DIXARIT Coated tablet Ref.[50231] Active ingredients: Clonidine

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 patients with depression or a history thereof.

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 (see section 4.2 Posology and Method of Administration).

Patients should be instructed not to discontinue therapy without consulting their physician. Following sudden discontinuation of Dixarit after prolonged treatment with high doses, 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 adolescent has little supporting evidence in randomized controlled trials and therefore can not be recommended for use in this population.

jIn particular, when clonidine is used off-label concomitantly with methylphenidate in children with ADHD, serious adverse reactions, including death, have been observed. Therefore, clonidine in this combination is not recommended.

This product contains 101.1 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 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 a 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.

Pregnancy

There are limited amount of data from the use of clonidine in pregnant women. Dixarit should not be used in pregnancy especially the first trimester, unless considered essential by the physician, and the expected benefit is thought to outweigh any possible risk to the foetus.

In animal studies involving doses higher than the equivalent maximum therapeutic dose in man, effects on foetal development were only seen in one species. Foetal malformations did not occur.

Careful monitoring of mother and child is recommended.

Clonidine passes the placental barrier and may lower the heart rate of the foetus. Post partum a transient rise in blood pressure in the newborn cannot be excluded.

There is no adequate experience regarding the long-term effects of prenatal exposure.

Lactation

Clonidine is excreted in human milk. However, there is insufficient information on the effect on newborns. The use of Dixarit is therefore not recommended during breast feeding.

Fertility

No clinical studies on the effect on human fertility have been conducted with clonidine. Non-clinical studies with clonidine indicate no direct or indirect harmful effects with respect to the fertility index.

No studies on the effects on the ability to drive and use machines have been performed.

However, patients should be advised that they may experience undesirable effects such as dizziness, sedation and accommodation disorder during treatment with Dixarit. If patients experience the above mentioned side effects they should avoid potentially hazardous tasks such as driving or operating machinery.

Most adverse effects are mild and tend to diminish with continued therapy.

Adverse events have been ranked under headings of frequency using the following convention: Very common ≥1/10, Common ≥1/100, <1/10, Uncommon ≥1/1000, <1/100, Rare ≥1/10000, <1/1000, Very rare <1/10000, Not known-Cannot be estimated from the available data.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA: Pharmacovigilance Section, Earlsfort Terrace IRL – Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, e-mail: medsafety@hpra.ie

Not applicable.