KOLISTIPOL 4.500.000

Indications

• Pneumonia caused by multidrug-resistant Gram-negative bacteria
• Urinary tract infections due to susceptible strains
• Bacteremia and sepsis caused by resistant organisms
• Inhalation for respiratory infections in cystic fibrosis patients

Dosage

Children: Refer to the BNF for Children for appropriate dosing information in paediatric patients.

Adults: Refer to the BNF for specific dosing information based on the type and severity of the infection, as well as renal function.

Mechanism of action

Colistimethate works by binding to the bacterial cell membrane, disrupting its integrity. This leads to increased permeability and eventually causes cell death. The drug primarily interacts with lipopolysaccharides and phospholipids in the bacterial membrane, which is critical for Gram-negative bacteria.

Pharmacodynamics

Colistimethate exhibits concentration-dependent bactericidal activity, meaning that its efficacy increases with higher concentrations. Its spectrum of activity includes a range of resistant Gram-negative pathogens, making it an important option in the management of severe infections caused by these organisms. The antibacterial activity is primarily due to the interaction with the cell membrane, leading to disruption and leakage of cellular contents.

Pharmacokinetics

Colistimethate is administered intravenously or via inhalation. After administration, it is converted to colistin in vivo. The volume of distribution is approximately 0.5 to 1 L/kg, and it is primarily eliminated by the kidneys. The half-life can vary depending on renal function, typically ranging from 2 to 3 hours in healthy individuals. Accumulation may occur in patients with renal impairment, necessitating dose adjustments.

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Respiratory distress
• Allergic reactions
• Hypersensitivity reactions

Interactions

• Potentially increased nephrotoxicity when used with other nephrotoxic agents such as aminoglycosides, vancomycin, or nonsteroidal anti-inflammatory drugs (NSAIDs)

Precautions

• Use with caution in patients with renal impairment
• Monitor renal function regularly during treatment
• Assess for signs of neuromuscular blockade, especially in patients with neuromuscular disorders

Pregnancy

Colistimethate is classified as Category C. Risk cannot be ruled out and should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colistimethate is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at 20-25 degrees Celsius. Protect from light and moisture. Do not freeze.

Formulations

• Colistimethate sodium for injection
• Colistimethate aerosol for inhalation

Indications

• Serious infections due to selected aerobic Gram-negative bacteria in patients with limited treatment options
• Septicaemia
• Urinary-tract infections
• Lower respiratory tract infections caused by susceptible Gram-negative bacteria
• Management of chronic pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis

Dosage

Children: For children aged 2-17 years, the recommended dosage is 1-

Adults: Initial loading dose of 9 million units daily in 2-3 divided doses; for critically ill patients, higher doses of up to 12 million units may be required. Maintenance doses typically include 2 million units every 12 hours or 2 million units every 8 hours for certain cases.

Mechanism of action

Colistimethate sodium disrupts the integrity of the bacterial cell membrane, leading to cell death. It binds to the lipopolysaccharide component of the outer membrane of Gram-negative bacteria, displacing divalent cations (such as calcium and magnesium), which destabilizes the membrane and increases permeability.

Pharmacodynamics

Colistimethate sodium exhibits concentration-dependent bactericidal activity. Its efficacy is influenced by the maximum concentration achieved in the serum and the duration of exposure above the minimum inhibitory concentration (MIC) for the targeted pathogens. Resistance can develop through modifications in the bacterial membrane that reduce drug binding.

Pharmacokinetics

Colistimethate sodium is administered parenterally, as it is poorly absorbed from the gastrointestinal tract. Following intravenous administration, it is converted to its active form, colistin, with variable distribution in body tissues, particularly in the kidneys and lungs. The elimination half-life is approximately 3 to 6 hours in patients with normal renal function, and dosages must be adjusted in cases of renal impairment due to the risk of accumulation.

Contra-indications

• Myasthenia gravis

Adverse effects

• Fever
• Myalgia
• Nervous system disorder
• Thrombophlebitis
• Anxiety
• Decreased appetite
• Drowsiness
• Ear congestion
• Diarrhea
• Flatulence

Precautions

• Accumulation of sodium can occur with high doses
• Caution in renal impairment as dose adjustments may be required
• Risk of severe haemoptysis when used by inhalation

Pregnancy

Not known to be harmful.

Breast-feeding

Trace amounts may be present in milk.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Powder for solution for injection, 250 mg vials