Consumer medicine information

Chemmart Amitriptyline Tablets

Amitriptyline hydrochloride

BRAND INFORMATION

Brand name

Chemmart Amitriptyline Tablets

Active ingredient

Amitriptyline hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Chemmart Amitriptyline Tablets.

What is in this leaflet

Read this leaflet carefully before taking your medicine.

This leaflet answers some common questions about amitriptyline. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

The information in this leaflet was last updated on the date listed on the last page. More recent information on this medicine may be available.

Ask your doctor or pharmacist:

  • if there is anything you do not understand in this leaflet,
  • if you are worried about taking your medicine, or
  • to obtain the most up-to-date information.

You can also download the most up-to-date leaflet from www.apotex.com.au.

All medicines have risks and benefits. Your doctor has weighed the risks of you using this medicine against the benefits they expect it will have for you.

Pharmaceutical companies cannot give you medical advice or an individual diagnosis.

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

What this medicine is used for

The name of your medicine is Chemmart Amitriptyline Tablets. It contains the active ingredient amitriptyline hydrochloride.

It is used to treat:

  • major depression - the 10 mg and 25 mg tablets can be used at any stage in treatment, however, the 50 mg tablets are approved only for maintenance treatment (i.e. after symptoms have improved).
  • bed wetting, provided there is no physical cause (e.g. problems with the bladder).

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed this medicine for another reason.

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

How it works

Amitriptyline belongs to a group of medicines called tricyclic antidepressants (TCAs). TCAs work by correcting the imbalance of certain chemicals in the brain. These chemicals, called amines, are involved in controlling mood. By correcting this imbalance, TCAs can help relieve the symptoms of depression.

There is no evidence that this medicine is addictive.

Use in children

Amitriptyline should not be used in children and adolescents aged less than 18 years for the treatment of depression. The safety and efficacy have not been satisfactorily established.

Before you take this medicine

When you must not take it

Do not take this medicine if:

  • You are hypersensitive to, or have had an allergic reaction to, amitriptyline or any of the ingredients listed at the end of this leaflet.
    Symptoms of an allergic reaction may include: cough, shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue, throat or other parts of the body; rash, itching or hives on the skin; fainting; or hay fever-like symptoms.
    If you think you are having an allergic reaction, do not take any more of the medicine and contact your doctor immediately or go to the Accident and Emergency department at the nearest hospital.
  • You are taking, or have taken within the last 14 days, a medicine called a monoamine oxidase inhibitor (MAOI), including selegiline.
    Check with your doctor whether you are, or have been, taking an MAOI, as the combination of amitriptyline with an MAOI may cause serious side effects, such as extreme fever and severe convulsions.
  • You are taking cisapride, which may cause serious side effects such as an abnormal heart rhythm.
  • You have recently had a heart attack.
  • You are breastfeeding. Amitriptyline may pass into human breast milk.
  • The expiry date (EXP) printed on the pack has passed.
  • The packaging is torn, shows signs of tampering or it does not look quite right.

Before you start to take it

Before you start taking this medicine, tell your doctor if:

  1. You have allergies to:
  • any other medicines
  • any other substances, such as foods, preservatives or dyes.
  1. You have or have had any medical conditions, especially the following:
  • other mental illnesses, such as schizophrenia
  • seizures
  • glaucoma
  • urinary problems
  • heart or blood vessel problems
  • thyroid problems
  • liver problems.
  1. You are receiving electroshock therapy.
  2. You are currently pregnant or you plan to become pregnant.
    Do not take this medicine whilst pregnant until you and your doctor have discussed the risks and benefits involved.
  3. You are currently breastfeeding or you plan to breastfeed.
    Do not take this medicine whilst breastfeeding.
  4. You are planning to have surgery or an anaesthetic.
  5. You are currently receiving or are planning to receive dental treatment.
  6. You are taking or are planning to take any other medicines.
    This includes vitamins and supplements that are available from your pharmacy, supermarket or health food shop.

