COLISTIMAX

Composition:

Each vial contains:

Colistimethate Sodium IP…… 10,00,000 IU (As Sterile Lyophilized Powder)

CLINICAL PHARMACOLOGY

Pharmacodynamics Mechanism of action:

Colistimethate is a polymyxin group of antibiotic. The polymyxin antibiotics are cationic agents that work by damaging the cell membrane. The resulting physiological affects are lethal to the bacterium. Polymyxins are selective for Gram-negative bacteria that have a hydrophobic outer membrane.

Pharmacokinetics

Absorption:
Absorption from the gastrointestinal tract does not occur to any appreciable extent in the normal individual. When given by nebulization, variable absorption has been reported that may depend on the aerosol particle size, nebulizer system, and lung status.

Distribution:
Protein binding is low. Polymyxin persists in the liver, kidney, brain, heart and muscle. One study in cystic fibrosis patients gives the steady-state volume of distribution as 0.09 L/kg.

Metabolism:
Colistimethate sodium is converted to the base in vivo. As 80% of the dose can be recovered unchanged in the urine and there is no biliary excretion, it can be assumed that the remaining drug is inactivated in the tissues. The mechanism is unknown.

Elimination:
The main route of elimination after parenteral administration is by renal excretion with 40% of a parenteral dose recovered in the urine within 8 hours and around 80% in 24 hours. Because colistimethate sodium is largely excreted in the urine, dose reduction is recommended in renal impairment to prevent accumulation. After intravenous administration to healthy adults, the elimination half-life is around 1.5 hrs. In a study of cystic fibrosis patients given a single 30-minute intravenous infusion the elimination half-life was 3.4 +1.4 hrs.

 

Therapeutic indications:
Colistimethate is indicated in the treatment of the following infections where sensitivity testing suggests that they are caused by susceptible bacteria: Intravenous administration for the treatment of some serious infections caused by Gram-negative bacteria, including those of the lower respiratory tract and urinary tract, when more commonly used systemic antibacterial agents may be contra-indicated or may be ineffective because of bacterial resistance.

Treatment by inhalation of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF).