Consumer medicine information

APO-Clonidine

Clonidine hydrochloride

BRAND INFORMATION

Brand name

APO-Clonidine

Active ingredient

Clonidine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using APO-Clonidine.

What is in this leaflet

This leaflet answers some common questions about APO-CLONIDINE

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking APO-CLONIDINE against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

This leaflet was last updated on the date at the end of this leaflet. More recent information may be available. The latest Consumer Medicine Information is available from your pharmacist, doctor, or from www.medicines.org.au and may contain important information about the medicine and its use of which you should be aware.

Keep this leaflet with your medicine. You may need to read it again.

What APO-CLONIDINE is used for

APO-CLONIDINE lowers high blood pressure, also called hypertension.

Everyone has blood pressure. This pressure helps your blood move around your body. Your blood pressure may be different at different times of the day. You have hypertension when your blood pressure stays higher than normal, even when you are calm or relaxed.

There are usually no signs of hypertension. The only way of knowing that you have hypertension is to have your blood pressure checked on a regular basis. You may feel fine and have no symptoms, but if high blood pressure is not treated, it can lead to serious health problems (such as heart disease).

APO-CLONIDINE works by relaxing and widening blood vessels and so helps to lower your blood pressure.

APO-CLONIDINE is also used to prevent migraine headache and to relieve symptoms of menopausal flushing.

Ask your doctor if you have any questions about why APO-CLONIDINE has been prescribed for you. Your doctor may have prescribed APO-CLONIDINE for another reason.

Before you are given APO-CLONIDINE

When you must not be given it

Do not take APO-CLONIDINE if you have an allergy to:

  • any medicine containing clonidine
  • any of the other ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take APO-CLONIDINE if you have the rare hereditary condition of galactose intolerance.

Do not take APO-CLONIDINE if you have certain heart problems, such as irregular/slow heart beat.

Do not take APO-CLONIDINE if you are pregnant. It may affect your developing baby if you take it during pregnancy.

Do not breast-feed if you are taking this medicine. The active ingredient in APO-CLONIDINE passes into breast milk and there is a possibility that your baby may be affected.

This medicine should not be given to a child under the age of 18 years. Serious side effects have been observed when clonidine, the active ingredient in APO-CLONIDINE, is used with methylphenidate in children with ADHD. Therefore, APO-CLONIDINE in this combination is not recommended.

Do not take APO-CLONIDINE after the expiry date printed on the carton or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • heart failure or any heart or circulation problem
  • stroke, or transient ischaemic attack (TIA)
  • mental depression
  • sugar diabetes
  • nerve damage, which may lead to weakness in the arms and legs
  • constipation
  • phaeochromocytoma (a rare tumour of the adrenal gland)
  • any problems with your kidneys.

If you are uncertain as to whether you have, or have had, any of these conditions you should raise those concerns with your doctor.

If you have not told your doctor about any of the above, tell him/her before you start taking APO-CLONIDINE.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and APO-CLONIDINE may interfere with each other. These include:

  • other medicines for high blood pressure
  • medicines for heart problems
  • alcohol
  • medicines used to control mood swings and some types of depression
  • medicines used to relieve pain, swelling or other symptoms of inflammation.

These medicines may be affected by APO-CLONIDINE, or may affect how well it works. You may need different amounts of your medicine, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while being given this medicine.

How APO-CLONIDINE is given

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor or pharmacist for help.

How much to take

Your doctor will tell you how much of your medicine you need to take every day. This depends on your condition and whether you are taking other medicines.

The usual starting dose for high blood pressure is 50 micrograms (half a tablet), two or three times a day. Your doctor may increase the daily dosage by half-tablet increments, depending on how your blood pressure responds. For migraine and menopausal flushing the usual starting dose is 25 micrograms two times a day. Your doctor may increase this to 50 micrograms two times a day. If necessary, your doctor may increase this to a total daily dose of 150 micrograms.

How to take it

Swallow the tablets with a full glass of water.

When to take it

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it

Continue taking APO-CLONIDINE for as long as your doctor tells you.

APO-CLONIDINE helps to control your condition, but does not cure it. It is important to keep taking your medicine even if you feel well.

