COLY-MYCIN M

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COLY-MYCIN M (COLY-MYCIN M).

How it works

Colistin acts as a cationic detergent, binding to and disrupting the bacterial cell membrane, leading to cell death. It is active primarily against gram-negative bacteria.

What the body does with it

Metabolism	Colistin is primarily eliminated via renal excretion as unchanged drug. Metabolism is minimal, with no significant hepatic metabolism.
Excretion	Primarily renal (approximately 60-70% of colistin [formed from CMS] excreted unchanged in urine via glomerular filtration and tubular secretion); ~10-20% biliary/fecal as unchanged drug. Colistimethate sodium (CMS) is also renally cleared. In renal impairment, clearance is significantly reduced.
Half-life	Terminal elimination half-life of colistin (active formed moiety) is approximately 3-4 hours in patients with normal renal function; prolonged to 3-4 days in end-stage renal disease. Half-life of CMS itself is shorter (~2 hours). Clinical context: Dosing adjustments are critical in renal impairment to avoid accumulation and neuro/nephrotoxicity.
Protein binding	Colistin is ~50-60% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution of colistin in adults: approximately 0.09-0.19 L/kg (range 0.06-0.3 L/kg), indicating limited extravascular distribution. Higher Vd has been reported in critically ill patients (e.g., 0.27 L/kg). Clinical meaning: Low Vd suggests colistin is primarily distributed in plasma and interstitial fluid; poor penetration into epithelial lining fluid, lung parenchyma, and CSF explains need for high-dose regimens or adjunctive inhaled therapy.
Bioavailability	Intravenous: 100% (administered as CMS). Intramuscular: Not recommended due to erratic absorption. Oral: Bioavailability is negligible (<1%) as colistin is not absorbed from the GI tract. Inhaled via nebulizer: Variable systemic bioavailability (~5-20%) but direct lung delivery achieves high local concentrations; systemic absorption contributes to potential toxicity.
Onset of Action	Intravenous: Peak serum concentrations of active colistin achieved within 2-4 hours after IV administration of CMS (prodrug). Inhaled: Onset of clinical effect typically within 24-48 hours for treatment of respiratory infections.
Duration of Action	Duration of antibacterial effect: The prolonged post-antibiotic effect (PAE) against Gram-negative organisms is limited (1-2 hours). Dosing interval is typically every 8-12 hours due to concentration-dependent killing and half-life. Inhaled route: Aerosolized CMS given every 12-24 hours.

Classification & Brands

Dosing & administration

2.5 to 5 mg/kg/day of colistin base activity divided every 8-12 hours intravenously; alternatively, 1.25 to 2.5 mg/kg every 12 hours. For inhalation, 75 mg (1 million units) of colistimethate sodium in 3 mL normal saline nebulized twice daily.

Dosage form	INJECTABLE
Renal impairment	For CrCl 20-50 mL/min: 1.9-2.5 mg/kg every 24 hours; CrCl 10-19 mL/min: 1.5-1.9 mg/kg every 36 hours; CrCl <10 mL/min: 1.0-1.5 mg/kg every 48 hours. For hemodialysis: 1.0-1.5 mg/kg after dialysis.
Liver impairment	Not required; colistin is primarily renally eliminated. No dosage adjustment recommended for hepatic impairment.
Pediatric use	For children ≥1 year: 2.5-5 mg/kg/day of colistin base activity divided every 6-12 hours intravenously. For inhalation: 75 mg (1 million units) nebulized twice daily for children ≥2 years; for younger children, 37.5 mg (500,000 units) twice daily.
Geriatric use	Dose based on renal function; increased risk of nephrotoxicity and neurotoxicity; monitor renal function closely; consider lower end of dosing range if CrCl <50 mL/min.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for COLY-MYCIN M (COLY-MYCIN M).

Breastfeeding

Colistimethate is excreted into breast milk in low levels (M/P ratio approximately 0.3-0.4). Due to potential for infant gut microbiome disruption and rare absorption, use with caution. Monitor infant for diarrhea, thrush, or lethargy. AAP considers it compatible with breastfeeding, but alternatives preferred.

Teratogenic Risk

Colistimethate (Coly-Mycin M) is classified as FDA Pregnancy Category C. Animal studies have shown fetal harm (e.g., reduced ossification, delayed development) at doses toxic to mothers. No adequate human studies exist. In first trimester: potential teratogenicity unknown, avoid unless essential. Second and third trimesters: use only if maternal benefit outweighs fetal risk, as systemic absorption may cause fetal toxicity (e.g., nephrotoxicity, neurotoxicity).

