COLY-MYCIN M
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COLY-MYCIN M (COLY-MYCIN M).
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.
| 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. |
| Molecular Weight | 1155.5 |
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. |
| 1st trimester | Avoid; risk of fetal harm based on animal data and potential for nephrotoxicity/ototoxicity. |
| 2nd trimester | Avoid; potential fetal nephrotoxicity and ototoxicity. |
| 3rd trimester | Avoid; risk of neonatal toxicity if administered near term. |
Clinical note
Comprehensive clinical and safety monograph for COLY-MYCIN M (COLY-MYCIN M).
| Placental transfer | Crosses placenta; data limited but expected due to low molecular weight. |
| Breastfeeding | Not recommended; colistin is excreted into breast milk in small amounts, but safety to infant is unknown due to potential for gastrointestinal disturbance and alteration of gut flora. |
| Lactation Rating |
■ 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.
| Serious Effects |
Hypersensitivity to colistin or any componentMyasthenia gravis (relative, but caution)
| 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. |
| Food/Dietary | No clinically significant food interactions. Take with or without food. Maintain adequate hydration to reduce nephrotoxicity risk. |
Loading safety data…
| L5 - Contraindicated |
| 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). |
| Fetal Monitoring | Monitor maternal renal function (serum creatinine, urine output) and neurological status (paresthesias, weakness, seizures) due to colistin toxicity. For fetus: ultrasound monitoring for growth and amniotic fluid volume if prolonged therapy. Monitor for signs of neonatal nephrotoxicity (urine output, BUN) if administered near delivery. |
| Fertility Effects | Animal studies show no direct effects on fertility. Human data limited. Possible reversible ovarian or testicular toxicity at high doses but not clinically significant at standard doses. No recommended routine fertility monitoring. |
| Clinical Pearls | Colistimethate sodium (Coly-Mycin M) is a prodrug of colistin, a polymyxin antibiotic. It is renally cleared; dose adjustment required for CrCl <50 mL/min. Neurotoxicity (paresthesias, vertigo, seizures) and nephrotoxicity (acute kidney injury) are dose-limiting. Monitor renal function and neuromuscular status. Inhalation form for cystic fibrosis patients with Pseudomonas aeruginosa. Intrathecal use for CNS infections. Do not administer intramuscularly or intravenously via rapid bolus; infuse over 30-60 min. Cross-reactivity with polymyxin B. |
| Patient Advice | Take this medication exactly as prescribed, even if you feel well. · Do not stop or change dose without consulting your doctor. · Report any signs of kidney problems: decreased urination, swelling, fatigue, confusion. · Tell your doctor immediately if you experience numbness, tingling, dizziness, or seizures. · If using the inhalation form, follow instructions for nebulizer use and cleaning. · Avoid driving or operating machinery if you experience dizziness or blurred vision. · Complete the full course of therapy to prevent resistance. |