If your doctor tells you to stop taking APO-CLONIDINE, you should reduce the dose of medicine gradually over a period of a week or more. This is to avoid a sudden increase in your blood pressure.

Ask your doctor or pharmacist if you have any concerns.

If you forget to take it

It is important to take APO-CLONIDINE as directed.

If you miss a dose, take it as soon as you remember. However, if you remember when it is almost time for your next dose, take only your usual dose at that time.

Do not take a double dose to make up for the dose that you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone 13 11 26) for advice, or go to Emergency at your nearest hospital, if you have taken more than the recommended or prescribed dose of APO-CLONIDINE. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Signs of overdose may include slow heart beat, drowsiness, temporarily stopping breathing and coma. Other signs include dizziness, weakness, lethargy, feeling cold, vomiting, looking pale, or having an irregular heart beat.

While you are being given APO-CLONIDINE

Things you must do

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking APO-CLONIDINE.

Tell any other doctors, dentists and pharmacists who treat you that you are taking APO-CLONIDINE.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking APO-CLONIDINE. It may affect other medicines used during surgery.

If you become pregnant while taking APO-CLONIDINE, tell your doctor immediately.

Have your blood pressure checked as instructed by your doctor, to make sure APO-CLONIDINE is working.

Tell your doctor if, for any reason, you have not taken APO-CLONIDINE exactly as prescribed. Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Things you must not do

Do not take APO-CLONIDINE to treat any other complaints unless your doctor tells you to.

Do not give APO-CLONIDINE to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how APO-CLONIDINE affects you. APO-CLONIDINE, like other medicines used to treat high blood pressure, may cause dizziness or drowsiness in some people. Make sure you know how you react to APO-CLONIDINE before you drive or operate machinery.

If you feel light-headed, dizzy or faint, get up slowly when getting out of bed or standing up. You may feel light-headed or dizzy when you begin to take APO-CLONIDINE or if the dose is increased.

This is because your blood pressure is falling suddenly. Standing up slowly will help your body get used to the change in position and blood pressure. The problem usually goes away after the first few days.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking APO-CLONIDINE.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following list of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

The more frequently reported side effects of APO-CLONIDINE are lightheadedness when you stand up suddenly, drowsiness, dryness of the mouth, nausea and vomiting.

Less frequently reported side effects of APO-CLONIDINE include the following:

  • blurred vision
  • dizziness
  • confusion
  • headache
  • sleep disturbances
  • mental depression
  • irrational or abnormal thoughts
  • irritability
  • decreased sexual drive / impotence
  • generally feeling unwell
  • thinning of hair
  • rash / hives / itching
  • constipation
  • dryness of the nose and eyes
  • pain in the salivary glands
  • tingling or numbness of the hands or feet
  • larger breasts than normal, in men
  • slow or irregular heart beat
  • blood glucose increased.

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

Tell your doctor or pharmacist as soon as possible if you experience any side effects during or after taking APO-CLONIDINE, so that these may be properly treated.

Other side effects not listed above may also occur in some people.

Tell your doctor or pharmacist if you notice anything unusual, during or after taking APO-CLONIDINE.

After being given APO-CLONIDINE

Storage

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store APO-CLONIDINE or any other medicine in the bathroom or near a sink. Do not leave it in the car or on the window sill. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

APO-CLONIDINE is the brand name of your medicine.

APO-CLONIDINE tablets are scored, pink tablets, marked with YS 01 on one side and a score line on the reverse side.

APO-CLONIDINE tablets are available in bottles of 100 tablets.

Ingredients

Each APO-CLONIDINE tablet contains 100 micrograms clonidine hydrochloride.

The other ingredients are: Allura Red AC, hydroxypropylcellulose, microcrystalline cellulose, magnesium stearate, maize starch, lactose, calcium hydrogen phosphate, colloidal anhydrous silica

Supplier

Southern Cross Pharma Pty Ltd
Suite 2 Level 2 19-23 Prospect
Street VIC 3128

Distributor

Arrotex Pharmaceuticals Pty Ltd
15-17 Chapel Street
Cremorne VIC 3121
www.arrotex.com.au

Australian registration numbers:

AUST R 265776

Date of preparation: October 2023.