Some medicines may interact with amitriptyline. These include:

  • cisapride, a medicine used to treat stomach reflux.
    You must not take amitriptyline whilst taking cisapride.
  • monoamine oxidase inhibitors (MAOIs), used to treat depression (e.g. phenelzine, tranylcypromine, moclobemide) and Parkinson's disease (e.g. selegiline).
    You must not take amitriptyline whilst taking MAOIs. Wait at least 14 days after stopping your MAOI before starting amitriptyline.
  • selective serotonin reuptake inhibitors (SSRIs), a group of medicines used to treat depression and other mental illnesses, such as fluoxetine, sertraline and paroxetine
  • other medicines used to treat depression and other mental illnesses (e.g. schizophrenia)
  • some medicines used to treat high blood pressure, such as guanethidine
  • anticholinergics, found in some medicines used to relieve stomach cramps; travel sickness; hayfever and allergies; cough and colds
  • medicines used to control an irregular heartbeat such as quinidine and flecainide
  • cimetidine, a medicine used to treat reflux and ulcers
  • sleeping tablets/sedatives, anti-anxiety medicines
  • medicines for epilepsy
  • thyroid medicines
  • disulfiram, a medicine used to deter alcohol consumption
  • central nervous system (CNS) depressants such as barbiturates and alcohol
  • tramadol, a medicine used to relieve pain.

If you are taking any of these you may need a different dose or you may need to take different medicines.

Other medicines not listed above may also interact with amitriptyline.

How to take this medicine

Follow carefully all directions given to you by your doctor. Their instructions may be different to the information in this leaflet.

How much to take

Your doctor will tell you how much of this medicine you should take. This will depend on your condition and whether you are taking any other medicines.

For depression, it is recommended that the dose is started at a low level and increased gradually. When satisfactory improvement has been reached, the dose should be reduced to the lowest amount that will maintain relief of symptoms.

For bed wetting, the doses recommended are low compared with those used for depression.

Do not stop taking your medicine or change your dosage without first checking with your doctor.

How to take it

Swallow the tablet(s) whole with a glass of water.

When to take it

Amitriptyline may be taken as a single dose (e.g. at bedtime) or as divided doses (e.g. three times a day), your doctor will advise you when to take it.

Take your dose(s) at the same time each day, this will have the best effect and will also help you remember when to take it.

It does not matter if you take it before, with or after food.

How long to take it for

Some people notice an improvement in their depressive symptoms after 3 or 4 days however it may take up to 4 weeks.

Most children respond to bed wetting treatment in the first few days.

Please note your doctor may ask you to continue taking amitriptyline even after your symptoms have improved. It is important you continue taking your medicine for as long as your doctor tells you.

Make sure you have enough to last over weekends and holidays.

If you forget to take it

If you take more than one dose a day and it is almost time to take your next dose, skip the missed dose and take your next dose at the usual time. Otherwise, take it as soon as you remember and then go back to taking your medicine as you would normally.

However, if you only take one dose a day at bedtime, ask your doctor for advice regarding missed doses, as taking it another time when you remember may mean you have difficulty waking up in the morning or experience drowsiness in the day.

Do not take a double dose to make up for missed doses.

This may increase the chance of you experiencing side effects.

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

If you take too much (overdose)

If you think that you or anyone else may have taken too much of this medicine, immediately telephone your doctor or the Poisons Information Centre (Tel: 13 11 26 in Australia) for advice. Alternatively, go to the Accident and Emergency department at your nearest hospital.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

While you are taking this medicine

Things you must do

Tell your doctor that you are taking this medicine if:

  • you are about to be started on any new medicine
  • you are pregnant or are planning to become pregnant
  • you are breastfeeding or are planning to breastfeed
  • you are about to have any blood tests
  • you are going to have surgery or an anaesthetic or are going into hospital.

Your doctor may occasionally do tests to make sure the medicine is working and to prevent side effects. Go to your doctor regularly for a check-up.

Tell any other doctors, dentists and pharmacists who are treating you that you take this medicine.

Amitriptyline may cause dry mouth. Tell your doctor or dentist if your mouth continues to feel dry for more than 2 weeks. Continuing dryness of the mouth may increase the chance of dental disease, including tooth decay and gum disease.

Tell your doctor immediately if you have any suicidal thoughts or other mental/mood changes. Occasionally, the symptoms of depression may include thoughts of harming yourself or committing suicide. These symptoms may continue or get worse during the first one to two months of treatment until the fullantidepressant effect of the medicine becomes apparent.

Contact your doctor or a mental health professional right away or go to the nearest hospital for treatment if you or someone you know is showing any of the following warning signs of suicide:

  • worsening of your depression
  • thoughts or talk of death or suicide
  • thoughts or talk of self-harm or harm to others
  • any recent attempts of self-harm
  • increase in aggressive behaviour, irritability or any other unusual changes in behaviour or mood. All mentions of suicide or violence must be taken seriously.

