Antiemetics and gastroenteritis

Vomiting is a common symptom in acute gastroenteritis. It affects about 75% of children with rotavirus infection, interferes with oral rehydration and often determines the necessity for venous access and hospitalization with higher direct and indirect costs for the community and the family.
The use of antiemetic drugs is not encouraged by international guidelines, even though the American Academy of Pediatrics¹ and the ESPGHAN² admit they could allow an easier management of mild to moderate dehydration in acute gastroenteritis. If medical literature is still cautious in promoting the use of antiemetic drugs, practice says that in the Emergency Rooms and Pediatric Departments their use is very common. In the United States and in Europe 2-23% of children with acute gastroenteritis is treated with antiemetics. In fact, 61% of US physicians³ and 79% of pediatricians in Italy⁴ use these drugs. In 30% of the cases, their use is off-label for indications or age.⁵ The principal pharmacological classes in use are: dopamine antagonists (phenothiazines, domperidone, metoclopramide), serotonin or 5-hydroxytryptamine antagonists (granisetron, ondansetron, tropisetron), anticholinergics, antihistamines, benzodiazepines and corticosteroids (desametasone), by oral, intravenous or rectal administration. In Italy, metoclopramide, domperidone and ondansetron are the most used in Pediatrics and we will discuss them shortly.

Metoclopramide

Evidences that intravenous administration of metoclopramide is effective for treating vomiting in acute gastroenteritis are lacking.^6,7 Besides, metoclopramide causes important adverse reactions, both neurological (extrapyramidal symptoms and irreversible tardive dyskinesia) and cardiovascular, that suggest caution when using it in case of QT interval prolongation, electrolytic imbalances and bradycardia. A recent EMA-AIFA note (22/01/2014) forbids its use in children less than 1 year old and allows it for 1-18 years old, exclusively for treating post-surgery nausea and vomiting (intravenously) or in chemotherapy (orally or intravenously). The suggested dose is 0.1-0.15 mg/kg to be repeated maximum three times per day (maximum dose: 0.5 mg/kg/day).

Domperidone

Evidences are scarce also for domperidone that, however, is the most used antiemetic in Italy (also in outpatient Pediatrics), France and Spain.⁴ A recent Japanese study reports that domperidone administering in addition to oral rehydration does not reduce vomiting in the early phases of acute gastroenteritis.⁸ Because of several cases of adverse reactions (mostly neurological) in children exposed to overdose or inappropriate use for their age, AIFA (note 11/09/2007) invited to a cautious use of domperidone in children who manifest vomiting and to a careful evaluation of risks/benefits.
Risks that include ventricular arrhythmias and sudden cardiac death due to QTc prolongation (AIFA note 14/11/2011). In 2013, EMA (EMA/140423/2013) reported that, because of more cardiac adverse events, the Belgian Agency decided to advice against the use of domperidone for patients with QTc prolongation or other underlying cardiac problems.

Ondansetron

Better possibilities seem to appear for ondansetron – indicated for emesis in chemotherapy – that, in recent years, has been object of several repeated studies which showed quite convincingly its effectiveness in acute gastroenteritis.^6,7,9,10 When confronted with placebo, ondansetron reduces vomiting (relative risk 0.45), the use of intravenous rehydration (relative risk 0.41) and the necessity for hospitalization (relative risk 0.52) at the expenses of occasional increase in diarrhoea.¹¹ The recommended oral doses are 2 mg, 4 mg and 8 mg respectively for children who weight 8-15 kg, 16-30 kg and >30 kg, i.e. 0.1-0.15 mg/kg (maximum dose 8 mg).^12,13 It has been estimated that in the United Stated the use of ondansetron could avoid 30,000 venous accesses and 7,000 hospitalizations for a total saving of more than 120 million dollars.¹⁴ Among the possible relevant adverse effects, it has to be reported the risk of QT interval prolongation and torsades de point arrhythmias after intravenous administration of a single 32 mg dose in adults (maximum recommended dose intravenously: 16 mg).¹⁵ In order to further investigate ondansetron effectiveness in acute gastroenteritis (off-label, at the moment), a multicentre randomized controlled study in respect to domperidone has been recently concluded in Italy, whose results are expected by the end of 2014.¹⁶

Conclusion

The antiemetic approach in acute gastroenteritis seems reasonable and potentially convenient both for the child and the healthcare organization. Among the drugs commonly used, ondansetron seems to have the best profile in terms of effectiveness and tolerability and the evidences piling up could set forth an indication in this direction shortly.