EU update to paediatric information:-
Section 4.2 Posology and method of administration
· Paediatric population
The safety and efficacy of clopidogrel in children and adolescents under 18 years old have not yet been established.
Clopidogrel should not be used in children because of efficacy concerns (see section 5.1).
Section 5.1 Pharmacodynamic properties
Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with Plavix in one or more subsets of the paediatric population for the prevention of thromboembolic events (see section 4.2 for information on paediatric use).
In a dose escalation study of 86 neonates or infants up to 24 months of age at risk for thrombosis (PICOLO), clopidogrel was evaluated at consecutive doses of 0.01, 0.1 and 0.2 mg/kg in neonates and infants and 0.15 mg/kg only in neonates. The dose of 0.2 mg/kg achieved the mean percent inhibition of 49.3% (5 µM ADP‑induced platelet aggregation) which was comparable to that of adults taking Plavix 75 mg/day.
In a randomised, double‑blind, parallel‑group study (CLARINET), 906 paediatric patients (neonates and infants) with cyanotic congenital heart disease palliated with a systemic‑to‑pulmonary arterial shunt were randomised to receive clopidogrel 0.2 mg/kg (n=467) or placebo (n=439) along with concomitant background therapy up to the time of second stage surgery. The mean time between shunt palliation and first administration of study medicinal product was 20 days. Approximately 88% of patients received concomitant ASA (range of 1 to 23 mg/kg/day). There was no significant difference between groups in the primary composite endpoint of death, shunt thrombosis or cardiac‑related intervention prior to 120 days of age following an event considered of thrombotic nature (89 [19.1%] for the clopidogrel group and 90 [20.5%] for the placebo group) (see section 4.2). Bleeding was the most frequently reported adverse reaction in both clopidogrel and placebo groups; however, there was no significant difference in the bleeding rate between groups. In the long‑term safety follow‑up of this study, 26 patients with the shunt still in place at one year of age received clopidogrel up to 18 months of age. No new safety concerns were noted during this long‑term follow‑up.
The CLARINET and the PICOLO trials were conducted using a constituted solution of clopidogrel. In a relative bioavailability study in adults, the constituted solution of clopidogrel showed a similar extent and slightly higher rate of absorption of the main circulating (inactive) metabolite compared to the authorised tablet.
|