Published by MIMS November 2023

BRAND INFORMATION

Brand name

APO-Clonidine

Active ingredient

Clonidine hydrochloride

Schedule

S4

 

Notes

Distributed by Arrotex Pharmaceuticals Pty Ltd

1 Name of Medicine

Clonidine hydrochloride.

2 Qualitative and Quantitative Composition

APO-Clonidine tablets contains the active ingredient clonidine hydrochloride.
Each APO-Clonidine tablet contains 100 micrograms of clonidine hydrochloride.
Clonidine hydrochloride is a white or almost white, crystalline powder. It is soluble in ethanol, slightly soluble in chloroform and practically insoluble in ether. One gram is soluble in 13 mL of water (20°C).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

APO-Clonidine tablets are scored, pink, compressed tablets, impressed with the symbol YS 01 on one side and the score line on the reverse side. Each tablet contains 100 micrograms of clonidine hydrochloride.

4 Clinical Particulars

4.1 Therapeutic Indications

Oral.

All grades of essential hypertension.
Renal hypertension.
The prophylactic management of migraine or recurrent vascular headaches which occur in adult patients with a frequency of more than once a month and are not adequately relieved by appropriate therapy for the acute attack. Alleviation of symptoms due to localised vasodilatation in menopausal flushing.

4.2 Dose and Method of Administration

The dosage recommendations are as follows:

Antihypertensive.

Initially 50-100 micrograms two to three times daily adjusted in small increments according to the patient's individual blood pressure response. If adequate control is not achieved with a daily dose of 600 micrograms of clonidine hydrochloride alone, additional therapy should be considered. Since the hypotensive effect of clonidine hydrochloride is dose dependent, it is usual to titrate the dose to satisfy the requirements for each patient. In impaired renal and hepatic function the half-life is prolonged and the dosage regime should be monitored carefully.

Migraine prophylaxis.

Initially 25 micrograms morning and evening. If necessary, after two weeks, this may be increased to 50 micrograms twice daily, then to a total daily dose of 150 micrograms. If the frequency of attacks is significantly reduced, consideration may be given to gradually ceasing therapy as remission may be sustained in a proportion of patients. Duration of treatment will depend upon the frequency and severity of attacks.

Menopausal flushing.

Initially 25 micrograms morning and evening. If after two weeks there has been no remission, increase to 50 micrograms twice daily. If necessary this may be increased to a total daily dose of 150 micrograms. Duration of treatment will depend upon the frequency and severity of attacks but long-term efficacy (longer than 8 weeks) in the treatment of menopausal flushing has not been established.

Renal insufficiency.

Dosage must be adjusted according to the individual antihypertensive response which can show high variability in patients with renal insufficiency; according to the degree of renal impairment.
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.

4.3 Contraindications

Clonidine hydrochloride should not be used in patients with known hypersensitivity to the active ingredient, clonidine hydrochloride, and in patients with severe bradyarrhythmia resulting from either sick sinus syndrome or AV block of second or third degree.
In case of rare hereditary conditions that may be incompatible with an excipient of the product (see Section 4.4 Special Warnings and Precautions for Use) the use of the product is contraindicated.

4.4 Special Warnings and Precautions for Use

Identified precautions.

Special care should be exercised in treating patients who have a history of depression or who have advanced cerebrovascular disease. Reduction of blood pressure in the latter circumstances may itself cause mental changes. Concurrent administration of tricyclic antidepressants may require adjustment of clonidine hydrochloride dosage.
Although a transient rise in blood sugar has been noted occasionally in humans treated with clonidine hydrochloride, which may be due to a pharmacologic alpha-adrenomimetic effect of the drug, no case of induced diabetes mellitus due to clonidine hydrochloride has been reported. Patients with clinical diabetes mellitus should be watched for a possible increase in their requirements of anti-diabetic therapy.
Clonidine hydrochloride should be used with caution in patients with mild to moderate bradyarrhythmia such as low sinus rhythm, with disorders of cerebral or peripheral perfusion, polyneuropathy, and constipation.
No therapeutic effect of clonidine hydrochloride can be expected in the treatment of hypertension caused by phaeochromocytoma.
As with other anti-hypertensives, treatment with clonidine hydrochloride should be monitored particularly carefully in patients with heart failure or severe coronary heart disease.
Termination of oral therapy should be gradual (e.g. over more than 7 days).
Sudden cessation of antihypertensive therapy is known to be associated in some instances with rebound hypertension which in some cases may be severe. This may occur with clonidine hydrochloride particularly in patients receiving more than the maximum recommended dose of 900 micrograms per day.
Following sudden discontinuation of clonidine hydrochloride after prolonged treatment with high doses, restlessness, palpitations, rapid rise in blood pressure, nervousness, tremor, headache or nausea have been reported.
An excessive rise in blood pressure following discontinuation of clonidine hydrochloride therapy can be reversed by intravenous phentolamine (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
If long-term treatment with a β-blocker needs to be interrupted, the β-blocker should be gradually phased out first, then clonidine.
Patients who wear contact lenses should be warned that treatment with clonidine hydrochloride may cause decreased lacrimation.
APO-Clonidine tablets contain 209.8 mg of Lactose per maximum recommended daily dose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia should not take this medicine.

