HPE Managing CINV pocket guide 2019 | Page 63

was thought to be one of the most effective single agents for prevention of emesis in CINV. Although it was part of former international guidelines, its use is no longer recommended for prevention of acute CINV. Its use is related to the risk of irreversible tardive dyskinesia with higher doses and long-term use and a special alert due to its association with extrapyramidal symptoms in children. 56 Domperidone is a selective peripheral dopamine (D 2 ) antagonist, less likely to cross the blood–brain barrier than other agents, and thus is less prone to, but not free from, extrapyramidal reactions. Administration of these drugs to children and young adolescents as first-line treatment is not recommended. 1,3 Its use is no longer mentioned in current guidelines. 6–9 Alizapride has shown to be inferior to metoclopramide when given as monotherapy, or in combination with a corticosteroid or benzodiazepine but might be effective in managing breakthrough CINV in patients already treated with a 5-HT 3 RA and a corticosteroid. The most common adverse effect is drowsiness and extrapyramidal symptoms. 1,3,57 Phenothiazines act predominantly by antagonising dopaminergic receptors (D 2 ) involved in emesis. All phenothiazines (chlorpromazine, perphenazine) have antiemetic properties, although the relative efficacy of these agents remains unclear. Main adverse effects are extrapyramidal reactions such as dystonia and, with prolonged use, tardive dyskinesia. 3 Butyrophenones (haloperidol, droperidol) are major tranquilisers that have an antiemetic effect when used alone. In general, doses used to obtain emesis control are lower than thoseused as for antipsychotic effects. 7 Side- effects and antiemetic efficacies appear to be similar to those of phenothiazines. Intravenous administration of haloperidol and droperidol has a dose-dependent risk of QT-prolongation and torsades de pointes. Other side effects include hypotension and acute dystonia. 3,7 Olanzapine, an atypical antipsychotic agent indicated for treatment of schizophrenia and bipolar disorder, has been effective in preventing both acute and delayed CINV (olanzapine is used off-label as an anti-emetic). Olanzapine shows activity at multiple receptors, particularly dopamine, 5-HT receptors, and histamine receptors, involved in nausea and emesis, suggesting that it may have significant antiemetic properties.1 ,3,58–64 A dose of 5mg olanzapine per os has been determined as the recommended dose and an acceptable safety profile. 63,64 hospitalpharmacyeurope.com | 2019 | 63