Things you must not do

Do not:

  • Give this medicine to anyone else, even if their symptoms seem similar to yours.
  • Take your medicine to treat any other condition unless your doctor tells you to.
  • Stop taking your medicine, or change the dosage, without first checking with your doctor.

Things to be careful of

Be careful when driving or operating machinery until you know how this medicine affects you.

Amitriptyline may reduce your alertness, cause drowsiness or dizziness in some people. If you experience any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous. For the same reasons, children should not ride a bike, climb trees or do anything else that could be dangerous if they are drowsy. Combining amitriptyline with alcohol can make you more drowsy or dizzy. Your doctor may suggest you avoid alcohol while being treated for depression. Be careful getting up from a sitting or lying position. Dizziness, light-headedness or fainting may occur, especially when you get up quickly. Getting up slowly may help.

Possible side effects

Tell your doctor as soon as possible if you do not feel well while you are taking amitriptyline or if you have any questions or concerns.

Do not be alarmed by the following lists of side effects. You may not experience any of them. All medicines can have side effects. Sometimes they are serious but most of the time they are not.

Tell your doctor if you notice any of the following:

  • dry mouth, altered sense of taste
  • nausea (feeling sick), vomiting
  • diarrhoea, constipation
  • blurred vision, difficulty in focussing
  • drowsiness, tiredness, headache
  • dizziness, light-headedness
  • increased sweating
  • weight gain or loss
  • changes in sex drive.

Tell your doctor as soon as possible if you notice any of the following.

These may be serious side effects and you may need medical attention:

  • fast or irregular heart beats
  • larger breast than normal (in men and women)
  • tingling or numbness of the hands or feet
  • uncontrolled movements, including trembling and shaking of the hands and fingers, twisting movements of the body, shuffling walk and stiffness of the arms and legs
  • difficulty in passing urine
  • signs of frequent infections such as fever, chills, sore throat or mouth ulcers
  • yellowing of the eyes or skin (jaundice)
  • unusual bruising or bleeding
  • feeling anxious, restless or confused
  • abnormal ideas, hallucinations
  • sudden switch of mood to one of excitement, overactivity, talkativeness and uninhibited behaviour.

If you experience any of the following, stop taking your medicine and contact your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

  • severe sunburn, blistering or swelling of the skin
  • fainting or collapse
  • chest pain
  • seizures or fits.

Other side effects not listed above may occur in some patients.

Allergic reactions

If you think you are having an allergic reaction to amitriptyline, do not take any more of this medicine and tell your doctor immediately or go to the Accident and Emergency department at your nearest hospital.

Symptoms of an allergic reaction may include some or all of the following:

  • cough, shortness of breath, wheezing or difficulty breathing
  • swelling of the face, lips, tongue, throat or other parts of the body
  • rash, itching or hives on the skin
  • fainting
  • hay fever-like symptoms.

Storage and disposal

Storage

Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep your medicine in a cool dry place where the temperature will stay below 25°C.

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

Keep this medicine 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 it has passed its expiry date, your pharmacist can dispose of the remaining medicine safely.

Product description

What Chemmart Amitriptyline tablet looks like

10 mg tablet: Blue colour, circular, biconvex, film coated tablets with "IA" over "10" debossed on one side and plain on the other side.

25 mg tablet: Yellow colour, circular, biconvex, film coated tablets with "IA" over "25" debossed on one side and plain on the other side.

50 mg tablet: Brown colour, circular, biconvex, film coated tablets with "IA" over "50" debossed on one side and plain on the other side.

Blister pack of 20, 50 and 100.

Bottles of 100.

* Not all strengths, pack types and/or pack sizes may be available.

Ingredients

Each tablet contains 10, 25 or 50 mg of amitriptyline hydrochloride as the active ingredient.

It also contains the following inactive ingredients:

  • Lactose
  • Cellulose-microcrystalline
  • Crospovidone
  • Starch-maize (Dried)
  • Silica-colloidal anhydrous
  • Talc-purified
  • Magnesium stearate
  • Hypromellose
  • Titanium dioxide
  • Macrogol 6000
  • Quinoline yellow aluminium lake (only 25 mg)
  • Brilliant blue FCF aluminium lake (only 10 mg)
  • Sunset yellow FCF aluminium lake (only 50 mg)
  • Indigo carmine aluminium lake (only 50 mg).

This medicine is gluten-free, sucrose-free, tartrazine-free and free of other azo dyes.

