Baciject Product Monograph

RECENT MAJOR LABEL CHANGES

TABLE OF CONTENTS

Sections or subsections that are not applicable at the time of authorization are not listed.

RECENT MAJOR LABEL CHANGES ........................................................................................... 2

TABLE OF CONTENTS ............................................................................................................. 2

PART I: HEALTH PROFESSIONAL INFORMATION ..................................................................... 4

1 INDICATIONS .............................................................................................................. 4

1.1 Pediatrics ................................................................................................................... 4

1.2 Geriatrics ................................................................................................................... 4

2 CONTRAINDICATIONS ................................................................................................. 4

3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 5

4 DOSAGE AND ADMINISTRATION ................................................................................. 5

4.1 Dosing Considerations .............................................................................................. 5

4.2 Recommended Dose and Dosage Adjustment ......................................................... 5

4.3 Reconstitution ........................................................................................................... 5

4.4 Administration .......................................................................................................... 6

5 OVERDOSAGE ............................................................................................................. 6

6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 6

7 WARNINGS AND PRECAUTIONS .................................................................................. 6

7.1 Special Populations ................................................................................................... 8

7.1.1 Pregnant Women ................................................................................................ 8

7.1.2 Breast-feeding ..................................................................................................... 8

7.1.3 Pediatrics ............................................................................................................. 8

7.1.4 Geriatrics ............................................................................................................. 8

8 ADVERSE REACTIONS.................................................................................................. 8

8.1 Adverse Reaction Overview ...................................................................................... 8

9 DRUG INTERACTIONS ................................................................................................. 8

9.1 Serious Drug Interactions ......................................................................................... 8

9.4 Drug-Drug Interactions ............................................................................................. 8

9.5 Drug-Food Interactions ............................................................................................. 9

9.6 Drug-Herb Interactions ............................................................................................. 9

9.7 Drug-Laboratory Test Interactions............................................................................ 9

10 CLINICAL PHARMACOLOGY ......................................................................................... 9

10.1 Mechanism of Action .......................................................................................... 9

10.3 Pharmacokinetics ................................................................................................ 9

11 STORAGE, STABILITY AND DISPOSAL ........................................................................... 9

12 SPECIAL HANDLING INSTRUCTIONS ............................................................................. 9

PART II: SCIENTIFIC INFORMATION ...................................................................................... 10

13 PHARMACEUTICAL INFORMATION ........................................................................... 10

14 CLINICAL TRIALS ....................................................................................................... 10

15 MICROBIOLOGY ....................................................................................................... 10

16 NON-CLINICAL TOXICOLOGY ..................................................................................... 10

PATIENT MEDICATION INFORMATION ................................................................................. 11

PART I: HEALTH PROFESSIONAL INFORMATION

1 INDICATIONS

BaciJect (Bacitracin for Injection USP) is indicated for:

• The treatment of infants with pneumonia and empyema caused by staphylococci shown to be susceptible to the drug.
• The treatment of secondarily infected wounds, ulcers, pyodermas and other superficial skin and eye infections when used as a topically applied solution.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of BaciJect and other antibacterial drugs, BaciJect should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Bacitracin is not indicated as an irrigation solution for intraoperative prophylaxis nor for pre-soaking of medical devices or implants prior to surgery. Anaphylactic reactions and nephrotoxicity can occur when bacitracin is used in this manner.

1.1 Pediatrics

Pediatrics (infancy: 0 – 2 years of age): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of BaciJect in infants has been established. Therefore, Health Canada has authorized an indication for infant use. (See 4.2 Recommended Dose and Dosage Adjustment)

1.2 Geriatrics

Geriatrics: No data are available to Health Canada; therefore, Health Canada has not authorized an indication for geriatric use.

2 CONTRAINDICATIONS

Bacitracin is contraindicated in patients:

• with a history of previous hypersensitivity or toxic reaction to it.
• who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• with impaired renal function, including those taking nephrotoxic drugs.

3 SERIOUS WARNINGS AND PRECAUTIONS BOX

Serious Warnings and Precautions

4 DOSAGE AND ADMINISTRATION

4.1 Dosing Considerations

Bacitracin should be used only where adequate laboratory facilities are available and when constant supervision of the patient is possible.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of BaciJect and other antibacterial drugs, BaciJect should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Renal function should be carefully determined prior to, and daily during therapy.

Adequate fluid intake should be maintained orally, or if necessary, by parenteral method.

