4.1. Therapeutic indications

a) The prophylactic management of migraine or recurrent vascular headache.

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

4.2. Posology and method of administration

Adults:

Initially 5ml (50 micrograms) twice daily. If after two weeks there has been no remission, increase to 7.5ml (75 micrograms) 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 Clonidine hydrochloride is fully effective.

Elderly:

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.

Paediatric Population:

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.

Patients with renal impairment

Clonidine hydrochloride should be used with caution in patients with renal insufficiency. Careful monitoring of blood pressure is required.

Method of administration

For oral administration.

Take Clonidine Oral Solution with a glass of water.

The correct quantity of Clonidine hydrochloride 50micrograms/5ml Oral Solution should be measured and administered using the dosage syringe provided.

The dosage syringe provided with the pack is for oral administration only.

Instructions for use of the syringe

1. To open the bottle, press the cap down and turn it anti-clockwise (figure 1).

2. Put the syringe adaptor into the bottle neck (figure 2).

3. Take the syringe and put it into the adaptor opening (figure 3).

4. Turn the bottle upside down (figure 4).

5. Fill the syringe with a small amount of solution by pulling the plunger down (figure 4A). Then push the plunger upward in order to remove any possible bubbles (figure 4B). Finally, pull the plunger down to the graduation mark corresponding to the quantity in millilitres (ml) prescribed by your doctor. The top flat edge of the piston should be in line with the graduation mark you are measuring to (Figure 4C).

6. Turn the bottle the right way up (Figure 5A).

7. Remove the syringe from the adaptor (Figure 5B).

8. Put the end of the syringe into your mouth and push the plunger slowly back in to take the medicine (Figure 6).

9. Wash the syringe with water and let it dry before you use it again.

10. Close the bottle with the plastic screw cap - leave the syringe adaptor in the bottle.

4.3. Contraindications

Clonidine hydrochloride should not be used in patients with severe bradyarrhythmia resulting from either sick-sinus syndrome or AV block of 2nd or 3rd degree, or hypersensitivity to the clonidine hydrochloride or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Clonidine hydrochloride 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 Clonidine hydrochloride 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, Clonidine hydrochloride can cause bradycardia. In patients with pre-existing cardiac conduction abnormalities, arrhythmias have been observed after high doses of Clonidine hydrochloride.

Patients with renal failure require extreme care (See Section 4.2).

Patients should be instructed not to discontinue therapy without consulting their physician. Following sudden discontinuation of Clonidine hydrochloride 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 Clonidine hydrochloride, the physician should reduce the dose gradually over 2-4 days.

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

Excipients warnings

This product contains methyl and propyl hydroxybenzoate ((E218, E217), which may cause allergic reactions (possibly delayed).

4.5. Interaction with other medicinal products and other forms of interaction

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 Clonidine hydrochloride, 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 Clonidine hydrochloride, 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 Clonidine hydrochloride.

4.6. Fertility, pregnancy and lactation

Pregnancy

There is limited amount of data from the use of clonidine in pregnant women. As with all medicines, Clonidine hydrochloride should not be used in pregnancy, especially the first trimester, unless 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 Clonidine hydrochloride 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.

4.7. Effects on ability to drive and use machines

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 Clonidine hydrochloride. If patients experience the above-mentioned side effects, they should avoid potentially hazardous tasks such as driving or operating machinery.

4.8. Undesirable effects

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

Common

Uncommon

Rare

Very rare

Not known

> 1/10

> 1/100 to <1/10

>1/1000 to <1/100

>1/10000 to <1/1000

<1/10000

Cannot be estimated from the available data.

System Organ Class

Adverse Reaction

Frequency

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 Disorder

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

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 the Yellow Card Scheme Website at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms:

Manifestations of intoxication are due to generalised sympathetic depression and include pupillary constriction, somnolence including coma, hypotension, orthostatic hypotension, bradycardia, hypothermia, respiratory depression including apnoea, occasionally vomiting, very occasionally hypertension, dryness of the mouth.

Treatment:

There is no specific antidote for clonidine overdose. Administration of activated charcoal should be performed where appropriate.

Supportive care may include atropine sulphate for symptomatic bradycardia, and intravenous fluids and/or inotropic sympathomimetic agents for hypotension. Severe persistent hypertension may require correction with alpha adrenoceptor blocking drugs.

Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression.