When this drug is given IM, IV, 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 blood urea nitrogen (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 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 or muscle relaxants.
The safety of this drug in human pregnancy has not been established.
Dosage guidance:
Dosing: Doses are presented as units: 10,000 units = 1 mg. Use actual body weight to calculate dose for patients with normal BMI (Ref).
Clinical considerations: Reserve for extensively drug-resistant gram-negative infections (eg, A. baumannii, difficult-to-treat P. aeruginosa) when other agents cannot be used (Ref).
Gram-negative infection, extensively drug resistant (eg, A. baumannii, difficult-to-treat P. aeruginosa)
IV:
Note: Usually used in combination with other antibiotics, although supportive data are limited (Ref). When a polymyxin is required for treatment of urinary tract infections, colistimethate is preferred over polymyxin B (Ref).
IV: 20,000 to 25,000 units/kg loading dose, followed by a maintenance dose of 12,500 to 15,000 units/kg every 12 hours (Ref). Safety data for single infusions >2,000,000 units are limited; pharmacokinetic data do not support capping at a maximum dose, but infusion-related adverse effects (eg, sudden thoracic pain, paresthesias, dizziness, dyspnea, hypoxemia) may increase with higher doses (Ref).
Inhalation for nebulization (adjunctive agent) (off-label route):
Note: When inhaled polymyxin use is necessary for hospital-acquired or ventilator-associated pneumonia, some experts prefer inhaled colistimethate over polymyxin B (Ref). Administer an aerosolized beta2 agonist ~20 minutes prior to inhaled polymyxin B (Ref).
Inhalation for nebulization: 500,000 units every 12 hours in combination with systemic antimicrobial therapy (Ref). Pharmacokinetic data suggest higher doses are needed for efficacy although clinical data are limited (Ref).
Intrathecal/Intraventricular (adjunctive agent):
Note: Intraventricular administration is generally reserved for meningitis or ventriculitis that is refractory to appropriate parenteral therapy or associated with intraventricular devices that cannot be removed (Ref). When intrathecal or intraventricular polymyxin use is warranted, colistimethate is preferred over polymyxin B due to limited experience with polymyxin B (Ref).
Intrathecal/Intraventricular (use a preservative-free preparation): 50,000 units once daily, in combination with systemic therapy (Ref). When intraventricular polymyxin B is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in cerebrospinal fluid) (Ref).
Duration of therapy: Duration of therapy depends on source, extent of infection, and clinical response) (Ref).
Ocular infections:
Note: For the treatment of eye infections caused by P. aeruginosa. Avoid total systemic and ophthalmic doses of >25,000 units/kg/day.
Ophthalmic: Instill 1 to 3 drops of an extemporaneously prepared 0.1% to 0.25% (10,000 to 25,000 units/mL) ophthalmic solution every hour; may extend the dosing interval based on response. Note: A subconjunctival injection of ≤100,000 units/day may also be used.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Manufacturer labeling recommends a dosage reduction in kidney impairment, and some additional studies suggest a relationship between kidney function and polymyxin B clearance (Ref). However, the majority of clinical data suggest that total body clearance of polymyxin B is not altered substantially in kidney impairment (Ref). Decreasing daily doses in renal impairment may lead to suboptimal plasma exposure, adverse clinical outcomes, clinical failures, and resistance development (Ref).
Altered kidney function: IV: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2):
Note: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
IV: There are no specific dosage adjustments recommended although there may be a need for higher doses; limited pharmacokinetic data are available (Ref). Therapeutic drug monitoring has been recommended to guide polymyxin B dosing in patients with ARC (Ref).
Hemodialysis, intermittent (thrice weekly): IV: Extent of dialyzability unknown: No dosage adjustment necessary (Ref). Because the extent of dialyzability is unknown, one of the twice daily doses should be administered after the dialysis on dialysis days (Ref).
Peritoneal dialysis: IV: No dosage adjustment necessary (Ref).
CRRT: IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): IV: No dosage adjustment necessary (Ref). Because the extent of dialyzability is unknown, one of the twice daily doses should be administered after PIRRT treatment on PIRRT treatment days (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
Pharmacokinetic data do not support capping upper absolute doses in patients with high total body weight, however, data on the safety of infusions >2,000,000 units remain limited (Ref). Infusion-related adverse effects may increase with higher doses (Ref). Due to minimal data in morbidly obese patients, consider dosing based on adjusted body weight in these patients (Ref).
Refer to adult dosing.
