Colistimethate warning issued by ASHP and ISMP

July 5, 2011

The American Society of Health-System Pharmacists (ASHP) and the Institute for Safe Medication Practices (ISMP) last week issued a serious medication alert about colistimethate.

The American Society of Health-System Pharmacists (ASHP) and the Institute for Safe Medication Practices (ISMP) last week issued a serious medication alert about colistimethate.

The two groups issued a National Alert Network (NAN) Alert for Serious Medication Errors (http://www.ashp.org/menu/PracticePolicy/ResourceCenters/PatientSafety/NAN-Alerts.aspx) after a fatal error involving injections of the antibiotic colistimethate was reported to NAN. “It is more commonly used in hospitals because it is an injectable and because of antibiotic drug resistance. We have heard about [this dosing] before, but when we got an actual report of a fatal event, we had to get the word out to more organizations,” said Michael Cohen, president of ISMP.

Colistimethate is a prodrug, a precursor of a drug that converts to an active drug as it is metabolized in the body. However, the strength of all FDA-approved colistimethate injection products is labeled in terms of the base drug, colistin, not the prodrug, according to the alert. The label indicates the strength as 150 mg of colistin base per vial.

The confusion stems from some journal articles and online resources that base dosing information on the prodrug colistimethate. “This has resulted in situations where the prodrug dose is ordered, but is confused as a colistin dose, which results in doses approximately 2.5 times higher than intended,” stated the NAN alert.

In the fatal case that led to the NAN alert, a physician mistakenly ordered a dose of colistimethate as the prodrug, but the amount was dispensed as the colistin base. “It has renal toxicity. The patient developed acute renal failure, then died a few days later,” Cohen said. Cohen cannot release further details on the case because health professionals report medication errors and safety information in confidence to NAN.

To prevent an error, the NAN alert recommends that colistimethate for injection be prescribed only as colistim in terms of base activity, with a dose range of 2.5 to 5 mg/kg/day for patients with normal renal function. Drug reduction in the setting of renal insufficiency is recommended (see product labeling).