PATIENT INFORMATION LEAFLET

ELAVIL

Amitriptyline Hydrochloride

PLEASE READ THIS LEAFLET CAREFULLY BEFORE YOU START TAKING THIS MEDICINE

What is in your medicine?

The name of this medicine is ELAVIL. It is available in tablets containing 10 mg and 25 mg of Amitriptyline Hydrochloride, together with the following ingredients: Lactose, calcium hydrogen phosphate, maize starch, micro crystalline cellulose, colloidal anhydrous silica, stearic acid, magnesium stearate, hydroxymethylpropylcellulose, ethylcellulose, diethyl phthalate hydroxypropylcellulose (E463) titanium dioxide (E171).

The 10 mg tablet also contains indigo carmine (E132).

The 25 mg tablet also contains quinoline yellow (E104) and sunset yellow (E110).

ELAVIL 10 mg tablets are round, blue, film-coated tablets, engraved DDSA. ELAVIL 25 mg tablets are round, yellow, film-coated tablets engraved DDSA.

Both strengths are available in packs of 100 and 500 tablets.

The manufacturer of ELAVIL tablets is:

DDSA Pharmaceuticals Ltd.,

Chatfield Road, off York Road, London SW11 3SE.

The product licence holder of ELAVIL tablets is:

Chelonia Healthcare Limited,

Boumpoulinas 11, 3rd Floor,

Nicosia, Cyprus, P.C.1060, Cyprus

What are ELAVIL tablets for?

ELAVIL belongs to a group of medicines known as the antidepressants and is used in the treatment of the symptoms of depression, especially where sedation is required.

ELAVIL is also effective in treating bedwetting in children, known as nocturnal enuresis.

Check before you take ELAVIL

Before taking this medicine, tell your doctor if you have ever had any unusual or allergic reactions to Amitriptyline, or to any of the other ingredients of ELAVIL.

If your doctor has told you that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Sunset yellow E110 may cause allergic reactions.

Also tell your doctor if you are pregnant, likely to become pregnant, or are breast-feeding a baby.

Because the presence of other medical problems may affect the use of ELAVIL, make sure to tell your doctor if you have had any of the following:

•    Heart disease such as coronary artery disease, or heart block which is a condition where the heart beats slowly causing dizziness, tiredness, or fainting.

•    Liver disease.

•    Epilepsy (seizures).

•    Urinary problems such as being unable to pass urine.

•    Prostate problems, especially enlargement of the prostate.

•    Glaucoma (increased eyeball pressure).

•    Thyroid disease.

•    Mania or schizophrenia.

•    Phaeochromocytoma (characterised by high blood pressure).

•    Porphyria.

Also tell your doctor if you are about to receive any surgical procedure.

Precautions while using this medicine

Although you can take these tablets with other medicines, it is important to tell your doctor or pharmacist about all the medicines that you are taking, whether or not they are prescribed by your doctor or bought without a prescription from the pharmacy or elsewhere. This is because using antidepressants together with ELAVIL may possibly increase the effect of ELAVIL. The use of drugs known as mono-amine oxidase inhibitors (MAOIs), for example, can increase the effects of amitriptyline and cause an increase in body temperature and convulsions. A minimum of 14 days should elapse between discontinuing an MAOI and starting amitriptyline.

The drug fluoxetine increases the effects of amitriptyline.

The use of drugs known as protease inhibitors such as ritonavir may also increase the effects of amitriptyline.

Amitriptyline may block the blood pressure-lowering action of the following:

•    Guanethidine

•    Debrisoquine

•    Bethanidine

•    And possibly Clonidine

Amitriptyline should not be taken with the following:

•    Adrenaline

•    Ephedrine

•    Isoprenaline

•    Noradrenaline

•    Phenylephrine

•    Phenylpropanolamine

•    Amiodarone and dysopyramide for irregular heart beat Amitriptyline may cause an increase in blood pressure when used together with the above.

Amitriptyline may increase the response to alcohol, barbiturates and depressants of the central nervous system. Delirium has been reported in patients taking amitriptyline with disulfiram. Barbiturates and carbamazepine may decrease the anti-depressant action of amitriptyline and methylphenidate may increase the anti-depressant action.

Anti-cholinergic drugs, such as atropine when combined with Amitriptyline may cause paralysis of the small intestine, retention of urine, or glaucoma, especially in the elderly.

Cimetidine can reduce the breakdown of amitriptyline, which is necessary for this drug to be removed from the body (excreted).

The anti-convulsant effect of anti-epileptic drugs such as Primodone may be reduced when taken with amitriptyline, whose breakdown rate will be increased.

Caution should be used if you are taking large doses of ethchlorvynol.

If you get a bad sore throat or high fever, or become gradually more tired and pale, or notice bruises or nose bleeds, stop taking Amitriptyline and contact your doctor at once.

Do not abruptly stop taking ELAVIL as there may be some side effects such as nausea, headache and weakness.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming of killing yourself. These may be increased when first starting antidepressants, since these medicines all take time to work, usually about two weeks but sometimes longer.

You may be more likely to think like this:

—    If you have previously had thoughts about killing or harming yourself.

—    If you are a young adult. Information from clinical trial studies has shown an increased risk of suicidal behaviour in adults aged less than 25 years with psychiatric conditions who were treated with an anti-depressant.

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder and ask them to read this leaflet. You might ask them to tell you if they think

your depression or anxiety is getting worse, or if they are worried about changes in your behaviour.

Effects on ability to drive and use machinery

As Amitriptyline may impair your alertness, any activity made hazardous by diminished alertness, such as driving motorised vehicles or using machinery, should be avoided.

Amitriptyline will also enhance the effects of alcohol. It is therefore inadvisable to drive or operate machinery.