(For additional information see "Polymyxin B: Pediatric drug information")
Note: Due to toxicity risks, the systemic use of polymyxin B should be limited to life-threatening, multidrug-resistant infection when less toxic alternatives are not effective or not tolerated. Multiple routes of administration available for use (eg, IV, IM, intrathecal, ophthalmic) and dosing differs based upon route; use extra caution in verification of dose and route of administration. Dosing presented in units; 10,000 units = 1 mg; use extra caution with prescribing and/or dispensing.
Severe, life-threatening, multidrug-resistant infection (excluding meningitis): Note: From experience in adult patients, safety data for single doses >30,000 units/kg/dose or total daily doses >2,000,000 units/day are extremely limited (Ref). Data in pediatrics are extremely limited; optimal dose unknown (Ref).
Infants:
IV: Usual dose: 25,000 to 30,000 units/kg/day divided every 12 hours; reported range: 15,000 to 40,000 units/kg/day divided every 12 hours (Ref). Based on adult recommendations, an initial loading dose of 25,000 units/kg has also been recommended (Ref).
IM: 25,000 to 40,000 units/kg/day divided every 4 to 6 hours. Note: Routine IM administration not recommended due to severe pain at injection site.
Children and Adolescents:
IV: Usual dose: 25,000 to 30,000 units/kg/day divided every 12 hours; reported range: 15,000 to 40,000 units/kg/day (Ref). Manufacturer's labeling recommends a maximum dose of 25,000 units/kg/day; however, doses up to 40,000 units/kg/day have been reported in patients ≤12 years in a small case series (Ref). Based on adult recommendations, an initial loading dose of 25,000 units/kg has also been recommended (Ref).
IM: 25,000 to 30,000 units/kg/day divided every 4 to 6 hours; Note: Routine IM administration not recommended due to severe pain at injection site.
CNS infection (including meningitis, ventriculitis, cerebrospinal fluid [CSF] shunt infections):
Manufacturer's labeling:
Children <2 years: Intrathecal: 20,000 units/dose once daily for 3 to 4 days or 25,000 units/dose once every other day; continue 25,000 units/dose once every other day for at least 2 weeks after cultures of the CSF are negative.
Children ≥2 years and Adolescents: Intrathecal: 50,000 units/dose daily for 3 to 4 days, then every other day for at least 2 weeks after cultures of CSF are negative.
Alternate recommendations: Limited data available: Children and Adolescents: Intraventricular or intrathecal: 20,000 to 50,000 units/day; due to the smaller CSF volume in infants, some guidelines recommend decreasing the infant dose; because adult dosage recommendations are based on ventricle size, smaller doses should be used in smaller patients (Ref).
Ocular infections: Infants, Children, and Adolescents: Ophthalmic:
Topical: 0.1% to 0.25% solution (prepared from parenteral injection): 1 to 3 drops every hour, then increasing the interval as response indicates.
Subconjunctival injection: Up to 100,000 units/day not to exceed 25,000 units/kg/day.
Note: Combined total therapy (systemic and ophthalmic instillation) should not exceed 25,000 units/kg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Renal impairment:
Baseline: Infants, Children, and Adolescents: The manufacturer's labeling recommends a dosage reduction; however, based on limited experience in adults, dosage adjustment may not be necessary (Ref).
Renal toxicity during therapy: If renal impairment (increased BUN or decreased urine output) occurs due to polymyxin B therapy, consider discontinuing therapy.
Hemodialysis, intermittent: Infants, Children, and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling. No supplemental dose necessary (Ref).
There are no dosage adjustments provided in manufacturer's labeling
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Postmarketing:
Dermatologic: Desquamation (Wen 2020), skin hyperpigmentation (Wen 2020), urticaria
Endocrine & metabolic: Albuminuria, hypocalcemia (Goldin 2022), hypochloremia (O’Regan 1977), hypokalemia (Goldin 2022), hypomagnesemia (Goldin 2022), hyponatremia (O’Regan 1977)
Gastrointestinal: Clostridioides difficile-associated diarrhea
Genitourinary: Azotemia
Local: Local thrombophlebitis (IV injection site), pain at injection site (IM injection site)
Nervous system: Drug fever, meningism (with intrathecal administration), neurotoxicity (including asthenia, ataxia, blurred vision, dizziness, drowsiness, facial flushing, irritability, numbness of extremities, peripheral paresthesia [including oral paresthesia and stocking glove]) (Xing 2021)
Neuromuscular & skeletal: Rhabdomyolysis (Ni 2020), state of neuromuscular blockade (including respiratory paralysis [Ning 2022]),
Renal: Casts in urine, nephrotoxicity (Zavascki 2017), renal tubular disease (Goldin 2022)
Hypersensitivity to polymyxin B or any component of the formulation
Concerns related to adverse effects:
• Local reactions: May cause severe pain at IM injection site or thrombophlebitis at IV infusion site.
