HPE Managing CINV pocket guide 2019 | Page 62

antiemetic dexamethasone administration on days 2 and 3 can be spared when combined with an NK 1 RA and palonosetron in HEC. 54 Glucocorticosteroids alone are insufficient as first-line therapy for patients receiving moderate or highly emetogenic chemotherapy. The increased efficacy and booster effect of 5-HT 3 RAs combined with dexamethasone makes this combination the standard of care for prevention of acute CINV induced by moderately to highly emetogenic chemotherapy in both adults and children 1,3,55 unless contraindicated. However, glucocorticosteroids should be prescribed with caution because there is some evidence that they interfere with the antineoplastic effect of chemotherapy (for example, in osteosarcoma and brain tumours). 3,4 They may also reduce the delivery of chemotherapy to brain tumours by repairing damage in the blood–brain barrier. 4 Glucocorticosteroids should not be added to chemotherapy regimens in which glucocorticosteroids are already included. 7 Patients might experience short-term hyperglycaemia and immunosuppression and adrenal suppression when used for a prolonged period. Use of glucocorticosteroids as antiemetic premedication should be avoided for 3–5 days prior to and 90 days after chimeric antigen 62 | 2019 | hospitalpharmacyeurope.com receptor (CAR)-T therapies. During lymphodepleting chemotherapy regimens, a glucocorticosteroid- sparing approach to antiemetic prophylaxis should be maintained. 7 Their use should also be avoided with immune checkpoint inhibitors when administered without cytotoxic chemotherapy. As there are still inconclusive data for the concurrent use of glucocorticosteroids with immune checkpoint inhibitors combined with emetogenic chemotherapy, a corticosteroid-sparing approach to antiemetic prophylaxis on a case-by-case and regimen basis is recommended. 7 Agents with a low therapeutic index Dopamine RAs, benzodiazepines, cannabinoids and others are classified as agents with a low therapeutic index. They are characterised by a lower efficacy and a greater potential for adverse effects compared with agents having a high therapeutic index. Their use should be restricted to patients intolerant of or refractory to first-line agents and they may have some place as salvage agents for patients with breakthrough emesis. Metoclopramide, is a substituted benzamide dopamine antagonist, causing central and peripheral dopamine D 2 antagonism at low doses. Before the introduction of 5-HT 3 RAs, metoclopramide