Anaesthesia.

Abrupt withdrawal of clonidine hydrochloride is undesirable. Limited evidence suggests that it is unnecessary to withdraw clonidine hydrochloride before anaesthesia and that maintenance of therapy is preferable to abrupt withdrawal. In the peri-operative period clonidine hydrochloride can, where necessary, be administered parenterally until oral therapy is resumed.
Where therapy with clonidine hydrochloride is to be suspended before operation, withdrawal should be gradual (i.e. over more than 7 days) and monitored by regular observation of blood pressure.

Menopausal flushing.

The efficacy of clonidine in the treatment of menopausal flushing has only been demonstrated in the first year after onset of symptoms.

Use in renal impairment.

Since clonidine hydrochloride and its metabolites are extensively excreted in the urine, careful adjustment of dosage is required in patients with renal insufficiency (see Section 4.2 Dose and Method of Administration).

Use in the elderly.

No data available.

Paediatric use.

The use and the safety of clonidine in children and adolescents has little supporting evidence in randomised controlled trials and therefore cannot be recommended for use in this population.
In particular, when clonidine is used off-label concomitantly with methylphenidate in children with ADHD, serious adverse reactions, including death, have been observed. Therefore, clonidine in this combination is not recommended.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

If the patient is on antihypertensive therapy, care should be taken as even a small dose of clonidine may further lower blood pressure and necessitate adjustment of the antihypertensive regimen.
When clonidine hydrochloride is used as an antihypertensive agent, additional clonidine for the prophylaxis of migraine or the alleviation of symptoms in menopausal flushing should not be prescribed. Clonidine hydrochloride may potentiate the effects of alcohol, sedatives, hypnotics or other centrally active substances.
Although retinal, lens or corneal damage have not been detected with clonidine therapy, follow up procedures, such as ophthalmoscopy, are recommended.
Substances which raise blood pressure or induce a sodium and water retaining effect such as nonsteroidal anti-inflammatory drugs can reduce the therapeutic effect of clonidine.
Substances with α2-adrenergic receptor blocking properties, such as phentolamine, may abolish the α2-adrenergic receptor mediated effects of clonidine in a dose-dependent way.
Concomitant administration of drugs with a negative chronotropic or dromotropic effect such as β-blockers or digitalis glycosides can cause or potentiate bradycardiac rhythm disturbances.
It cannot be ruled out that concomitant administration of a β-blocker will cause or potentiate peripheral vascular disorders.
The antihypertensive effect of clonidine may be reduced or abolished and orthostatic regulation disturbances may be provoked or aggravated by concomitant administration of tricyclic antidepressants or neuroleptics with α-receptor blocking effects.
Based on observations in patients in a state of delirium alcoholicum, 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.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Clinical studies on the effect of clonidine on human fertility have not been conducted.
Clonidine had no effect on fertility in male or female rats when administered orally at doses up to 0.15 mg/kg/day (35% higher than the maximum recommended total daily dose of clonidine in humans, based on body surface area).
(Category B3)
Clonidine hydrochloride has not shown teratogenic potential when tested in rats, but in some circumstances the incidence of embryonic and perinatal deaths was increased with doses comparable to those used clinically for antihypertensive therapy.
There are limited data from the use of clonidine in pregnant women, but the experience with clonidine hydrochloride since marketing does not include any positive evidence of adverse effect on the foetus. Since this experience cannot exclude such an effect, clonidine hydrochloride should be used during pregnancy only when the benefit clearly justifies the possible risk to the foetus.
Clonidine passes the placental barrier, and may lower the heart rate of the foetus. There is no adequate experience regarding the long-term effects of prenatal exposure.
Clonidine hydrochloride may also induce transitory elevation of blood glucose and impairment of glucose tolerance. Children born to mothers treated with clonidine hydrochloride during pregnancy should be specifically examined for changes in glucose metabolism.
During pregnancy the oral forms of clonidine are preferred. Intravenous injection of clonidine should be avoided.
Non-clinical studies in rats do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Effects on fertility).
Post partum a transient rise in blood pressure in the newborn cannot be excluded.
 Clonidine is excreted in human milk. As the effect on the newborn is not known, infants born to mothers being treated with clonidine hydrochloride should not be breast fed.

