(and dosage form):
Every 10 drops (0,50 mL) contain:
Clonidine hydrochloride 25 micrograms
Sodium benzoate 0,2% m/v
A 7.3 Migraine preparations
Clonidine is a centrally acting alpha2-agonist. The central inhibiting effect on noradrenergic neurotransmission generally dominates the peripheral excitatory alpha2-effect. The mode of action of clonidine in the prophylaxis of migraine is still unclear.
The pharmacokinetics of clonidine is dose-proportional in the range of 100-600 micrograms. Clonidine is well absorbed and no first pass effect exists. It is rapidly and extensively distributed into the tissues and crosses the blood-brain barrier as well as the placenta. The mean plasma half-life of clonidine is about 13 hours ranging between 10 and 20 hours. The half-life does not depend on the sex or race of the patient but can be prolonged in patients with severely impaired renal function for up to 41 hours. About 70% of the dose administered is excreted in the urine mainly in the form of the unchanged parent drug (40-60% of the dose). The main metabolite, p-hydroxy-clonidine is pharmacologically inactive. Approximately 20% of the total amount is excreted in the faeces.
MENOGRAINE DROPS is indicated for the prevention of migraine and other recurrent vascular headaches.
MENOGRAINE DROPS should not be used in patients with known hypersensitivity to clonidine, and in patients with severe bradyarrhythmia resulting from either sick sinus syndrome or AV block of the 2nd or 3rd degree.
MENOGRAINE DROPS is not suitable for the treatment of acute migraine attacks or for use in children under 12 years of age.
Safety in pregnancy and lactation has not been established. Clonidine is excreted in breast milk.
Patients receiving monoamine oxidase inhibitor treatment, or within 14 days of termination of treatment.
Patients should not drive or operate dangerous machinery as this medicine may lead to drowsiness, impaired concentration, which may be aggravated by the simultaneous intake of alcohol or other central nervous system depressant agents.
DOSAGE AND DIRECTIONS FOR USE:
Unless otherwise prescribed by a doctor the following dosage is recommended:
Adults (including elderly patients) and children 12 years and older:
Therapy should be started with 10 drops (25 micrograms) in the mouth twice daily (morning and evening). If there is no relief after 2 weeks the dosage can be increased gradually to 30 drops (75 micrograms) twice daily. The duration of the treatment depends on the course of the disease. If symptoms continue to occur the patient should be informed that it may take up to 2-4 weeks before MENOGRAINE DROPS is fully effective.
SIDE EFFECTS AND SPECIAL PRECAUTIONS: SIDE-EFFECTS
Most adverse effects are mild and tend to diminish with continued therapy. More frequent side effects are dryness of mouth, sedation, headache, constipation and reduction of blood pressure. Less frequently nausea and vomiting, anorexia, malaise, decreased libido, gynaecomastia, orthostatic complaints, paresthesia of the extremities, Raynaud's disease, fluid retention, congestive heart failure, urinary retention or incontinence, transient abnormalities of liver function tests, cramp, pain in the parotid gland, drying of the nasal mucosa and reduced lacrymal flow with itching or burning sensations of the eye (caution: contact lens wearers), as well as skin reactions with symptoms such as rash, urticaria, pruritis, and alopecia have been observed.
Sleep disturbances, nightmares, depression, perceptual disorders, hallucinations, confusion and disturbances of accommodation may occur.
Clonidine may occur or potentiate bradyarrhythmic conditions such as sinus bradycardia or AV-block. Infrequently, transient elevations of blood sugar levels have been reported. In very infrequent cases pseudo-obstruction of the large bowel has been observed in predisposed patients.
MENOGRAINE DROPS should be used with caution in patients with mild to moderate bradyarrhythmia such as low sinus rhythm, with disorders of cerebral or peripheral perfusion such as Raynaud's disease, depression, polyneuropathy, constipation also in patients with ischaemic heart disease including myocardial infarction.
Clonidine and its metabolites are extensively excreted in the urine. MENOGRAINE DROPS should be used with caution in patients with renal insufficiency.
Treatment with MENOGRAINE DROPS should be monitored particularly carefully in patients with heart failure or severe coronary heart disease.
Clonidine causes drowsiness, and patients should not drive or operate machinery where loss of concentration may occur.
Patients should be instructed not to discontinue therapy without consulting a doctor. Following sudden discontinuation of MENOGRAINE DROPS 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 MENOGRAINE DROPS, the doctor should reduce the dose gradually over 2-4 days.
If long term treatment with a beta-receptor blocker has to be interrupted, then the beta-receptor blocker should first be gradually phased out and then MENOGRAINE DROPS; also gradually being reduced over several days if previously given in high doses.
In much higher doses than recommended for prophylactic management of migraine, clonidine is an effective anti hypertensive agent. Where clonidine is already being used, MENOGRAINE DROPS should not be administered. Caution should be exercised where MENOGRAINE DROPS is used in patients on anti hypertensive therapy.
The anti hypertensive effect of MENOGRAINE DROPS can be enhanced by other drugs used to lower blood pressure. This has been shown with clonidine in combination with diuretics, vasodilators, beta-receptor blockers, calcium antagonists and ACE-inhibitors. Substances with alpha2-receptor blocking properties such as phentolamine or tolazoline may abolish the alpha2-receptor mediated effects of clonidine in a dose-dependent manner.
Concomitant administration of substances with negative chronotrophic or dromotrophic effect such as beta-receptor blockers or digitalis glycosides can cause or potentiate bradycardiac rhythm disturbances. Concomitant administration of a beta-receptor blocker will not cause or potentiate peripheral vascular disorders.
Orthostatic regulation disturbances may be provoked or aggravated by concomitant administration of tricyclic antidepressants or neuroleptics with alpha-receptor blocking properties. The effects of centrally depressant substances or alcohol can be potentiated by clonidine.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Clonidine has a wide therapeutic range. Symptoms of an overdose are due to generalised sympathetic depression and include miosis, lethargy, bradycardia, hypotension, hypothermia, coma and apnoea. Paradoxic hypertension caused by stimulation of peripheral alpha1- receptors may occur.
Treatment is essentially symptomatic and supportive. If hypertension should occur, an alpha adrenoreceptor blocker, e.g. phentolamine may be used.
A clear colourless, particle free solution with a bitter taste and a faint characteristic odour.
Amber glass bottles with a dropper insert and screw-on cap filled with 5 mL solution.
Store below 25°C. Protect from light.
KEEP OUT OF REACH OF CHILDREN
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
7 March 2002
New addition to this site: January 2008
Source: Pharmaceutical Industry
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