• Nephrotoxicity: May cause nephrotoxicity. Usual risk factors include preexisting renal impairment, advanced age and dehydration. Polymyxin B-induced nephrotoxicity may be manifested by albuminuria, cellular casts, and azotemia; monitor BUN, serum creatinine, and urinary analysis at baseline and as clinically indicated. Data suggest polymyxin B undergoes a selective uptake process into renal cells, which plays a primary role in nephrotoxicity potential (Abdelraouf 2014). One small study in patients receiving polymyxin B with a normal baseline renal function observed an overall prevalence rate of nephrotoxicity of 46% with a median onset of 9 days (Dubrovaskaya 2015).
• Neurotoxicity: 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.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides difficile–associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Renal impairment: Manufacturer labeling recommends a dosage reduction in kidney impairment, and some additional studies suggest a relationship between kidney function and polymyxin B clearance (Avedissian 2018; Manchandani 2018; Yu 2021); however, the majority of clinical data suggest that total body clearance of polymyxin B is not altered substantially in kidney impairment (Kwa 2011; Sandri 2013a; Thamlikitkul 2016; Zavascki 2008). Decreasing daily doses in renal impairment may lead to suboptimal plasma exposure, adverse clinical outcomes, clinical failures, and resistance development (Elias 2010; ESCMID/EUCAST [Tsuji 2019]; Nelson 2015; Sandri 2013a; Zavascki 2008).
Special populations:
• Pregnancy: Safety in pregnancy is not established.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Generic: 500,000 units (1 ea)
Solution Reconstituted, Injection [preservative free]:
Generic: 500,000 units (1 ea)
Yes
Solution (reconstituted) (Polymyxin B Sulfate Injection)
500000 unit (per each): $5.23 - $17.50
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IV: Infuse over 1 hour (Ref).
Inhalation for nebulization (off-label use/route): Use with standard jet nebulizer connected to an air compressor; an aerosolized beta-2 agonist should be given ~20 minutes prior to polymyxin (Ref).
Intrathecal/intraventricular: May be administered intrathecally; intrathecal injections should only be administered in a hospital. Use a preservative-free preparation.
Ophthalmic: May be administered as a subconjunctival injection or as topical ophthalmic drops.
Parenteral:
IV: Infuse over 60 to 90 minutes (Ref) or by continuous infusion (per manufacturer's labeling).
IM: Not recommended for routine use in infants and children because of the severe pain associated with injection; should only be administered to hospitalized patients.
Intrathecal: May be administered intrathecally; only administer intrathecally to hospitalized patients.
Ophthalmic: May be administered as a subconjunctival injection or as topical ophthalmic drops.
Gram-negative infection, extensively drug resistant (eg, Acinetobacter baumannii, difficult-to-treat Pseudomonas aeruginosa): Treatment of serious infections (bacteremia, meningitis, etc) caused by gram-negative pathogens when less potentially toxic drugs are ineffective or contraindicated. For meningeal infection, local administration (ie, intrathecal) is preferred to systemic administration. Note: Although included as an FDA-approved use, clinical practice guidelines do not recommend polymyxin B for the treatment of urinary tract infections due to its predominant clearance by nonrenal mechanisms (ESCMID/EUCAST [Tsuji 2019]; IDSA [Tamma 2023]).
Ocular infection: Treatment of infections of the eye caused by susceptible strains of P. aeruginosa.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (epidural and intrathecal medications) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: Polymyxin B may increase nephrotoxic effects of Aminoglycosides. Polymyxin B may increase neurotoxic effects of Aminoglycosides. Risk X: Avoid
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
Bacitracin (Systemic): Polymyxin B may increase nephrotoxic effects of Bacitracin (Systemic). Risk X: Avoid
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Capreomycin: May increase neuromuscular-blocking effects of Polymyxin B. Risk C: Monitor
Cefazedone: May increase nephrotoxic effects of Polymyxin B. Risk C: Monitor
Cephaloridine: Polymyxin B may increase nephrotoxic effects of Cephaloridine. Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Colistimethate: May increase nephrotoxic effects of Polymyxin B. Colistimethate may increase neurotoxic effects of Polymyxin B. Polymyxin B may increase neuromuscular-blocking effects of Colistimethate. Management: Coadministration of polymyxin B and other potentially neurotoxic or nephrotoxic agents, such as colistimethate, is generally not recommended. If this combination must be used, monitor carefully for enhanced neurotoxic and nephrotoxic effects. Risk D: Consider Therapy Modification
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Kanamycin: Polymyxin B may increase adverse/toxic effects of Kanamycin. Management: Coadministration of kanamycin and other potentially ototoxic or nephrotoxic agents, such as polymyxin B, is not recommended. If this combination must be used, monitor carefully neurotoxic, ototoxic, or nephrotoxic effects. Risk D: Consider Therapy Modification
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Mecamylamine: Polymyxin B may increase neuromuscular-blocking effects of Mecamylamine. Risk X: Avoid
Methoxyflurane: May increase nephrotoxic effects of Polymyxin B. Risk X: Avoid
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Netilmicin (Ophthalmic): Polymyxin B may increase nephrotoxic effects of Netilmicin (Ophthalmic). Risk X: Avoid
Neuromuscular-Blocking Agents: Polymyxin B may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
[US Boxed Warning]: Safety in pregnancy has not been established.
