Amitriptyline


Description

Amitriptyline hydrochloride, also known as _Elavil_, is a tricyclic antidepressant (TCA) with analgesic properties, widely used to treat depression and neuropathic pain [

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Pharmacology

Indication

This drug in indicated for the following conditions [FDA label]:

Major depressive disorder in adu...
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Pharmacodynamic

**Effects in pain and depression**

Amitriptyline is a tricyclic antidepressant and an analgesic....
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Mechanism of action

The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inh... Read more

Absorption

Rapidly absorbed following oral administration (bioavailability is 30-60% due to first pass metaboli... Read more

Protein binding

Very highly protein bound (95%) in plasma and tissues [FDA Label].

Volume of distribution

The apparent volume of distribution (Vd)β estimated after intravenous administration is 1221 L±280 L... Read more

Clearance

The mean systemic clearance (Cls) is 39.24 ± 10.18 L/h (range: 24.53-53.73 L/h) [FDA Label]. No clea... Read more

Half life

The elimination half-life (t1⁄2 β) amitriptyline after peroral administration is about 25 hours (24.... Read more

Route of elimination

Amitriptyline and its metabolites are mainly excreted in the urine. Virtually the entire dose is exc... Read more

Toxicity

**Toxicity Data**: Oral TDLO (child): 4167 μg/kg; Oral TDLO (man): 714 μg/kg/1D (intermittent); Oral... Read more


Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Syndrome of inappropriate ADH secretion US
Varying Reports
Tinnitis US
Varying Reports
Alteration in EEG patterns US
Varying Reports
Paralytic Ileus US
Varying Reports
Hyperpyrexia US
Varying Reports
Urinary Retention US
Varying Reports
Dilation of the urinary tract US
Varying Reports
Constipation US
Varying Reports
Insomnia US
Varying Reports
Restlessness US
Varying Reports
Nightmares US
Varying Reports
Drowsiness US
Varying Reports
Dizziness US
Varying Reports
Weakness US
Varying Reports
Fatigue US
Varying Reports
Headache US
Varying Reports
Extrapyramidal Symptoms US
Varying Reports
Tingling or parasthesias of the extremities US
Varying Reports
Tardive Dyskinesia US
Varying Reports
Involuntary movement US
Varying Reports
Disturbed concentration US
Varying Reports
Dysarthria US
Varying Reports
Anxiety US
Varying Reports
Excitement US
Varying Reports
Confusional states US
Varying Reports
Delusions US
Varying Reports
Incoordination US
Varying Reports
Disorientation US
Varying Reports
Tremors US
Varying Reports
Ataxia US
Varying Reports
Numbness US
Varying Reports
Peripheral neuropathy US
Varying Reports
Black tongue US
Varying Reports
Testicular swelling US
Varying Reports
Diarrhea US
Varying Reports
Parotid swelling US
Varying Reports
Glactorrhea US
Varying Reports
Increased libido US
Varying Reports
Gynecomastia US
Varying Reports
Breast enlargement US
Varying Reports
Nausea US
Varying Reports
Epigastric distress US
Varying Reports
Altered liver function US
Varying Reports
Jaundice US
Varying Reports
Stomatitis US
Varying Reports
Peculiar taste US
Varying Reports
Vomiting US
Varying Reports
Anorexia US
Varying Reports
Leukopenia US
Varying Reports
Agranulocytosis US
Varying Reports

Contraindications

  • Regions: US
  • Below Age:
    • Amount: 6
    • Unit: year
  • Regions: US
  • Patient Conditions:
      • Name: Severe liver disease
      • Drugbank Id: DBCOND0108367
      • Modification Of:
        • Base:
          • Name: Liver Disease
          • Drugbank Id: DBCOND0028338
        • Severity:
          • Includes:
            • severe
  • Regions: US
  • With Categories:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: US
  • Patient Conditions:
      • Name: Coronary Artery Insufficiency
      • Drugbank Id: DBCOND0033888
  • Regions: US
  • Patient Conditions:
      • Name: Cardiac Rhythm Disorders
      • Drugbank Id: DBCOND0055728
  • Regions: US
  • Patient Conditions:
      • Name: Heart Block
      • Drugbank Id: DBCOND0032425
  • Regions: US
  • Patient Conditions:
      • Name: Recent Myocardial Infarction
      • Drugbank Id: DBCOND0043731
  • Regions: US
  • Patient Conditions:
      • Name: Hypersensitivity to the active substance or to any of the excipients
      • Drugbank Id: DBCOND0117394
  • Regions: US
  • With Categories Coadmin:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: US
  • With Drugs Coadmin:
      • Name: Cisapride
      • Drugbank Id: DB00604

Food Interactions

  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (caffeine).
  • Avoid St.John's Wort.
  • Take with food to reduce irritation.

Interactions

Type in a drug name to check for interaction with Amitriptyline

The metabolism of Amitriptyline can be decreased when combined with (R)-warfarin.
The metabolism of Amitriptyline can be decreased when combined with (S)-Warfarin.
The risk or severity of hypertension can be increased when Amitriptyline is combined with 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
The risk or severity of hypertension can be increased when Amitriptyline is combined with 1-benzylimidazole.
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 1,10-Phenanthroline.
Amitriptyline may decrease the hypoglycemic activities of 2,4-thiazolidinedione.
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 2,5-Dimethoxy-4-ethylamphetamine.
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 2,5-Dimethoxy-4-ethylthioamphetamine.
The metabolism of Amitriptyline can be decreased when combined with 3,5-diiodothyropropionic acid.
The therapeutic efficacy of Amitriptyline can be decreased when used in combination with 4-Bromo-2,5-dimethoxyamphetamine.
The therapeutic efficacy of 4-Bromo-2,5-dimethoxyphenethylamine can be decreased when used in combination with Amitriptyline.
The metabolism of 4-hydroxycoumarin can be decreased when combined with Amitriptyline.
The risk or severity of adverse effects can be increased when Amitriptyline is combined with 4-Methoxyamphetamine.
The metabolism of Amitriptyline can be decreased when combined with 5-androstenedione.
The risk or severity of adverse effects can be increased when Amitriptyline is combined with 5-methoxy-N,N-dimethyltryptamine.
The metabolism of Amitriptyline can be decreased when combined with 6-Deoxyerythronolide B.
The metabolism of Amitriptyline can be decreased when combined with 6-O-benzylguanine.
The metabolism of Amitriptyline can be decreased when combined with 7-ethyl-10-hydroxycamptothecin.
The risk or severity of adverse effects can be increased when Amitriptyline is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the serotonergic activities of Amitriptyline.

References

  • 1 . Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6. [PubMed: 15943846]
  • 2 . Hisaoka K, Tsuchioka M, Yano R, Maeda N, Kajitani N, Morioka N, Nakata Y, Takebayashi M: Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production. J Biol Chem. 2011 Jun 17;286(24):21118-28. doi: 10.1074/jbc.M111.224683. Epub 2011 Apr 22. [PubMed: 21515689]
  • 3 . Yan L, Wang Q, Fu Q, Ye Q, Xiao H, Wan Q: Amitriptyline inhibits currents and decreases the mRNA expression of voltage-gated sodium channels in cultured rat cortical neurons. Brain Res. 2010 Jun 8;1336:1-9. doi: 10.1016/j.brainres.2010.04.016. Epub 2010 Apr 14. [PubMed: 20398637]
  • 4 . Olesen OV, Linnet K: Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology. 1997 Nov;55(5):235-43. doi: 10.1159/000139533. [PubMed: 9399333]
  • 5 . Lawson K: A Brief Review of the Pharmacology of Amitriptyline and Clinical Outcomes in Treating Fibromyalgia. Biomedicines. 2017 May 17;5(2). pii: biomedicines5020024. doi: 10.3390/biomedicines5020024. [PubMed: 28536367]
  • 6 . Bryson HM, Wilde MI: Amitriptyline. A review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging. 1996 Jun;8(6):459-76. doi: 10.2165/00002512-199608060-00008. [PubMed: 8736630]
  • 7 . Guaiana G, Barbui C, Hotopf M: Amitriptyline versus other types of pharmacotherapy for depression. Cochrane Database Syst Rev. 2003;(2):CD004186. doi: 10.1002/14651858.CD004186 . [PubMed: 12804503]
  • 8 . Nishishinya B, Urrutia G, Walitt B, Rodriguez A, Bonfill X, Alegre C, Darko G: Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology (Oxford). 2008 Dec;47(12):1741-6. doi: 10.1093/rheumatology/ken317. Epub 2008 Aug 12. [PubMed: 18697829]
  • 9 . Moret C, Briley M: The importance of norepinephrine in depression. Neuropsychiatr Dis Treat. 2011;7(Suppl 1):9-13. doi: 10.2147/NDT.S19619. Epub 2011 May 31. [PubMed: 21750623]
  • 10 . Gupta SK, Shah JC, Hwang SS: Pharmacokinetic and pharmacodynamic characterization of OROS and immediate-release amitriptyline. Br J Clin Pharmacol. 1999 Jul;48(1):71-8. [PubMed: 10383563]
  • 11 . Amitriptyline FDA information, Approval [Link]
  • 12 . Elavil Monograph [File]
  • 13 . Safety data sheet, amitriptyline [File]

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