Professional Leaflet_

Catapres® Ampoules    /jjT\ Boehringer

150 micrograms in 1 ml    ^Ing^elheim

Solution for Injection

(clonidine hydrochloride)

Name of the medicinal product

CATAPRES Ampoules 150 micrograms in 1 ml Solution for Injection

Qualitative and quantitative composition

Each 1 ml ampoule contains clonidine hydrochloride 150 micrograms. For excipients, see List of excipients.

Pharmaceutical form

Solution for injection. Clear, colourless solution Clinical particulars Therapeutic indications

CATAPRES is indicated for the treatment of hypertensive crises.

Posology and method of administration Adults, including the elderly:

In hypertensive crises 150 to 300 micrograms (1 to 2 ampoules) should be given by slow intravenous injection. This dose may be repeated up to a maximum 750 micrograms (5 ampoules) in a 24 hour period. Patients undergoing anaesthesia should continue their CATAPRES treatment before, during and after anaesthesia using oral or intravenous administration according to individual circumstances.

Intravenous injection of CATAPRES should be given slowly over 10-15 minutes to avoid a possible transient pressor effect. CATAPRES injection solution is compatible with 0.9% sodium chloride solution and with 5% dextrose solution.

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.

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 Contraindications

CATAPRES should not be used in children (please refer to Special warnings and precautions for use) or in patients with known hypersensitivity to the active ingredient or other components of the product, and in patients with severe bradyarrhythmia resulting from either sick sinus syndrome or AV block of 2^nd or 3^rd degree.

Special warnings and precautions for use Clonidine should only be used with caution in patients with depression or a history thereof, with Raynaud’s disease, or other peripheral vascular occlusive disease. The product should only be used with caution in patients with cerebrovascular or coronary insufficiency.

CATAPRES should be used with caution in patients with mild to moderate bradyarrhythmia such as low sinus rhythm, and with polyneuropathy or constipation.

As with other antihypertensive drugs, treatment with CATAPRES should be monitored particularly carefully in patients with heart failure.

In hypertension caused by phaeochromocytoma no therapeutic effect of CATAPRES can be expected.

Clonidine, the active ingredient of CATAPRES, and its metabolites are extensively excreted with the urine. Dosage must be adjusted to the individual antihypertensive response, which can show high variability in patients with renal insufficiency (see Section Posology and method of administration); 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.

Patients who wear contact lenses should be warned that treatment with CATAPRES may cause decreased lacrimation.

The use and 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.

Interaction with other medicinal products and other forms of interaction.

The reduction in blood pressure induced by clonidine can be further potentiated by concurrent administration of other hypotensive agents. This can be of therapeutic use in the case of other antihypertensive agents such as diuretics, vasodilators, beta-receptor blockers, calcium antagonists and ACE-inhibitors, but the effect of alpha₁-blockers is unpredictable.

The antihypertensive effect of clonidine may be reduced or abolished and orthostatic hypotension may be provoked or aggravated by concomitant administration of tricyclic antidepressants or neuroleptics with alpha-receptor blocking properties.

Substances which raise blood pressure or induce a sodium ion (Na+) and water retaining effect such as non-steroidal anti-inflammatory agents can reduce the therapeutic effect of clonidine.

Substances with alpha₂-receptor blocking properties, such as mirtazapine, may abolish the alpha₂-receptor mediated effects of clonidine in a dose-dependent manner.

Concomitant administration of substances with a negative chronotropic or dromotropic effect such as beta-receptor blockers or digitalis glycosides can cause or potentiate bradycardic rhythm disturbances.

It cannot be ruled out that concomitant administration of a beta-receptor blocker will cause or potentiate peripheral vascular disorder.

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Based on observations in patients in a state of alcoholic delirium 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. Causal relationship and relevance for antihypertensive treatment have not been established.

The effect of centrally depressant substances or alcohol can be potentiated by clonidine.

Fertility, pregnancy and lactation

Pregnancy

There are limited amount of data from the use of clonidine in pregnant women. This product should only be used in pregnancy if considered essential by the physician. Careful monitoring of mother and child are 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.

Non-clinical studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Lactation

Clonidine is excreted in human milk. However, there is insufficient information on the effect on newborns. The use of CATAPRES 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.

