Acute Porphyria Drug Database

J01XB01 - Colistin
Propably not porphyrinogenic
PNP

Important Information
Nephrotoxicity is a very common side effect of colistin. This motivates reduced doses of the drug in patients with pre-existing renal damage, such is the case in some carriers of acute porphyria, to avoid overdosing.
Side effects
Renal cytotoxicity signaled by reduced GFR is a very common side effect. This motivates reduced doses of the drug in patients with pre-existing renal damage, such is the case in some carriers of acute porphyria, to avoid overdosing. Common adverse reactions of colistin that can be confused with an acute porphyric attack are nausea and vomiting. These side effects may potentially be porphyrinogenic if leading to a decrease in carbohydrate intake.
Rationale
Colistin is not a substrate, inhibitor or inducer of CYP450 enzymes. No pharmacokinetic porphyrinogenic effects are suspected.
Chemical description
Colistin is a cyclic polypeptide
Therapeutic characteristics
Colistin is a polymyxin antibiotic indicated for the treatment of gram-negative infections, especially those due to Pseudomonas Aeruginosa. Colistimethate sodium might be administered parenterally either by intramuscular injection or intravenous injection or infusion. Colistimethate sodium is also used by inhalation (nebulizer) in the management of respiratory infections in patients with cystic fibrosis. Colistin sulphate administered orally may be used in the treatment of gastrointestinal infections. Half-life is 2-3 hours following either intravenous or intramuscular administration.
Metabolism and pharmacokinetics
Colistimethate sodium is a prodrug which is hydrolyzed to the active drug colistin, whereby only 30 % is converted to colistin (Uptodate). Colistin sulphate and colistimethate sodium are poorly absorbed from the gastrointestinal tract and the lungs (SPC). Metabolism is not known, but colistin is not suspected to be a CYP450 substrate. The excretion is primarily renal with over 80 % of the dose recovered unchanged in the urine (SPC). Colisin and colistimethate do not induce or inhibit CYP450 enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C19 and 3A4/5) in vitro (SPC).

References

  1. Drug reference publications
  2. Martindale in Micromedex® 2.0 (electronic version). Colistin. #1652
  3. Drug interaction databases
  4. Lexi-Comp in UpToDate. Colistin: Drug information. #1651
  5. Summary of Product Characteristics
  6. The electronic Medicines Compendium (emc). Summary of Product Characteristics (SPC). (Colomycin). #1653

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