Central a-agonists (alpha- agonists, centrally-acting antihypertensives)

clonidine hydrochloride

Each tablet contains 100 micrograms of clonidine hydrochloride.

Tablet White, circular, flat, bevel-edged tablets impressed with the identifying code on one side and the company symbol on the reverse.

Catapres is indicated for the treatment of all grades of essential and secondary hypertension.

Catapres Tablets are for oral administration only.

Adults:

Oral treatment should commence with 50 - 100 micrograms three times daily. This dose should be increased gradually every second or third day until control is achieved. Most patients will be controlled on divided daily doses of 300 - 1200 micrograms. However, some patients may require higher doses, e.g. 1800 micrograms or more.

Catapres may be added to an existing antihypertensive regimen where blood pressure control has not been satisfactorily achieved. If side-effects with existing therapy are troublesome the concomitant use of Catapres may allow a lower dose of the established regimen to be employed. Patients changing treatment should have their existing therapy reduced gradually whilst Catapres is added to their regimen.

Patients undergoing anaesthesia should continue their Catapres treatment before, during and after anaesthesia using oral or i.v. administration according to individual circumstances.

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.

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

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

Caution should be exercised in patients with Raynaud's disease or other peripheral vascular disease. As with all drugs used in hypertension Catapres should be used with caution in patients with cerebrovascular or coronary insufficiency.

Catapres should also be used with caution in patients with mild to moderate bradyarrhythmia such as low sinus rhythm, and with polyneuropathy or constipation.

Patients with a known history of depression should be carefully supervised while under long-term treatment with Catapres as there have been occasional reports of further depressive episodes during oral treatment in such patients.

As with other antihypertensive drugs, treatment with Catapres should be monitored particularly carefully in patients with heart failure.

In hypertension caused by phaeochromocytoma no therapeutic effect of Catapres can be expected.

Clonidine, the active ingredient of Catapres, and its metabolites are extensively excreted in the urine. Dosage must be adjusted to the individual antihypertensive response, which can show high variability in patients with renal insufficiency; careful monitoring is required. Since only a minimal amount of clonidine is removed during routine haemodialysis there is no need to give supplemental clonidine following dialysis.

Sudden withdrawal of Catapres, particularly in those patients receiving high doses, may result in rebound hypertension. Cases of agitation, restlessness, palpitations, nervousness, tremor, headache and abdominal symptoms have also been reported. Patients should be instructed not to discontinue therapy without consulting their physician. When discontinuing therapy the physician should reduce the dose gradually. However, if withdrawal symptoms should nevertheless occur, these can usually be treated with reintroduction of clonidine or with alpha and beta adrenoceptor blocking agents.

If Catapres is being given concurrently with a beta-blocker, Catapres should not be discontinued until several days after the withdrawal of the beta-blocker.

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

This product contains 36.1 mg of lactose per tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The use and the safety of clonidine in children and adolescents has little supporting evidence in randomized controlled trials and therefore cannot 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.

The reduction in blood pressure induced by clonidine can be further potentiated by concurrent administration of other hypotensive agents. This can be of therapeutic use in the case of other antihypertensive agents such as diuretics, vasodilators, beta-receptor blockers, calcium antagonists and ACE-inhibitors, but the effect of alpha₁-blockers is unpredictable.

The antihypertensive effect of clonidine may be reduced or abolished and orthostatic hypotension may be provoked or aggravated by concomitant administration of tricyclic antidepressants or neuroleptics with alpha-receptor blocking properties.

Substances which raise blood pressure or induce a sodium ion (Na⁺) and water retaining effect such as non-steroidal anti-inflammatory agents can reduce the therapeutic effect of clonidine.

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

Concomitant administration of substances with a negative chronotropic or dromotropic effect such as beta-receptor blockers or digitalis glycosides can cause or potentiate bradycardic rhythm disturbances.

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

Based on observations in patients in a state of alcoholic delirium it has been suggested that high intravenous doses of clonidine may increase the arrhythmogenic potential (QT-prolongation, ventricular fibrillation) of high intravenous doses of haloperidol. Causal relationship and relevance for antihypertensive treatment have not been established.

The effects of centrally depressant substances or alcohol can be potentiated by clonidine.

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:

There are occasional reports of fluid retention during initial stages of oral treatment. This is usually transitory and can be corrected by the addition of a diuretic.

Occasional reports of abnormal liver function tests and two cases of hepatitis have also been reported.

Boehringer Ingelheim Limited

(POM)

15 February 2012