Central a-agonists (central alpha-agonists).

Clonidine hydrochloride

Each tablet contains clonidine hydrochloride 25 micrograms.

Coated tablet. Blue, biconvex, sugar-coated tablet

-  The prophylactic management of migraine or recurrent vascular headache.

-  The management of vasomotor conditions commonly associated with the menopause and characterised by flushing.

Initially 2 tablets twice daily. If after two weeks there has been no remission, increase to 3 tablets twice daily.

The duration of treatment depends upon the severity of the condition.

If symptoms continue to occur the patient should be informed that it may take 2 - 4 weeks until Dixarit is fully effective.

There is insufficient evidence for the application of clonidine in children and adolescents younger than 18 years. Therefore the use of clonidine is not recommended in paediatric subjects under 18 years.

No specific information on the use of this product in the elderly is available.

Clinical trials have included patients over 65 years and no adverse reactions specific to this age group have been reported.

Dixarit should not be used in patients with severe bradyarrhythmia resulting from either sick-sinus syndrome or AV block of 2nd or 3rd degree, or in patients with known hypersensitivity to the active ingredient, clonidine, or other components of the product.

In case of rare hereditary conditions that may be incompatible with an excipient of the product the use of the product is contraindicated.

Dixarit should be used with caution in patients with cerebrovascular disease, coronary insufficiency, heart failure, occlusive peripheral vascular disorders, such as Raynaud's disease, polyneuropathy, constipation or those with a history of depression.

At doses higher than those recommended above, clonidine is an effective antihypertensive agent. Caution should therefore be observed where antihypertensive agents are being used, as potentiation of the hypotensive effect may occur. Provided the recommended Dixarit dosage regimen is followed, no difficulty with hypotension should arise during the routine management of patients with either migraine or menopausal flushing.

Depending on the dose given, Dixarit can cause bradycardia. In patients with pre-existing cardiac conduction abnormalities, arrhythmias have been observed after high doses of Dixarit.

Patients with renal failure require extreme care.

Patients should be instructed not to discontinue therapy without consulting their physician. Following sudden discontinuation of Dixarit after prolonged treatment with high doses, agitation, restlessness, palpitations, rapid rise in blood pressure, nervousness, tremor, headache or nausea have been reported. When discontinuing therapy with Dixarit, the physician should reduce the dose gradually over 2-4 days.

Patients who wear contact lenses should be warned that treatment with Dixarit may cause decreased lacrimation.

The use and the safety of clonidine in children and adolescents has little supporting evidence in randomized controlled trials and therefore can not be recommended for use in this population.

Serious adverse events, including sudden death, have been reported in concomitant use with methylphenidate. The safety of using methylphenidate in combination with clonidine has not been systematically evaluated.

This product contains 106.5 mg of lactose per maximum daily dose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This product contains 122.3 mg sucrose per maximum daily dose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Clonidine is available for the management of hypertension as Catapres Tablets (100 micrograms and 300 micrograms) and Ampoules (150 micrograms in 1 ml). Where Catapres is already being used Dixarit therapy is obviously not indicated.

Concurrent administration of antihypertensive agents, vasodilators or diuretics, may lead to an increased hypotensive effect.

Substances with alpha₂-receptor blocking properties, such as mirtazapine, may abolish the alpha₂-receptor mediated effects of clonidine in a dose-dependent manner.

Concomitant use of beta-blockers and/or cardiac glycosides can cause bradycardia or dysrhythmia (AV-block) in isolated cases.

It cannot be ruled out that concomitant administration of a beta-receptor blocker will cause or potentiate peripheral vascular disorders.

If during combined treatment with a beta-blocker there is need to interrupt or discontinue antihypertensive therapy, the beta-blocker must always be discontinued slowly first, (reducing the dose gradually to avoid sympathetic hyperactivity) and then the Dixarit, which should also be reduced gradually over several days if previously given in high doses.

Orthostatic hypotension may be provoked or aggravated by concomitant administration of tricyclic antidepressants or neuroleptics with alpha-receptor blocking properties.

As the effects of clonidine can be antagonised by tricyclic anti-depressants, it may be necessary to adjust the dosage of Dixarit, if these agents are administered concurrently.

Although there is no experience from clinical trials, the effect of tranquillisers, hypnotics or alcohol could theoretically be potentiated by Dixarit.

Boehringer Ingelheim Limited

(POM)

15 February 2012