1. Name Of The Medicinal Product
Clonidine 25 microgram Tablets BP
2. Qualitative And Quantitative Composition
Each tablet contains clonidine, as 25 micrograms of clonidine hydrochloride.
For a full list of excipients, see section 6.1
3. Pharmaceutical Form
Tablet
A white biconvex uncoated tablet.
4. Clinical Particulars
4.1 Therapeutic Indications
a) Prophylactic management of migraine and recurrent vascular headache
b) Treatment of menopausal flushing
4.2 Posology And Method Of Administration
Adults: 2 tablets twice per day. If necessary after 2 weeks the dose can be increased to 3 tablets twice a day.
Long term prophylactic treatment is undesirable, continuing therapy should be reviewed at 6 monthly intervals.
Children: Not recommended for children under 12 years
Elderly: No specific information available, however in clinical trials no characteristic adverse reactions have been reported in patients over 65 years.
Route of Administration
Oral
4.3 Contraindications
Clonidine 25 microgram Tablets are contraindicated in the following circumstances
- Patients with severe bradyarrhythmia as a result of sick sinus syndrome or 2nd or 3rd degree AV block.
- Patients with known hypersensitivity to clonidine or any other ingredients in the product.
4.4 Special Warnings And Precautions For Use
Caution is advised in those patients with cerebrovascular disease, heart failure, coronary insufficiency, occlusive peripheral vascular disorders e.g. Raynaud's phenomenon, constipation, porphyria or those with a history of depression.
Clonidine can be used as a treatment for hypertension at doses higher than those recommended. Therefore caution should be taken when a patient is being treated with other antihypertensives as the hypotensive effect maybe potentiated. Hypotension should not occur in those patients being treated with the dosage described in Section 4.2.
Following high doses of clonidine in patients with cardiac conduction abnormalities, arrhythmias have been observed. Dose dependent bradycardia may be observed at higher doses of clonidine.
Administer with extreme caution to patients with severe renal impairment or renal failure. Clonidine plasma concentrations increase by 2-3 times in those with extreme renal impairment. Treatment should begin on a low dose and increase gradually to obtain the therapeutic effect.
As this product contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
If clonidine is discontinued abruptly there may be rebound severe hypertension. Symptoms of this withdrawal syndrome may appear 18-72 hours after the last dose of clonidine, and may include agitation, sweating, tachycardia, headache and nausea. Therefore clonidine treatment should be reduced gradually over a number of days or weeks to avoid hypertensive crisis.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
An increase in the hypotensive effect may be seen when antihypertensives, ACE inhibitors, adrenergic neurone blockers, alcohol, aldesleukin, alpha-blockers, alprostadil, general anaesthetics, angiotensin-II receptor antagonists, tricyclic antidepressants, anxiolytics and hypnotics, baclofen, calcium channel blockers, diazoxide, hydralazine, levodopa, MAOIs, methyldopa, minoxidil, moxisylyte, moxonidine, nitrates, nitroprusside, phenothiazines, tizanidine, vasodilators or diuretics are used concomitantly with clonidine.
Possible risk of hypertension when clonidine is given concomitantly with adrenaline or noradrenaline; and serious adverse events reported with concomitant use of clonidine and methylphenidate (causality not established).
α2 Receptor blockers e.g. phentolamine, tolazoline and phenoxybenzamine may prevent the α adrenoceptor mediated effect of clonidine. This antagonism is dose related.
Beta-blockers and/or cardiac glycosides can cause bradycardia or dysrhythmia (AV block) in some rare cases when used concurrently with clonidine.
Concurrent use of betablockers with clonidine can lead to or potentiate peripheral vascular disorders.
Concurrent betablockers may exacerbate rebound hypertension if clonidine is withdrawn. Therefore, when treatment needs to be discontinued the betablockers should be gradually reduced first. Clonidine should then be discontinued gradually several days after betablocker withdrawal. Clonidine should always be gradually reduced over several days to prevent withdrawal syndrome (see Section 4.4 Special Warnings and Special Precautions for Use).
Drugs with α receptor blocking properties such as neuroleptics (e.g. haloperidol and chlorpromazine) and tricyclic antidepressants may provoke orthostatic hypotension.
CNS depressants such as tranquillisers, hypnotics and alcohol may be potentiated by clonidine, causing excessive drowsiness in patients.
When tricyclic antidepressants and clonidine are used concomitantly, the dose of clonidine may need to be adjusted. There is an increased risk of rebound hypertension if clonidine is withdrawn whilst taking tricyclics.