Warnings & precautions

■ FDA Black Box Warning

WARNING: Nephrotoxicity and Neurotoxicity. Colistin can cause nephrotoxicity, including acute kidney injury, and neurotoxicity, which may manifest as paresthesias, peripheral neuropathy, vertigo, dizziness, visual disturbances, and rarely respiratory paralysis. Monitor renal function closely. Use with caution in patients with renal impairment and adjust dose accordingly.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to colistin or any component of the formulation","Colistin products are contraindicated in patients with known hypersensitivity to polymyxins"]

Clinical Precautions

Precautions

["Nephrotoxicity: Monitor renal function; may require dose adjustment.","Neurotoxicity: Observe for signs such as paresthesias, muscle weakness, or respiratory depression.","Use caution in patients with myasthenia gravis or other neuromuscular disorders.","Superinfection: Prolonged use may result in overgrowth of nonsusceptible organisms.","Respiratory: Inhalation use may cause bronchospasm; use with caution in asthma."]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

COLY-MYCIN M

Clinical safety rating: caution

Comprehensive clinical and safety monograph for COLY-MYCIN M (COLY-MYCIN M).

How it works

Colistin acts as a cationic detergent, binding to and disrupting the bacterial cell membrane, leading to cell death. It is active primarily against gram-negative bacteria.

What the body does with it

Metabolism	Colistin is primarily eliminated via renal excretion as unchanged drug. Metabolism is minimal, with no significant hepatic metabolism.
Excretion	Primarily renal (approximately 60-70% of colistin [formed from CMS] excreted unchanged in urine via glomerular filtration and tubular secretion); ~10-20% biliary/fecal as unchanged drug. Colistimethate sodium (CMS) is also renally cleared. In renal impairment, clearance is significantly reduced.
Half-life	Terminal elimination half-life of colistin (active formed moiety) is approximately 3-4 hours in patients with normal renal function; prolonged to 3-4 days in end-stage renal disease. Half-life of CMS itself is shorter (~2 hours). Clinical context: Dosing adjustments are critical in renal impairment to avoid accumulation and neuro/nephrotoxicity.
Protein binding	Colistin is ~50-60% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution of colistin in adults: approximately 0.09-0.19 L/kg (range 0.06-0.3 L/kg), indicating limited extravascular distribution. Higher Vd has been reported in critically ill patients (e.g., 0.27 L/kg). Clinical meaning: Low Vd suggests colistin is primarily distributed in plasma and interstitial fluid; poor penetration into epithelial lining fluid, lung parenchyma, and CSF explains need for high-dose regimens or adjunctive inhaled therapy.
Bioavailability	Intravenous: 100% (administered as CMS). Intramuscular: Not recommended due to erratic absorption. Oral: Bioavailability is negligible (<1%) as colistin is not absorbed from the GI tract. Inhaled via nebulizer: Variable systemic bioavailability (~5-20%) but direct lung delivery achieves high local concentrations; systemic absorption contributes to potential toxicity.
Onset of Action	Intravenous: Peak serum concentrations of active colistin achieved within 2-4 hours after IV administration of CMS (prodrug). Inhaled: Onset of clinical effect typically within 24-48 hours for treatment of respiratory infections.
Duration of Action	Duration of antibacterial effect: The prolonged post-antibiotic effect (PAE) against Gram-negative organisms is limited (1-2 hours). Dosing interval is typically every 8-12 hours due to concentration-dependent killing and half-life. Inhaled route: Aerosolized CMS given every 12-24 hours.

Classification & Brands

Dosing & administration

Dosage form	INJECTABLE
Renal impairment	For CrCl 20-50 mL/min: 1.9-2.5 mg/kg every 24 hours; CrCl 10-19 mL/min: 1.5-1.9 mg/kg every 36 hours; CrCl <10 mL/min: 1.0-1.5 mg/kg every 48 hours. For hemodialysis: 1.0-1.5 mg/kg after dialysis.
Liver impairment	Not required; colistin is primarily renally eliminated. No dosage adjustment recommended for hepatic impairment.
Pediatric use	For children ≥1 year: 2.5-5 mg/kg/day of colistin base activity divided every 6-12 hours intravenously. For inhalation: 75 mg (1 million units) nebulized twice daily for children ≥2 years; for younger children, 37.5 mg (500,000 units) twice daily.
Geriatric use	Dose based on renal function; increased risk of nephrotoxicity and neurotoxicity; monitor renal function closely; consider lower end of dosing range if CrCl <50 mL/min.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for COLY-MYCIN M (COLY-MYCIN M).

Breastfeeding

Teratogenic Risk

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to colistin or any component of the formulation","Colistin products are contraindicated in patients with known hypersensitivity to polymyxins"]