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AMITRIPTYLINE Film-coated tablets (2018)

Therapeutic indications

Amitriptyline tablets are indicated for:

  • Τhe treatment of major depressive disorder in adults.
  • Τhe treatment of neuropathic pain in adults.
  • Τhe prophylactic treatment of chronic tension type headache (CTTH) in adults.
  • Τhe prophylactic treatment of migraine in adults.
  • Τhe treatment of nocturnal enuresis in children aged 6 years and above when organic pathology, including spina bifida and related disorders, have been excluded and no response has been achieved to all other non-drug and drug treatments, including antispasmodics and vasopressin-related products. This medicinal product should only be prescribed by a healthcare professional with expertise in the management of persistent enuresis.

Posology and method of administration

Posology

Not all dosage schemes can be achieved with all the pharmaceutical forms/strengths. The appropriate formulation/strength should be selected for the starting doses and any subsequent dose increments.

Major depressive disorder

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

Adults

Initially 25 mg 2 times daily (50 mg daily). If necessary, the dose can be increased by 25 mg every other day up to 150 mg daily divided into two doses.

The maintenance dose is the lowest effective dose.

Elderly patients over 65 years of age and patients with cardiovascular disease

Initially 10 mg–25 mg daily.

The daily dose may be increased up to 100 mg – 150 mg divided into two doses, depending on individual patient response and tolerability.

Doses above 100 mg should be used with caution.

The maintenance dose is the lowest effective dose.

Paediatric population

Amitriptyline should not be used in children and adolescents aged less than 18 years, as long term safety and efficacy have not been established (see section 4.4).

Duration of treatment

The antidepressant effect usually sets in after 2-4 weeks. Treatment with antidepressants is symptomatic and must therefore be continued for an appropriate length of time usually up to 6 months after recovery in order to prevent relapse.

Neuropathic pain, prophylactic treatment of chronic tension type headache and prophylactic treatment of migraine prophylaxis

Patients should be individually titrated to the dose that provides adequate analgesia with tolerable adverse drug reactions. Generally, the lowest effective dose should be used for the shortest duration required to treat the symptoms.

Adults

Recommended doses are 25 mg-75 mg daily in the evening. Doses above 100 mg should be used with caution.

The initial dose should be 10 mg-25 mg in the evening. Doses can be increased with 10 mg-25 mg every 3–7 days as tolerated.

The dose can be taken once daily, or be divided into two doses. A single dose above 75 mg is not recommended.

The analgesic effect is normally seen after 2-4 weeks of dosing.

Elderly patients over 65 years of age and patients with cardiovascular disease

A starting dose of 10 mg-25 mg in the evening is recommended.

Doses above 75 mg should be used with caution.

It is generally recommended to initiate treatment in the lower dose range as recommended for adult. The dose may be increased depending on individual patient response and tolerability.

Paediatric population

Amitriptyline should not be used in children and adolescents aged less than 18 years, as safety and efficacy have not been established (see section 4.4).

Duration of treatment

Neuropathic pain: Treatment is symptomatic and should therefore be continued for an appropriate length of time. In many patients, therapy may be needed for several years. Regular reassessment is recommended to confirm that continuation of the treatment remains appropriate for the patient.

Prophylactic treatment of chronic tension type headache and prophylactic treatment of migraine in adults: Treatment must be continued for an appropriate length of time. Regular reassessment is recommended to confirm that continuation of the treatment remains appropriate for the patient.

Nocturnal enuresis

Paediatric population

The recommended doses for:

  • Children aged 6 to 10 years: 10 mg–20 mg. A suitable dosage form should be used for this age group.
  • Children aged 11 years and above: 25 mg–50 mg daily.

The dose should be increased gradually.

Dose to be administered 1-1½ hours before bedtime.

An ECG should be performed prior to initiating therapy with amitriptyline to exclude long QT syndrome.

The maximum period of treatment course should not exceed 3 months.

If repeated courses of amitriptyline are needed, a medical review should be conducted every 3 months.

When stopping treatment, amitriptyline should be withdrawn gradually.

Special populations

Reduced renal function

This medicinal product can be given in usual doses to patients with renal failure.