Australian Registration Numbers

Chemmart Amitriptyline 10 mg tablet (blister pack): AUST R 215344.
Chemmart Amitriptyline 25 mg tablet (blister pack): AUST R 215397.
Chemmart Amitriptyline 50 mg tablet (blister pack): AUST R 215403.

Sponsor

Apotex Pty Ltd
16 Giffnock Avenue
Macquarie Park NSW 2113

This leaflet was last updated in 22 August 2014.

BRAND INFORMATION

Brand name

Chemmart Amitriptyline Tablets

Active ingredient

Amitriptyline hydrochloride

Schedule

S4

 

Name of the medicine

Amitriptyline hydrochloride.

Excipients.

Lactose, microcrystalline cellulose, crospovidone, maize starch, anhydrous colloidal silica, purified talc, magnesium stearate, hypromellose, titanium dioxide, macrogol 6000, brilliant blue FCF aluminium lake (10 mg only), quinoline yellow aluminium lake (25 mg only), sunset yellow FCF aluminium lake and indigo carmine aluminium lake (50 mg only).

Description

Chemical name: 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N- dimethylpropylamine hydrochloride. Molecular formula: C20H23N.HCl. MW: 313.9. CAS: 549-18-8. Amitriptyline hydrochloride occurs as colourless crystals or a white or almost white powder; odourless or almost odourless; taste, bitter and burning, followed by a sensation of numbness. It is soluble in 1 part of water, in 1.5 parts of ethanol (96%), in 1.2 parts of chloroform and in 1 part of methanol. It is practically insoluble in ether. pKa of amitriptyline hydrochloride is 9.4.

Pharmacology

Amitriptyline is a tricyclic antidepressant with sedative properties.

Mechanism of action.

The mechanism of action of amitriptyline in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system. In broad clinical use, amitriptyline has been found to be well tolerated.
Amitriptyline inhibits the membrane pump mechanism responsible for uptake of noradrenaline and serotonin in adrenergic and serotonergic neurons. Pharmacologically, this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating its transmitting activity. This interference with the uptake of noradrenaline and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Amitriptyline has also been found to be effective in the treatment of enuresis in some cases where organic pathology has been excluded. The mode of action of amitriptyline in enuresis is not known. However, amitriptyline does have anticholinergic properties and medicines of this group, such as belladonna, have been used in the treatment of enuresis.

Pharmacokinetics.

Amitriptyline is readily absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within approximately 6 hours of oral administration.
The mean apparent elimination half-life for amitriptyline was reported by one source to be 22.4 hours; the mean half-life of its active metabolite, nortriptyline was 26 hours.
Amitriptyline is approximately 96% bound to plasma proteins.
Amitriptyline undergoes extensive metabolism in the liver, primarily through N-demethylation, to nortriptyline. Paths of metabolism of both amitriptyline and nortriptyline include hydroxylation and N-oxidation.
Amitriptyline is excreted in the urine, mainly in the form of metabolites, either free or as glucuronide and sulphate conjugates. Very little unchanged medicine is excreted in the urine. From one-third to one-half of an oral radioactive dose is excreted in the urine within 24 hours of administration.

Indications

For the treatment of major depression. Amitriptyline 50 mg tablets are indicated only for the maintenance treatment of major depression (see Precautions).
Nocturnal enuresis where organic pathology has been excluded.

Contraindications

Amitriptyline is contraindicated in patients who have shown prior hypersensitivity to it.

Monoamine oxidase inhibitors (MAOIs).

Amitriptyline should not be given concurrently with monoamine oxidase inhibitors, including selegiline. The combination of amitriptyline with a monoamine oxidase inhibitor has caused severe convulsions, hyperpyretic crises and death.
When it is desired to substitute amitriptyline for a monoamine oxidase inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued. Amitriptyline should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.

Cisapride.

Amitriptyline is contraindicated in patients taking cisapride due to the possibility of adverse cardiac interactions including prolongation of the QT interval, cardiac arrhythmias and conduction system disturbances.

Myocardial infarction.

Amitriptyline is not recommended for use during the acute recovery phase following myocardial infarction.
See Precautions, Use in pregnancy and Use in lactation.

Precautions

Clinical worsening and suicide risk associated with psychiatric disorders.