Please refer to section 4.2 Recommended Dose and Dosage Adjustment.

4.2 Recommended Dose and Dosage Adjustment

Infant Dose:

For infants under 2500 grams - 900 units/kg/24 hours in 2 or 3 divided doses. For infants over 2500 grams - 1,000 units/kg/24 hours, in 2 or 3 divided doses. Intramuscular injections of the solution should be given in the upper outer quadrant of the buttocks, alternating right and left and avoiding multiple injections in the same region because of the transient pain following injection.

4.3 Reconstitution

INTRAMUSCULAR Use

Preparation of Solutions: Should be dissolved in Sodium Chloride Injection containing 2 percent procaine hydrochloride. The concentration of the antibiotic in the solution should not be less than 5,000 units per mL nor more than 10,000 units per mL.

Diluents containing parabens should not be used to reconstitute bacitracin; cloudy solutions and precipitate formation have occurred. Reconstitution of the 50,000 unit vial with 9.8 mL of diluent will result in a concentration of 5,000 units per mL.

Reconstituted solution should be clear, pale yellow to light brown in colour and free of foreign particles.

TOPICAL Use

Table 1 - Reconstitution

4.4 Administration

Bacitracin solutions, applied locally in the form of compresses or instillations, may be used once or twice daily in secondarily infected wounds, ulcers, pyodermas and other superficial skin infections and in superficial infections of the eye caused by bacitracin-susceptible organisms. Bacitracin solutions may be instilled into the nasal cavities or administered by inhalation as an aerosol in the treatment of bacitracin-susceptible infections of the upper and lower respiratory tract. In severe or extensive infections, appropriate antibacterial therapy should be given in addition to local treatment with bacitracin.

5 OVERDOSAGE

6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING

Table 2 – Dosage Forms, Strengths, Composition and Packaging

Packaging

BaciJect, 50,000 Units/Vial, is available in 20 mL Vial.

7 WARNINGS AND PRECAUTIONS

Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.

General

Bacitracin is not indicated as an irrigation solution for intraoperative prophylaxis nor for pre-soaking of medical devices or implants prior to surgery. Anaphylactic reactions and nephrotoxicity can occur when

bacitracin is used in this manner.

Adequate fluid intake should be maintained orally, or if necessary, by parenteral method.

As with other antibiotics, use of this drug may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be instituted.

Immune

Serious hypersensitivity, including anaphylactic reactions, and allergic contact dermatitis have been reported in patients treated with bacitracin administered intramuscularly and through local exposure (see 1 INDICATIONS and 7 WARNINGS AND PRECAUTIONS, General). These reactions may occur following the first dose.

Monitoring and Laboratory Tests

Close monitoring of renal function is recommended in patients treated with bacitracin. Glomerular and tubular kidney function must be evaluated and checked before commencement of therapy, as well as during and after treatment.

Renal

Nephrotoxicity

There have been reports of nephrotoxicity in patients exposed to bacitracin via intramuscular and non-intramuscular routes, including local exposure. Bacitracin may cause renal failure due to tubular and glomerular necrosis due to high systematic absorption.

• Bacitracin should be used only where adequate laboratory facilities are available and when constant supervision of the patient is possible.
• Intramuscular use should be restricted to infants with Staphylococcal pneumonia and empyema due to organisms shown to be susceptible to bacitracin.
• Renal function should be carefully determined prior to, and daily during therapy.
• The recommended daily dose should not be exceeded and fluid intake and urinary output maintained at proper levels to avoid kidney toxicity.
• Patients /caregivers should stop taking BaciJect and seek immediate medical attention if the signs of kidney problems occur. Patients /caregivers should be informed of symptoms such as urinating less than usual or not at all, blood in the urine, lower back pain, or painful urination.
• If renal toxicity occurs, the drug should be discontinued.
• Concurrent use of other nephrotoxic drugs should be avoided (see 7.1.3 WARNINGS AND PRECATIONS, General; Special Populations, Pediatrics).

Sensitivity/Resistance

Development of Drug Resistant Bacteria

Prescribing BaciJect in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and risks the development of drug-resistant bacteria.

7.1 Special Populations

7.1.1 Pregnant Women

The safety and efficacy of BaciJect in pregnant women have not yet been established. No data are available.

7.1.2 Breast-feeding

It is unknown if BaciJect (Bacitracin for Injection USP) is excreted in human milk. Precaution should be exercised because many drugs can be excreted in human milk.

