Amitriptyline

Registered South African indications:

• Depression
• Nocturnal enuresis

Contraindications

South African recommendations

• Hypersensitivity to amitriptyline hydrochloride, tricyclic antidepressants or to any of the ingredients
• The acute-phase after myocardial infarction and in patients with heart block
• History of myocardial infarction, dysrhythmias, congestive heart failure, coronary artery insufficiency
• Treatment of depression in children
• Those receiving monoamine oxidase inhibitors or for at least 14 days after their discontinuation
• Concurrent use with linezolid
• Concurrent use with antihypertensive medicines
• Pregnancy
• Lactation
• Severe liver disease
• Mania

Recommendations in other jurisdictions

• Hypersensitivity to the active substance or to any of the excipients
• Recent myocardial infarction. Any degree of heart block or disorders of cardiac rhythm and coronary artery insufficiency
• Concomitant treatment with MAOIs (monoamine oxidase inhibitors). Simultaneous administration of amitriptyline and MAOIs may cause serotonin syndrome (a combination of symptoms, possibly including agitation, confusion, tremor, myoclonus and hyperthermia)
• Treatment with amitriptyline may be instituted 14 days after discontinuation of irreversible non-selective MAOIs and minimum one day after discontinuation of the reversible moclobemide. Treatment with MAOIs may be introduced 14 days after discontinuation of amitriptyline
• Severe liver disease
• Children under 6 years of age

Cautions

• Pregnancy
• Mild to moderate hepatic impairment
• Elderly (≥60-74 years)
• Hyponatraemia
• Epilepsy
• Phaeochromocytoma
• Urinary retention
• Prostatic hypertrophy
• Narrow angle glaucoma
• Gastroesophageal reflux
• Hiatus hernia
• Cardiovascular disorder
• Thyroid disorders
• QT interval prolongation
• Diabetes mellitus
• Schizophrenia
• Suicide risk
• Electroconvulsive therapy
• Anaesthesia
• Abrupt discontinuation
• Blood dyscrasias
• Enuresis

Forms avail. in SA and covered in this monograph: fct, tab

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Endogenous depression

• Oral (fct): Initial: 25mg, 8hrly OR 50-100mg, dly at night; Titrate by 25-50mg, as required up to 150mg/day; Maintenance: 50-100mg, dly; Treatment duration: ≥3 months

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The antidepressant activity may be evident within 3-4 days or may take up to 30 days to develop adequately

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Treatment should be continued for at least 3 months before being gradually withdrawn. Hospitalised patients may be given doses of up to 200mg/day and, occasionally, up to 300mg/day

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Depression

• Oral (tab): Initial: 75-150mg/day, in divided doses; Maintenance: 50-100mg/day, in divided doses

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Indications and dosages registered in other jurisdictions

Major depressive disorder

• Oral (fct): Initial: 25mg, 12hrly; Titrate by 25mg at an interval of every other day up to 150mg/day in 2 divided doses; Treatment duration: Up to 6 months after recovery

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Dosage should be initiated at a low level and increased gradually, noting the clinical response and any evidence of intolerability carefully. The maintenance dose is the lowest effective dose

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

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Neuropathic pain
Chronic tension-type headache (CTTH) prophylaxis
Migraine prophylaxis

• Oral (fct): Initial: 10-25mg, at night; Titrate by 10-25mg at intervals of 3-7 days, as tolerated; Maintenance: 25-75mg/day in 1-2 divided doses

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A single dose above 75mg is not recommended. The analgesic effect is normally seen after 2-4 weeks of dosing. Doses above 100mg should be used with caution

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Titrate individually 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

Paed. forms avail. in SA and covered in this monograph: fct

Paed. dosages below include:

• South African Standard Treatment Guidelines indications and dosages
• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African Standard Treatment Guidelines indications and dosages

• Click here for the Pain Control (Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition)

South African registered indications and dosages

Nocturnal enuresis
- Adjunctive therapy, where organic pathology has been excluded

Oral (fct)

• Younger than 6 years: Not established for use
• Between 6-10 years: 10-20mg, at bedtime: Treatment duration: ≤3 months
• Between 11-16 years: 25-50mg, at bedtime: Treatment duration: ≤3 months

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Treatment of depression in children is contraindicated

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Indications and dosages registered in other jurisdictions

This medicinal product should only be prescribed by a healthcare professional with expertise in the management of persistent enuresis

Nocturnal enuresis
- 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

Oral (fct)

• Younger than 6 years: Contraindicated
• Between 6-10 years: 10-20mg, at bedtime: Treatment duration: ≤3 months
• Older than 11 years: 25-50mg, at bedtime: Up-titrate dose gradually; Treatment duration: ≤3 months