Limited data related to systemic use in pregnancy are available (Heinonen 1977; Kazy 2005). Based on the relative toxicity compared to other antibiotics, systemic use in pregnancy is not recommended (Knothe 1985). Due to poor tissue diffusion, topical use would be expected to have only minimal risk to the mother or fetus (Leachman 2006).
It is not known if polymyxin B is present in breast milk.
If present in breast milk, polymyxin B is not absorbed well from a normal gastrointestinal tract.
Neurologic symptoms and signs of superinfection; renal function (decreasing urine output and increasing BUN may require discontinuance of therapy); polymyxin serum concentrations (to ensure adequate drug exposure particularly early in therapy) (ESCMID/EUCAST [Tsuji 2019]).
Target serum concentration is 2 mg/L for susceptible organisms (irrespective of reported MIC) (ESCMID/EUCAST [Tsuji 2019]). Serum concentrations >5 mcg/mL are toxic in adults (Hoeprich 1970).
Binds to phospholipids, alters permeability, and damages the bacterial cytoplasmic membrane permitting leakage of intracellular constituents
Absorption: Not absorbed from GI tract.
Distribution: Tissue diffusion is poor; critically ill patients: Central Vd: ~0.09 L/kg; peripheral Vd: 0.33 L/kg (Sandri 2013a); does not cross blood brain barrier into CSF or into the eye (Hoeprich 1970)
Protein binding: ~60% (Kassamali 2015); 79% to 92% (critically ill patients) (Zavascki 2008)
Half-life elimination: 10.1 to 13.6 hours (Kwa 2008; Manchandani 2018).
Time to peak, serum: IM: Within 2 hours (Hoeprich 1970)
Excretion: Urine (<1% as unchanged drug within first 12 hours; as therapy continues, up to 60% as unchanged drug in the urine [Evans 1999]); Critically ill adults: Urine (median: 4% [range: 0.98% to 17.4%] as unchanged drug) (Sandri 2013a)
Anti-infective considerations:
Parameters associated with efficacy: Concentration dependent; associated with AUC24/minimum inhibitory concentration (MIC), goal: AUC24 at steady state ~50 to 100 mg•hour/L, or an average plasma concentration at steady state (Css,avg) of 2 to 4 mg/L (Abdul-Aziz 2020; ESCMID/EUCAST [Tsuji 2019]; Lakota 2018).
Organism specific:
K. pneumoniae: Goal: fAUC0–24/MIC: 3.7 to 28 (Abdul-Aziz 2020; Landersdorfer 2018).
Expected drug concentrations in patients with normal renal function:
Cmax (peak):
Children ≥3 years of age and adolescents <18 years of age: IV: 1.5 to 2.5 mg/kg every 12 hours for 2 doses followed by 0.75 to 1.25 mg/kg every 12 hours, multiple dose: 4.42 ± 1.49 mg/L (Wang 2022).
Adults: IV: 2.5 mg/kg loading dose (3-hour infusion) followed by 1.25 mg/kg every 12 hours (2-hour infusion), multiple dose: IV: 5.42 ± 1.69 mg/L (Yu 2022).
AUC0-24 (total):
Children ≥3 years of age and adolescents <18 years of age: IV: 1.5 to 2.5 mg/kg every 12 hours for 2 doses followed by 0.75 to 1.25 mg/kg every 12 hours, multiple dose: ~37.97 ± 9.84 mg•hour/L (Wang 2022).
Adults: 2.5 mg/kg loading dose (3-hour infusion) followed by 1.25 mg/kg every 12 hours (2-hour infusion), multiple dose: IV: 79.6 ± 25 mg•hour/L (Yu 2022).
Postantibiotic effect: Bacterial killing may continue after polymyxin B concentrations fall below the MIC of targeted pathogen and varies based on the organism, duration of antimicrobial exposure, and concentrations of antimicrobial exposure (ESCMID/EUCAST [Tsuji 2019]).
Parameters associated with toxicity: An AUC24 >100 mg•hour/L has been associated with increased risk of nephrotoxicity (Abdul-Aziz 2020; Lakota 2018).