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doxepin (Sinequan, Adapin, Zonalon, Silenor)
Tradenames: Adapin, Sinequan, Zonalon (topical) (Doxepin HCl)
Indications:
1) depression, depressive psychosis, mania
2) anxiety
3) analgesic for neuropathic pain
4) panic attacks
5) insomnia [7]
6) pruritus, atopic dermatitis, lichen simplex chronicus [7]
Contraindications:
- narrow-angle glaucoma
- constipation
- angina pectoris
Caution:
1) taper dosage when discontinuing
2) avoid unnecessary sunlight exposure
3) avoid alcohol
Dosage:
Antidepressant: start 75 mg PO BID/TID; max 400 mg/day
Pruritus: apply BID
Tabs: 10, 25, 50, 75, 100, 150 mg.
Silenor: 3, 6 mg for insomnia [7]
Liquid: 10 mg/mL.
Topical: cream 5%.
Pharmacokinetics:
1) peak effect may take > 2 weeks
2) metabolized by liver to active metabolite desmethyldoxepin
-> 1/2 life of desmethyldoxepin is 40-60 hours; 31 hours [9]
3) eliminated in the urine
4) 1/2life 6-8 hours; 15 hours [9]
Adverse effects:
1) common (> 10%)
- dizziness, drowsiness, dry mouth, constipation, headache, increased appetite, nausea, weakness, unpleasant taste, weight gain
2) 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
3) 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
4) 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 interactions:
1) coadministration enhances metabolism of doxepin
a) barbiturates
b) carbamazepine
c) smoking
2) coadministration inhibits metabolism of doxepin
a) cimetidine
b) fluoxetine
c) chloramphenicol
d) haloperidol
e) methylphenidate
f) oral contraceptives
g) phenothiazines
3) doxepin may increase effects & toxicity of:
a) carbamazepine
b) sympathomimetics
c) thyroid preparations
4) fluoxetine, MAO inhibitors, albuterol, CNS depressants, anticholinergic agents, cimetidine may increase toxicity of doxepin
5) guanethidine, clonidine, terfenadine, astemizole
6) alcohol
Laboratory:
1) specimen:
a) serum, plasma (EDTA)
b) collect at steady state trough concentration; > 12 hours after dose
c) doxepin in serum/plasma
- therapeutic range: 75-200 ng/mL
2) methods: HPLC, GLC, GC-MS, RIA
3) interferences:
a) amitriptyline interferes with HPLC analysis
b) doxepin may be displaced from protein-binding sites by plasticizers in collecting devices
4) labs with Loincs
- doxepin in specimen
- doxepin in tissue
- doxepin in gastric fluid
- doxepin in serum/plasma
- doxepin in serum/plasma
Mechanism of action:
1) tricyclic antidepressant
2) inhibits serotonin & norepinephrine re-uptake
Interactions
drug interactions
drug adverse effects (more general classes)
General
tricyclic antidepressant (TCA)
Properties
MISC-INFO: elimination route LIVER
1/2life 17 +/- 6 HOURS
therapeutic-range 150-250 NG/ML
toxic-range >500 NG/ML
protein-binding 80%
elimination by hemodialysis -
peritoneal dialysis -
pregnancy-category C
B
safety in lactation -
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- 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#: 261005
(subscription needed) http://www.prescribersletter.com
- Deprecated Reference
- 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
PMID: 29669228
http://www.nejm.org/doi/full/10.1056/NEJMcpc1800322
- Talebraza S et al
Geriatrics Evaluation & Management Tools
American Geriatrics Society. 2021
https://geriatricscareonline.org/ProductAbstract/geriatrics-evaluation-management-tools/B007/