Consumer medicine information

Clonidine Lupin

Clonidine hydrochloride

BRAND INFORMATION

Brand name

Clonidine Lupin

Active ingredient

Clonidine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Clonidine Lupin.

SUMMARY CMI

Clonidine Lupin

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using Clonidine Lupin?

Clonidine Lupin contains the active ingredient clonidine hydrochloride. Clonidine Lupin is used to lower high blood pressure, also called hypertension. Clonidine Lupin is also used to prevent migraine headache and to relieve symptoms of menopausal flushing.

For more information, see Section 1. Why am I using Clonidine Lupin? in the full CMI.

2. What should I know before I use Clonidine Lupin?

Do not use if you have ever had an allergic reaction to clonidine hydrochloride or any of the ingredients listed at the end o f the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use Clonidine Lupin? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Clonidine Lupin and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Clonidine Lupin?

  • 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.
  • Swallow the tablets with a full glass of water.

More instructions can be found in Section 4. How do I use Clonidine Lupin? in the full CMI.

5. What should I know while using Clonidine Lupin?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using Clonidine Lupin.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are taking Clonidine Lupin.
    It may affect other medicines used during surgery.
  • If you become pregnant while taking Clonidine Lupin, tell your doctor immediately.
Things you should not do
  • Do not stop taking your medicine or lower the dosage without checking with your doctor.
  • Do not take Clonidine Lupin to treat any other complaints unless your doctor tells you to.
Driving or using machines
  • Be careful driving or operating machinery until you know how Clonidine Lupin affects you.
  • Clonidine Lupin like other medicines used to treat high blood pressure, may cause dizziness or drowsiness in some people.
Drinking alcohol
  • Alcohol may affect how well your medicine works. You may need different amounts of your medicine, or you may need to take different medicines.
Looking after your medicine
  • Keep your tablets in the blister strip until it is time to take them.
  • Keep your tablets in a cool dry place where the temperature stays below 30°C.

For more information, see Section 5. What should I know while using Clonidine Lupin? in the full CMI.

6. Are there any side effects?

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Clonidine Lupin.

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

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Clonidine Lupin

Active ingredient: clonidine hydrochloride

Consumer Medicine Information (CMI)

This leaflet provides important information about using Clonidine Lupin. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Clonidine Lupin.

Where to find information in this leaflet:

1. Why am I using Clonidine Lupin?
2. What should I know before I use Clonidine Lupin?
3. What if I am taking other medicines?
4. How do I use Clonidine Lupin?
5. What should I know while using Clonidine Lupin?
6. Are there any side effects?
7. Product details

1. Why am I using Clonidine Lupin?

Clonidine Lupin contains the active ingredient clonidine hydrochloride. Clonidine Lupin lowers high blood pressure, also called hypertension. Clonidine Lupin works by relaxing and widening blood vessels and so helps to lower your blood pressure.

Clonidine Lupin is used to lower high blood pressure, also called hypertension.

Clonidine Lupin is also used to prevent migraine headache and to relieve symptoms of menopausal flushing.

2. What should I know before I use Clonidine Lupin?

Warnings

Do not use Clonidine Lupin if:

  • you are allergic to clonidine hydrochloride, or any of the ingredients listed at the end of this leaflet.
    - Always check the ingredients to make sure you can use this medicine.
  • if you have the rare hereditary condition of galactose intolerance.
  • if you have certain heart problems, such as irregular/slow heartbeat

Check with 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.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Do not take Clonidine Lupin 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 Clonidine Lupin passes into breast milk and there is a possibility that your baby may be affected.

Children and adolescents

Do not give Clonidine Lupin to a child under the age of 18 years.

Serious side effects have been observed when clonidine, the active ingredient in Clonidine Lupin, is used with methylphenidate in children with ADHD. Therefore, Clonidine Lupin in this combination is not recommended.

3. What if I am taking other medicines?

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

Some medicines and Clonidine Lupin 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 interfere with Clonidine Lupin and affect how it works.

You may need different amounts of your medicine, or you may need to take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Clonidine Lupin.

4. How do I use Clonidine Lupin?

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.
  • Swallow the tablets with a full glass of water.
  • Follow the instructions provided and use Clonidine Lupin until your doctor tells you to stop.

When to take Clonidine Lupin

  • Clonidine Lupin should be taken at about the same time each day.
  • Continue taking Clonidine Lupin for as long as your doctor tells you.
  • Clonidine Lupin 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 Clonidine Lupin, 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.