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. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience the above mentioned side effects they should avoid potentially hazardous tasks such as driving or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

The following adverse events (regardless of causality) and incidences are based on a review of 22 clinical studies comprising 640 patients treated with clonidine hydrochloride.

Endocrine disorders.

≥ 0.01% and < 0.1%: gynaecomastia.

Psychiatric disorders.

≥ 1% and < 10%: depression, sleep disorder.
≥ 0.1% and < 1%: delusional perception, hallucination, nightmare.
Not known: confusional state, libido decreased.

Nervous system disorders.

≥ 10%: dizziness, sedation.
≥ 1% and < 10%: headache.
≥ 0.1% and < 1%: paraesthesia.

Eye disorder.

≥ 0.01% and < 0.1%: lacrimation decreased.
Not known: accommodation disorder.

Cardiac disorders.

≥ 0.1% and < 1%: sinus bradycardia.
≥ 0.01% and < 0.1%: atrioventricular block.
Not known: bradyarrhythmia.

Vascular disorders.

≥ 10%: orthostatic hypotension.
≥ 0.1% and < 1%: Raynaud's phenomenon.

Respiratory, thoracic and mediastinal disorders.

≥ 0.01% and < 0.1%: nasal dryness.

Gastrointestinal disorders.

≥ 10%: dry mouth.
≥ 1% and < 10%: constipation, nausea, salivary gland pain, vomiting.
≥ 0.01% and < 0.1%: colonic pseudo-obstruction.

Skin and subcutaneous tissue disorders.

≥ 0.1% and < 1%: pruritus, rash, urticaria.
≥ 0.01% and < 0.1%: alopecia.

Reproductive system and breast disorders.

≥ 1% and < 10%: erectile dysfunction.

General disorders and administration site conditions.

≥ 1% and < 10%: fatigue.
≥ 0.1% and < 1%: malaise.

Investigations.

≥ 0.01% and < 0.1%: blood glucose increased.
Most adverse effects are mild and tend to diminish with continued therapy.
Occasional reports of abnormal liver function tests and cases of hepatitis have also been reported.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medical 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 at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms.

The most important features of clonidine overdosage are likely to be bradycardia and sedation, respiratory depression including apnoea and somnolence including coma. Blood pressure response may be variable and may vary from severe hypotension (due to central sympathetic inhibition and vagal stimulation) to severe hypertension (due to direct alpha agonist activity). Treatment must therefore be appropriate to the clinical features (i.v. atropine followed by a pressor amine if necessary in patients with hypotension or an alpha blocker such as phentolamine for patients with hypertension). Other features which may be seen include weakness, vomiting, diminished or absent reflexes, skin pallor, hypothermia, cardiac arrhythmias and constricted pupils with poor reaction to light.

Management.

General supportive measures with regular checks of pulse, B.P., ECG, blood sugar and body temperature should be undertaken. The blood pressure should be monitored carefully for 48 hours following the overdosage, as a later hypertensive phase may be associated with declining blood levels of clonidine.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Antihypertensive effect.