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

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    > 1/10

Common    > 1/100, <1/10

Uncommon    > 1/1000, <1/100

Rare    > 1/10000, <1/1000

Very rare    < 1/10000

Not known    Cannot be estimated from

the available data

Endocrine disorders:

Gynaecomastia    rare

Psychiatric disorders: Confusional state Delusional perception Depression Hallucination Libido decreased Nightmare Sleep disorder

Gastrointestinal disorders:

Colonic pseudo-obstruction

Constipation

Dry mouth

Nausea

Salivary gland pain Vomiting

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

Fluid retention and abnormal liver function tests have been reported occasionally. Two cases of hepatitis have also been reported.

Reporting 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:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie e-mail: medsafety@hpra.ie

Overdose

Symptoms:

Manifestations of intoxication are due to a generalised sympathetic depression and include pupillary constriction, lethargy, bradycardia, hypotension, hypothermia, somnolence including coma and respiratory depression including apnoea. Paradox'cal hypertension caused by stimulation of peripheral alpha_rreceptors may occur. Transient hypertension may be seen if the total dose is over 10 mg.

Treatment:

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

Supportive care may include atropine sulfate 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.

Pharmacological properties

Pharmacodynamic properties

Clonidine acts primarily on the central nervous system, resulting in reduced sympathetic outflow and a decrease in peripheral resistance, renal vascular resistance, heart rate and blood pressure. Renal blood flow and glomerular filtration rate remain essentially unchanged. Normal postural reflexes are intact and therefore orthostatic symptoms are mild and infrequent. During long-term therapy, cardiac output tends to return to control values, while peripheral resistance remains decreased. Slowing of the pulse rate has been observed in most patients given clonidine, but the drug does not alter normal haemodynamic response to exercise.

The efficacy of clonidine in the treatment of hypertension has been investigated in five clinical studies in paediatric patients. The efficacy data confirms the properties of clonidine in reduction of systolic and diastolic blood pressure. However, due to limited data and methodological insufficiencies, no definitive conclusion can be drawn on the use of clonidine for hypertensive children.

The efficacy of clonidine has also been investigated in a few clinical studies with paediatric patients with ADHD, Tourette syndrome and stuttering. The efficacy of clonidine in these conditions has not been demonstrated.

There were also two small paediatric studies in migraine, neither of which demonstrated efficacy. In the paediatric studies the most frequent adverse events were drowsiness, dry mouth, headache, dizziness and insomnia. These adverse events might have serious impact on daily functioning in paediatric patients.

Overall, the safety and efficacy of clonidine in children and adolescents have not been established (see posology and method of administration).

Pharmacokinetic properties

The pharmacokinetics of clonidine is dose-proportional in the range of 100-600 micrograms. Clonidine, the active ingredient of CATAPRES, is well absorbed and no first pass effect exists. It is rapidly and extensively distributed into tissues and crosses the blood brain barrier as well as the placental barrier. The plasma protein binding is 30-40%.

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 up to 41 hours.

About 70% of the dose administered is excreted with the urine mainly in the form of the unchanged parent drug (40-60%). The main metabolite p-hydroxy-clonidine is pharmacologically inactive. Approximately 20% of the total amount is excreted with the faeces.

The antihypertensive effect is reached at plasma concentrations between about 0.2 and 1.5 ng/ml in patients with normal excretory function. A further rise in the plasma levels will not enhance the antihypertensive effect.

Pharmaceutical particulars

List of excipients Sodium chloride Water for injections Hydrochloric acid

Incompatibilities

None known

Shelf life

Unopened: 5 years

Once opened, use immediately and discard any unused contents.

Special precautions for storage

Do not store above 30°C

Keep the ampoules in the outer carton

Nature and contents of container 1 ml colourless glass (Ph. Eur. Type I) ampoules, marketed in packs of 5.

Special precautions for disposal

For single use only. Discard any unused contents.

Marketingauthorisation holder

Boehringer Ingelheim Limited,

Ellesfield Avenue, Bracknell, Berkshire,

RG12 8YS, United Kingdom.

Marketingauthorisation number

PL00015/5008R PA 7/14/3

Manufacturer of the product

Boehringer Ingelheim Espana, S.A.