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Dose to be administered 60-90mins before bedtime. An electrocardiogram (ECG) should be performed prior to initiating therapy with amitriptyline to exclude long QT syndrome

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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

Pregnancy

• Contraindicated 
• Amitriptyline should not be taken during pregnancy. Safety in pregnancy and lactation has not been established, only limited data is available. Animal studies have shown reproductive toxicity

Breastfeeding

• Contraindicated
• Amitriptyline and its metabolites are excreted into breast milk (corresponding to 0.6% - 1% of the maternal dose). A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from the therapy of this medicinal product taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility

• Amitriptyline reduced the pregnancy rate in rats. No data on the effects of amitriptyline on human fertility are available

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated 

Elderly

• ≥60-74 years: Caution; dose adjustment recommended
  Limit use for clinical cases of depression and postherpetic neuralgia
  Use with high caution; Max: 50-100mg/24hrs  
• ≥75 years or elderly with a cardiac condition: Contraindicated

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Delusions
• Hallucinations
• Mania
• Hypomania
• Anxiety
• Agitation
• Suicidal ideation 
• Suicidal behaviours  
• Increased libido
• Decreased libido
• Anorgasmia
• Delayed orgasm in women
• Fatigue
• Headache
• Drowsiness
• Weakness
• Nightmares
• Confusional states
• Disturbed concentration
• Disorientation
• Insomnia
• Peripheral neuropathy
• Incoordination
• Ataxia
• Tremors
• Convulsions
• Coma
• Extrapyramidal effects
• Hyperpyrexia

Cardiovascular Disorders

• Hypotension
• Syncope
• Postural hypotension
• Dizziness
• Hypertension
• Tachycardia
• Palpitations
• Myocardial infarction
• Arrhythmias
• Heart block
• Sudden cardiac death
• Stroke
• Alteration of the ECG 
• Arrhythmias 
• Severe hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Epigastric distress
• Anorexia
• Dysgeusia
• Stomatitis
• Parotid swelling
• Black tongue
• Taste dysfunction
• Dry mouth
• Constipation
• Paralytic ileus

Hepatobiliary Disorders

• Hepatitis 
• Hepatic necrosis

Genitourinary Disorders

• Urinary frequency
• Urinary retention
• Urinary tract dilatation
• Gynaecomastia
• Breast enlargement
• Galactorrhoea
• Testicular swelling
• Sexual dysfunction
• Impotence

Endocrine and Metabolic Disorders

• Syndrome of inappropriate antidiuretic hormone secretion
• Hyponatraemia
• Disturbances in blood glucose levels
• Increased appetite
• Increased weight  
• Decreased weight

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Increased perspiration
• Alopecia

Immune, Blood and Lymphatic System Disorders

• Bone marrow depression 
• Skin rash
• Urticaria
• Photosensitisation
• Oedema of face and tongue

Sensory Disorders

• Mydriasis
• Blurred vision
• Disturbance of accommodation
• Increased intra-ocular pressure
• Tinnitus

• Monoamine oxidase inhibitors
• Linezolid
• Antihypertensives
• QT prolonging agents
• Alcohol
• Alpha-2 agonists
• Anaesthetics
• Analgesics
• Antiarrhythmics
• Antibacterials
• Anticholinergics
• Anticoagulants
• Antidepressants
• Antiepileptics
• Antifungals
• Antihistamines
• Antipsychotics
• Antivirals
• Central nervous system depressants
• Beta blockers
• Central nervous system stimulants
• Diuretics
• Dopaminergics
• Muscle relaxants
• Nitrates
• Oestrogens 
• Progestogens
• Smoking
• St John's wort
• Sympathomimetics
• Thyroid hormone
• Cimetidine

None routine. Specific cases may require

• Vital signs
• Blood glucose
• ECG

Amitriptyline is a tricyclic antidepressant.  It is metabolized to nortriptyline, which inhibits the membrane pump mechanism responsible for re-uptake of norepinephrine and serotonin in adrenergic and serotonergic neutrons.  It also decreases the amount of time spent in REM sleep, stimulates vasopressin secretion and relaxes the detrusor muscle.

Tablet 10mg

• Amitriptyline 10mg (Austell Laboratories)
• Amderip 10 (Strides Pharma)
• Trepiline (Pharmacare)
• Veikirin 10 (Strides Pharma)

Tablet 25mg

• Amderip 25 (Strides Pharma)
• Gulf amitriptyline (Gulf Drug)
• Sandoz amitriptyline (Sandoz)
• Trepiline (Pharmacare)
• Tryptanol (MSD) Originator
• Veikirin 25 (Strides Pharma)