Plain-language summary, compiled from the cited regulatory records
Amitriptyline is a medication classified as a non-selective monoamine reuptake inhibitor [1]. It is approved for the relief of symptoms associated with depression [1]. Studies suggest that endogenous depression is more likely to respond to treatment with amitriptyline compared to other forms of depressive states [1].
This active ingredient is available under various brand names in the market [1].
This is not medical advice. Consult a qualified healthcare professional.
GBOfficial regulatory label· revised May 29, 2026[1]
• the treatment of major depressive disorder in adults • the treatment of neuropathic pain in adults • the prophylactic treatment of chronic tension type headache (CTTH) in adults • the prophylactic treatment of migraine in adults • the 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
How to take
USUnited States· FDA
10 products
Uses
USOfficial regulatory label· revised January 23, 2026[2]
INDICATIONS AND USAGE
For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than are other depressive states.
How to take
US
CACanada· Health Canada
4 products
Uses
CAOfficial regulatory label· revised March 22, 2025[3]
Amitriptyline Hydrochloride Tablets USP (amitriptyline hydrochloride) is indicated for: • Drug management of depressive illness. • Depressive illness of psychotic or endogenous nature and in selected patients with neurotic depression.
Endogenous depression is more likely to be alleviated than are other depressive states. Amitriptyline Hydrochloride Tablets USP, because of its sedative action, is also of value in alleviating the anxiety component of depression. As with other tricyclic antidepressants, Amitriptyline Hydrochloride Tablets USP may precipitate hypomanic episodes in patients with bipolar depression.
These drugs are not indicated in mild depressive states and depressive reactions. 1 Pediatrics Pediatrics (˂ 18 years of age): Health Canada has not authorized an indication for pediatric use. 2 Geriatrics Geriatrics: Evidence from clinical studies and experience suggests that use in the geriatric population is associated with differences in safety or effectiveness.
Drug interactions
Known interactions involving Amitriptyline. Select one for details. This list is informational and not a complete interaction checker.
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Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[2]FDA DailyMed · 147d2f8f-842d-4f… · revised January 23, 2026 [PDF]
[3]Health Canada (DPD) · 02462737 · revised March 22, 2025
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
GBOfficial regulatory label· revised May 29, 2026[1]
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 25mg (5ml of the 25mg/5ml strength) 2 times daily. If necessary, the dose can be increased by 25mg (5ml of the 25mg/5ml strength) every other day up to 150mg (30ml of the 25mg/5ml strength) 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 10mg (2ml of the 25mg/5ml strength) - 25mg (5ml of the 25mg/5ml strength) daily. The daily dose may be increased up to 100mg (20ml of the 25mg/5ml strength) – 150mg (30ml of the 25mg/5ml strength) divided into two doses, depending on individual patient response and tolerability.
Daily doses above 100mg (20ml of the 25mg/5ml strength) should be used with caution. The maintenance dose is the lowest effective dose. 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 in adults 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 25mg (5ml of the 25mg/5ml strength) - 75mg (15ml of the 25mg/5ml strength) daily in the evening.
Doses above 100mg (20ml of the 25mg/5ml strength) should be used with caution. The initial dose should be 10mg (2ml of the 25mg/5ml strength) – 25mg (5ml of the 25mg/5ml strength) in the evening. Doses can be increased with 10mg (2ml of the 25mg/5ml strength) – 25mg (5ml of the 25mg/5ml strength) every 3 – 7 days as tolerated.
The dose can be taken once daily, or be divided into two doses. A single dose above 75mg (15ml of the 25mg/5ml dose) 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 10mg (2ml of the 25mg/5ml strength) - 25mg (5ml of the 25mg/5ml strength) in the evening is recommended.
Doses above 75mg (15ml) 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.
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: 10mg (2ml of the 25mg/5ml strength) - 20mg (4ml of the 25mg/5ml strength). • children aged 11 years and above: 25mg (5ml of the 25mg/5ml strength) – 50mg (10ml of the 25mg/5ml strength) 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. Duration of treatment 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. g. 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 For oral administration Use the measuring syringe to measure the appropriate amount, whether its use is for an adult or child. 5ml. 5mg of amitriptyline for the 25mg/5ml strength.
Using the syringe: • Place the end of the syringe into the bottle • To fill the syringe, gently pull the plunger drawing the medicine to the correct mark on the syringe. Your doctor will tell you the right dose • Remove the syringe and place the end into your mouth.
Press the plunger down to slowly and gently release the medicine • After use, replace the bottle cap. Wash the syringe in warm water and allow to dry. Store out of […]
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised May 29, 2026[1]
Amitriptyline may induce side effects similar to other tricyclic antidepressants. g. headache, tremor, disturbance in attention, constipation and decreased libido may also be symptoms of depression and usually attenuate when the depressive state improves.
4) In the listing below the following convention is used: MedDRA system organ class / preferred term; Very common (> 1/10); Common (> 1/100, < 1/10); Uncommon (> 1/1,000, < 1/100); Rare (> 1/10,000, < 1/1,000); Very rare (< 1/10,000);Not known (cannot be estimated from the available data).
MedDRA SOC Frequency Preferred Term Blood and lymphatic system disorders Rare Bone marrow depression, including agranulocytosis, leucopenia, eosinophilia, thrombocytopenia. Immune system disorders Uncommon Face oedema, tongue oedema.
Rare Decreased appetiteMetabolism and nutrition disorders Not known Anorexia, elevation or lowering of blood sugar levels. Very common Aggression. Common Confusional state, libido decreased, agitation Uncommon Hypomania, mania, anxiety, insomnia, nightmare Rare Delirium (in elderly patients), hallucination, suicidal thoughts or behaviours* Psychiatric disorders Not known Paranoia Very common Somnolence, tremor, dizziness, headache, drowsiness, speech disorder, (dysarthria) Common Disturbance in attention, dysgeusia, paraesthesia, ataxia Uncommon Convulsion Very Rare Akathisia, polyneuropathy Nervous system disorders Not known Extrapyramidal disorder Very common Accommodation disorder Common Mydriasis Very rare Acute glaucoma Eye disorders Not known Dry eye Ear and Labyrinth disorders Uncommon Tinnitus Very common Palpitations, tachycardia Common Atrioventricular block, bundle branch block Uncommon Collapse conditions, worsening of cardiac failure Rare Arrhythmia Very Rare Cardiomyopathies, torsades de pointes Cardiac disorders Not known Hypersensitivity myocarditis Very common Orthostatic hypotension Common Hypertension Vascular disorders Not known Hyperthermia Very common Congested noseRespiratory, thoracic and mediastinal disorders Rare Allergic inflammation of the pulmonary alveoli and of the lung tissue, respectively (alveolitis, Löffler’s syndrome) Very common Dry mouth, constipation, nausea Uncommon Diarrhoea, vomiting, tongue oedema Rare Salivary gland enlargement, ileus paralytic Gastrointestinal disorders Not known Epigastric distress, stomatitis.
4). Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown. Side-effects in enuresis Behavioural changes have been observed in children receiving tricyclics for treatments of enuresis.
Dosages used in enuresis are low compared with those used in depression and side-effects are therefore less frequent. The most common are drowsiness and anticholinergic effects. The only other side-effects, reported infrequently at these dosages, have been mild sweating and itching.
The recommended dosage must not be exceeded.
Withdrawal symptoms:
The symptoms associated with withdrawal of tricyclic antidepressants, particularly after prolonged administration, include gastrointestinal disturbances such as nausea; generalised somatic symptoms such as malaise, chills, headache and increased perspiration; irritability, restlessness, anxiety and agitation; sleep disturbances (insomnia and vivid dreams); parkinsonism or akasthisia; hypomania or mania (reported rarely, occurring within 2-7 days of stopping chronic therapy with tricyclic antidepressants); cardiac arrhythmias.
These symptoms are not indicative of addiction. Withdrawal symptoms seem to be more common and more severe in children. Adverse reactions such as withdrawal symptoms, respiratory depression and agitation have been reported in neonates whose mothers had taken tricyclic antidepressants in the last trimester of pregnancy.