4.6 Pregnancy And Lactation
Clonidine has been widely used for many years and there is no evidence of unwanted effects during pregnancy. However unless the benefit outweighs the potential risk, clonidine should not be used in pregnancy, especially during the first trimester.
If clonidine is used during pregnancy, both mother and foetus should be carefully monitored. Clonidine does pass through the placental barrier and can lower the heart rate of the foetus. There may be a reversible increase in the blood pressure of the newborn child.
Animal studies that have involved doses higher than the equivalent therapeutic doses in man only affected the development of the foetus in one of the species. There were no foetal malformations.
There are no satisfactory data on the long term effects of prenatal exposure.
Due to the lack of supporting data regarding lactation, clonidine should not be used by breast feeding mothers.
4.7 Effects On Ability To Drive And Use Machines
Clonidine may cause drowsiness, if affected the patient should be warned that their ability to drive or operate machinery may be impaired. Sedation and drowsiness are particularly likely during the initial phase of treatment.
4.8 Undesirable Effects
In the initial stages of treatment drowsiness and dry mouth have been reported, but disappear during long term treatment. Dizziness, nausea, insomnia, bradycardia and nocturnal unrest have also been reported. There have been reports of orthostatic hypotension, but these are usually as a consequence of a high first dose administration.
Constipation, impotence and peripheral blood flow disturbances (such as Raynaud's phenomenon) have been reported in rare cases.
Other side effects include headache, fatigue, vomiting, malaise, decreased libido, hallucinations, confusion, disturbances of accommodation, euphoria, fluid retention and paraesthesia of the extremities.
Very rarely at high doses of clonidine hypersensitivity reactions have been observed eg skin rash, urticaria and pruritus. Alopecia, nightmares, perceptual disorders, gynaecomastia, parotid pain, depression, anxiety, drying nasal mucosa and reduced lachrymal flow (caution contact lens wearers) have also been reported very rarely.
Very rarely bowel pseudo-obstruction has been reported.
Bradycardia or AV block may be aggravated by clonidine.
There have been reports of brief increases in blood sugar levels, however these are rare and often as a result of large doses on clonidine.
4.9 Overdose
Symptoms include transient hypertension or extreme hypotension, bradycardia, sedation, miosis, respiratory depression, convulsions, coma, orthostatic hypotension, hypothermia, dry mouth, apnoea and occasional vomiting.
Where appropriate, gastric lavage and/or activated charcoal should be administered. General supportive measure should be available and appropriate symptomatic measures should be taken. Hypotension can be treated via fluid replacement, bradycardia by administering vasopressors or atropine and hypertension by α adrenoceptor blockade or vasodilators.
Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
ATC Code: N02C X02
Clonidine is an adrenoceptors agonist that acts by stimulating both peripheral and central α2 adrenoceptors. As a result of long term treatment, the peripheral vessels response to constrictor and dilator stimuli is reduced. This prevents the vascular changes that are associated with migraine. The action also helps to control the vascular changes associated with menopausal flushing. Clonidine also reduces sympathetic tone that leads to a fall in diastolic and systolic blood pressure and a decrease in heart rate.
5.2 Pharmacokinetic Properties
Clonidine is well absorbed from the gastrointestinal tract following oral administration. Peak plasma concentrations can be seen 3-5 hours after administration. The half life is about 23 hours for those with normal renal function and about 40 hours for those with severe renal impairment.
Clonidine is widely distributed throughout the body, with about 20-40% bound to circulating plasma proteins. About 50% of the drug is metabolised by the liver and about 40-60% of unchanged drug and metabolites is excreted within 24 hours. The majority of the unchanged drug and metabolites are eliminated by in the urine, with about 20% via faeces.
5.3 Preclinical Safety Data
There is no additional data of relevance.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Microcrystalline Cellulose
Maize Starch
Lactose
Pregelatinised Maize Starch
Sodium starch glycollate
Magnesium stearate
Talc
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
24 months
6.4 Special Precautions For Storage
Do not store above 30°C.
6.5 Nature And Contents Of Container
White opaque PVC/PVDC/Aluminium foil blister strips containing 28 tablets per strip. Four strips are packed in an outer carton. Pack size: 112.
6.6 Special Precautions For Disposal And Other Handling
No special requirements.
7. Marketing Authorisation Holder
Sandoz Ltd
Woolmer Way
Bordon
Hampshire
GU35 9QE
8. Marketing Authorisation Number(S)
PL 04416/0380
9. Date Of First Authorisation/Renewal Of The Authorisation
25th September 2002
10. Date Of Revision Of The Text
30th December 2009
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