Use in pregnancy and lactation

The safety of Amitriptyline for use during pregnancy and lactation has not been established. Amitriptyline is not recommended during pregnancy especially during the first and third three months, unless there are compelling reasons.

Withdrawal symptoms including depression of breathing and agitation have been reported in infants whose mothers have taken Amitriptyline during the last three months of pregnancy.

As Amitriptyline passes into breast milk it should be avoided while breast-feeding.

Proper use of this medicine

Take this medicine by mouth and only in the doses prescribed by your doctor. Your pharmacist can also help if you are not sure.

You should take these tablets exactly as your doctor has ordered. Do not take more of them, and do not take them more often or for a longer time than your doctor ordered. Do not stop the treatment without talking to your doctor first.

Dosages:

Adults:

Initial dose:

Usually 75 mg daily in divided doses (or a single dose at night). This may be increased if necessary to a total of 150-200 mg a day, with the additional doses being given in the late afternoon and/or at bedtime.

The sedative effect is usually rapidly apparent while antidepressant activity may be seen within three or four days or may take up to 30 days to develop adequately.

Maintenance dosage:

The usual maintenance dosage is 50-100 mg daily. The total dosage may be given in a single dose preferably in the evening or at bedtime. When satisfactory improvement has been reached, dosage should be reduced to the lowest amount that will maintain relief of symptoms. Maintenance therapy should be continued for three months or longer to lessen chances of relapse.

Elderly:

In general lower dosages are recommended for these patients, as they are more prone to side effects, especially confusion, agitation and postural hypotension.

An initial dosage of 10-25 mg three times daily is recommended, which should be increased slowly. A daily dosage of 50 mg may be satisfactory in elderly patients who may not tolerate higher dosages. The required dosage may be administered either as divided doses or a single dose preferably in the evening or at bedtime.

Children:

Not recommended for the treatment of depression in children under 16 years of age due to lack of clinical experience. Enuresis (bed-wetting):

Children from 7-10 years may receive 10-20 mg a day, while those aged 11-16 years may need 25-50 mg a day.

Treatment should not exceed three months.

If you forget to take your medicine, just carry on with the next dose as normal. Do not take an extra dose to make up for the missed dose. If you are not sure, ask your doctor or pharmacist for advice.

What to do in case of taking an overdose

If you should accidentally swallow a greater quantity of Amitriptyline tablets than have been prescribed for you, contact your doctor or the Accident & Emergency Department of your nearest hospital at once. Always keep any remaining tablets in the labelled container

in which they were given to you so that the medicine can be identified by the doctor or pharmacist at the hospital.

The symptoms of overdose are abnormal heartbeats, palpitations, dilated pupils, drowsiness, a drop in body temperature and convulsions (seizures).

Can ELAVIL tablets cause problems?

Generally Amitriptyline is well tolerated.

The most common side effects of amitriptyline are a dry mouth, skin rashes, dizziness upon standing up, confusion, hallucinations and inflammation of the liver with yellowing of the whites of the eye and yellowing of the skin.

Other side effects may occur with the use of tricyclic antidepressants including Amitriptyline. These are:

Blood related reactions: increased blood pressure, palpitations, rapid heartbeat, fainting, heart block, stroke, and water retention. Bone marrow depression causing a reduction in the number of certain types of blood cells may occur.

Nervous system reaction: There may be disturbance of concentration, insomnia, nightmares, delusions, excitement, anxiety, restlessness, numbness, tingling and pins and needles of the extremities, difficulty in co-ordination, unstable walking, tremors, tics, ringing in the ears, seizures, blurred vision, difficulty in visual focusing, increased eyeball pressure, inability to pass urine and raised temperature.

Allergic reactions: Hives, sensitivity to light and swelling of the face and/or tongue.

Gastro-intestinal reactions: Nausea, vomiting, diarrhoea, constipation, paralysis of the small intestine, loss of appetite, inflammation of the mouth and of the parotid gland, black tongue.

Hormonal reactions: enlargement of the breasts, production of breast milk, swelling of the testicles and changes in sexual desire and sexual function.

Other reactions weakness, fatigue, headache, fever, increased perspiration, frequency in passing urine, hair loss and drowsiness. Increased appetite and weight gain (or occasionally weight loss).

An increased risk of bone fractures has been observed in patients taking this type of medicines.

Abrupt withdrawal of Amitriptyline after prolonged treatment has caused nausea, headaches and a feeling of being generally unwell.

When Amitriptyline has been slowly withdrawn this has been accompanied by passing symptoms such as irritability, restlessness and sleep disturbances. In the first two weeks of dosage reduction a condition known as hypermania (increased excitement) or hypomania (reduced excitement verging on depression) have been, rarely, reported within 2 to 7 days of stopping treatment.

Behavioural changes have been observed in children receiving ELAVIL for the treatment of bedwetting. Other side effects in children receiving the treatment for this condition are drowsiness, mild sweating and itching.

Storing your medicine

You must keep the medicine in a safe place where children cannot get it. Your medicine could harm them.

Keep your medicine in a dry place and store below 25°C.

Keep the tablets in the closed container in which they were given to you.

If your doctor tells you to stop the treatment, return any remaining tablets to the pharmacist. Only keep the medicine if the doctor tells you to.

On the label you will find the words "Expiry Date" followed by some numbers indicating the month and year. This is the date when the medicine is no longer fit for use. Do not use the medicine after this date, but return it to your pharmacist.

A reminder

REMEMBER this medicine is for you. Never give it to someone else, even if their symptoms are the same as yours. This leaflet does not contain the complete information about

your medicine. If you have any questions or are not sure about anything, ask your doctor or pharmacist who have access to additional information.

This leaflet was revised in June 2010