Each tablet contains 25mg Amitriptyline Hydrochloride.

Film-coated tablet. Yellow, circular, biconvex, film-coated tablets impressed “C” on one face and the identifying letters “AB” on the reverse.

1) Symptoms of depressive illness (especially where sedation is required).

2) Relief of nocturnal enuresis in children.

Posology

Adults: Initially 50-75mg daily in divided doses or as a single dose at night, increasing to 150-200mg daily according to clinical response.

Maintenance dose 50-100mg at night which should be continued for at least three months to lessen chances of relapse.

Adolescents and the elderly: 25-50mg daily in divided doses or as a single dose at night. Half the normal maintenance dose may be sufficient to produce a satisfactory clinical response.

Children: For nocturnal enuresis only. The maximum period of treatment (including gradual withdrawal) should not exceed three months. A further course of treatment should not be started until a full physical examination, including an ECG, has been made.

(11-16 years): 25-50mg daily.

(7-10 years): A more suitable dosage form should be used for this age group.

(Under 7 years): Not recommended for this age group.

Method of Administration

For oral administration.

• hypersensitivity to tricyclic antidepressants or to any of the ingredients in the tablets;

• history of myocardial infarction, arrhythmias, particularly heart block to any degree, congestive heart failure, coronary artery insufficiency;

• mania;

• severe liver disease;

• children under 7 years;

• breast feeding;

• patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days.

The elderly are particularly liable to experience adverse reactions, especially agitation, confusion and postural hypotension.

Behavioural changes may occur in children receiving amitriptyline for the treatment of nocturnal enuresis.

Avoid if possible in patients with narrow angle glaucoma, urinary retention, hepatic insufficiency, blood dyscrasias, symptoms suggestive of prostatic hypertrophy and a history of epilepsy. Even average doses may precipitate an attack of glaucoma in patients with narrow-angle glaucoma.

Patients with cardiovascular disorders, hyperthyroid patients and those receiving thyroid medication or anticholinergic drugs should be closely monitored. The dosage of all medications will need to be carefully adjusted.

When used for the depressive component of schizophrenia, amitriptyline should be used with caution as it may aggravate psychotic symptoms. In manic-depressives, a shift towards the manic phase may occur. Paranoid delusions, with or without associated hostility, may be aggravated. A major tranquilliser should be given concurrently in such cases, or dosage of amitriptyline reduced.

Unless essential, it is inadvisable to combine amitriptyline and electroconvulsive therapy (ECT).

Cardiac arrhythmias and severe hypotension are likely to occur with high dosages or in patients with pre-existing heart disease.

If possible, amitriptyline should be discontinued several days before surgery. If emergency surgery is unavoidable, the anaesthetist should be informed that the patient is being treated with amitriptyline.

Suicide/suicidal thoughts or clinical worsening

Suicidal thoughts and behaviours may also develop during early treatment with antidepressants for other disorders, the same precautions observed when treating patients with depression should therefore be followed when treating patients with other disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Alcohol: Enhances the sedative effect.

Alpha₂-adrenoceptor stimulants: Concomitant use of apraclonidine and brimonidine should be avoided.

Altretamine: Risk of severe postural hypotension.

Anaesthetics: Concomitant therapy may increase the risk of arrhythmias and hypotension. If surgery is necessary, the anaesthetist should be informed that a patient is being so treated.

Analgesics: There is a possibility of increased side effects with nefopam. The risk of CNS toxicity is increased with tramadol. There is a possibility of increased sedation with opioid analgesics.

Anti-arrhythmics: there is an increased risk of ventricular arrhythmias with drugs which prolong the QT interval, including amiodarone (avoid concomitant use), disopyramide, procainamide, propafenone and quinidine.

Antibacterials: Plasma concentrations of some tricyclics are reduced by rifampicin (reduces antidepressant effect). Concomitant use with linezolid may result in CNS excitation and hypertension.

Anticholinergics: Excessive anticholinergic effects may occur when tricyclic antidepressants are combined with anticholinergic drugs. Paralytic ileus, urinary retention or acute glaucoma may be precipitated, especially in elderly patients.

Antidepressants: Concomitant use with MAOIs results in CNS excitation and hypertension. Severe convulsions and fatalities have occurred. Therefore, amitriptyline should not be given with a MAOI, and a minimum of 14 days should elapse between discontinuing a MAOI and starting amitriptyline. After this time, amitriptyline should be used cautiously and dosage increased gradually. Concomitant use of reboxetine should be with caution. The plasma concentrations of some tricyclics are increased by SSRIs. Fluoxetine markedly inhibits Cytochrome P450 II D6, which is involved in the metabolism of a number of tricyclic antidepressants. Patients should be monitored for increased antidepressant plasma levels and toxicity when fluoxetine is used concurrently. Adjustment of the antidepressant dosage may be necessary.

Antiepileptics: Concomitant use of antiepileptics may lower the convulsive threshold. The plasma concentrations of some tricyclics may be reduced (eg by barbiturates, carbamazepine) resulting in reduced antidepressant effect.

Antifungals: Increased serum concentraions have occurred in patients also taking Fluconazole. Serious adverse effects have been reported due to increased amitriptyline plasma concentration.

Antihistamines: Increased anticholinergic and sedative effects. Concomitant use of terfenadine should be avoided due the increased risk of ventricular arrhythmias.

