Colistate 150

Colistin (equivalent to colistimethate sodium).

Each vial contains colistimethate sodium equivalent to colistin 150 mg.

Pharmacology: Pharmacodynamics: Colistimethate sodium is a polymyxins antibiotic. It is inactive until hydrolyzed to colistin; this hydrolysis occurs in vitro in aqueous solutions of the drug and in vivo. Colistin has bactericidal activity against gram-negative bacilli. Colistin acts as a cationic detergent which damages the bacterial cytoplasmic membrane causing leaking of intracellular substances and cell death.
Colistin is active in vitro against many strains of Acinetobacter spp., Citrobacter spp., Escherichia coli, Enterobacter spp., Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella spp., Shigella spp. and some strains of Bordetella spp. and Vibrio spp.
Most strains of Proteus spp., Providencia spp., Serratia spp., Neisseria gonorrhoeae, Neisseria meningitidis, and Bacteroides fragilis are resistant to colistin. The drug is inactive against gram-positive bacteria, fungi, and viruses.
Pharmacokinetics: Absorption: Colistimethate sodium is poorly absorbed from the gastrointestinal tract of adults and must be given parenterally. The drug is not absorbed through mucous membranes, or intact or denuded skin. Peak plasma concentrations usually occur 2 to 3 hours after an intramuscular injection and 10 minutes after an intravenous injection of colistimethate sodium.
Distribution: Following IM or IV administration of colistimethate sodium, the drug is widely distributed into body tissues, but only negligible concentrations of antimicrobial activity are attained in synovial, pleural, or pericardial fluids. Colistin crosses the placenta and is distributed into breast milk but diffusion into the CSF is negligible. Plasma protein binding of colistin is reported to be more than 50%.
Metabolism and Elimination: Colistimethate sodium is hydrolyzed in vivo to colistin and possibly other metabolites with fewer substituted amino groups. The serum half-life of colistimethate sodium is 2 to 3 hours but is prolonged in renal impairment; values of 10 to 20 hours have been reported in patients with a creatinine clearance of less than 20 mL/minute. Following administration of colistimethate sodium in a few anuric patients, half-life of antimicrobial activity reportedly ranged up to 2-3 days.
Colistimethate is mainly excreted by glomerular filtration as changed and unchanged drug and up to 80% of a parenteral dose may be recovered in the urine within 24 hours. Excretion is more rapid in children than in adults; it is reduced in patients with renal impairment.

Treatment of infections due to sensitive strains of certain gram-negative bacilli which are resistant to other antibacterial or in patients allergic to other antibacterial (e.g., Acinetobacter spp., Citrobacter spp., Escherichia coli, Enterobacter spp., Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella spp., Shigella spp. and some strains of Bordetella spp. and Vibrio spp.).
Aerosolized colistin has been shown to be beneficial in the treatment of sensitive Pseudomonas infections in patients with cystic fibrosis by oral inhalation via nebulization.

Parenteral Dosage: Usual dosage: 2.5 to 5 mg/kg/day IM or IV or IV infusion in 2 to 4 divided doses, depending upon the severity of the infection. Maximum dose: 5 mg/kg/day.
Dosage in renal impairment: Reduce the daily dose in the presence of any renal impairment.
Recommended dose for adults with impaired renal function is provided in Table. (See Table.)
Oral Inhalation Dosage: For treatment of Pseudomonas aeruginosa respiratory tract infection in cystic fibrosis patients, colistimethate sodium has been given by oral inhalation via nebulization in a dosage of 33.33-66.66 mg of colistin 2 or 3 times daily. This corresponds to a dosage of 1-2 million international units 2 or 3 times daily.