If you forget to use Clonidine Lupin

Clonidine Lupin should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember.

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Do not take a double dose to make up for the dose 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 use too much Clonidine Lupin

If you think that you have used too much Clonidine Lupin you may need urgent medical attention.

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

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using Clonidine Lupin?

Things you should do

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking Clonidine Lupin.

It may affect other medicines used during surgery.

Have your blood pressure checked as instructed by your doctor, to make sure Clonidine Lupin is working.

Tell your doctor if, for any reason, you have not taken Clonidine Lupin exactly as prescribed.

Otherwise, your doctor may think that it was not effective and change your treatment unnecessarily.

Call your doctor straight away if you:

  • If you become pregnant while taking Clonidine Lupin

Remind any doctor, dentist or pharmacist you visit that you are using Clonidine Lupin.

Things you should not do

  • Do not stop taking your medicine or lower the dosage without checking with your doctor.
  • Do not take Clonidine Lupin to treat any other complaints unless your doctor tells you to.
  • Do not give Clonidine Lupin to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Clonidine Lupin affects you.

Clonidine Lupin 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 Clonidine Lupin 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 Clonidine Lupin 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.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may affect how well your medicine works. You may need different amounts of your medicine, or you may need to take different medicines.

Looking after your medicine

  • Keep your tablets in the blister strip until it is time to take them.
    - The blister strip protects the tablets. If you take the tablets out of the blister strip they may not keep well.
  • Keep your tablets in a cool dry place where the temperature stays below 30°C.
  • Heat and dampness can destroy some medicines.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines

Keep it where young children cannot reach it.

When to discard your medicine

Do not take Clonidine Lupin after the expiry date printed on the carton or blister strips or if the packaging is torn or shows signs of tampering.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

More frequently reported side effects

Side effectsWhat to do
  • light-headedness when you stand up suddenly
  • drowsiness
  • dryness of the mouth
  • nausea and vomiting
Speak to your doctor if you have any of these side effects and they worry you.

Less frequently reported side effects

Side effectsWhat to do
  • 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 heartbeat
  • blood glucose increased.
  • occasional reports of abnormal liver function tests and cases of hepatitis have also been reported.
Speak to your doctor if you have any of these side effects and they worry you.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Clonidine Lupin contains

Active ingredient
(main ingredient)		Clonidine hydrochloride 100 micrograms.
Other ingredients
(inactive ingredients)		Maize starch, colloidal anhydrous silica, povidone, stearic acid, calcium hydrogen phosphate and lactose monohydrate
Potential allergensLactose monohydrate

Do not take this medicine if you are allergic to any of these ingredients.

What Clonidine Lupin looks like

Clonidine Lupin is the brand name of your medicine.

Clonidine Lupin tablets are scored, pink, marked with ‘YS 01’ on one side and a score line on the reverse side (AUST R 265778).

Who distributes Clonidine Lupin tablets

Generic Health Pty Ltd
Suite 2, Level 2
19-23 Prospect Street
Box Hill, VIC, 3128
Australia

ii1374601  [email protected]

ii1374602  +61 3 9809 7900

ii1374603  www.generichealth.com.au

This leaflet was prepared in May 2024.

Published by MIMS July 2024

BRAND INFORMATION

Brand name

Clonidine Lupin

Active ingredient

Clonidine hydrochloride

Schedule

S4

 

Notes

Distributed by Generic Health Pty Ltd

1 Name of Medicine

Clonidine hydrochloride.

2 Qualitative and Quantitative Composition

Clonidine Lupin tablets contains the active ingredient clonidine hydrochloride. Each Clonidine Lupin tablet contains 100 microgram 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).

List of excipients with known effect.

Each tablet contains 34.9 mg lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clonidine Lupin 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 microgram 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 microgram 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 microgram 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 microgram morning and evening. If necessary, after two weeks, this may be increased to 50 microgram twice daily, then to a total daily dose of 150 microgram. 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 microgram morning and evening. If after two weeks there has been no remission, increase to 50 microgram twice daily. If necessary this may be increased to a total daily dose of 150 microgram. 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 microgram 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.
Clonidine Lupin 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 regime.
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 microgram. 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

Clonidine Lupin 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

Clonidine Lupin tablets should be stored below 25°C.

6.5 Nature and Contents of Container

Clonidine Lupin 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