HPE CINV Pocket Guide 2018 | Page 67

are a class effect of the first- generation 5-HT3 RAs, although they have not been reported with transdermal or extended- release subcutaneous granisetron. Moreover, QTc prolongation has not been observed with palonosetron. The most serious consequence of QTc prolongation is the occurence of life-threatening ventricular arrhythmias, including torsades de pointes. Numerous other drugs have the ability to prolong the QTc interval such as: anti-arrhythmics (amiodarone, dronedarone, sotalol, dofetilide), antidepressants (citalopram, escitalopram), gastroprokinetics (domperidone, metoclopramide), antipsyhcotics (thioridazine, haloperidol, chlorpromazine), antibiotics (clarithromycin, azithromycin, ciprofloxacin), methadone, lithium, tacrolimus and others. The concomitant use of first-generation 5-HT3 RAs and QTc-prolonging drugs should be avoided if possible. 12,13 Serotonin syndrome, characterised by altered mental status, autonomic instability and neuromuscular abnormalities, has been observed following concurrent administration of 5-HT3 RAs with selective serotonin reuptake inhibitor antidepressants (fluoxetine, citalopram, escitalopram, Effect and suggested action Decreased exposure to antiemetics and consequently decreased efficacy. The oral clearance of ondansetron might increase, leading to reduced efficacy. In patients treated with potent inducers of CYP3A4 (that is, phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron was increased and ondansetron blood concentrations were decreased. Other 5-HT3 RAs may be an alternative. Concomitant administration of NK1 RAs or corticosteroids with strong CYP3A4 inducers should be avoided as the combination may result in their decreased efficacy. Concomitant administration with strong CYP3A4 inhibitors may increase exposure to NK1 RA (except rolapitant) and corticosteroids and consequently the risk of AEs. Caution is warranted hospitalpharmacyeurope.com | 2018 | 67