Antihypertensives: In general, the hypotensive effect is enhanced, but the effect of adrenergic neurone blockers (egguanethidine, debrisoquine, bethanidine) and clonidine may be antagonised. There is an increased risk of hypertension on clonidine withdrawal. It is advisable to review all antihypertensive therapy during treatment with tricyclic antidepressants.

Antipsychotics: Increased risk of ventricular arrhythmias. Avoid concomitant use with pimozide or thioridazine. Concomitant use with antipsychotics may increase plasma concentrations of tricyclic antidepressants and increase the anticholinergic side-effects of phenothiazines and possibly clozapine.

Antivirals: Based on the known metabolism of amitriptyline, the protease inhibitor, ritonavir, may increase the serum levels of amitriptyline. Therefore, careful monitoring of therapeutic and adverse effects is recommended when these drugs are administered concomitantly.

Anxiolytics and hypnotics: Concomitant use enhances the sedative effect. Caution is advised if patients receive large doses of ethchlorvynol concurrently. Transient delirium has been reported in patients treated with 1g ethchlorvynol and 75mg to 150mg of amitriptyline.

Beta-blockers: There is an increased risk of ventricular arrhythmias associated with concomitant use of sotalol.

Calcium-channel blockers: Diltiazem and verapamil may possibly increase the plasma concentration of amitriptyline.

Disulfiram: Concomitant use may inhibit the metabolism of tricyclics. Delirium has been reported in patients taking amitriptyline with disulfiram.

Diuretics: increased risk of postural hypotension.

Dopaminergics: Concomitant use with entacapone should be avoided. CNS toxicity has been reported with selegiline.

Muscle relaxants: Concomitant use of baclofen enhances its muscle relaxant effect.

Nitrates: Reduced effect of sublingual nitrates (owing to dry mouth).

Oestrogens and progestogens: Oral contraceptives antagonise the antidepressant effect but side-effects may be increased due to increased plasma concentrations of tricyclics.

Sibutramine: Concomitant use is not recommended due to the increased risk of CNS toxicity.

Sympathomimetics: Amitriptyline should not be given with sympathomimetic agents such as adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine and phenylpropanolamine due to hypertension and arrhythmias. Local anaesthetics with adrenaline appear to be safe. Methylphenidate may inhibit the metabolism of tricyclics and therefore increase the antidepressant action of amitriptyline.

Ulcer-healing drugs: Plasma concentrations of amitriptyline are increased by cimetidine (inhibition of metabolism).

In general, amitriptyline is well tolerated. Not all of the side-effects listed below have been reported with amitriptyline but are included due to the similar pharmacology of other tricyclics. Antidepressant effects of amitriptyline may not become apparent for the first 2-4 weeks of therapy so patients should be closely monitored during this period.

Allergic reactions: Skin rashes, urticaria, photosensitisation, oedema of face and tongue.

Blood and lymphatic system disorders: Bone marrow depression including agranulocytosis, eosinophilia, leucopenia, thrombocytopenia and purpura.

Endocrine disorders: Gynaecomastia, breast enlargement, galactorrhoea, testicular swelling, libido fluctuations, interference with sexual function, syndrome of inappropriate ADH secretion.

Metabolism and nutrition disorders: Elevation or lowering of blood sugar levels. Increased appetite and weight gain may be a drug reaction or due to relief of depression.

Nervous system disorders: Dizziness, fatigue, headache, drowsiness, weakness, disturbed concentration, disorientation, confusional states, insomnia, nightmares, delusions, hallucinations, hypomania, excitement, anxiety, restlessness, peripheral neuropathy, numbness, tingling and paraesthesia of the extremities, inco-ordination, ataxia, tremors, convulsions, altered ECG, extrapyramidal effects, tinnitus. Cases of suicidal ideation and suicidal behaviours have been reported during Amitriptyline therapy or early after treatment discontinuation (see section 4.4). Anticholinergic effects include: dry mouth, hyperpyrexia, blurred vision, accommodation disturbance, increased intra-ocular pressure, mydriasis, constipation, paralytic ileus, urinary retention, urinary tract dilatation.

Cardiovascular disorders: Postural hypotension, hypertension, palpitations, tachycardia, myocardial infarction, heart block and stroke. Arrhythmias and severe hypotension are likely to occur with high doses or overdosage.

Gastrointestinal disorders: Nausea, vomiting, diarrhoea, epigastric distress, anorexia, dysgeusia, stomatitis, parotid swelling, black tongue.

Hepato-biliary disorders: Rarely hepatitis (including altered liver function and jaundice).

Skin and subcutaneous tissue disorders: Increased perspiration and alopecia.

Renal and urinary disorders: Urinary frequency.

Class effects

Epidemiological studies show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this increased risk is unknown.

Abrupt withdrawal after prolonged administration has caused nausea, headache and malaise. Gradual withdrawal has been associated with transient symptoms such as dream and sleep disturbances, irritability and restlessness during the first two weeks of dosage reduction. These are not thought to be signs associated with addiction.

Mania or hypomania have been reported rarely within 2-7 days of stopping therapy with tricyclic antidepressants.

Side-effects in enuresis: As dosages used in enuresis are low compared to those used for depression, side-effects are less frequent. The most common are drowsiness and anticholinergic effects. Infrequently, mild sweating and itching have been reported. Behavioural changes have been observed in children receiving tricyclics for treatment of enuresis.

Actavis UK Ltd

POM-Prescription Only Medicine

21 November 2011