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4. Drug-Drug Interactions

Patient profiles will be reviewed to identify those drug regimens, which may result in clinically significant drug-drug interactions. The following drug-drug interactions summarized in Table 4 are considered clinically relevant for serotonin 5-HT3 receptor antagonists. Only those drug-drug interactions classified as clinical significance of contraindicated or those considered life-threatening which have not yet been classified will be reviewed.

Table 4. Major Drug-Drug Interactions for Serotonin 5HT3 Receptor Antagonists [1]
Target DrugInteracting DrugInteractionRecommendationClinical Significance Level*
granisetron, ondansetron, palonosetronQTc interval-prolonging medications (e.g., class Ia anti-arrhythmic agents†, class III anti-arrhythmic agents††, erythromycin, gemifloxacin, ziprasidone, tricyclic antidepressants, phenothiazines, pimozide)increased risk of cardiotoxicity (QTc prolongation, torsades de pointes, cardiac arrest) due to potential for additive QT interval prolongationmonitor for interaction; alternative drug therapy may be preferredcontraindicated
granisetron, ondansetronapomorphinepotential for profound hypotension and loss of consciousness due to additive hypotensive effectsavoid concurrent usemoderate - major
granisetron, ondansetronQTc interval-prolonging medications (e.g., cisapride, dronedarone, azole antifungals, pimozide, quinidine, thioridazine)increased risk of cardiotoxicity (QTc prolongation, torsades de pointes, cardiac arrest) due to potential for additive QT interval prolongationconcurrent use is contraindicatedcontraindicated
granisetron, ondansetron, palonosetronserotonergic agentspotential for serotonin syndrome with combined therapy due to additive serotonergic effectsmonitor for signs/ symptoms of serotonin syndrome (e.g., hyperthermia, hypertension, rigidity) and discontinue combined therapy, if symptoms presentmoderate - major

Legend:

  • † Class Ia anti-arrhythmic agents include quinidine, disopyramide, procainamide
  • †† Class III anti-arrhythmic agents include amiodarone, sotalol, dofetilide 
  • * CP = Clinical Pharmacology