M. Gallo¹, M.G. Contessa¹, M. Bosisio², M.L. Farina¹

1 Poison Control Centre - Bergamo Ospedali Riuniti Hospital, Bergamo, Italy

2 Pediatric Emergency Dept. - Bergamo Ospedali Riuniti Hospital, Bergamo, Italy

Oxatomide is a first-generation H₁-histamine receptor antagonist chemically related to cinnarizine. The drug is effective in the treatment of histamine-mediated disorders. First-generation antihistamines are highly lipophilic and readily cross the blood-brain barrier, contributing to adverse central nervous system effects, including sedation, drowsiness, and decreased cognitive processing [1]. The incidence of drowsiness with oxatomide appears similar to other antihistamines.
Case report
On 15 august 2010, a 11-year-old male child had been admitted to emergency department of Bergamo hospital with vital signs within reference limits and an oromandibular dystonia (mouth and tongue) and dysartria. Two days before the boy
has developed typical varicella skin lesions treated with oral 2,5% Tinset^® (oxatomide): ninety drops during the first day, and thirty-five drups plus a 30 mg tablet the day before hospital admission. Dystonia and dysartria appeared five hours later last administration The patient was treated with diazepam ten drops and was discharged home in a healthy condition the day after. A retrospective analysis of calls received from January 2009 to February 2011 by the Poison Control Center of Bergamo showed thirty-three clinical cases of oxatomide dosing error in paediatric patients. Out of thirty-three, eleven patients developed neurologic symptoms (sedation, drowsiness, extra-pyramidal signs, seizures).
Discussion
Dyskinesia and extrapyramidal symptoms have been reported as adverse oxatomide effects, in particular, in the children. In fact, during the development because of the immaturity of the blood-brain barrier children may be more susceptible to the central nervous drug effects. Moreover, children are at higher risk of medication errors than adults [2]; errors occur frequently, about 50% of parents make errors when dosing liquid medications. [3]. On february 2009, many severe adverse drug reactions related to medication errors of oxatomide were reported to Italian Pharmacovigilance Network. Thus, in order to reduce these errors and to limit acute toxicity in paediatric patients, the Italian Medicines Agency (AIFA) modified the summary of product characteristics, as well as the package leaflets of Tinset^®, and 30-mg tablets were contraindicated in children <18 years old. Moreover, on march 2010, AIFA stated the market withdrawal for the 0,25% Tinset^® drops, and issued safety alert concerning use of 2,5% Tinset^® drops in paediatric population younger than one year old. Despite these preventive actions oxatomide is again prescribed in unappropriate manner. In the present case report a 3-fold higher than the therapeutic dosage were administered during the first day and a 2-fold higher dosage during the day later. Moreover, a 30-mg Tinset^® tablet was used although controindicated in paediatric population. The oxatomide overdosing can explain the observed acute dystonic reactions and dysartria. Higher incidence of neurological symptoms in pediatric population could be related to the immaturity of the blood-brain barrier and to the immaturity of the hepatic enzyme system in such patients.In conclusion, our report highlights once again the importance of caution in the use of first-generation H₁antihistamines in paediatric population.
References
1. Richards DM, Brogden RN, Heel RC, Speight TM, Avery GS: Oxatomide: a review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1984;27(3):210-31
2. Wong IC, Ghaleb MA, Franklin BD, Barber N: Incidence and nature of dosing errors in paediatric medications: a systematic review. Drug Saf 2004;27(9): 661–70
3. Frush KS, Luo X, Hutchinson P, Higgins JN. Evaluation of a method to reduce over-the-counter medication dosing error. Arch Pediatr Adolesc Med. 2004;158(7):620-4.