Source: Health Products Regulatory Authority (IE) Revision Year: 2015 Publisher: Boehringer Ingelheim Limited, Ellesfield Avenue, Bracknell, Berkshire RG12 8YS, United Kingdom
Clonidine is an antihypertensive agent which acts centrally by stimulating alpha2 -adrenergic receptors and producing a reduction in sympathetic tone, resulting in a fall in diastolic and systolic blood pressure and a reduction in heart rate.
Treatment with Dixarit diminishes the responsiveness of peripheral vessels to constrictor and dilator stimuli, thereby preventing the vascular changes associated with migraine. The same direct action on peripheral vessels moderates the vascular changes associated with menopausal flushing.
The efficacy of clonidine in the treatment of hypertension has been investigated in five clinical studies in paediatric patients. The efficacy data confirms the properties of clonidine in reduction of systolic and diastolic blood pressure. However, due to limited data and methodological insufficiencies, no definitive conclusion can be drawn on the use of clonidine for hypertensive children.
The efficacy of clonidine has also been investigated in a few clinical studies with paediatric patients with ADHD, Tourette syndrome and stuttering. The efficacy of clonidine in these conditions has not been demonstrated.
There were also two small paediatric studies in migraine, neither of which demonstrated efficacy. In the paediatric studies the most frequent adverse events were drowsiness, dry mouth, headache, dizziness and insomnia. These adverse events might have serious impact on daily functioning in paediatric patients.
Overall, the safety and efficacy of clonidine in children and adolescents have not been established (see section 4.2).
The pharmacokinetics of clonidine is dose-proportional in the range of 75-300 micrograms; over this range, dose linearity has not been fully demonstrated. Clonidine, the active ingredient of Dixarit, is highly absorbed and undergoes a minor first pass effect. Peak plasma concentrations are reached within 1-3 h after oral administration. The plasma protein binding is 30-40%. Clonidine is rapidly and extensively distributed into tissues and crosses the blood-brain barrier, as well as the placental barrier. Clonidine is excreted in human milk. However, there is insufficient information on the effect on newborns.
The terminal elimination half-life of clonidine has been found to range from 5 to 25.5 hours. It can be prolonged in patients with severely impaired renal function up to 41 hours. About 70% of the dose administered is excreted with the urine mainly in form of the unchanged parent drug (40-60% of the dose). The main metabolite p-hydroxy-clonidine is pharmacologically inactive. Approximately 20% of the total amount is excreted with the faeces. There is no definitive data about food or race effects on the pharmacokinetics of clonidine.
The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2.0 ng/ml in patients with normal renal function. The hypotensive effect is attenuated or decreases with plasma concentrations above 2.0 ng/ml.
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
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