Prokinetic agents and QT prolongation: a familiar scene with new actors.
Prokinetic agents are a very large family of drugs with different mechanisms of action. Only QT prolongation by cisapride has made notable impact and deserved its partial restriction and/or withdrawal from the market. Postmarketing surveillance initially showed that cisapride was generally safe and well tolerated, but in the past decade, more recent data have shown some risk in the patient populations. QT prolongation by prokinetic agents can raised from different mechanisms: some involve increased plasma concentrations of cisapride due to increased bioavailability by inhibiting P glycoprotein, and inhibition of metabolism or deficit in the elimination. On the other hand, pharmacodynamic interactions can also enhance the arrhythmogenic effect of cisapride. The present article presents the mechanisms and reviews the main interactions studied so far, and the role of pharmacovigilance in the detection of rare clinical events. We emphasize the need for physicians to look for conditions (either clinical or not) prone to increase the risk of QT interval prolongation.
Keller
Guillermo Alberto
GA
Pharmacovigilance Unit, Second Chair of Pharmacology, School of Medicine, Universidad de Buenos Aires, Argentina. catedra2@farmaco-vigilancia.com.ar
Di Girolamo
Guillermo
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D016907:Adverse Drug Reaction Reporting Systems; D000818:Animals; D001682:Biological Availability; D020117:Cisapride / Q000009:adverse effects* / Q000493:pharmacokinetics; D004347:Drug Interactions; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced*; D012307:Risk Factors; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005765:Gastrointestinal Agents; D017366:Serotonin Receptor Agonists; D020117:Cisapride