The risk of suicide attempt is inherent in depression and may persist until significant remission occurs. This risk must be considered in all depressed patients.
Patients with depression, both adult and paediatric, may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviour (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored for clinical worsening and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or whose emergent suicidality is severe, abrupt in onset, or was not part of the patient's presenting symptoms.
Patients (and caregivers of patients) should be alerted about the need to monitor for any worsening of their condition and/or the emergence of suicidal ideation/ behaviour or thoughts of harming themselves and to seek medical advice immediately if these symptoms present. Patients with comorbid depression associated with other psychiatric disorders being treated with antidepressants should be similarly observed for clinical worsening and suicidality.
Pooled analyses of short-term placebo controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behaviour (suicidality) in children, adolescents and young adults (ages 18-24) with major depressive disorder and other psychiatric disorders. Short-term studies did not show an increase in risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
Pooled analyses of 24 short-term (4 to 16 weeks), placebo controlled trials of nine antidepressant medicines (SSRIs and others) in 4400 children and adolescents with major depressive disorder (16 trials), obsessive compulsive disorder (4 trials), or other psychiatric disorders (4 trials) have revealed a greater risk of adverse events representing suicidal behaviour or thinking (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients treated with an antidepressant was 4%, compared with 2% of patients given placebo. There was considerable variation in risk among the antidepressants, but there was a tendency towards an increase for almost all antidepressants studied. The risk of suicidality was most consistently observed in the major depressive disorder trials, but there were signals of risk arising from trials in other psychiatric indications (obsessive compulsive disorder and social anxiety disorder) as well. No suicides occurred in these trials. It is unknown whether the suicidality risk in children and adolescent patients extends to use beyond several months. The nine antidepressant medicines in the pooled analyses included five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and four non-SSRIs (bupropion, mirtazapine, nefazodone, venlafaxine).
The pooled analyses of placebo controlled trials in adults with major depressive disorder or other psychiatric disorders included a total of 295 short-term trials (average duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. Absolute risk of suicidality varied across the different indications, with the highest incidence in major depressive disorder. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.
There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e. beyond several months. However, there is substantial evidence from placebo controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
Symptoms of anxiety, agitation, panic attacks, insomnia, irritability, hostility (aggressiveness), impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adults, adolescents and children being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either worsening of depression and/or emergence of suicidal impulses has not been established, there is concern that such symptoms may be precursors of emerging suicidality.
Families and caregivers of children, adolescents and young adults (ages 18-24) being treated with antidepressants for major depressive disorder or for any other condition (psychiatric or nonpsychiatric) should be informed about the need to monitor these patients for the emergence of agitation, irritability, unusual changes in behaviour, and other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. It is particularly important that monitoring be undertaken during the initial few months of antidepressant treatment or at times of dose increase or decrease.
Prescriptions for amitriptyline should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Amitriptyline 50 mg tablets.

The 50 mg tablets are indicated only for the maintenance treatment of major depression. The 50 mg tablets should not be used in acutely ill patients where there is a risk of suicide. There is an increased risk of completed suicide by overdose with the 50 mg tablet compared with the 25 mg tablet.
To prevent accidental overdose and the potentially fatal consequences, patients should be made aware of the unusual toxicity of tricyclic antidepressants and the need to maintain strict control over the tablets as well as the need to store them out of reach of children.

Bipolar disorder and activation of mania/ hypomania.

A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed that treating such an episode with an antidepressant alone can increase the likelihood of precipitation of a mixed/ manic episode in patients at risk of bipolar disorder. Prior to initiating treatment with an antidepressant, patients should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include detailed psychiatric history, including a family history of suicide, bipolar disorder and depression.

Seizures.

Amitriptyline should be used with caution in patients with a history of seizures.

Central nervous disorders.

The possibility of suicide in depressed patients remains during treatment. Patients should not have access to large quantities of this medicine during treatment.
When amitriptyline hydrochloride is used to treat the depressive component of schizophrenia, psychotic symptoms may be aggravated. Likewise, in manic depressive psychosis, depressed patients may experience a shift toward the manic phase. Paranoid delusions, with or without associated hostility, may be exaggerated. In any of these circumstances, it may be advisable to reduce the dose of amitriptyline or to use a major tranquillising medicine, such as perphenazine, concurrently.

Glaucoma and urinary retention.

Due to its atropine-like action, amitriptyline should be used with caution in patients with a history of urinary retention, or with narrow angle glaucoma or increased intraocular pressure. In patients with narrow angle glaucoma, even average doses precipitate an attack.

Cardiovascular disorders.

Patients with cardiovascular disorders should be watched closely. Tricyclic antidepressant medicines, including amitriptyline hydrochloride, particularly when given in high doses, have been reported to produce arrhythmias, sinus tachycardia, and prolongation of the conduction time. Myocardial infarction and stroke have been reported with medicines of this class.

