doxepin (Sinequan, Adapin, Zonalon, Silenor)
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Introduction
Tradenames: Adapin, Sinequan, Zonalon (topical) (Doxepin HCl)
Indications
- depression, depressive psychosis, mania
- anxiety
- analgesic for neuropathic pain
- panic attacks
- insomnia[7]
- pruritus, atopic dermatitis, lichen simplex chronicus[7]
Contraindications
Caution:
Dosage
Antidepressant: start 75 mg PO BID/TID; max 400 mg/day
Tabs: 10, 25, 50, 75, 100, 150 mg.
Silenor: 3, 6 mg for insomnia[7]
Liquid: 10 mg/mL.
Topical: cream 5%.
Pharmacokinetics
- peak effect may take > 2 weeks
- metabolized by liver to active metabolite desmethyldoxepin
- 1/2 life of desmethyldoxepin is 40-60 hours; 31 hours[9]
- eliminated in the urine
- 1/2life 6-8 hours; 15 hours[9]
elimination via liver
protein binding = 80 %
elimination by hemodialysis = -
elimination by peritoneal dialysis = -
Adverse effects
- common (> 10%)
- dizziness, drowsiness, dry mouth, constipation, headache, increased appetite, nausea, weakness, unpleasant taste, weight gain
- less common (1-10%)
- blurred vision, confusion, delirium, hallucinations, difficult urination, eye pain, arrhythmias, fine tremor, hypotension, nervousness, restlessness, parkinsonism, impotence, diarrhea, excessive sweating, heartburn, insomnia
- uncommon (< 1%)
- agranulocytosis, leukopenia, eosinophilia, anxiety, seizures, SIADH, tinnitus, breast enlargement, galactorrhea, testicular swelling, cholestatic jaundice, hepatitis, GERD due to decreased lower esophageal sphincter tone, gingivitis, increased intraocular pressure, alopecia, allergic reactions, photosensitivity
- other[2][3]
- sedation is high compared to other TCAs
- anticholinergic effects are low
- orthostatic hypotension is high
- arrhythmias
- confusion
- overdose results in prolongation of the QT interval
- case report of cardiac arrest in a young woman[8]
- urine may turn blue-green
- drug adverse effects of tricyclic antidepressants
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- coadministration enhances metabolism of doxepin
- coadministration inhibits metabolism of doxepin
- doxepin may increase effects & toxicity of:
- carbamazepine
- sympathomimetics
- thyroid preparations
- fluoxetine, MAO inhibitors, albuterol, CNS depressants, anticholinergic agents, cimetidine may increase toxicity of doxepin
- guanethidine, clonidine, terfenadine, astemizole
- alcohol
- drug interaction(s) of tricyclic antidepressants with physostigmine
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- 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 antidepressant with opiates
Laboratory
- specimen:
- serum, plasma (EDTA)
- collect at steady state trough concentration; > 12 hours after dose
- doxepin in serum/plasma
- therapeutic range: 75-200 ng/mL
- methods: HPLC, GLC, GC-MS, RIA
- interferences:
- amitriptyline interferes with HPLC analysis
- doxepin may be displaced from protein-binding sites by plasticizers in collecting devices
- labs with Loincs
Mechanism of action
- tricyclic antidepressant
- inhibits serotonin & norepinephrine re-uptake
More general terms
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ 2.0 2.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 3.0 3.1 Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 56
- ↑ Prescriber's Letter 17(10): 2010 COMMENTARY: Oleptro (Trazodone) and Silenor (Doxepin) CHART: Comparison of Insomnia Treatments Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=261005&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 7.2 7.3 Deprecated Reference
- ↑ 8.0 8.1 Goldstein JN, Dudzinski DM, Erickson TB, Linder G. Case 12-2018: A 30-Year-Old Woman with Cardiac Arrest. N Engl J Med 2018; 378:1538-1549. April 19, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29669228 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMcpc1800322
- ↑ 9.0 9.1 9.2 Talebraza S et al Geriatrics Evaluation & Management Tools American Geriatrics Society. 2021 https://geriatricscareonline.org/ProductAbstract/geriatrics-evaluation-management-tools/B007/
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3158
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=14675
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=667468
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=667477
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5281088