Colistimethate is used for the management of acute and long-term infections caused by susceptible gram-negative bacilli. It is especially effective against infections produced by sensitive strains of Pseudomonas aeruginosa. This medicine is not recommended for infections caused by Proteus species or Neisseria species. Colistimethate is highly active against several gram-negative bacteria including Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

Colistimethate Sodium acts as a surface-active antibacterial agent that penetrates and damages the bacterial cell membrane. It exhibits bactericidal activity against aerobic gram-negative bacteria such as Enterobacter aerogenes, E. coli, Klebsiella pneumoniae, and Pseudomonas species.

Each vial contains Colistimethate Sodium equivalent to:

1 MIU or 34 mg Colistin

2 MIU or 68 mg Colistin

3 MIU or 102 mg Colistin

4.5 MIU or 150 mg Colistin

Colistimethate works by penetrating the bacterial cell membrane and disrupting its structure. Being a polycationic compound with both hydrophobic and lipophilic properties, it interacts with the cytoplasmic membrane of bacteria and alters membrane permeability, ultimately leading to bacterial death. Research also suggests that polymyxins may enter bacterial cells and precipitate intracellular substances, mainly ribosomes.

Maintenance dose: 9 MIU/day in 2–3 divided doses. In patients who are critically ill, a loading dose of 9 MIU should be administered.

Renal impairment patients: Dose adjustments in renal impairment patients are necessary. Dose reductions are recommended for patients with creatinine clearance < 50 ml/min. Twice daily dosing is recommended.

• Creatinine clearance <50–30 ml/min: daily dose 5.5–7.5 MIU
• Creatinine clearance <30–10 ml/min: daily dose 4.5–5.5 MIU
• Creatinine clearance <10 ml/min: daily dose 3.5 MIU

Haemodialysis (HD) patients:

• No-HD days: 2.25 MIU/day (2.2–2.3 MIU/day)
• HD days: 3 MIU/day (should be given after the HD session). Twice daily dosing is recommended.

Pediatric population: The dose should be based on lean body weight.

• Children ≤40 kg: 75,000–150,000 IU/kg/day divided into 3 doses
• Children >40 kg: >150,000 IU/kg/day has been reported in children with cystic fibrosis

Hepatic impairment patients: There are no data in patients with hepatic impairment. Caution is advised when administering colistimethate sodium in these patients.

Direct Intermittent Administration: Slowly inject one-half of the total daily dose over 3 to 5 minutes every 12 hours.

Continuous Infusion: Slowly inject one-half of the total daily dose over 3 to 5 minutes. Add the remaining half of the total daily dose of Colistimethate for injection to one of the following:

• 0.9% NaCl
• 5% dextrose in 0.9% NaCl
• 5% dextrose in water
• 5% dextrose in 0.45% NaCl
• 5% dextrose in 0.225% NaCl
• Lactated Ringer’s solution

There are not sufficient data to recommend the use of Colistimethate for injection with other drugs or infusion solutions other than those listed above. Administer the second half of the total daily dose by slow intravenous infusion, starting 1 to 2 hours after the initial dose, over the next 22 to 23 hours. In the presence of impaired renal function, reduce the infusion rate depending on the degree of renal impairment. The choice of intravenous solution and the volume to be used depend on fluid and electrolyte management requirements. Any infusion solution containing colistimethate sodium should be freshly prepared and used for no longer than 24 hours.

Alternative method: As per specialized references for intermittent infusion, the prescribed dose may be diluted in 50–100 ml of 0.9% NaCl and administered over 30–60 minutes via IV route.

Colistimethate should not be used together with certain antibiotics such as aminoglycosides and polymyxins, as there are reports of interference with nerve transmission at the neuromuscular junction. It should also be avoided with muscle relaxants like tubocurarine, as well as other agents including ether, succinylcholine, gallamine, decamethonium, and sodium citrate. Concurrent use of sodium cephalothin with colistimethate should also be avoided.

Colistimethate Sodium is contraindicated in patients with a known history of hypersensitivity to the drug or any of its components.

Reported adverse effects include gastrointestinal disturbances, tingling sensation in extremities and tongue, slurred speech, dizziness, vertigo, paresthesia, generalized itching, urticaria, rash, fever, increased blood urea nitrogen (BUN), elevated creatinine, reduced creatinine clearance, respiratory distress, apnea, nephrotoxicity, and decreased urine output.

There are no adequate and well-controlled studies in pregnant women. Since colistimethate can cross the placental barrier, it should be used during pregnancy only if clearly needed and when the potential benefit outweighs the possible risk to the fetus. It is not known whether the drug passes into human breast milk; therefore, caution is advised during breastfeeding.

Colistimethate should be used carefully in patients with impaired kidney function. In cases of renal impairment, the drug may still be used but with extreme caution and dose adjustment according to the level of impairment. Special caution is also required in neonates, infants, and children.

Overdose of colistimethate sodium may lead to neuromuscular blockade, presenting with symptoms such as tingling, lethargy, confusion, dizziness, ataxia, nystagmus, speech difficulty, and apnea. Severe cases may cause respiratory muscle paralysis leading to respiratory arrest and death. Acute kidney injury may also occur, shown by reduced urine output and increased serum BUN and creatinine levels. Treatment involves immediate discontinuation of the drug and supportive care.

Other antibacterial preparation

Before reconstitution: Store below 30°C. After reconstitution: Store at 2°C to 8°C (do not freeze) and use within 24 hours.