Dosing and uses of Polymyxin B
Systemic Infections
IV: 15,000-25,000 units/kg/day divided q12hr; not to exceed 25,000 units/kg/day
IM: 25,000-30,000 units/kg/day divided q4-6hr
Intrathecal: 50,000 qDay for 3-4 days; then qDay or qODay for at least 2 weeks after CSF cultures are negative and normal for glucose content
Total daily dose not to exceed 2,000,000 units/day
Renal Impairment
CrCl >20 mL/minute: give 75-100% usual dose/day divided q12hr
CrCl 5-20 mL/minute: give 50% usual dose/day divided q12hr
CrCl <5 mL/minute: give 15% usual dose/day q12hr
Other Information
Monitor: renal function
Other Indications & Uses
Bacterial Septicemia due to P. aeruginosa, E. aerogenes, & K. pneumoniae, H. Influenzae Meningitis, UTI due to E. coli
Pediatric dosage forms and strengths
Systemic Infections
Infants
- IM: May receive up to 40,000 units/kg/day divided q6hr if renal function healthy
- IV: May receive up to 40,000 units/kg/day divided q12hr;
- Intrathecal: 20,000 units/day for 3-4 days; follow with 25,000 units qODay for at least 2 weeks after CSF cultures are negative and CSF (glucose) has returned to normal
Children
- IM: 25,000-30,000 units/kg/day divided q12hr
- IV: 15,000-25,000 units/kg/day divided q12hr; not to exceed 25,000 units/kg/day
- Intrathecal: 50,000 qDay for 3-4 days; then qDay or qODay for at least 2 weeks after CSF cultures are negative and normal for glucose content
Renal Impairment
CrCl >20 mL/min: give 75-100% usual dose/day divided q12hr
CrCl 5-20 mL/min: give 50% usual dose/day divided q12hr
CrCl <5 mL/min: give 15% usual dose/day q12hr
Other Information
Monitor: renal function
Polymyxin B adverse (side) effects
Frequency not defined
Anaphylactoid reactions with dyspnea and tachycardia
Eosinophilia
Fever
Nephrotoxicity
Neurotoxicity
Skin exanthemata
Urticaria
Warnings
Contraindications
Hypersensitivity
Cautions
Oliguria, myasthenia gravis, pregnancy, renal disease
Potential risk of nephrotoxicity and neurotoxicity
May inhibit neuromuscular transmission
Inactivated by strong acidic or alkaline solution
Discontinue if diminished urine output, rise in SCr or BUN, or signs of respiratory paralysis appear
Do not use IM routinely, particularly in peds, because of severe inj site pain
Pregnancy and lactation
Pregnancy category: B: use when benefits outweigh risks
Lactation: use caution; no data
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.
Pharmacology of Polymyxin B
Distribution: wide, does not cross placenta or aqueous humor of eye; does not appear in CSF or synovial fluid
Peak Plasma
Time: IM: 2 hr
Concentration: 20-40 KU IM dose: 1-8 mcg/mL
Other Information
Protein Bound: 79-92%
Half-life elimination: 4.3-6 hr with normal renal function
Metabolism: N/A
Excretion: urine 60% (<1% as unchanged drug)
Dialyzable: HD; no; PD: no
Mechanism of action
Bactericidal; causes leakage of bacterial membrane by binding to phospholipids.
Administration
IV Incompatibilities
Additive: amphotericin B, chloramphenicol Na succinate, chlorothiazide, heparin, MgSO4
Syringe: ampicillin(?)
IV Compatibilities
Additive: amikacin, ascorbic acid, colistimethate, diphenhyramine, erythromycin lactobionate, hydrocortisone Na succinate, kanamycin, pencillin G potassium, penicillin G Na, phenobarbital, ranitidine, vit B/C
Syringe: penicillin G Na
Y-site: esmoloL
IV/IM/IT Preparation
IV: dilute 500,000 U in 300-500 mL D5W
IM: reconstitute vial with 2 mL SWI , NS, or procaine HCl 1% solution
Intrathecal (IT): reconstitute vial with10 mL NS; DO NOT use procaine HCl for It
IV/IM Administration
IV: infuse over 60-90 min
IM: give deep into upper outer quadrant of gluteal muscles
