Polymyxin B

POLYMYXIN B- polymyxin b sulfate injection, powder, lyophilized, for solution
X-GEN Pharmaceuticals, Inc.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of polymyxin B and other antibacterial drugs, polymyxin B should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

WARNINGS

CAUTION: WHEN THIS DRUG IS GIVEN INTRAMUSCULARLY, INTRAVENOUSLY AND/OR INTRATHECALLY, IT SHOULD BE GIVEN ONLY TO HOSPITALIZED PATIENTS, SO AS TO PROVIDE CONSTANT SUPERVISION BY A PHYSICIAN.

RENAL FUNCTION SHOULD BE CAREFULLY DETERMINED AND PATIENTS WITH RENAL DAMAGE AND NITROGEN RETENTION SHOULD HAVE REDUCED DOSAGE. PATIENTS WITH NEPHROTOXICITY DUE TO POLYMYXIN B SULFATE USUALLY SHOW ALBUMINURIA, CELLULAR CASTS, AND AZOTEMIA. DIMINISHING URINE OUTPUT AND A RISING BUN ARE INDICATIONS FOR DISCONTINUING THERAPY WITH THIS DRUG.

NEUROTOXIC REACTIONS MAY BE MANIFESTED BY IRRITABILITY, WEAKNESS, DROWSINESS, ATAXIA, PERIORAL PARESTHESIA, NUMBNESS OF THE EXTREMITIES, AND BLURRING OF VISION. THESE ARE USUALLY ASSOCIATED WITH HIGH SERUM LEVELS FOUND IN PATIENTS WITH IMPAIRED RENAL FUNCTION AND/OR NEPHROTOXICITY.

THE CONCURRENT OR SEQUENTIAL USE OF OTHER NEUROTOXIC AND/OR NEPHROTOXIC DRUGS WITH POLYMYXIN B SULFATE, PARTICULARLY BACITRACIN, STREPTOMYCIN, NEOMYCIN, KANAMYCIN, GENTAMICIN, TOBRAMYCIN, AMIKACIN, CEPHALORIDINE, PAROMOMYCIN, VIOMYCIN, AND COLISTIN SHOULD BE AVOIDED.

THE NEUROTOXICITY OF POLYMYXIN B SULFATE CAN RESULT IN RESPIRATORY PARALYSIS FROM NEUROMUSCULAR BLOCKADE, ESPECIALLY WHEN THE DRUG IS GIVEN SOON AFTER ANESTHESIA AND/OR MUSCLE RELAXANTS.

USAGE IN PREGNANCY: THE SAFETY OF THIS DRUG IN HUMAN PREGNANCY HAS NOT BEEN ESTABLISHED.

DESCRIPTION

Polymyxin B for Injection is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aerosporous). Polymyxin B sulfate is the sulfate salt of Polymyxins B1 and B2 , which are produced by the growth of Bacillus polymyxa (Prazmowski) Migula (Fam. Bacillacea). It has a potency of not less than 6000 polymyxin B units per mg, calculated on the anhydrous basis. The structural formulae are:

structure
(click image for full-size original)

structure

Polymyxin B 1 (R=CH 3 )            Polymyxin B 2 (R=H)

Each vial contains 500,000 polymyxin B units for parenteral or ophthalmic administration.

Polymyxin B for Injection, USP is in powder form suitable for preparation of sterile solutions for intramuscular, intravenous drip, intrathecal, or ophthalmic use.

In the medical literature, dosages have frequently been given in terms of equivalent weights of pure polymyxin B base. Each milligram of pure polymyxin B base is equivalent to 10,000 units of polymyxin B and each microgram of pure polymyxin B base is equivalent to 10 units of polymyxin B.

Aqueous solutions of polymyxin B sulfate may be stored up to 12 months without significant loss of potency if kept under refrigeration. In the interest of safety, solutions for parenteral use should be stored under refrigeration and any unused portion should be discarded after 72 hours. Polymyxin B sulfate should not be stored in alkaline solutions since they are less stable.

CLINICAL PHARMACOLOGY

Polymyxin B sulfate has a bactericidal action against almost all gram-negative bacilli except the Proteus group. Polymyxins increase the permeability of the bacterial cell membrane leading to death of the cell. All gram positive bacteria, fungi, and gram-negative cocci, are resistant to polymyxin B. Appropriate methods should be used when performing in vitro susceptibility testing of polymyxin B 1,2,3. The following in vitro susceptibility test criteria should only be used for interpreting the results of polymyxin B susceptibility testing against P.aeruginosa when the indicated quality control parameters are met during testing.

In Vitro Susceptibility Test Interpretive Criteria for Polymyxin B Sulfate Against Pseudomonas aeruginosa
Minimal Inhibitory Concentration (MIC) (mcg/mL)
Pathogen Susceptible Intermediate Resistant
Pseudomonas aeruginosa ≤2 4 ≥8
Disk Diffusion Interpretive Criteria (300 unit disk) (mm)
Pathogen Susceptible Intermediate Resistant
Pseudomonas aeruginosa ≥12 - ≤11
In Vitro Susceptibility Test Quality Control Ranges for Polymyxin B Sulfate Against Pseudomonas aeroginosa
Quality Control Organism (ATCC* Number) Minimal Inhibitory Concentration MIC) Range (mcg/mL) Disk Diffusion Quality Control Range (300 Unit Disck) (mm)

Pseudomonas aeruginosa (27853)

1 to 4 14 to 18

Polymyxin B sulfate is not absorbed from the normal alimentary tract. Since the drug loses 50 percent of its activity in the presence of serum, active blood levels are low. Repeated injections may give a cumulative effect. Levels tend to be higher in infants and children.

The drug is excreted slowly by the kidneys. Tissue diffusion is poor and the drug does not pass the blood brain barrier into the cerebrospinal fluid. In therapeutic dosage, polymyxin B sulfate causes some nephrotoxicity with tubule damage to a slight degree.

INDICATIONS AND USAGE

Acute Infections Caused by Susceptible Strains of Pseudomonas aeruginosa.

Polymyxin B sulfate is a drug of choice in the treatment of infections of the urinary tract, meninges, and bloodstream caused by susceptible strains of Ps. aeruginosa. It may also be used topically and subconjunctivally in the treatment of infections of the eye caused by susceptible strains of Ps. aeruginosa.

It may be indicated in serious infections caused by susceptible strains of the following organisms, when less potentially toxic drugs are ineffective or contraindicated:

H influenzae , specifically meningeal infections.

Escherichia coli , specifically urinary tract infections.

Aerobacter aerogenes , specifically bacteremia.

Klebsiella pneumoniae , specifically bacteremia.

NOTE: IN MENINGEAL INFECTIONS, POLYMYXIN B SULFATE SHOULD BE ADMINISTERED ONLY BY THE INTRATHECAL ROUTE.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Polymyxin B for Injection USP and other antibacterial drugs, Polymyxin B for Injection should be used only to treat or prevent 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.

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