COLIVETO 4800

Indications

• Treatment of infections due to multidrug-resistant Gram-negative bacteria
• Complicated urinary tract infections
• Pneumonia caused by susceptible organisms
• Bacteremia and sepsis caused by resistant Gram-negative strains
• Infections in cystic fibrosis patients

Dosage

Adults: For the treatment of infections, the typical adult dose of colistin (as col

Mechanism of action

Colistin exerts its antibacterial effects by binding to the lipid A component of lipopolysaccharides in the outer membrane of Gram-negative bacteria. This disrupts the integrity of the bacterial cell membrane, leading to cell lysis and death. The binding process is dependent on the presence of divalent cations, such as calcium and magnesium, which stabilize the membrane structure. The disruption of the membrane also allows for increased permeability, facilitating the entry of additional antibiotics.

Pharmacodynamics

Colistin is bactericidal against susceptible Gram-negative bacteria. Its effectiveness is influenced by the concentration of the drug at the site of infection, with higher doses leading to a more rapid bactericidal effect. Colistin exhibits time-dependent killing characteristics, where the duration of exposure above the minimum inhibitory concentration (MIC) is critical for efficacy. Resistance to colistin can occur, primarily through modifications of lipid A, which reduce the binding affinity of the antibiotic.

Pharmacokinetics

Colistin is administered as a prodrug, colistimethate sodium, which is converted to the active form, colistin, in the body. Following intravenous administration, colistin distributes widely in body tissues and fluids, with variable penetration into the central nervous system. The elimination half-life is approximately 3 to 5 hours, and the drug is primarily excreted by the kidneys. Adjustments in dosing may be required in patients with renal impairment due to altered clearance.

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Allergic reactions
• Respiratory distress

Interactions

• Increased nephrotoxicity with other nephrotoxic agents
• Potential interaction with neuromuscular blockers

Precautions

• Monitor renal function regularly during therapy
• Use with caution in patients with renal impairment
• Assess for potential allergic reactions

Pregnancy

Colistin should only be used during pregnancy if the potential benefits justify the risks to the fetus, as safety in pregnancy has not been established.

Breast-feeding

Colistin is excreted in breast milk; caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place, protected from light. Once reconstituted, use as per specific guidelines provided.

Formulations

• Colistimethate sodium for injection
• Colistin sulfate for oral use