COLISTIMETHATE SODIUM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COLISTIMETHATE SODIUM (COLISTIMETHATE SODIUM).
Colistimethate sodium is a prodrug that hydrolyzes to colistin, a polymyxin antibiotic. Colistin disrupts bacterial cell membrane integrity by binding to lipopolysaccharides and phospholipids, increasing permeability leading to cell death.
| Metabolism | Colistimethate sodium is partially hydrolyzed to colistin in plasma. The exact metabolic pathways are not fully characterized; renal excretion is the primary elimination route for both colistimethate and colistin. |
| Excretion | Primarily renal (tubular secretion and glomerular filtration); 60-70% of the dose is excreted unchanged in urine within 24 hours, with up to 80% recovered over 48 hours. Minor biliary/fecal elimination (<4%). |
| Half-life | In adults with normal renal function: 2-3 hours (terminal). Prolonged to 20-40 hours in moderate-severe renal impairment; >40 hours in anuria. Dose adjustment required for CrCl <50 mL/min. |
| Protein binding | Approximately 50-60% bound to plasma proteins (albumin). Binding is reversible and may be concentration-dependent. |
| Volume of Distribution | 0.3-0.6 L/kg (adults). Indicates moderate distribution; predominantly extracellular fluid. Penetration is poor into central nervous system, bone, and aqueous humor; achieves adequate levels in lung and urine. |
| Bioavailability | Intravenous: 100%. Intramuscular: Essentially complete (well absorbed). Inhaled: Systemic bioavailability is low (<5-10% of inhaled dose) due to limited pulmonary absorption; largely local effect in airways. Oral: Not bioavailable (not administered via this route; colistimethate is not absorbed orally). |
| Onset of Action | Intravenous: Clinical response (bacteriostatic effect) within 2-4 hours after first dose. Intramuscular: Effect within 3-4 hours. Inhaled: Local lung concentrations achieved within 1-2 hours, but systemic levels variable. |
| Duration of Action | Plasma levels fall below MIC in about 6-8 hours; usual dosing frequency every 8-12 hours in normal renal function. In renally impaired patients, duration extends proportional to half-life prolongation. Note: colistimethate is a prodrug; its active form (colistin) has slower elimination. |
2.5-5 mg/kg/day IV divided every 8-12 hours, based on colistin base activity (CBA). The typical dose is 2.5-5 mg/kg/day of colistimethate sodium (CMS) administered intravenously in 2-3 divided doses. For critically ill patients, a loading dose of 5 mg/kg CBA (approximately 9 million IU) may be given, followed by maintenance doses adjusted for renal function.
| Dosage form | INJECTABLE |
| Renal impairment | GFR ≥50 mL/min: 2.5-5 mg/kg/day IV divided every 8-12 hours. GFR 30-49 mL/min: 2.5-3.8 mg/kg/day IV divided every 12 hours. GFR 10-29 mL/min: 2.5 mg/kg/day IV every 24 hours. GFR <10 mL/min or on hemodialysis: 1.5 mg/kg IV every 36-48 hours (or after dialysis). Dose based on colistin base activity (CBA). Monitor serum creatinine and adjust accordingly. |
| Liver impairment | No specific dose adjustment recommended for hepatic impairment. Colistimethate sodium is primarily renally eliminated; however, careful monitoring is advised in patients with severe hepatic dysfunction due to limited data. |
| Pediatric use | Children (≥1 year): 2.5-5 mg/kg/day IV divided every 6-12 hours (based on CBA). Maximum daily dose: 5 mg/kg/day. For neonates and infants <1 year: Limited data; consider 2.5-5 mg/kg/day IV divided every 8-12 hours. Use with caution and monitor renal function closely. |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COLISTIMETHATE SODIUM (COLISTIMETHATE SODIUM).
| Breastfeeding | Colistimethate is excreted into breast milk in small amounts. The milk-to-plasma ratio (M/P ratio) is unknown for colistimethate; for colistin (its active moiety), M/P ratio is approximately 0.2-0.5. Oral bioavailability of colistin in infants is low; therefore, it is considered compatible with breastfeeding. However, caution is advised in preterm or low-birth-weight infants due to immature renal function. Monitor infant for diarrhea or rash. |
| Teratogenic Risk | Colistimethate sodium crosses the placenta. Animal studies show no teratogenicity at clinically relevant doses. Human data are limited; however, no major malformations have been reported. Risk cannot be excluded. Because colistin is a polymyxin antibiotic, avoidance during first trimester is prudent unless no alternative. In second and third trimesters, use only if clearly needed; no known specific fetal risks. |
■ FDA Black Box Warning
WARNING: NEPHROTOXICITY AND NEUROTOXICITY. Colistimethate sodium can cause nephrotoxicity and neurotoxicity. Monitor renal function and adjust dose accordingly. Neurotoxicity may manifest as paresthesias, vertigo, seizures, or confusion.
| Serious Effects |
Hypersensitivity to colistimethate sodium or any polymyxin antibiotic.
| Precautions | Monitor renal function closely, especially in patients with pre-existing renal impairment or concomitant nephrotoxic agents. Neurotoxicity risk increases with high doses, renal impairment, or concurrent use of other neurotoxic drugs. May cause respiratory muscle paralysis. Use caution in patients with myasthenia gravis or other neuromuscular disorders. |
Loading safety data…
| Elderly patients often have age-related decline in renal function. Dose adjustment based on estimated GFR (e.g., Cockcroft-Gault) is recommended. Start at lower end of dosing range (e.g., 2.5-3 mg/kg/day CBA) and titrate based on response and renal function. Monitor for neurotoxicity and nephrotoxicity, which may be more common. |
| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN, urine output), neurologic status (for paresthesias, neuromuscular weakness), and serum electrolytes regularly. Monitor fetal growth and well-being via ultrasound if prolonged use; assess for oligohydramnios if nephrotoxic. Neurotoxicity monitoring in mother is critical as renal impairment increases risk. |
| Fertility Effects | No human data on fertility impairment. In animal studies, no adverse effects on fertility were observed at clinically relevant doses. Theoretical risk due to nephrotoxicity with prolonged high-dose therapy; no direct effect on gametes or reproductive organs is known. |