7.1.3 Pediatrics

Pediatrics (0 – 2 years of age): For Intramuscular Use

Nephrotoxicity: Bacitracin in parenteral (intramuscular) therapy may cause renal failure due to tubular and glomerular necrosis. Its use should be restricted to infants with staphylococcal pneumonia and empyema when due to organisms shown to be susceptible to bacitracin. It should be used only where adequate laboratory facilities are available and when constant supervision of the patient is possible.

Renal function should be carefully determined prior to and daily during therapy. The recommended daily dose should not be exceeded and fluid intake and urinary output maintained at proper levels to avoid kidney toxicity. If renal toxicity occurs the drug should be discontinued. The concurrent use of other nephrotoxic drugs, particularly streptomycin, kanamycin, polymyxin B, polymyxin E (colistin), neomycin, and viomycin, should be avoided.

7.1.4 Geriatrics

Not applicable.

8 ADVERSE REACTIONS

8.1 Adverse Reaction Overview

Nephrotoxic reactions: Albuminuria, Cylindruria Azotemia. Rising blood levels without any increase in dosage (see 7 WARNINGS AND PRECAUTIONS, Renal).

Other reactions: Nausea and vomiting. Pain at site of injection. Skin rashes.

9 DRUG INTERACTIONS

9.1 Serious Drug Interactions

Serious Drug Interactions

• Do not use with nephrotoxic medications (see 2 CONTRAINDICATIONS and 9.4 Drug-Drug Interactions).

9.4 Drug-Drug Interactions

Do not use BaciJect at the same time as other nephrotoxic drugs, especially streptomycin kanamycin, polymyxin B, polymyxin E (colistin), neomycin, and viomycin (see 2 CONTRAINDICATIONS).

Interactions with other drugs have not been established.

9.5 Drug-Food Interactions

Interactions with food have not been established.

9.6 Drug-Herb Interactions

Interactions with herbal products have not been established.

9.7 Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.

10 CLINICAL PHARMACOLOGY

10.1 Mechanism of Action

Bacitracin, an antibiotic substance derived from cultures of Bacillus subtilis (Tracey), exerts pronounced antibacterial action in vitro against a variety of gram-positive and a few gram-negative organisms.

However, among systemic diseases, only staphylococcal infections qualify for consideration of bacitracin therapy. Bacitracin is assayed against a standard and its activity is expressed in units, 1 mg having a potency of not less than 50 units.

Susceptibility plate testing: If the Kirby-Bauer method of disc susceptibility is used, a 10-unit bacitracin disc should give a zone over 13 mm when tested against a bacitracin-susceptible strain of Staphylococcus aureus.

10.3 Pharmacokinetics

Absorption:

Absorption of bacitracin following intramuscular injection is rapid and complete. A dose of 200 or 300 units/kg every six hours gives serum levels of 0.2 to 2 mcg/mL in individuals with normal renal function.

Distribution:

BaciJect (Bacitracin for Injection USP) is widely distributed in all body organs and is demonstrable in ascitic and pleural fluids after intramuscular injection.

Elimination:

The drug is excreted slowly by glomerular filtration.

11 STORAGE, STABILITY AND DISPOSAL

Store unreconstituted bacitracin in a refrigerator 2°C to 8°C. Solutions are rapidly inactivated at room temperature but are stable for one week when stored in a refrigerator 2°C to 8°C.

12 SPECIAL HANDLING INSTRUCTIONS

None.

PART II: SCIENTIFIC INFORMATION

13 PHARMACEUTICAL INFORMATION

Drug Substance

Proper name: bacitracin

Molecular formula: C₆₆H₁₀₃N₁₇O₁₆S

Structural formula:

Physicochemical properties: Bacitracin is a white to pale buff, hygroscopic powder, odorless or having a slight odor. It is freely soluble in water; insoluble in acetone, chloroform, and ether. While soluble in alcohol, methanol, and glacial acetic acid, there is some insoluble residue. It is precipitated from its solutions and inactivated by many of the heavy metals.

14 CLINICAL TRIALS

This information is not available for this drug product.

15 MICROBIOLOGY

No microbiological information is required for this drug product.

16 NON-CLINICAL TOXICOLOGY

No long-term animal studies have been performed to evaluate carcinogenic or mutagenic potential or whether BaciJect affects fertility in males or females.