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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication (intrathecal administration) among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Pronunciation
(pol i MIKS in bee)
U.S. Brand Names
Index Terms
Generic Available
Yes
Pharmacologic Category
Use: Labeled Indications
Treatment of acute infections caused by susceptible strains of Pseudomonas aeruginosa; used occasionally for gut decontamination; parenteral use of polymyxin B has mainly been replaced by less toxic antibiotics, reserved for life-threatening infections caused by organisms resistant to the preferred drugs (eg, pseudomonal meningitis - intrathecal administration)
Pregnancy Risk Factor
B
Pregnancy Considerations
[U.S. Boxed Warning]: Safety in pregnant women has not been established. A teratogenic potential has not been identified for polymyxin B, but very limited data is available. Based on the relative toxicity compared to other antibiotics, systemic use in pregnancy cannot be recommended. Due to limited absorption through the maternal skin, limited fetal exposure would be expected after topical polymyxin use.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
It is not known if polymyxin B is excreted in human milk. Due to the limited oral bioavailability, toxicity in a breastfed infant may be unlikely. Infant exposure would be even less after topical use due to the limited maternal skin absorption. Nondose-related effects could include modification of the bowel flora.
Contraindications
Hypersensitivity to polymyxin B or any component of the formulation; concurrent use of neuromuscular blockers
Warnings/Precautions
Boxed warnings:
• I.M./I.T. administration: See “Other warnings/precautions” below.
• Nephrotoxicity: See “Concerns related to adverse effects” below.
• Neurotoxicity: See “Concerns related to adverse effects” below.
• Pregnancy: See “Special populations” below.
Concerns related to adverse effects:
• Nephrotoxicity: [U.S. Boxed Warning]: May cause nephrotoxicity; avoid concurrent or sequential use of other nephrotoxic drugs (eg, aminoglycosides). Usual risk factors include pre-existing renal impairment, advanced age and dehydration. Polymyxin B-induced nephrotoxicity may be manifested by albuminuria, cellular casts, and azotemia; discontinue therapy with decreasing urinary output and increasing BUN.
• Neurotoxicity: [U.S. Boxed Warning]: May cause neurotoxicity, which can also result in respiratory paralysis from neuromuscular blockade especially when the drug is given soon after anesthesia or muscle relaxants. Avoid concurrent or sequential use of other neurotoxic drugs. Neurotoxic reactions are usually associated with high serum levels, often in patients with renal dysfunction.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Use with caution in patients with impaired renal function; modify dosage.
Special populations:
• Pregnancy: [U.S. Boxed Warning]: Safety in pregnant women not established.
Other warnings/precautions:
• I.M./I.T. administration: [U.S. Boxed Warning]: Intramuscular/intrathecal administration only to hospitalized patients.
• Parenteral administration: Polymyxin B sulfate is most toxic when given parenterally; avoid parenteral use whenever possible.
Adverse Reactions
Frequency not defined.
Cardiovascular: Facial flushing
Central nervous system: Neurotoxicity (irritability, drowsiness, ataxia, perioral paresthesia, numbness of the extremities, and blurred vision); dizziness, drug fever, meningeal irritation with intrathecal administration
Dermatologic: Urticarial rash
Endocrine & metabolic: Hypocalcemia, hyponatremia, hypokalemia, hypochloremia
Local: Pain at injection site
Neuromuscular & skeletal: Neuromuscular blockade, weakness
Renal: Nephrotoxicity
Respiratory: Respiratory arrest
Miscellaneous: Anaphylactoid reaction
Drug Interactions
Capreomycin: May enhance the neuromuscular-blocking effect of Polymyxin B. Risk C: Monitor therapy
Colistimethate: Polymyxin B may enhance the neuromuscular-blocking effect of Colistimethate. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Polymyxin B may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk D: Consider therapy modification
Storage
Prior to reconstitution, store at room temperature of 15°C to 30°C (59°F to 86°F) and protect from light. After reconstitution, store under refrigeration at 2°C to 8°C (36°F to 46°F). Discard any unused solution after 72 hours.
Compatibility
Y-site administration: Compatible: Esmolol.
Compatibility in syringe: Compatible: Penicillin G sodium. Variable (consult detailed reference): Ampicillin.
Compatibility when admixed: Compatible: Amikacin, ascorbic acid injection, colistimethate, diphenhydramine, erythromycin lactobionate, hydrocortisone sodium succinate, kanamycin, lincomycin, penicillin G potassium, penicillin G sodium, phenobarbital, ranitidine, vitamin B complex with C. Incompatible: Amphotericin B, calcium chloride, calcium gluconate, cefazolin, chloramphenicol, chlorothiazide, heparin, magnesium sulfate.
Mechanism of Action
Binds to phospholipids, alters permeability, and damages the bacterial cytoplasmic membrane permitting leakage of intracellular constituents
Pharmacodynamics/Kinetics
Absorption: Well absorbed from peritoneum; minimal from GI tract (except in neonates) from mucous membranes or intact skin. Clinically insignificant amounts are absorbed following irrigation of an intact urinary bladder; systemic absorption may occur from a denuded bladder. Small amounts are systemically absorbed following ophthalmic installation.