Reduced liver function

Careful dosing and, if possible, a serum level determination is advisable.

Cytochrome P450 inhibitors of CYP2D6

Depending on individual patient response, a lower dose of amitriptyline should be considered if a strong CYP2D6 inhibitor (e.g. bupropion, quinidine, fluoxetine, paroxetine) is added to amitriptyline treatment (see section 4.5).

Known poor metabolisers of CYP2D6 or CYP2C19

These patients may have higher plasma concentrations of amitriptyline and its active metabolite nortriptyline. Consider a 50% reduction of the recommended starting dose.

Method of administration

Amitriptyline tablet is for oral use.

The tablets should be swallowed with water.

Discontinuation of treatment

When stopping therapy the drug should be gradually withdrawn during several weeks.

Overdose

Symptoms

Anticholinergic symptoms: Mydriasis, tachycardia, urinary retention, dry mucous membranes, reduced bowel motility. Convulsions. Fever. Sudden occurrence of CNS depression. Lowered consciousness progressing into coma. Respiratory depression. Hyperreflexia may be present with extensor plantar reflexes. Hypothermia may occur.

Cardiac symptoms: Arrhythmias (ventricular tachyarrhythmias, torsade de pointes, ventricular fibrillation). The ECG characteristically show prolonged PR interval, widening of the QRS-complex, QT prolongation, T-wave flattening or inversion, ST segment depression, and varying degrees of heart block progressing to cardiac standstill. Widening of the QRS-complex usually correlates well with the severity of the toxicity following acute overdoses. Heart failure, hypotension, cardiogenic shock. Metabolic acidosis, hypokalemia.

Ingestion of 750 mg or more by an adult may result in severe toxicity. The effects in overdose will be potentiated by simultaneous ingestion of alcohol and other psychotropic.

There is considerably individual variability in response to overdose. Children are especially susceptible to cardiotoxicity and seizures.

During awakening possibly again confusion, agitation and hallucinations and ataxia.

Treatment

  1. Admission to hospital (intensive care unit) if required. Treatment is symptomatic and supportive.
  2. Assess and treat ABC’s (airway, breathing and circulation) as appropriate. Secure an IV access. Close monitoring even in apparently uncomplicated cases.
  3. Examine for clinical features. Check urea and electrolytes—look for low potassium and monitor urine output. Check arterial blood gases—look for acidosis. Perform electrocardiograph—look for QRS>0.16 seconds
  4. Do not give flumazenil to reverse benzodiazepine toxicity in mixed overdoses.
  5. Consider gastric lavage only if within one hour of a potentially fatal overdose.
  6. Give 50 g of charcoal if within one hour of ingestion.
  7. Patency of the airway is maintained by intubation, where required. Treatment in respirator is advised to prevent a possible respiratory arrest. Continuous ECG-monitoring of cardiac function for 3-5 days. Treatment of the following will be decided on a case by case basis:
    • Wide QRS-intervals, cardiac failure and ventricular arrhthmias
    • Circulatory failure
    • Hypotension
    • Hyperthermia
    • Convulsions
    • Metabolic acidosis.
  8. Unrest and convulsions may be treated with diazepam.
  9. Patients who display signs of toxicity should be monitored for a minimum of 12 hours.
  10. Monitor for rhabdomyolysis if the patient has been unconscious for a considerable time.
  11. Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Deaths by deliberate or accidental overdosage have occurred with this class of medicament.

For further information or treatment in children discuss with your local poisons information service in the UK NPIS 0844 892 0111.

Shelf life

Shelf life: 3 years.

Special precautions for storage

Container pack: Do not store above 25°C.

Store in the original container. Keep the container tightly closed.

Blister pack: Do not store above 25°C. Store in the original package.

Nature and contents of container

  1. High density polystyrene container with polythene lid and polyurethene/polythene insert. Pack size 100 and 500 Tablets.
  2. Polypropylene container with polypropylene or polythene lids and polyurethene/polythene insert. Pack size 100 and 500 Tablets.
  3. Blister pack of PVC/PVdC – Aluminium, containing 28 tablets.

Not all the pack sizes may be marketed.

Special precautions for disposal and other handling

No special instructions.