Ondansetron × Venlafaxine

Venlafaxine blocks the reuptake of serotonin and noradrenaline, and ondansetron blocks serotonin type 3 (5-HT3) receptors. Serotonin syndrome has occurred when ondansetron was given with serotonin and noradrenaline reuptake inhibitors, the antidepressant group that includes venlafaxine (ondansetron SmPC). Ondansetron also prolongs the QT interval in a dose-dependent way. Post-marketing reports with venlafaxine describe QT prolongation and ventricular arrhythmias, mostly in overdose or with other risk factors, so the cardiac effects of the two drugs add up (both SmPCs). Levels of both drugs barely change, because ondansetron does not induce or inhibit the metabolism of other drugs and several liver enzymes clear it (ondansetron SmPC).

Most reports of serotonin syndrome with ondansetron come from post-anaesthesia care units and infusion centres (US Food and Drug Administration, FDA, ondansetron label). Signs include agitation, confusion, hallucinations, sweating, fever, fast heart rate, swings in blood pressure, tremor, muscle twitching and stiffness, overactive reflexes, nausea, vomiting and diarrhoea. QT prolongation itself causes no symptoms and shows only on an electrocardiogram. If torsade de pointes develops, it causes palpitations, dizziness or fainting.

Avoid combining venlafaxine with drugs that prolong the QT interval (venlafaxine SmPC). Ondansetron prolongs QT in a dose-dependent way (ondansetron SmPC). If the patient still needs ondansetron, correct low potassium and magnesium before dosing and do not give a single intravenous dose above 16 mg (ondansetron SmPC). Monitor the electrocardiogram in patients taking other QT-prolonging drugs or with electrolyte abnormalities, heart failure or bradyarrhythmias (ondansetron label, US Food and Drug Administration, FDA). Warn the patient about serotonin syndrome and watch closely for it, especially at the start of the combination and after a venlafaxine dose increase (venlafaxine and ondansetron labels). If symptoms appear, stop ondansetron and start supportive treatment (ondansetron FDA label).