Prat de la Riba, 50, 08174 Sant Cugat del Valles, Barcelona, Spain

Legal category

POM

Date of revision of the text

This Professional Leaflet was revised in May 2015.

© Boehringer Ingelheim Limited 2015

Catapres® Ampoules    Boehringer

150 micrograms in 1 ml    ^In§^elheim

Solution for Injection

(clonidine hydrochloride)

Read all of this leaflet carefully before you start taking this medicine

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If any of the side effects gets troublesome or serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What CATAPRES Ampoules are and what they are used for

2.    Before you receive CATAPRES Ampoules

3.    How cAtAPRES Ampoules will be given

4.    Possible side effects

5.    How to store CATAPRES Ampoules

6.    Further information

1.    WHAT CATAPRES AMPOULES ARE AND WHAT THEY ARE USED FOR

The name of your medicine is CATAPRES Ampoules 150 micrograms in 1 ml Solution for Injection (called CATAPRES Ampoules in this leaflet). Your medicine is a solution for injection.

CATAPRES Ampoules contain a medicine called clonidine. This belongs to a group of medicines called antihypertensives.

CATAPRES is used to lower high blood pressure in cases of hypertensive crisis (a rapid rise in blood pressure that needs treating straight away).

2.    BEFORE YOU RECEIVE CATAPRES AMPOULES

You should not be given CATAPRES Ampoules if:

•    You are pregnant, likely to get pregnant or are breast-feeding

•    You are allergic (hypersensitive) to clonidine or any of the other ingredients of CATAPRES (see section 6: Further information)

•    You have a slow heart rate due to heart problems

•    You are under 18 years old

You should not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having CATAPRES Ampoules.

Take special care with CATAPRES Ampoules

Check with your doctor or pharmacist before having CAtApRES if:

•    You have Raynaud’s disease (a problem with circulation to the fingers and toes) or other blood circulation problems, including circulation to the brain

•    You have heart or kidney problems

•    You have or have ever had depression

•    You have constipation

•    You have a nerve disorder that causes your hands and feet to feel different (‘altered sensation’)

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before receiving cAtAPRES Ampoules.

As you may get dry eyes whilst taking this medicine, this may be a problem if you wear contact lenses.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription and herbal medicines. This is because CATApRES Ampoules can affect the way some other medicines work. Also some other medicines can affect the way CATAPRES Ampoules works.

In particular tell your doctor or pharmacist if you are taking any of the following medicines:

•    Other medicines that make you drowsy

•    Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen

•    Medicines for depression such as imipramine or mirtazapine

•    Medicines for severe mental illness such as schizophrenia. These are also known as ‘antipsychotics’ and include chlorpromazine and haloperidol

Please also tell your doctor or pharmacist if you are taking any of the following medicines for high blood pressure or other heart problems:

•    Beta blockers such as atenolol

•    Water tablets (‘diuretics’) such as frusemide

•    Alpha blockers such as prazosin or doxazosin. These can also be used for prostate problems in men.

•    Vasodilators such as diazoxide or sodium nitroprusside

•    Calcium antagonists such as verapamil or diltiazem hydrochloride

•    ACE inhibitors such as captopril or lisinopril

•    Digitalis glycosides such as digoxin

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before receiving cAtAPRES Ampoules.

Tests

If you are having any blood tests, tell the person giving the test that you are taking this medicine. This is because CATAPRES can affect results relating to your liver.

Operations

If you are going to have an operation, you will need to still receive CATAPrEs Ampoules.

Having CATAPRES Ampoules with food and drink

You may feel drowsy while receiving CATAPRES Ampoules. Drinking alcohol while receiving CATAPRES Ampoules can make this worse.

Pregnancy and breast-feeding

You should not be given CATAPRES Ampoules if you are pregnant, likely to get pregnant or are breast-feeding.

Driving and using machines

You may feel drowsy, dizzy, or could have some disturbances of vision. If affected, you should not drive, operate machinery or take part in any activities where these may put you or others at risk.

