Dilution Polymyxin B

Polymyxin B (polymyxin b sulfate) injection

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Usual Diluents

D5W, NS

Standard Dilution [Amount of drug] [Infusion volume] [Infusion rate]

[See dosage and administration below]

Other:
[500,000 units] [ 300 - 500 ml] [As directed -see dosage and administration below]

Stability / Miscellaneous

Storage.

WARNING

CAUTION: WHEN THIS DRUG IS GIVEN INTRAMUSCULARLY 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.

Polymyxin B for Injection, USP is one of a group of basic polypeptide antibiotics derived from B polymyxa (B aerosporous).

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 bacterial cell wall membranes. All gram-positive bacteria, fungi, and the gram-negative cocci, N gonorrhoeae and N meningitidis, are resistant.

Susceptibility plate testing: If the Kirby-Bauer method of disc susceptibility testing is used, a 300-unit polymyxin B disc should give a zone of over 11 mm when tested against a polymyxin B susceptible bacterial strain.

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
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. 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.

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 P aeruginosa. It may also be used topically and subconjunctivally in the treatment of infections of the eye caused by susceptible strains of P 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.

CONTRAINDICATIONS
This drug is contraindicated in persons with a prior history of hypersensitivity reactions to polymyxins.

PRECAUTIONS
See “WARNING” box.

General
Prescribing polymyxin B in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug resistant bacteria.

Baseline renal function should be done prior to therapy, with frequent monitoring of renal function and blood levels of the drug during parenteral therapy.

Avoid concurrent use of a curariform muscle relaxant and other neurotoxic drugs (ether, tubocurarine, succinylcholine, gallamine, decamethonium and sodium citrate) which may precipitate respiratory depression. If signs of respiratory paralysis appear, respiration should be assisted as required, and the drug discontinued.

As with other antibiotics, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi.

If superinfection occurs, appropriate therapy should be instituted.

DOSAGE AND ADMINISTRATION
Parenteral -------------------
Intravenous
Dissolve 500,000 polymyxin B units in 300 to 500 mL solutions for parenteral dextrose injection 5% for continuous drip.

Adults and children: 15,000 to 25,000 units/kg body weight/day in individuals with normal kidney function. This amount should be reduced from 15,000 units/kg downward for individuals with kidney impairment. Infusions may be given every 12 hours; however, the total daily dose must not exceed 25,000 units/kg/day.

Infants: Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects.

Intramuscular
Not recommended routinely because of severe pain at injection sites, particularly in infants and children. Dissolve 500,000 polymyxin B units in 2 mL sterile water for injection or sodium chloride injection or procaine hydrochloride injection 1%.

Adults and children: 25,000 to 30,000 units/kg/day. This should be reduced in the presence of renal impairment. The dosage may be divided and given at either 4 or 6 hour intervals.

Infants: Infants with normal kidney function may receive up to 40,000 units/kg/day without adverse effects.

Note: Doses as high as 45,000 units/kg/day have been used in limited clinical studies in treating prematures and newborn infants for sepsis caused by P aeruginosa.

Intrathecal
A treatment of choice for P aeruginosa meningitis. Dissolve 500,000 polymyxin B units in 10 mL sodium chloride injection USP for 50,000 units per mL dosage unit.

Adults and children over 2 years of age: Dosage is 50,000 units once daily intrathecally for 3 to 4 days, then 50,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.

Children under 2 years of age: 20,000 units once daily, intrathecally for 3 to 4 days or 25,000 units once every other day. Continue with a dose of 25,000 units once every other day for at least 2 weeks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal.

IN THE INTEREST OF SAFETY, SOLUTIONS OF PARENTERAL USE SHOULD BE STORED UNDER REFRIGERATION, AND ANY UNUSED PORTIONS SHOULD BE DISCARDED AFTER 72 HOURS.

Topical----------------------------
Ophthalmic: Dissolve 500,000 polymyxin B units in 20 to 50 mL sterile water for injection or sodium chloride injection USP for a 10,000 to 25,000 units per mL concentration.