Endocrine disorders.

Close supervision is required when amitriptyline is given to hyperthyroid patients or those receiving thyroid medication (see Interactions with Other Medicines).

Other antidepressant medicines.

The addition of other antidepressant medicines generally does not result in any additional therapeutic benefit. Untoward reactions have been reported after the combined use of antidepressant agents having varying modes of activity. Therefore, combined use of amitriptyline hydrochloride and other antidepressant medicines should be undertaken only with due recognition of the possibility of potentiation and with a thorough knowledge of the pharmacology of both medicines. There has been no evidence of potentiation when patients receiving amitriptyline hydrochloride were changed immediately to protriptyline or vice versa.

Elective surgery.

Discontinue the medicine several days before elective surgery if possible.

Impairment of motor coordination.

Amitriptyline may impair alertness in some patients; operation of motor vehicles and other activities made hazardous by diminished alertness should be avoided.

Use in hepatic impairment.

In the presence of hepatic disease, amitriptyline should be used cautiously.

Use in pregnancy.

(Category C)
Withdrawal symptoms in newborn infants have been reported with prolonged maternal use of this class of medicines.
Tricyclic antidepressants have not been shown to be associated with an increased incidence of birth defects. However, there is evidence of interference with central monoamine neurotransmission in rats. Care should be taken that there are sound indications for the use of these antidepressants in pregnancy.
There are no well controlled studies in pregnant women; therefore, in administering amitriptyline to pregnant women or women who may become pregnant, the potential benefits must be weighed against the possible hazards to mother and child.

Use in lactation.

Amitriptyline is detectable in breast milk. Because of the potential for serious adverse effects in infants from amitriptyline, a decision should be made whether to discontinue nursing or discontinue the medicine.

Use in children and adolescents (< 18 years).

The safety and efficacy of amitriptyline for the treatment of depression or other psychiatric disorders in children and adolescents aged less than 18 years has not been satisfactorily established. Amitriptyline should not be used in this age group for the treatment of depression.

Carcinogenicity.

Long-term carcinogenicity studies in rodents have not been performed with amitriptyline. Genotoxicity studies have not been performed with amitriptyline. Accumulated data from up to 19 years follow-up in approximately 200 patients showed no statistically significant association between treatment with amitriptyline and the incidence of cancers. Clinical experience over 30 years has produced no evidence of an altered carcinogenic risk.

Genotoxicity.

Genotoxicity studies have not been performed with amitriptyline.

Interactions

Other antidepressant medicines.

A potentially lethal interaction can occur between monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants. It is advisable to discontinue the MAOI for at least 2 weeks before taking amitriptyline (see Contraindications).
Concurrent use of fluoxetine and tricyclic antidepressants has produced increased plasma concentrations of the tricyclic antidepressants. Some clinicians recommend dosage reductions for tricyclic antidepressants of about 50% if used concurrently with fluoxetine. Any patient receiving amitriptyline and fluoxetine concurrently should be observed closely for adverse effects and consideration should be given to monitoring the plasma levels of the tricyclic antidepressant with dosage reduction where necessary.
There have been no reports of untoward events when patients receiving amitriptyline hydrochloride were changed immediately to protriptyline or vice versa.

Guanethidine.

Amitriptyline may block the antihypertensive action of guanethidine or similarly acting compounds.

Anticholinergic agents/ sympathomimetic medicines.

When amitriptyline is given with anticholinergic agents or sympathomimetic medicines, including adrenaline combined with local anaesthetics, close supervision and careful adjustment of dosage are required. Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic type medicines.

Anticholinergic agents/ neuroleptic medicines.

Hyperpyrexia has been reported when tricyclic antidepressants are administered with anticholinergic agents or with neuroleptic medicines, particularly during hot weather. Concurrent use of phenothiazines and tricyclic antidepressants have the potential to elevate plasma levels of both agents. The sedative and anticholinergic effects may be prolonged and the risk of seizures and neuroleptic malignant syndrome increased.

Medicines metabolised by cytochrome P450 2D6.

Concomitant use of tricyclic antidepressants with medicines that can inhibit cytochrome P450 2D6 (e.g. quinidine; cimetidine) and those that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the type 1C antiarrhythmics, e.g. flecainide) may require lower doses than usually prescribed for either the tricyclic antidepressant or the other medicine. Whenever one of these other medicines is withdrawn from cotherapy, an increased dose of tricyclic antidepressant may be required. While all the selective serotonin reuptake inhibitors (SSRIs), e.g. fluoxetine, sertraline and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.

