase with the eschar

Mixed 8.8% gel application

• Apply within 15 minutes of preparation
• Moisten treatment area by sprinkling sterile 0.9% NaCl irrigation onto burn wound
• Using a sterile tongue depressor, completely cover moistened treatment area with anacaulase mixture in a 3-mm thick layer (~thickness of tongue depressor) that completely covers burn wound area
• Cover treated wound with sterile occlusive film dressing
• Gently press occlusive film dressing at area of contact with ointment barrier to ensure adherence between the occlusive film dressing and the sterile ointment barrier and to achieve complete containment of anacaulase on treatment area; anacaulase gel should fill entire volume of treatment area, and there should be no visible air under the occlusive film dressing
• Cover dressed wound with sterile loose, thick, fluffy dressing and secure with sterile bandage
• Leave dressing and gel mixture in place for 4 hr
• Discard any unused portions anacaulase

Remove anacaulase after 4 hr

• Sterile supplies

  • Blunt-edged instruments (eg, tongue depressor)
  • Large dry gauze
  • Gauze soaked with 0.9% NaCl irrigation
  • Dressing soaked with antibacterial solution

• Removal procedure

  • Implement and maintain pain management
  • Remove occlusive film dressing using aseptic technique
  • Remove ointment barrier using sterile blunt-edged instrument
  • Remove dissolved eschar from wound by scraping it away with sterile bluntedged instrument
  • Wipe wound thoroughly with large sterile dry gauze, then wipe with sterile gauze that has been soaked with sterile 0.9% NaCl irrigation
  • Rub treated area until appearance of a clean dermis or subcutaneous tissues with pinpoint bleeding
  • To remove remnants of dissolved eschar, apply dressing soaked with an antibacterial solution for at least 2 hr

Second application 24 hr later may be considered if

• Wound area >15% BSA, or
• Multiple wound areas on different body surfaces require 2 treatments for logistical reasons (eg, body position), or
• First application’s eschar removal was incomplete

Wound care after eschar removal

• Wound care following eschar removal based on the healthcare provider’s clinical judgement (eg, observe for spontaneous reepithelization or proceed with autograft)

Monitoring

• Monitor for signs of local or systemic allergic reactions
• If hypersensitivity reaction occurs, remove anacaulase (if applicable) from treatment area and initiate appropriate therapy

Storage

Store package upright in refrigerator at 2-8ºC (36-46ºF) in original carton to protect from light

Do not freeze

Do not use if vial or jar are damaged