Distribution: Minimal into CSF; Vd: 71-194 mL/kg
Protein binding: 79% to 92% (critically ill patients)
Half-life elimination: 6 hours; 2-3 days with anuria
Time to peak, serum: I.M.: ~2 hours
Excretion: Urine (<1% as unchanged drug)
Dosage
Otic (in combination with other drugs): 1-2 drops, 3-4 times/day; should be used sparingly to avoid accumulation of excess debris
Infants <2 years:
I.M.: Up to 40,000 units/kg/day divided every 6 hours (not routinely recommended due to pain at injection sites)
I.V.: Up to 40,000 units/kg/day divided every 12 hours
Intrathecal: 20,000 units/day for 3-4 days, then 25,000 units every other day for at least 2 weeks after CSF cultures are negative and CSF (glucose) has returned to within normal limits
Children ?2 years and Adults:
I.M.: 25,000-30,000 units/kg/day divided every 4-6 hours (not routinely recommended due to pain at injection sites)
I.V.: 15,000-25,000 units/kg/day divided every 12 hours
Intrathecal: 50,000 units/day for 3-4 days, then every other day for at least 2 weeks after CSF cultures are negative and CSF (glucose) has returned to within normal limits
Total daily dose should not exceed 2,000,000 units/day
Bladder irrigation: Continuous irrigant or rinse in the urinary bladder for up to 10 days using 20 mg (equal to 200,000 units) added to 1 L of normal saline; usually no more than 1 L of irrigant is used per day unless urine flow rate is high; administration rate is adjusted to patient's urine output
Topical irrigation or topical solution: 500,000 units/L of normal saline; topical irrigation should not exceed 2 million units/day in adults
Gut sterilization: Oral: 15,000-25,000 units/kg/day in divided doses every 6 hours
Clostridium difficile enteritis: Oral: 25,000 units every 6 hours for 10 days
Ophthalmic: A concentration of 0.1% to 0.25% is administered as 1-3 drops every hour, then increasing the interval as response indicates to 1-2 drops 4-6 times/day
Dosing adjustment/interval in renal impairment:
Clcr 20-50 mL/minute: Administer 75% to 100% of the normal daily dose given in divided doses every 12 hours
Clcr 5-20 mL/minute: Administer 50% of normal daily dose given in divided doses every 12 hours
Clcr <5 mL/minute: Administer 15% of normal daily dose given in divided doses every 12 hours
Administration: I.M.
Administer into upper outer quadrant of gluteal muscle; however, I.M. route is not recommended due to severe pain at injection site.
Administration: I.V.
Infuse over 60-90 minutes.
Administration: I.V. Detail
Extravasation management: Monitor I.V. site closely; extravasation may cause serious injury with possible necrosis and tissue sloughing. Rotate infusion site frequently.
pH: 5.0-7.5
Monitoring Parameters
Neurologic symptoms and signs of superinfection; renal function (decreasing urine output and increasing BUN may require discontinuance of therapy)
Reference Range
Serum concentrations >5 mcg/mL are toxic in adults
Patient Education
Wound irrigation/bladder irrigation/gut sterilization/I.V.: Immediately report numbness or tingling of mouth, tongue, or extremities; blurring of vision; increased nervousness or irritability; excessive drowsiness; or respiratory difficulty. For I.V., immediately report swelling, redness, burning, or pain at infusion site.
Ophthalmic: Tilt head back, place medication into eyes (as frequently as prescribed), close eyes, apply light pressure over inside corner of the eye for 1 minute. Do not let tip of applicator touch eye; do not contaminate tip of applicator (may cause eye infection, eye damage, or vision loss). You may experience some stinging or burning or temporary blurring of vision; use caution driving or when engaging in hazardous tasks until vision clears. Report any adverse effects including respiratory difficulty or unusual numbness or tingling of mouth or tongue, increased nervousness or irritability, or excessive drowsiness.
Additional Information
1 mg = 10,000 units
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May rarely cause irritability, drowsiness, or ataxia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Perform culture and sensitivity tests and assess patient's allergy history prior to starting therapy. Use caution with impaired renal function; dosage adjustment may be necessary. Assess potential for interactions with other pharmacological agents and herbal products patient may be taking (eg, other nephrotoxic and neurotoxic drugs, neuromuscular-blocking agents). See Administration for I.V. and I.M. specifics. Infusion site must be monitored closely to prevent extravasation; extravasation may cause serious injury with possible necrosis and tissue sloughing (infusion site should be rotated frequently). Assess therapeutic effectiveness (resolution of infection) and adverse reactions (eg, impaired renal function, neurotoxicity, neuromuscular blockade, rash, respiratory paralysis, ototoxicity). Teach patient possible side effects/appropriate interventions and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 500,000 units
Powder [for prescription compounding]:
Poly-Rx: 100 million units (13 g)
References
Evans ME, Feola DJ, and Rapp RP, “Polymyxin B Sulfate and Colistin: Old Antibiotics for Emerging Multiresistant Gram-Negative Bacteria,” Ann Pharmacother, 1999, 33(9):960-7.
Horton J and Pankey GA, “Polymyxin B, Colistin, and Sodium Colistimethate,” Med Clin North Am, 1982, 66(1):135-42.
Zavascki AP, Goldani LZ, Cao G, et al, “Pharmacokinetics of Intravenous Polymyxin B in Critically Ill Patients,” Clin Infect Dis, 2008, 47(10):1298-304.
International Brand Names
Lexi-Comp.com
Last full review/revision July 2009
Content last modified July 2009
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