Cimetidine.

Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these medicines.

Central nervous system depressants.

Amitriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.

Disulfiram.

Delirium has been reported with concurrent administration of amitriptyline and disulfiram.

Electroshock therapy.

Concurrent administration of amitriptyline and electroshock therapy may increase the hazards of therapy. Such treatment should be limited to patients for whom it is essential.

Antithyroid medicines.

Concurrent use may increase the risk of agranulocytosis.

Thyroid hormones.

Concurrent use with tricyclic antidepressants may increase the therapeutic and toxic effects of both medications. Toxic effects include cardiac arrhythmias and CNS stimulation.

Analgesics.

Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol.

Selective serotonin reuptake inhibitors (SSRIs).

The 'serotonin syndrome' (alterations in cognition, behaviour, autonomic nervous system function, and neuromuscular activity) has been reported with amitriptyline when given concomitantly with other serotonin enhancing medicines including selective serotonin reuptake inhibitors (SSRIs).

Other medicines.

Because tricyclic antidepressants may delay gastric emptying and decrease intestinal motility, careful dosage monitoring is essential with any medicine that may be subject to gastric inactivation (i.e. levodopa) or which may be absorbed to a greater extent because of the increased time available for absorption (i.e. anticoagulants).

Adverse Effects

Note.

Included are a few adverse effects which have not been reported with this specific medicine. However, pharmacological similarities among the tricyclic antidepressants require that each of the effects be considered when amitriptyline is administered.

Cardiovascular.

Hypotension, syncope, hypertension, tachycardia, palpitations, myocardial infarction, arrhythmias, heart block, stroke, nonspecific ECG changes and changes in A-V conduction.

Central nervous system and neuromuscular.

Confusional states, disturbed concentration, disorientation, delusions, hallucinations, excitement, anxiety, restlessness, insomnia, drowsiness, nightmares; numbness, tingling, paraesthesiae of the extremities, peripheral neuropathy, incoordination, ataxia, tremors, coma, seizures, alteration in EEG patterns, extrapyramidal symptoms including abnormal voluntary movements and tardive dyskinesia; dysarthria, tinnitus, thrombocytopenia.

Anticholinergic.

Dry mouth, blurred vision, disturbance of accommodation, constipation, paralytic ileus, urinary retention, dilatation of urinary tract, increased intraocular pressure, hyperpyrexia.

Allergic.

Skin rash, urticaria, pruritus, photosensitisation, oedema of face and tongue.

Haematological.

Bone marrow depression including agranulocytosis, leucopenia, eosinophilia, purpura.

Gastrointestinal.

Nausea, epigastric distress, vomiting, anorexia, stomatitis, peculiar taste, diarrhoea, parotid swelling, black tongue, rarely hepatitis (including altered liver function and jaundice).

Endocrine.

Testicular swelling and gynaecomastia in the male, breast enlargement and galactorrhoea in the female, increased or decreased libido, impotence, elevation or lowering of blood sugar levels, syndrome of inappropriate ADH (antidiuretic hormone) secretion.

Other.

Dizziness, weakness, fatigue, headache, weight gain or loss, oedema, increased perspiration, urinary frequency, mydriasis, drowsiness, alopecia.

Serotonin syndrome.

The serotonin syndrome (alterations in cognition, behaviour, autonomic nervous system function, and neuromuscular activity) has been reported with amitriptyline when given concomitantly with other serotonin enhancing medicines.

Withdrawal symptoms.

Abrupt cessation of treatment after prolonged administration may produce nausea, headache and malaise. Gradual dosage reduction has been reported to produce, within two weeks, transient symptoms including irritability, restlessness, and dream and sleep disturbance. These are not indicative of addiction. Rare instances have been reported of mania or hypomania occurring within 2 to 7 days following cessation of chronic therapy with tricyclic antidepressants.

In enuresis.

The doses of amitriptyline recommended in the treatment of enuresis are low compared with those used in the treatment of depression, even allowing for differences in age and weight. Consequently, side effects are less frequent than when the medicine is used in treating depression. The most common side effects are drowsiness and anticholinergic effects.

Causal relationship unknown.

A lupus-like syndrome (migratory arthritis, positive ANA and rheumatoid factor) has been reported rarely; however, a causal relationship to therapy with amitriptyline could not be established.

Dosage and Administration

Depression.

Dosage considerations.

Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.

Initial dosage for outpatient adults.