Important information about some of the ingredients of CATAPRES Ampoules

CATAPRES Ampoules contain sodium chloride, the sodium content per 1 ml ampoule is less than 1 mmol (23 mg). The total sodium content if you are given 5 ampoules in 24 hours is less than 1 mmol (23 mg). This means that CATAPRES Ampoules are essentially sodium free.

3. HOW CATAPRES AMPOULES WILL BE GIVEN

CATAPRES Ampoules are usually given by a doctor or nurse. You will normally be given 1 to 2 CATAPRES Ampoules but over 24 hours up to 5 ampoules may be given.

Your doctor will start you on a low dose but may increase the dose if you need more medicine to control your blood pressure.

Receiving the injection

•    CATAPRES Ampoules are slowly injected into a vein over 10-15 minutes

•    CATAPRES Ampoules may be diluted with other solutions if needed

CATAPRES Ampoules are not recommended for children or adolescents under 18 years old.

If you have more CATAPRES Ampoules than you should

It is unlikely that you will be given too much of this medicine. However, tell the doctor or nurse if you think that you have been given too much.

If you have any further questions on the use of CATAPRES, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, CATAPRES Ampoules can cause side effects, although not everybody gets them.

The side effects described below have been experienced by people taking CATAPRES. They are listed as either very common, common, uncommon, rare or not known.

Very common (affects more than 1 in 10 people)

•    Dizziness, feeling tired and more relaxed than usual (sedation)

•    Feeling dizzy when you stand up (because your blood pressure has fallen sharply)

•    Dry mouth

Common (affects less than 1 in 10 people, more than 1 in 100 people)

•    Depression, sleeping problems

•    Headache

•    Constipation, feeling sick (nausea), pain below the ear (from the salivary gland), being sick (vomiting)

•    Erectile dysfunction

•    Fatigue

Uncommon (affects less than 1 in 100 people, more than 1 in 1,000 people)

•    Problems with understanding what is happening around you, hallucinations, nightmares

•    Your hands and feet feeling different (‘altered sensation’)

•    Regular unusually slow heart beat

•    Raynaud’s phenomenon (a problem with circulation to the fingers and toes)

•    Itching, rash, urticaria (nettle rash)

•    A feeling of discomfort and fatigue (‘malaise’)

Rare (affects less than 1 in 1,000 people, more than 1 in 10,000 people)

•    Breast growth (‘gynaecomastia’) in men

•    Dry eyes

•    Irregular heartbeat

•    Drying out of the lining of the nose

•    Pseudo-obstruction of the large bowel, which causes colicky pain, vomiting and constipation. Contact your doctor straight away if you have all these side effects.

•    Hair loss

•    Increase in your blood sugar Not known

•    Confusion, loss of libido

•    Blurred vision

•    Abnormally slow heart beat

Two cases of hepatitis (inflammation of the liver) have also been reported. This might show up in some blood tests. Your body may also hold onto more water than usual (fluid retention).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

Ireland

HPRA Pharmacovigilance Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie E-mail: medsafety@hpra.ie

5.    HOW TO STORE CATAPRES AMPOULES

Keep out of the reach and sight of children.

The ampoules should not be stored above 30°C and should be kept in the outer carton.

CATAPRES Ampoules should not be used after the expiry date which is stated on the ampoule label and carton. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6.    FURTHER INFORMATION

What CATAPRES Ampoules contain

•    The active substance is clonidine hydrochloride. Each 1 ml ampoule contains 150 micrograms of clonidine hydrochloride

•    The other ingredients in the injection are: sodium chloride, water for injections and hydrochloric acid

What CATAPRES Ampoules looks like and contents of the pack

CATAPRES Ampoules are clear glass ampoules containing a clear, colourless solution. CATAPRES Ampoules are supplied in cartons of 5 ampoules.

Marketing Authorisation Holder and Manufacturer

The Marketing Authorisations for CATAPRES Ampoules are held by:

Boehringer Ingelheim Limited, Ellesfield Avenue, Bracknell, Berkshire, RG12 8YS, United Kingdom

and the ampoules are manufactured at

Boehringer Ingelheim Espana, S.A.

Prat de la Riba, 50, 08174 Sant Cugat del Valles, Barcelona, Spain

This leaflet was revised in May 2015.

©Boehringer Ingelheim Limited 2015

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