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.
Note: Dosing presented as units; 10,000 units = 1 mg.
CNS infection (adjunctive agent): Intrathecal/Intraventricular: 50,000 units once daily, in combination with systemic therapy (ESCMID/EUCAST [Tsuji 2019]; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]; Segal-Maurer 1999). When intraventricular polymyxin B is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in CSF) (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Note: Use a preservative-free preparation. Intraventricular administration is generally reserved for use in patients who fail parenteral therapy despite removal of CSF shunt or when CSF shunt cannot be removed (Baddour 2021).
Ocular infections: Ophthalmic: A concentration of 0.1% to 0.25% (10,000 to 25,000 units/mL) is administered as 1 to 3 drops every hour, then increasing the interval as response indicates. A subconjunctival injection of up to 100,000 units/day may be used for P. aeruginosa corneal and conjunctival infections. Note: Avoid total systemic and ophthalmic doses of >25,000 units/kg/day.
Pulmonary infection (adjunctive agent) (off-label route): Inhalation for nebulization: 500,000 units every 12 hours; administer an aerosolized beta-2 agonist ~20 minutes prior to polymyxin B (Pereira 2007). Note: Use in combination with systemic antimicrobial therapy (ESCMID/EUCAST [Tsuji 2019]; IDSA/ATS [Kalil 2016]; Pereira 2007); some experts do not use inhaled polymyxin B (MacLaren 2021).
Systemic infections (eg, bacteremia, intraabdominal infections, meningitis, pneumonia [hospital-acquired or ventilator-associated], sepsis), due to multidrug-resistant gram-negative bacilli (eg, Pseudomonas aeruginosa, Acinetobacter spp.) :
Note: Use actual body weight to calculate dose for patients with normal BMI (ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015; Pai 2013; Sandri 2013a). To minimize development of resistance, use in combination with other antibiotics depending on infection site and susceptibilities (Bergen 2015; ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015; Rigatto 2015).
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 (ESCMID/EUCAST [Tsuji 2019]; Kassamali 2015; Sandri 2013a). 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 (ESCMID/EUCAST [Tsuji 2019]; John 2017; Sandri 2013a).
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 (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).
Altered kidney function: IV: No dosage adjustment necessary for any degree of kidney dysfunction (ESCMID/EUCAST [Tsuji 2019]).
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 (Bilbao-Meseguer 2018; Udy 2010).
IV: There are no specific dosage adjustments recommended although there may be a need for higher doses; limited pharmacokinetic data are available (Avedissian 2018; Manchandani 2018; Yu 2021). Therapeutic drug monitoring has been recommended to guide polymyxin B dosing in patients with ARC (Avedissian 2021).
Hemodialysis, intermittent (thrice weekly): IV: Extent of dialyzability unknown: No dosage adjustment necessary (ESCMID/EUCAST [Tsuji 2019]). Because the extent of dialyzability is unknown, one of the twice daily doses should be administered after the dialysis on dialysis days (expert opinion).
Peritoneal dialysis: IV: No dosage adjustment necessary (ESCMID/EUCAST [Tsuji 2019]).
CRRT: IV: No dosage adjustment necessary (ESCMID/EUCAST [Tsuji 2019]); Sandri 2013b).
PIRRT (eg, sustained, low-efficiency diafiltration): IV: No dosage adjustment necessary (ESCMID/EUCAST [Tsuji 2019]). Because the extent of dialyzability is unknown, one of the twice daily doses should be administered after PIRRT treatment on PIRRT treatment days (expert opinion).
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 (ESCMID/EUCAST [Tsuji 2019]; John 2017; Sandri 2013a). Infusion-related adverse effects may increase with higher doses (ESCMID/EUCAST [Tsuji 2019]; John 2017). Due to minimal data in morbidly obese patients, consider dosing based on adjusted body weight in these patients (Kassamali 2015; Pai 2013; Sandri 2013a).
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 (Kassamali 2015). Data in pediatrics are extremely limited; optimal dose unknown (Thomas 2019).
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 (Bradley 2019; Chiotos 2020; Red Book [AAP 2018], manufacturer's labeling). Based on adult recommendations, an initial loading dose of 25,000 units/kg has also been recommended (Chiotos 2020).
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 (Bradley 2019; Chiotos 2020; Hoeprich 1970; Siddiqui 2014; manufacturer's labeling). 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 (Siddiqui 2014). Based on adult recommendations, an initial loading dose of 25,000 units/kg has also been recommended (Chiotos 2020).
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 (Hoeprich 1970; Landman 2008; IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
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 (Chiotos 2020; ESCMID/EUCAST [Tsuji 2019]).
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 (Cunha 1988).
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: [US Boxed Warning]: May cause nephrotoxicity; avoid concurrent or sequential use of other nephrotoxic drugs. 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. Discontinue therapy with decreasing urinary output and increasing BUN. 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: [US 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. Avoid concurrent use of curariform muscle relaxants and other neurotoxic drugs (eg, ether, tubocurarine, succinylcholine, gallamine, decamethonium, sodium citrate), which may cause respiratory depression.
• 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: 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: [US Boxed Warning]: Safety in pregnant women not established.
Other warnings/precautions:
• IM/Intrathecal/IV administration: [US Boxed Warning]: Intramuscular/intrathecal/intravenous administration only to hospitalized patients.
• Parenteral administration: Polymyxin B sulfate is most toxic when given parenterally; avoid parenteral use whenever possible.
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): $6.54 - $17.50
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Infuse over 1 hour (ESCMID/EUCAST [Tsuji 2019]).
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 (Pereira 2007).
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 (Salvatore 2011; ESCMID/EUCAST [Tsuji 2019]) 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.
Pseudomonal infections: Treatment of infections of the meninges and bloodstream caused by susceptible strains of Pseudomonas aeruginosa.
Serious infections: Treatment of 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; Klebsiella aerogenes (formerly Enterobacter aerogenes), specifically bacteremia; Klebsiella pneumoniae, specifically bacteremia.
In meningeal infections, polymyxin B sulfate should be administered only by the intrathecal route.
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.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminoglycosides: Polymyxin B may enhance the nephrotoxic effect of Aminoglycosides. Polymyxin B may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
Bacillus clausii: Antibiotics may diminish the therapeutic effect 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 enhance the nephrotoxic effect of Bacitracin (Systemic). Risk X: Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Capreomycin: May enhance the neuromuscular-blocking effect of Polymyxin B. Risk C: Monitor therapy
Cefaloridine [Cephaloridine]: Polymyxin B may enhance the nephrotoxic effect of Cefaloridine [Cephaloridine]. Risk C: Monitor therapy
Cefazedone: May enhance the nephrotoxic effect of Polymyxin B. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect 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 combination
Colistimethate: May enhance the nephrotoxic effect of Polymyxin B. Polymyxin B may enhance the neuromuscular-blocking effect of Colistimethate. Colistimethate may enhance the neurotoxic effect of Polymyxin B. 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 diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Kanamycin: Polymyxin B may enhance the adverse/toxic effect 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 diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mecamylamine: Polymyxin B may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methoxyflurane: May enhance the nephrotoxic effect of Polymyxin B. Risk X: Avoid combination
Netilmicin (Ophthalmic): Polymyxin B may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). Risk X: Avoid combination
Neuromuscular-Blocking Agents: Polymyxin B may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Management: If possible, avoid concomitant use of neuromuscular-blocking agents and polymyxin B. If concomitant use cannot be avoided, monitor for deeper, prolonged neuromuscular-blocking effects (eg, respiratory paralysis) in patients receiving this combination. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect 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 diminish the therapeutic effect 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)
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