For the treatment of P aeruginosa infections of the eye, a concentration of 0.1 percent to 0.25 percent (10,000 units to 25,000 units per mL) is administered 1 to 3 drops every hour, increasing the intervals as response indicates.

Subconjunctival injection of up to 100,000 units/day may be used for the treatment of P aeruginosa infections of the cornea and conjunctiva.

Note: Avoid total systemic and ophthalmic instillation over 25,000 units/kg/day.

Topical irrigation or topical solution: 500,000 units/liter of normal saline. Topical irrigation should not exceed 2 million units/day in adults.

Renal Impairment

Source: Polymyxins Revisited. Clin. Microbiol. Rev. July 2008 vol. 21 no. 3 449-465. Table 2. https://cmr.asm.org/content/21/3/449/T2.expansion
	Normal Renal Function	Altered Renal Function
Polymyxin B	1.5-2.5 mg/kg/day in 2 doses	CrCl of 30-80 ml/min, 2.5 mg x 1 and then 1-1.5 mg/kg/day
		CrCl of <30 ml/min, 2.5 mg/kg and then 1-1.5 mg/kg/day every 2-3 days
		Anuric CrCl, 2.5 mg/kg and then 1 mg/kg every 5-7 days
Polymyxin B	1.5-2.5 mg/kg/day in 2-4 doses
Polymyxin B	1.5-2.5 mg/kg/day in divided doses
Polymyxin B	2.5-3.0 mg/kg/day in divided doses	CrCl of 30-80 ml/min, 2.5 mg x 1 and then 1-1.5 mg/kg/day
		CrCl of <25 ml/min, 2.5 mg/kg and then 1-1.5 mg/kg/day every 2-3 days
		Anuric CrCl, 2.5 mg/kg and then 1 mg/kg every 5-7 days
Polymyxin B	1.5-2.5 mg/kg/day in 2 doses	CrCl of 5-20 ml/min, 0.75-1.25 mg/kg/day in 2 doses
		CrCl of <10 ml/min, 0.225-0.375 mg/kg/day in 2 doses
Source: John Hopkins Antibiotic Guide (accessed: May 2016):
DOSING FOR GLOMERULAR FILTRATION OF 50-80 For CrCL 50-80 ml/min: 2.5 mg/kg (day 1), then 1-1.5 mg/kg/day. Avoid if possible in patients with impaired renal function. DOSING FOR GLOMERULAR FILTRATION OF 10-50 For CrCL 30-50 ml/min: 2.5 mg/kg (day 1), then 1-1.5 mg/kg/day. For CrCL < 30 ml/min: 2.5 mg/kg (day 1), then 1-1.5 mg/kg every 2-3 days. Avoid if possible. DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN For CrCL < 30 ml/min: 2.5 mg/kg (day 1), then 1-1.5 mg/kg every 2-3 days. DOSING IN HEMODIALYSIS Little data, some removal. 2.5 mg/kg (day 1), then 1 mg/kg every 5-7 days. Dose post-HD. DOSING IN PERITONEAL DIALYSIS Little data, some removal. 2.5 mg/kg (day 1), then 1 mg/kg every 5-7 days.

HOW SUPPLIED
Polymyxin B for Injection, 500,000 polymyxin B units per vial is supplied in rubber-stoppered glass vial with flip off cap, carton of 10, NDC55390-139-10.

Storage recommendations:
Before reconstitution: Store at controlled room temperature 15° to 30°C (59° to 86°F).

Protect from light. Retain in carton until time of use.

After reconstitution: Product must be stored under refrigeration, between 2° to 8°C (36° to 46°F) and any unused portion should be discarded after 72 hours.

Reference(s)

Package insert:

Manufactured for: Bedford Laboratories™, Bedford, OH 44146
Manufactured by: Ben Venue Laboratories, Inc., Bedford, OH 44146
February 2004