CATAPRES Solution for injection Ref.[2674] Active ingredients: Clonidine

Clonidine should only be used with caution in patients with depression or a history thereof, with Raynaud’s disease, or other peripheral vascular occlusive disease.

The product should only be used with caution in patients with cerebrovascular or coronary insufficiency. Catapres should be used with caution in patients with mild to moderate bradyarrhythmia such as low sinus rhythm, and with polyneuropathy or constipation.

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 urine. Dosage must be adjusted to the individual antihypertensive response, which can show high variability in patients with renal insufficiency (see Section 4.2 Posology and Method of Administration); 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.

Patients who wear contact lenses should be warned that treatment with Catapres 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 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.

Catapres Ampoules contain less than 1 mmol sodium (23 mg) per 1 ml ampoule, that is to say essentially ‘sodium-free’.

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 disorder.

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.

Pregnancy

There are limited amount of data from the use of clonidine in pregnant women. This product should only be used in pregnancy if considered essential by the physician. Careful monitoring of mother and child are 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.

Non-clinical studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Lactation

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

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 Catapres. 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.

Endocrine disorders:

Gynaecomastia rare

Psychiatric disorders:

Confusional state not known

Delusional perception uncommon
Depression common
Hallucination uncommon
Libido decreased not known
Nightmare uncommon
Sleep disorder common

Nervous system disorders:

Dizziness very common
Headache common
Paraesthesia uncommon
Sedation very common

Eye disorders:

Accommodation disorder not known
Lacrimation decreased rare

Cardiac disorders:

Atrioventricular block rare
Bradyarrhythmia not known
Sinus bradycardia uncommon

Vascular disorders:

Orthostatic hypotension very common
Raynaud’s phenomenon uncommon

Respiratory, thoracic and mediastinal disorders:

Nasal dryness rare

Gastrointestinal disorders:

Colonic pseudo-obstruction rare
Constipation common
Dry mouth very common
Nausea common
Salivary gland pain common
Vomiting common

Skin and subcutaneous tissue disorders:

Alopecia rare
Pruritus uncommon
Rash uncommon
Urticaria uncommon

Reproductive system and breast disorders:

Erectile dysfunction common

General disorders and administration site conditions:

Fatigue common
Malaise uncommon

Investigations:

Blood glucose increased rare
Fluid retention occurs occasionally. Two cases of hepatitis have also been reported.

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, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

None known.