Reporting of suspected adverse reactions:
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised May 29, 2026[1]
Amitriptyline should be used with caution in patients with a history of epilepsy, and in those with impaired liver function or phaeochromocytoma. Blood sugar concentrations may be altered in diabetic patients. When used for the depressive component of schizophrenia, amitriptyline may aggravate psychotic symptoms.
Cardiac arrhythmias and severe hypotension are likely to occur with high dosage. They may also occur in patients with pre-existing heart disease taking normal dosage. QT interval prolongation Cases of QT interval prolongation and arrhythmia have been reported during the post- marketing period.
Caution is advised in patients with significant bradycardia, in patients with uncompensated heart failure, or in patients concurrently taking QT- prolonging drugs. Electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia) are known to be conditions increasing the proarrythmic risk.
Anaesthetics given during tri/tetracyclic antidepressant therapy may increase the risk of arrhythmias and hypotension. If possible, discontinue this medicinal product several days before surgery; if emergency surgery is unavoidable, the anaesthetist should be informed that the patient is being so treated.
Great care is necessary if amitriptyline is administered to hyperthyroid patients or to those receiving thyroid medication, since cardiac arrhythmias may develop. Elderly patients are particularly susceptible to orthostatic hypotension.
This medical product should be used with caution in patients with convulsive disorders, urinary retention, prostatic hypertrophy, hyperthyroidism, paranoid symptomatology and advanced hepatic or cardiovascular disease, pylorus stenosis and paralytic ileus.
In patients with the rare condition of shallow anterior chamber and narrow chamber angle, attacks of acute glaucoma due to dilation of the pupil may be provoked. Suicide/suicidal thoughts Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events).
This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised May 29, 2026[1]
1. Recent myocardial infarction. Any degree of heart block or disorders of cardiac rhythm and coronary artery insufficiency. 5). 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. In children under 6 years of age.
This is not medical advice. Consult a qualified healthcare professional.
Oral Dosage Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. Initial Dosage for Adults For outpatients, 75 mg of amitriptyline hydrochloride a day in divided doses is usually satisfactory.
If necessary, this may be increased to a total of 150 mg per day. Increases are made preferably in the late afternoon and/or bedtime doses. A sedative effect may be apparent before the antidepressant effect is noted, but an adequate therapeutic effect may take as long as 30 days to develop.
An alternate method of initiating therapy in outpatients is to begin with 50 to 100 mg amitriptyline hydrochloride at bedtime. This may be increased by 25 or 50 mg as necessary in the bedtime dose to a total of 150 mg per day. Hospitalized patients may require 100 mg a day initially.
This can be increased gradually to 200 mg a day if necessary. A small number of hospitalized patients may need as much as 300 mg a day. Adolescent and Elderly Patients In general, lower dosages are recommended for these patients. Ten mg 3 times a day with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages.
Maintenance The usual maintenance dosage of amitriptyline hydrochloride is 50 to 100 mg per day. In some patients, 40 mg per day is sufficient. For maintenance therapy, the total daily dosage may be given in a single dose, preferably 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.
Usage in Pediatric Patients In view of the lack of experience with the use of this drug in pediatric patients, it is not recommended at the present time for patients under 12 years of age. 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. Because of increased intestinal transit time and decreased hepatic metabolism in elderly patients, plasma levels are generally higher for a given oral dose of amitriptyline hydrochloride than in younger patients.
Elderly patients should be monitored carefully and quantitative serum levels obtained as clinically appropriate. Adjustments in dosage should be made according to the patient's clinical response and not on the basis of plasma levels.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised January 23, 2026[2]
ADVERSE REACTIONS
Within each category the following adverse reactions are listed in order of decreasing severity. Included in the listing are a few adverse reactions which have not been reported with this specific drug. However, pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when amitriptyline hydrochloride is administered.
Cardiovascular:
Myocardial infarction; stroke; nonspecific ECG changes and changes in AV conduction; heart block; arrhythmias; hypotension, particularly orthostatic hypotension; syncope; hypertension; tachycardia; palpitation.
CNS and Neuromuscular:
Coma; seizures; hallucinations; delusions; confusional states; disorientation; incoordination; ataxia; tremors; peripheral neuropathy; numbness, tingling and paresthesias of the extremities; extrapyramidal symptoms including abnormal involuntary movements and tardive dyskinesia; dysarthria; disturbed concentration; excitement; anxiety; insomnia; restlessness; nightmares; drowsiness; dizziness; weakness; fatigue; headache; syndrome of inappropriate ADH (antidiuretic hormone) secretion; tinnitus; alteration in EEG patterns.
Anticholinergic:
Paralytic ileus, hyperpyrexia; urinary retention, dilatation of the urinary tract; constipation; blurred vision, disturbance of accommodation, increased ocular pressure, mydriasis; dry mouth.
Allergic:
Skin rash; urticaria; photosensitization; edema of face and tongue.
Hematologic:
Bone marrow depression including agranulocytosis, leukopenia, thrombocytopenia; purpura; eosinophilia.
Gastrointestinal:
Rarely hepatitis (including altered liver function and jaundice); nausea; epigastric distress; vomiting; anorexia; stomatitis; peculiar taste; diarrhea; parotid swelling; black tongue.
Endocrine:
Testicular swelling and gynecomastia in the male; breast enlargement and galactorrhea in the female; increased or decreased libido; impotence; elevation and lowering of blood sugar levels.
Other:
Alopecia; edema; weight gain or loss; urinary frequency; increased perspiration, hyponatremia. Withdrawal Symptoms After prolonged administration, abrupt cessation of treatment 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 symptoms 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. Causal Relationship Unknown Other reactions, reported under circumstances where a causal relationship could not be established, are listed to serve as alerting information to physicians: Body as a Whole: Lupus-like syndrome (migratory arthritis, positive ANA and rheumatoid factor).
Digestive:
Hepatic failure, ageusia. Postmarketing Adverse Events A syndrome resembling neuroleptic malignant syndrome (NMS) has been very rarely reported after starting or increasing the dose of amitriptyline hydrochloride, with and without concomitant medications known to cause NMS.
Symptoms have included muscle rigidity, fever, mental status changes, diaphoresis, tachycardia, and tremor. Very rare cases of serotonin syndrome (SS) have been reported with amitriptyline hydrochloride in combination with other drugs that have a recognized association with SS.
gov/medwatch.
USOfficial regulatory label· Warnings and precautions· revised January 23, 2026[2]
WARNINGS
Clinical Worsening and Suicide Risk Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.
Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.
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 behavior (suicidality) in children, adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other psychiatric disorders.
Short-term studies did not show an increase in the 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. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4,400 patients.
The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median 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.
There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. 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 1,000 patients treated) are provided in Table 1. Table 1 Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Patients Treated Increases Compared to Placebo <18 14 additional cases 18 to 24 5 additional cases Decreases Compared to Placebo 25 to 64 1 fewer case ≥65 6 fewer cases No suicides occurred in any of the pediatric trials.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised January 23, 2026[2]
CONTRAINDICATIONS
Amitriptyline hydrochloride is contraindicated in patients who have shown prior hypersensitivity to it. It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously.
When it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. Amitriptyline hydrochloride should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.
Amitriptyline hydrochloride should not be given with cisapride due to the potential for increased QT interval and increased risk for arrhythmia. This drug is not recommended for use during the acute recovery phase following myocardial infarction.
This is not medical advice. Consult a qualified healthcare professional.
How to take
CAOfficial regulatory label· revised March 22, 2025[3]
1 Dosing Considerations Dosage should be initiated at a low level and increased gradually according to tolerance and clinical response. Cardiac Prior to initiating treatment with Amitriptyline Hydrochloride Tablets USP, a cardiac evaluation, including blood pressure and electrocardiogram examinations, should be performed, particularly in patients with a history of cardiovascular disorders (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).
2 Recommended Dose and Dosage Adjustment Outpatient Adults The recommended initial dose for ambulatory patients is 25 mg 3 times a day. Depending upon Page 6 of 34 tolerance and response, this may be increased gradually 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 3 or 4 days or may take up to 30 days to develop adequately.
Hospitalized Patients Severely ill or hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg a day if necessary. A small number of hospitalized patients may need as much as 300 mg a day. Pediatric Patients Health Canada has not authorized an indication for pediatric use.
Elderly Patients When considering the use of amitriptyline in elderly patients, the potential risks must be balanced with clinical need. 4 Geriatrics. In general, lower dosages are recommended for these patients. In those patients who may not tolerate higher doses, 50 mg daily may be satisfactory.
The dose may be administered in divided doses or as a single dose preferably in the evening or at bedtime. Maintenance When satisfactory improvement has been reached, dosage should be reduced to the lowest amount that will maintain relief of symptoms.
The usual maintenance dose is 50 to 100 mg/day in divided doses; however, in suitable patients, the total daily dosage may be given in a single dose, preferably at bedtime. It is appropriate to continue maintenance therapy throughout the active phase of the depression and for the expected duration of the depressive episode, in order to lessen the possibility of relapse.
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 non- compliance is suspected.
Adjustments in dosage should be made according to the patient’s clinical response and not on the basis of plasma levels. 4 Drug-Drug Interactions). 4 Administration Amitriptyline Hydrochloride Tablets USP tablets should be swallowed whole with water.
Amitriptyline Hydrochloride Tablets USP can be administered with or without food. 5 Missed Dose If the patient misses a dose, instruct the patient to take the dose as soon as they remember. If it is almost time for the next dose, inform the patient to skip the missed dose and continue the regular dosing schedule.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[3]
Symptoms of overdose may vary in severity depending on various factors such as the amount of drug absorbed, the interval between drug ingestion and start of treatment, and the age of the patient. In patients with glaucoma, even average doses may precipitate an attack.
Treatment Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible. In managing overdose, consider the possibility of multiple drug overdose, interactions among drugs, and unusual drug kinetics.
Treatment is symptomatic and supportive. Cardiac arrhythmias and CNS involvement pose the greatest threat and may occur suddenly even when initial symptoms appear to be mild. Therefore, patients who may have ingested an overdosage of amitriptyline, particularly children, should be hospitalized and kept under close surveillance.
General:
Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient’s airway, establish an intravenous line and initiate gastric decontamination. A minimum of six hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary.
If signs of toxicity occur at any time during the period, extended monitoring is required. There are case reports of patients succumbing to fatal dysrhythmias late after overdose (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular); these patients had clinical evidence of significant poisoning prior to death and most received inadequate gastrointestinal decontamination.
Monitoring of plasma drug levels should not guide management of the patient.
Gastrointestinal Decontamination:
EMESIS IS CONTRAINDICATED. All patients suspected of tricyclic antidepressant overdose should receive gastrointestinal decontamination. This should include, large volume gastric lavage followed by activated charcoal. If consciousness is Page 8 of 34 impaired, the airway should be secured prior to lavage.
10 seconds may be the best indication of the severity of the overdose. 55. If the pH response is inadequate, hyperventilation may also be used. Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring.
60 or a pCO < 20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine or bretylium. , quinidine, disopyramide and procainamide and flecainide). In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity.
However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning.
CNS:
In patients with CNS depression early intubation is advised because of the potential for abrupt deterioration. , phenobarbital, phenytoin). 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 – Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral Tablet 10 mg, 25 mg, 50 mg, and 75 mg of amitriptyline hydrochloride Colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, purified talc and titanium dioxide.
In addition to the above ingredients the tablets also contain the following non- medicinal ingredients: Amitriptyline Hydrochloride Tablets USP 10 mg tablets: triacetin and the dye FD&C Blue No. A1. Lake.
For management of a suspected drug overdose, contact your regional poison control centre. Page 9 of 34 polyethylene glycol and the dye D&C Yellow No. 10 Lake. 6 and FD&C Blue No. 2 A1 Lake. Amitriptyline Hydrochloride Tablets USP 75 mg tablets: polyethylene glycol and the dye Lake Sunset Yellow.
Amitriptyline Hydrochloride Tablets USP 10 mg:
Round, blue colored, biconvex tablets, debossed “A” on one side and “10” on other side. Contains 10 mg of amitriptyline hydrochloride. Available in HDPE bottles of 100 and 1000 tablets, and blisters of Alu/Alu 10 x 10 tablets.
Amitriptyline Hydrochloride Tablets USP 25 mg:
Round, yellow colored, biconvex tablets debossed “A” on one side and “25” on other side. Contains 25 mg of amitriptyline hydrochloride. Available in HDPE bottles of 100 and 1000 tablets, and blisters of Alu/Alu 10 x 10 tablets.
Amitriptyline Hydrochloride Tablets USP 50 mg:
Round, brown colored, biconvex tablets debossed “A” on one side and ”50” on other side. Contains 50 mg of amitriptyline hydrochloride. Available in HDPE bottles of 100 and 1000 tablets, and blisters of Alu/Alu 10 x 10 tablets.
Amitriptyline Hydrochloride Tablets USP 75 mg:
Round, orange colored, biconvex tablets debossed “A” on one side and ”75” on other side. Contains 75 mg of amitriptyline hydrochloride. Available in HDPE bottles of 100 and 1000 tablets, and blisters of Alu/Alu 10 x 10 tablets. 7 WARNINGS AND PRECAUTIONS Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.
General Due to its anticholinergic activity, amitriptyline should be used with caution in patients with a history of urinary retention, or with narrow-angle glaucoma or increased intraocular pressure. The potency of amitriptyline is such that addition of other antidepressant drugs generally does not result in any additional therapeutic benefit.
Untoward reactions have been reported after the combined use of antidepressant agents having […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[3]
, Neurologic. Page 5 of 34 3 SERIOUS WARNINGS AND PRECAUTIONS BOX Serious Warnings and Precautions • Extreme caution should be used when Amitriptyline Hydrochloride Tablets USP is given in the following situations: • Cases of QT interval prolongation, cardiac arrhythmia and severe hypotension have been reported.
A few instances of unexpected death have also been reported in patients with cardiovascular disorders. Myocardial infarction and stroke have been reported with drugs of this class. , significant bradycardia, myocardial infarction, congestive or uncompensated heart failure), conduction abnormalities or those concurrently taking QT-prolonging drugs.
4 Drug-Drug Interactions. • In patients with a history or urinary retention or in patients with increased intraocular pressure or narrow angle glaucoma, because of the anticholinergic properties of amitriptyline hydrochloride. See 7 WARNINGS AND PRECAUTIONS, General; 7 WARNINGS AND PRECAUTIONS, Ophthalmologic.
• In patient with thyroid disease or those taking thyroid medication, because of the possibility of cardiovascular toxicity, including arrhythmias. See 7 WARNINGS AND PRECAUTIONS, Endocrine and Metabolism. • In patients with a history of a seizure disorder, because amitriptyline hydrochloride has been shown to lower the seizure threshold.
See 7 WARNINGS AND PRECAUTIONS, Neurologic. • Potential association with behavioural and emotional changes, including self-harm and suicidal ideation and behaviour. See 7 WARNINGS AND PRECAUTIONS, Psychiatric. 1 Dosing Considerations Dosage should be initiated at a low level and increased gradually according to tolerance and clinical response.
Cardiac Prior to initiating treatment with Amitriptyline Hydrochloride Tablets USP, a cardiac evaluation, including blood pressure and electrocardiogram examinations, should be performed, particularly in patients with a history of cardiovascular disorders (see 7 WARNINGS AND PRECAUTIONS, Cardiovascular).
2 Recommended Dose and Dosage Adjustment Outpatient Adults The recommended initial dose for ambulatory patients is 25 mg 3 times a day. Depending upon Page 6 of 34 tolerance and response, this may be increased gradually to a total of 150 mg a day.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
CAOfficial regulatory label· Contraindications· revised March 22, 2025[3]
Amitriptyline Hydrochloride Tablets USP (amitriptyline hydrochloride) is contraindicated in: • Patients who are hypersensitive to amitriptyline hydrochloride or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.
For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING. • Patients with recent myocardial infarction or acute congestive heart failure. • Patients with severe liver impairment. • Combination with a monoamine oxidase inhibitor (MAOI) due to the risk of serotonin toxicity (a combination of symptoms that may include agitation, confusion, tremor, myoclonus, and hyperthermia).
Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving concomitant tricyclic antidepressants and MAOIs. Treatment with a MAOI should be discontinued at least 14 days before initiating treatment with amitriptyline.
Similarly, amitriptyline treatment should be discontinued at least 14 days before starting a MAOI. See 7 WARNINGS AND PRECAUTIONS, Neurologic. Page 5 of 34
This is not medical advice. Consult a qualified healthcare professional.
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.
In manic-depressives, a shift towards the manic phase may occur; should the patient enter a manic phase amitriptyline should be discontinued. As described for other psychotropics, amitriptyline may modify insulin and glucose responses calling for adjustment of the antidiabetic therapy in diabetic patients; in addition the depressive illness itself may affect patients’ glucose balance.
Hyperpyrexia has been reported with tricyclic antidepressants when administered with anticholinergic or with neuroleptic medications, especially in hot weather. After prolonged administration, abrupt cessation of therapy may produce withdrawal symptoms such as headache, malaise, insomnia and irritability.
5). Nocturnal enuresis An ECG should be performed prior to initiating therapy with amitriptyline to exclude long QT syndrome. Amitriptyline for enuresis should not be combined with an anticholinergic drug. Suicidal thoughts and behaviours may also develop during early treatment with antidepressants for disorders other than depression; the same precautions observed when treating patients with depression should therefore be followed when treating patients with enuresis.
Severe cutaneous reactions Severe cutaneous adverse reactions (SCARs) including drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported in association with amitriptyline treatment.
Most of these reactions occurred within 2 to 6 weeks. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for cutaneous reactions. If signs and symptoms suggestive of these reactions appear, amitriptyline should be withdrawn immediately, treatment with amitriptyline must not be restarted in this patient at any time and, an alternative treatment should be considered (as appropriate).
5). If concomitant treatment with buprenorphine is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases. Symptoms of serotonin syndrome may include mental-status changes, autonomic instability, neuromuscular abnormalities, and/or gastrointestinal symptoms.
If serotonin syndrome is suspected, a dose reduction or discontinuation of therapy should be considered depending on the severity of the symptoms. Paediatric population Long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are not […]
There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. , 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.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients 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 the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers.
Such monitoring should include daily observation by families and caregivers. Prescriptions for amitriptyline hydrochloride tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Serotonin Syndrome:
The development of a potentially life-threatening serotonin syndrome has been reported with tricyclic antidepressants, including amitriptyline hydrochloride tablets, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, SSRI/SNRI, fentanyl, lithium, tramadol, tryptophan, buspirone, and St.
John's Wort) and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). , nausea, vomiting, diarrhea).
Patients should be monitored for the emergence of serotonin syndrome. The concomitant use of amitriptyline hydrochloride tablets with MAOIs intended to treat psychiatric disorders is contraindicated. Amitriptyline hydrochloride tablets should also not be started in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue.
All reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses.
There may be circumstances when it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking amitriptyline hydrochloride tablets. Amitriptyline hydrochloride tablets should be discontinued before initiating treatment with the MAOI (see CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).
If concomitant use of amitriptyline hydrochloride tablets with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and St. John's Wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
Treatment with amitriptyline hydrochloride tablets and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. Screening Patients for Bipolar Disorder A major depressive episode may be the initial presentation of bipolar disorder.
It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder.
Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
It should be noted that amitriptyline hydrochloride tablets are not approved for use in treating bipolar depression. Amitriptyline hydrochloride tablets may block the antihypertensive action of guanethidine or similarly acting compounds.
It should be used with caution in patients with a history of seizures and, because of its atropine-like action, in patients with a history of urinary retention or angle-closure glaucoma. In patients with angle-closure glaucoma, even average doses may precipitate an attack.
Patients with cardiovascular disorders should be watched closely. Tricyclic antidepressant drugs, including amitriptyline hydrochloride tablets, 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 drugs of this class. Close supervision is required when amitriptyline hydrochloride tablets are given to hyperthyroid patients or those receiving thyroid medication. Amitriptyline hydrochloride tablets may enhance the response to alcohol and the effects of barbiturates and other CNS depressants.
In patients who may use alcohol excessively, it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage. Delirium has been reported with concurrent administration of amitriptyline hydrochloride tablets and disulfiram.
Hyponatremia Hyponatremia has occurred as a result of treatment with amitriptyline hydrochloride tablets. In many cases, hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls.
Signs and symptoms associated with more severe and/or acute cases have included syncope, seizure, coma, respiratory arrest, and death. In patients with symptomatic hyponatremia, discontinue amitriptyline hydrochloride tablets and institute appropriate medical intervention.
Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with amitriptyline hydrochloride tablets. Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including amitriptyline hydrochloride tablets may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Usage in Pregnancy Teratogenic effects were not observed in mice, rats, or rabbits when amitriptyline was given orally at doses of 2 to 40 mg/kg/day (up to 13 times the maximum recommended human dose 1 ). Studies in literature have shown amitriptyline to be teratogenic in mice and hamsters when given by various routes of administration at doses of 28 to 100 mg/kg/day (9 to 33 times the maximum recommended human dose), producing multiple malformations.
Another study in the rat reported that an oral dose of 25 mg/kg/day (8 times the maximum recommended human dose) produced delays in ossification of fetal vertebral bodies without other signs of embryotoxicity. In rabbits, an oral dose of 60 mg/kg/day (20 times the maximum recommended human dose) was reported to cause incomplete ossification of cranial bones.
Amitriptyline has been shown to cross the placenta. Although a causal relationship has not been established, there have been a few reports of adverse events, including CNS effects, limb deformities, or developmental delay, in infants whose mothers had taken amitriptyline during pregnancy.
There are no adequate and well-controlled studies in pregnant women. Amitriptyline hydrochloride should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. 1 Based on a maximum recommended amitriptyline dose of 150 mg/day or 3 mg/kg/day for a 50 kg patient.
Nursing Mothers Amitriptyline hydrochloride is excreted into breast milk. In one report in which a patient received amitriptyline hydrochloride tablet 100 mg/day while nursing her infant, levels of 83 to 141 ng/mL were detected in the mother's serum.
Levels of 135 to 151 ng/mL were found in the breast milk, but no trace of the drug could be detected in the infant's serum. Because of the potential for serious adverse reactions in nursing infants from amitriptyline hydrochloride tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Usage in Pediatric Patients In view of the lack of experience with the use of this drug in pediatric patients, it is not recommended at the present time for patients under 12 years of age.
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 3 or 4 days or may take up to 30 days to develop adequately.
Hospitalized Patients Severely ill or hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg a day if necessary. A small number of hospitalized patients may need as much as 300 mg a day. Pediatric Patients Health Canada has not authorized an indication for pediatric use.
Elderly Patients When considering the use of amitriptyline in elderly patients, the potential risks must be balanced with clinical need. 4 Geriatrics. In general, lower dosages are recommended for these patients. In those patients who may not tolerate higher doses, 50 mg daily may be satisfactory.
The dose may be administered in divided doses or as a single dose preferably in the evening or at bedtime. Maintenance When satisfactory improvement has been reached, dosage should be reduced to the lowest amount that will maintain relief of symptoms.
The usual maintenance dose is 50 to 100 mg/day in divided doses; however, in suitable patients, the total daily dosage may be given in a single dose, preferably at bedtime. It is appropriate to continue maintenance therapy throughout the active phase of the depression and for the expected duration of the depressive episode, in order to lessen the possibility of relapse.
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 non- compliance is suspected.
Adjustments in dosage should be made according to the patient’s clinical response and not on the basis of plasma levels. 4 Drug-Drug Interactions). 4 Administration Amitriptyline Hydrochloride Tablets USP tablets should be swallowed whole with water.
Amitriptyline Hydrochloride Tablets USP can be administered with or without food. 5 Missed Dose If the patient misses a dose, instruct the patient to take the dose as soon as they remember. If it is almost time for the next dose, inform the patient to skip the missed dose and continue the regular dosing schedule.
5 OVERDOSAGE 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, disorders of ocular motility, convulsions, severe hypotension, stupor, coma, polyradiculoneuropathy and constipation.
Other symptoms may be agitation, hyperactive reflexes, muscle rigidity, vomiting, hyperpyrexia, or any of those listed under