POLYMYXIN B SULFATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for POLYMYXIN B SULFATE (POLYMYXIN B SULFATE).
Polymyxin B sulfate binds to lipopolysaccharides (LPS) in the outer membrane of gram-negative bacteria, disrupting membrane integrity and causing cell death. It also has anti-endotoxin activity.
| Metabolism | Primarily eliminated by renal tubular reabsorption and excretion; metabolism is limited, with minimal hepatic involvement. |
| Excretion | Primarily renal excretion of unchanged drug via glomerular filtration (approx. 60-70% of a dose is recovered in urine as active polymyxin B). A smaller fraction (approximately 10-20%) is eliminated via non-renal pathways (biliary/fecal) as unchanged drug and minor metabolites; biliary excretion accounts for <5%. |
| Half-life | Terminal elimination half-life is approximately 7-10 hours in adults with normal renal function. In patients with severe renal impairment (CrCl <30 mL/min), half-life may be prolonged to 2-3 days. Half-life is significantly extended in anuria (up to 48-72 hours). Clinically, dosing must be adjusted based on renal function and therapeutic drug monitoring is recommended. |
| Protein binding | Moderate protein binding, approximately 60-80% bound to serum proteins (predominantly to albumin and alpha-1-acid glycoprotein). Binding is saturable and may be reduced in hypoalbuminemia. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.5-0.8 L/kg. This indicates primarily extracellular distribution (plasma and interstitial fluid) with limited tissue penetration. Vd is increased in critically ill patients (up to 1.0 L/kg) due to altered fluid compartments and increased capillary permeability. |
| Bioavailability | Polymyxin B is not significantly absorbed orally (bioavailability <1%). Intramuscular administration results in nearly complete absorption (bioavailability ~90-100%) with peak concentrations achieved in 1-2 hours. Intravenous administration provides 100% bioavailability. |
| Onset of Action | For intravenous administration, onset of antimicrobial effect is within 30-60 minutes following a dose. For intramuscular administration, peak serum concentrations occur at 1-2 hours. For topical application, local onset is rapid (minutes to hours) but systemic absorption is minimal. |
| Duration of Action | Duration of antibacterial activity correlates with serum concentration above MIC. With standard dosing regimens (e.g., 1.5-2.5 mg/kg/day divided every 12h), therapeutic concentrations are maintained throughout the dosing interval in patients with normal renal function. Clinical effect persists for 8-12 hours post-dose. Duration is prolonged in renal impairment. |
| Molecular Weight | 1301.56 |
1.5 to 2.5 mg/kg/day IV divided every 12 hours; maximum 2.5 mg/kg/day. For topical use, apply 0.1% to 0.25% (10,000 to 25,000 units/g) ointment or cream 1-4 times daily.
| Dosage form | INJECTABLE |
| Renal impairment | Dose adjustment is required in renal impairment. For GFR 20-50 mL/min: reduce dose by 50% and monitor serum levels. For GFR <20 mL/min: administer 1-1.5 mg/kg IV every 48-72 hours; consider therapeutic drug monitoring (target AUC 50-100 mg·h/L). |
| Liver impairment | No specific adjustment for hepatic impairment; monitor renal function due to potential nephrotoxicity. |
| Pediatric use | Children: 1.5 to 2.5 mg/kg/day IV divided every 12 hours; maximum 2.5 mg/kg/day. Neonates: 1.5-2.5 mg/kg IV every 12 hours. Adjust dose in renal impairment. |
| Geriatric use | Elderly patients: use with caution due to age-related renal decline; start at lower end of dosing range (1.5 mg/kg/day) and adjust based on renal function and serum levels. |
| 1st trimester | Avoid; potential nephrotoxicity and neurotoxicity; use only if essential and no safer alternative. |
| 2nd trimester | Avoid; risk of fetal toxicity; use only if benefits outweigh risks. |
| 3rd trimester | Avoid; risk of neonatal toxicity; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for POLYMYXIN B SULFATE (POLYMYXIN B SULFATE).
| Placental transfer | Crosses placenta; limited data but transfer expected due to low molecular weight and high water solubility. |
| Breastfeeding | Excreted into breast milk in small amounts; potential for gastrointestinal disturbance and alteration of infant gut flora. Use with caution, especially in neonates with immature renal function. |
| Lactation Rating |
■ FDA Black Box Warning
Nephrotoxicity and neurotoxicity. Polymyxin B should be used only in patients with serious infections due to susceptible organisms, and renal function should be monitored closely. Neurotoxicity may present as irritability, weakness, drowsiness, ataxia, and respiratory paralysis.
| Serious Effects |
Hypersensitivity to polymyxin B or any componentMyasthenia gravis
| Precautions | Nephrotoxicity: Monitor renal function frequently; dose adjustment required in renal impairment., Neurotoxicity: Monitor for neurological symptoms; avoid concurrent use with other neurotoxic drugs., Superinfection: Prolonged use may result in overgrowth of nonsusceptible organisms., Respiratory paralysis: Use with caution in patients with myasthenia gravis or other neuromuscular disorders. |
| Food/Dietary | No significant food interactions; however, maintain adequate hydration to support renal function during treatment. |
Loading safety data…
| L3 - Moderately Safe |
| Teratogenic Risk | Polymyxin B is considered FDA Pregnancy Category B. Animal studies have not demonstrated fetal harm, but no adequate human studies exist. Risk cannot be ruled out. There is no evidence of teratogenicity; however, use only if clearly needed. No specific first trimester risk identified; second and third trimester risks are minimal, but avoid near term due to potential neurotoxicity and nephrotoxicity in the neonate. |
| Fetal Monitoring | Monitor renal function (serum creatinine, BUN, urine output) and neurologic status (paresthesias, dizziness, ataxia) in the mother. Assess fetal growth and well-being with ultrasound if prolonged therapy. Neonatal monitoring for neurotoxicity and nephrotoxicity if administered close to delivery. |
| Fertility Effects | No adequate data on human fertility effects. Animal studies have not shown impaired fertility. Theoretical risk of reversible spermatogenesis suppression at high doses, but not clinically significant at therapeutic doses. |
| Clinical Pearls | Polymyxin B is a nephrotoxic and neurotoxic antibiotic; monitor renal function and avoid concurrent use with other nephrotoxins. It requires a loading dose for rapid achievement of therapeutic levels in critically ill patients with multidrug-resistant Gram-negative infections. Neuromuscular blockade risk increases with high doses or concurrent use of neuromuscular blocking agents; have calcium and neostigmine available. Intrathecal or intraventricular administration may be necessary for central nervous system infections due to poor penetration across the blood-brain barrier. Polymyxin B is not absorbed orally; it is only for parenteral or topical use. |
| Patient Advice | Report any changes in urination, swelling, or tingling/numbness immediately as these may indicate kidney or nerve damage. · Avoid taking this medication with any other drugs that can harm the kidneys, such as nonsteroidal anti-inflammatory drugs or certain antibiotics, without consulting your doctor. · Inform your healthcare provider if you have any muscle weakness or breathing difficulties during treatment. · Polymyxin B may cause skin darkening or rashes; these are not harmful but should be reported if severe. · Complete the full course of therapy even if you feel better, and do not stop without medical advice. |