polymyxin B [Injectable]

Adult Dosing

Susceptible infection

15,000-25,000 units/kg/day IV in divided doses q12 hrs
Max: 25,000 units/kg/day
Note: Dilute 500,000 units in 300-500 mL of 5% Dextrose for continuous intravenous drip

25,000-30,000 units/kg/day IM in divided doses q4-6 hrs
Note: Dilute 500,000 units in 2 mL sterile water for injection or 0.9% sodium chloride injection or procaine hydrochloride injection 1%

Ps aeruginosa meningitis

50,000 units qd x 3-4 days; Followed by 50,000 units qod x 2wks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal
Note: Dilute 500,000 units in 10 mL 0.9% sodium chloride injection

Ps aeruginosa infections of the cornea and conjunctiva.

100,000 units/day subconjunctival injection
Note: Dissolve 500,000 polymyxin B units in 20-50 mL sterile water for injection or 0.9% sodium chloride injection for a 10,000 to 25,000 units per mL concentration

Pediatric Dosing

Susceptible infection

Children: 15,000 to 25,000 units/kg/day IV in dived doses q12 hrs; Max: 25,000 units/kg/day
Infants: 40,000 units/kg/day in divided doses q12 hrs

Children: 25,000-30,000 units/kg/day IM in divided doses q4-6 hrs
Infants: 40,000 units/kg/day in divided doses q6 hrs
Note: Dilute 500,000 units in 2 mL sterile water for injection or 0.9% sodium chloride injection or procaine hydrochloride injection 1%

Ps aeruginosa meningitis

Children >2 yrs: 50,000 units qd x 3-4 days; Followed by 50,000 units qod x 2wks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal
Children <2 yrs: 20,000 units qd x 3-4 days; Alt: 25,000 units qod x 2wks after cultures of the cerebrospinal fluid are negative and sugar content has returned to normal
Note: Dilute 500,000 units in 10 mL 0.9% sodium chloride injection

Ps aeruginosa infections of the cornea and conjunctiva.

100,000 units/day subconjunctival injection
Note: Dissolve 500,000 polymyxin B units in 20-50 mL sterile water for injection or 0.9% sodium chloride injection for a 10,000 to 25,000 units per mL concentration

[Outline]

Indications ⬆ ⬇

Infection of the urinary tract, meninges, and blood stream caused by susceptible strains of Ps. aeruginosa
May also be used for serious infections caused by susceptible strains of other organisms, when less potentially toxic drugs are ineffective or contraindicated

Contraindications ⬆ ⬇

Black Box Warnings ⬆ ⬇

When administered intramuscularly and/or intrathecallly, polymyxin B should be given only to hospitalized patients under constant supervision of a physician
Monitor renal function carefully and administer reduced dosage of polymyxin B to patients with renal damage and nitrogen retention
Albuminuria, cellular cast and azotemia have been reported in patients with nephrotoxicity due to polymyxin B sulfate. Consider discontinuing therapy if urine output diminishes and BUN rises.
Neurotoxic reactions are 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
Avoid concomitant 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
When given soon after anesthesia and/or muscle relaxants, the neurotoxicity of polymyxin b sulfate can result in respiratory paralysis from neuromuscular blockade
The safety of this drug in human pregnancy has not been established

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Hepatic Dose Adjustment

Warnings/Precautions ⬆ ⬇

Clostridium difficile associated diarrhea (CDAD) ranging from mild diarrhea to fatal colitis may occur with polymyxin B therapy as antibacterial agents alter the normal flora of the colon leading to overgrowth of C. difficile
C. difficile produces toxins A and B which contribute to CDAD. Hypertoxin producing strains cause increased morbidity and mortality since these infections can be refractory to antibiotic therapy and may require colectomy. Careful medical examination is necessary since CDAD may occur >2 months after administration of drug
If CDAD is suspected/confirmed discontinue the treatment, provide fluid, electrolyte, and protein supplementation along with antibiotics for C. difficile, and provide surgical evaluation as clinically needed
Prescribing antibiotics in the absence of proven or strongly suspected bacterial infection increases the risk of development of drug-resistant bacteria
Monitor renal function prior to therapy and during the parenteral therapy and also monitor blood levels of the drug
Avoid concomitant use of curariform muscle relaxants and other neurotoxic drugs which may precipitate respiratory depression. Discontinue the drug immediately and provide assisted respiration if respiratory paralysis occurs
Like other antibiotics, polymyxin B can cause overgrowth of nonsusceptible organisms, including fungi. Provide appropriate therapy if superinfection occurs

Caution: Use cautiously in

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category:NR

Breastfeeding: Safety unknown

Adverse Reactions ⬆ ⬇

GI: Clostridium difficile associated diarrhea
CNS: Neurotoxic reaction (Facial flushing, dizziness progressing to ataxia, drowsiness, peripheral paresthesias, apnea), meningeal irritation
DERM: Urticaria, rash
GU: Nephrotoxic reaction (Albuminuria, cylindruria, azotemia)
MISC: Fever, pain

Clinical Pharmacology ⬆ ⬇

Anti-Bacterial agent; interacts with the lipopolysaccharide of the cytoplasmic outer membrane of Gram-negative bacteria, altering membrane permeability and causing cell death
Not absorbed from the normal alimentary tract
Metabolism: Unknown
Renally excreted 60% (1% unchanged)
Half-life: 4.3-6 hrs, 2-3 days (renal impairment)

Brands and Availability ⬆ ⬇