Click on icon to see table/diagram/image

Mode of Administration: Colistimethate sodium is administered by IM injection, IV injection, or continuous IV infusion. The drug also has been administered by oral inhalation via nebulization.
IV Injection: The appropriate dose should be injected directly into a vein over 3- to 5-minute period.
IV Infusion: For continuous IV infusion, one-half of the total daily dose should be injected directly into a vein over 3- to 5-minute period; the remaining one-half of the total daily dose should be added to compatible IV solution and administered 1-2 hours later (over the next 22-23 hours) by slow IV infusion. The infusion rate should be 5-6 mg/hour in patients with normal renal function. For patients with impaired renal function, the infusion rate should be reduced depending on the degree of renal impairment.
Preparation for IM or IV administration: The 150 mg vial should be reconstituted with 2 ml of sterile water for injection. During reconstitution swirl gently to avoid frothing. The reconstituted solution provides; colistimethate sodium at a concentration equivalent to 75 mg/ml colistin base activity and should be used promptly after preparation.
Preparation for continuous IV infusion: The reconstituted solution should be added to a compatible IV solution (e.g., NSS, D5W, D5S, D5S/2·, D5S/4, Ringer's lactated or invert sugar 10%). The specific IV solution and volume of the solution used should be based on the patient's fluid and electrolyte requirements. Freshly prepare any infusion containing colistimethate sodium.
Preparation for Oral Inhalation: For oral inhalation via nebulization, an isotonic solution of colistimethate sodium has been prepared by diluting the appropriate dose in 2-4 ml of preservative-free 0.9% sodium chloride injection, sterile water, or a mixture of 0.9% sodium chloride injection and sterile water. Administer solution promptly following preparation to decrease possibility of high concentrations of colistin from forming which may lead to potentially life-threatening lung toxicity.

Overdosage of colistimethate sodium can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech, and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest, and death. Overdosage of the drug may also cause acute renal failure, manifested as decreased urine output and increases in serum concentrations of BUN and creatinine. If overdosage of colistimethate sodium occurs, the drug should be discontinued and general supportive measures initiated. Colistimethate sodium may be removed by hemodialysis and, to a lesser extent, by peritoneal dialysis.

Hypersensitivity to colistimethate, colistin, or any component of the formulation.

Nephrotoxicity has been reported; use with caution in patients with pre-existing renal disease or geriatric patients; dosage adjustments may be required. Respiratory arrest has been reported with use; impaired renal function may increase the risk for neuromuscular blockade and apnea.
Transient, reversible neurological disturbances (e.g., dizziness, numbness, paresthesia, tingling, and vertigo) may occur; patients should be warned that the drug may impair their ability to perform hazardous activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).
Prolonged use may result in fungal or bacterial super-infection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis.
If colistimethate sodium is administered via a nebulizer, the solution should be used promptly after being mixed. Premixing colistimethate sodium into an aqueous solution and storing it for longer than 24 hours results in increased concentrations of colistin in the solution and increases the potential for lung toxicity if the premixed solution is administered via nebulization. Adults and children who receive colistimethate sodium by oral inhalation via nebulization may be at risk of bronchoconstriction. Premedication with bronchodilators may reduce the potential for development of bronchoconstriction in patients receiving the drug by nebulization. The healthcare providers who choose to prescribe colistimethate sodium for administration by oral inhalation via nebulization should be familiar with the chemistry of the drug and aware of the potential for serious and life-threatening side effects from inhalation of premixed, ready-to­ use liquid preparations of the drug.

Use in Pregnancy: Category C: Adverse events have been observed in animal reproduction studies. There are no adequate and well­ controlled studies in pregnant women. Should be used in pregnant woman only if benefit to mother justifies potential risk to the fetus.
Use in Lactation: Colistin is distributed into breast milk. Therefore, should be used with caution in nursing women.

Frequency not defined: Central nervous system: Dizziness, fever, headache, slurred speech, vertigo.
Dermatologic: Pruritus, rash, urticaria.
Gastrointestinal: GI upset.
Neuromuscular & skeletal: Paresthesia (extremities, oral); weakness (lower limb).
Renal: BUN increased, creatinine increased, nephrotoxicity, proteinuria, urine output decreased.
Respiratory: Apnea, respiratory arrest.
Postmarketing, and/or case reports: Lung toxicity (bronchoconstriction, bronchospasm, chest respiratory distress, acute respiratory failure following inhalation).

Since nephrotoxic and/or neurotoxic effects may be additive, concurrent or sequential use of colistimethate sodium and other drugs with similar toxic potentials (e.g., aminoglycosides, amphotericin B, capreomycin, methoxyflurane, polymycin B sulfate, vancomycin) should be avoided, if possible.
Neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, ether, decamethonium, gallamine and other drugs (e.g., sodium citrate) potentiate neuromuscular blockade induced by colistimethate sodium and these drugs should be used with extreme caution on patients receiving colisfunethate sodium.

Colistimethate sodium powder for injection should be stored below 25°C.

Other Antibiotics

J01XB01 - colistin ; Belongs to the class of polymyxins. Used in the systemic treatment of infections.

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