Clonidine hydrochloride is predominantly an antihypertensive agent whose mechanism of action appears to be central alpha2 adrenergic stimulation, as demonstrated in animal studies. This results in the inhibition of bulbar sympathetic cardioaccelerator and sympathetic vasoconstrictor centres, thereby causing a decrease in sympathetic outflow from the brain. There is an increase in vagal activity which produces a decrease in heart rate. There is also an increase in baroreceptor activity. Additionally clonidine hydrochloride stimulates peripheral alpha1 adrenergic receptors. This is reflected by a small transient pressor effect (5-10 mmHg systolic blood pressure) following parenteral use. A transient rise in blood sugar may also occur following large doses of clonidine hydrochloride. The peripheral effects of clonidine hydrochloride generally require isolated organ type preparations for their demonstration, as in the intact animal or man, the central action predominates.

Use in migraine prophylaxis and menopausal flushing.

Smaller doses of clonidine hydrochloride may be used for migraine prophylaxis and the alleviation of symptoms in menopausal flushing. The mechanism of action appears to be modification of the response of peripheral blood vessels to vasoconstrictor and vasodilator stimuli including noradrenaline, isoprenaline and angiotensin.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The pharmacokinetics of clonidine is dose-proportional in the range of 75-300 micrograms. Clonidine, the active ingredient of clonidine hydrochloride, is well absorbed from the gastrointestinal tract and undergoes a minor first pass effect.
The pharmacokinetics of clonidine is not influenced by food.

Distribution.

Peak plasma concentrations are reached within 1-3 hours after oral administration. The duration of action varies from 6-12 hours, the duration of action being longer in the milder hypertensives. The plasma protein binding is 30-40%.
Given intravenously, clonidine hydrochloride is effective within five minutes, has a maximum hypotensive action within 20 to 30 minutes, and the effect lasts for several hours. Following intramuscular administration, clonidine hydrochloride is effective within 5 to 10 minutes. The maximum hypotensive effect is reached after 75 minutes and the duration of action is approximately 5 hours.
The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2.0 nanogram/mL in patients with normal renal function. The hypotensive effect is attenuated or decreases with plasma concentrations above 2.0 nanogram/mL.

Metabolism.

The metabolic pathway of clonidine involves cleavage of the imidazolidine ring and the hydroxylation of the phenyl ring. Five metabolites have been identified in man and include para- hydroxy-clonidine and dichlorophenylguanidine.
In a study designed to evaluate the pharmacokinetics of clonidine following administration of clonidine hydrochloride controlled release tablets (formulation not registered in Australia) in 30 patients (13 white patients, 6 black patients and 11 Hispanic patients), the pharmacokinetics was found to be similar between subjects from different racial groups.

Excretion.

The terminal elimination half-life of clonidine has been found to range from 9-26 hours in patients with normal renal function. With impaired renal function it has been reported to increase to 18-48 hours.
Two-thirds of an administered dose is excreted in the urine (about half of which is unchanged Clonidine hydrochloride) and the remainder is excreted in the faeces.

5.3 Preclinical Safety Data

Genotoxicity.

Comprehensive investigations have not been performed to assess the potential genotoxic effects of clonidine. Clonidine showed no activity in the Ames test for mutagenicity or mouse micronucleus test for clastogenicity.

Carcinogenicity.

The carcinogenic potential of clonidine has not been assessed in an adequate range of studies. In rats, dietary administration of clonidine at doses up to 1.2 mg/kg/day (males) or 1.5 mg/kg/day (females) did not cause carcinogenic effects. These doses are 10-14 times the maximum recommended human daily dose of clonidine, based on body surface area.

6 Pharmaceutical Particulars

6.1 List of Excipients

APO-Clonidine tablets contain the excipients Allura Red AC, hyprolose, microcrystalline cellulose, magnesium stearate, maize starch, lactose monohydrate, calcium hydrogen phosphate, colloidal anhydrous silica.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

APO-Clonidine tablets should be stored below 25°C.

6.5 Nature and Contents of Container

APO-Clonidine tablets are available in HDPE bottles fitted with PP child resistant closure containing 100 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: 2,6-dichloro-N-2-imidazolidinylidene-benzenamine hydrochloride.
Molecular formula: C9H9N3Cl2.HCl.
Molecular weight: 266.56.

CAS number.

4205-91-8.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes