amitriptyline (Elavil, Endep)
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Introduction
Tradename: Elavil, Endep.
Indications
- treatment of:
- prophylaxis for migraine headache
- management of anxiety/panic attacks
- bulimia nervosa[8]
- post-traumatic stress disorder (PTSD)
- fibromyalgia[8]
Contraindications
- use of a monoamine oxidase (MAO) inhibitor within 14 days
- narrow-angle glaucoma
- pregnancy
- severe benign prostatic hypertrophy (BPH)
Caution:
- to avoid cholinergic crisis, do not discontinue abruptly in patients taking high doses chronically
- in patients with:
- cardiac conduction disturbances
- hyperthyroidism
- renal or liver impairment
- bipolar illness
- use with caution or not at all in the elderly
- may worsen symptoms of BPH
* CPIC recommends alternative drug for CYP2D6 or CYP2C19 ultrarapid metabolizers & for CYP2D6 poor metabolizers[9] (see Laboratory)
Dosage
Tabs: 10, 25, 50, 75, 100, 150 mg.
Pharmacokinetics
- metabolized by cyt P450 1A2, cyt P450 2C19[6], cyt P450 2D6
- onset of therapeutic effect may take 3-4 weeks [6]
elimination via liver
1/2life = 9-25 hours
protein binding = 82-96 %
elimination by hemodialysis = -
elimination by hemoperfusion = -
elimination by peritoneal dialysis = -
Adverse effects
- anticholinergic effects
- may be pronounced
- moderate to marked sedation may occur
- tolerance usually occurs
- common > 10%
- less common (1-10%)
- hypotension, postural hypotension, arrhythmia, tachycardia, sudden death, nervousness, restlessness, parkinsonism, insomnia, sedation, fatigue, anxiety, impaired cognitive function, seizures, extrapyramidal symptoms, diarrhea, heartburn, impaired sexual function, urinary retention, tremor, eye pain, blurred vision, sweating
- uncommon (< 1%)
- alopecia, photosensitivity, breast enlargement, galactorrhea, SIADH (rare), gum disease, gastroesophageal reflux (GERD), testicular swelling, leukopenia, eosinophilia, agranulocytosis (rare), cholestatic jaundice, increased serum transaminases, increased intraocular pressure, tinnitus, hypersensitivity
- other - QT prolongation[7]
Overdose: see tricyclic antidepressant.
- drug adverse effects of parasympatholytics
- drug adverse effects of tricyclic antidepressants
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- decreases effect of guanethidine
- increases effects of:
- concurrent use of MAO inhibitors may result in:
- hyperpyrexia, tachycardia, hypertension, confusion, seizures death
- cimetidine may decrease metabolism of amitriptyline
- phenobarbital may increase metabolism of amitriptyline
- concurrent use of clonidine may result in hypertensive crisis
- avoid terfenadine, astemizole, cisapride
- any drug which inhibits cyt P450 1A2 or cyt P450 2D6 can increase amitriptyline levels
- any drug which induces cyt P450 1A2 or cyt P450 2D6 can diminish amitriptyline levels
- drug interaction(s) of tricyclic antidepressants with physostigmine
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of parasympatholytic with parasympathomimetic
Laboratory
- specimen:
- serum, plasma (EDTA), amitriptyline in serum
- collect at steady-state trough, 12 hours after dose
- separate plasma from cells as soon as possible & refrigerate
- stable for 4 months at -20 degrees C
- methods: HPLC, GLC, GC-MS, RIA
- interferences:
- doxepin may interfere with some HPLC assays
- amitriptyline may be displaced from plasma proteins by plasticizers in collecting devices
- amitriptyline may falsely elevate plasma metanephrine[10]
- CYP2D6 & CYP2C19 genotyping[9]
- other laboratory measurement with Loincs
Mechanism of action
- inhibition of re-uptake of serotonin & norepinephrine
Notes
Amitriptyline is a tertiary amine
More general terms
Additional terms
- cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
- cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 56
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 6.0 6.1 6.2 Prescriber's Letter 8(3):16-17 2001
- ↑ 7.0 7.1 Castro VM et al QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ 2013;346:f288 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23360890 <Internet> http://www.bmj.com/content/346/bmj.f288
- ↑ 8.0 8.1 8.2 Deprecated Reference
- ↑ 9.0 9.1 9.2 9.3 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline information for amitriptyline and CYP2C19, CYP2D6. https://www.pharmgkb.org/guideline/PA166105006
- ↑ 10.0 10.1 Medical Knowledge Self Assessment Program (MKSAP) 18, American College of Physicians, Philadelphia 2018