75 mg a day in divided doses is usually satisfactory. If necessary, this may be increased to a total of 150 mg a day. Increases are made preferably in the late afternoon and/or bedtime doses. The sedative effect is usually rapidly apparent. The antidepressant activity may be evident within three or four days or may take up to 30 days to develop adequately.
Alternative methods for initiating therapy in outpatients are: begin therapy with 50 to 100 mg preferably in the evening or at bedtime; this may be increased by 25 to 50 mg as necessary to a total of 150 mg per day.

Dosage for hospitalised patients.

100 mg a day may be required initially. This can be increased gradually to 200 mg a day if necessary. A small number of hospitalised patients may need as much as 300 mg per day.

Dosage for elderly patients.

In general, lower dosages are recommended for these patients. 50 mg daily may be satisfactory in those elderly patients who may not tolerate higher doses. The required daily dose may be administered either in divided doses or as a single dose preferably in the evening or at bedtime.

Maintenance dosage.

Usually from 50 to 100 mg per day. For maintenance therapy, the total daily 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. It is appropriate to continue maintenance therapy 3 months or longer to lessen the possibility of relapse.

Enuresis.

A dose of 10 mg at bedtime has been found effective in children under 6 years of age. In older children, the dosage should be increased as necessary according to weight and age. Children 6 to 10 years of age may receive 10 to 20 mg per day. In the age group from 11 to 16, a dose of 25 to 50 mg at bedtime may be required.
Most patients respond in the first few days of therapy. In those who do respond, the tendency is for increasing, continued improvement as the period of treatment is extended. Continued treatment is usually required to maintain the response until control is established.
The doses of amitriptyline recommended in the treatment of enuresis are low compared with those used in the treatment of depression, even allowing for differences in age and weight. This recommended dose must not be exceeded. This medication should be kept out of reach of children.

Plasma levels.

Because of the wide variation in the absorption and distribution of tricyclic antidepressants in body fluids, it is difficult to directly correlate plasma levels and therapeutic effect. However, determination of plasma levels may be useful in identifying patients who appear to have toxic effects and may have excessively high levels, or those in whom lack of absorption or noncompliance is suspected. Adjustments in dosage should be made according to the patient's clinical response and not on the basis of plasma levels.

Overdosage

Deaths by deliberate or accidental overdosage have occurred with this class of medicine.
There has been a report of fatal dysrhythmia occurring as late as 56 hours after amitriptyline overdose.

Symptoms.

High doses may cause temporary confusion, disturbed concentration, or transient visual hallucinations. Overdosage may cause drowsiness, hypothermia, tachycardia and other arrhythmic abnormalities, such as bundle branch block, ECG evidence of impaired conduction, congestive heart failure, dilated pupils, convulsions, severe hypotension, stupor, coma and polyradiculoneuropathy. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Other symptoms may be agitation, hyperactive reflexes, muscle rigidity, vomiting, hyperpyrexia, or any of those listed under Adverse Effects.

Treatment.

All patients suspected of having taken an overdosage should be admitted to a hospital as soon as possible. Treatment is symptomatic and supportive. Activated charcoal may reduce absorption of the medicine if given within one or two hours after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected. An ECG should be taken and close monitoring of cardiac function instituted if there is any sign of abnormality. Maintain an open airway and adequate fluid intake; regulate body temperature.
Standard measures should be used to manage circulatory shock and metabolic acidosis. Cardiac arrhythmias have been treated with propranolol. Should cardiac failure occur, the use of digitalis should be considered. Close monitoring of cardiac function for not less than five days is advisable. Anticonvulsants may be given to control convulsions. Amitriptyline increases the CNS depressant action but not the anticonvulsant action of barbiturates; therefore, an inhalation anaesthetic or diazepam is recommended for control of convulsions.
Dialysis is of no value because of low plasma concentrations of the medicine.
Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase.
In cases of overdosage, it is advisable to contact the Poisons Information Centre on 131 126 (Australia) for recommendation on the management and treatment of overdosage.

Presentation

Tablets (circular, biconvex, film coated, plain on one side), 10 mg (blue, marked IA/10 on reverse, AUST R 215344), 25 mg (yellow, marked IA/25 on reverse, AUST R 215397), 50 mg (brown, marked IA/50 on reverse, AUST R 215403): 20's*, 50's, 100's* (PVC/ Alu blister pack).
*Not currently marketed in Australia.
100 tablets pack size is for dispensing only.

Storage

Store below 25°C.

Poison Schedule

S4