doxepin SINEQUAN
Class: TCA/3° Amine Dibenzoxepine DerivativeFDA Indications: Psychotic Depressive Disorders With Associated Anxiety Including Involutional Depression & Manic-depressive Disorders, Psychoneurotic Patients With Depression And/or Anxiety, Depression/Anxiety Assoc W/ Alcoholism, Depression/Anxiety Assoc W/ Organic Disease, Sleep Maintenance Insomnia (Silenor®)
Off-Label Use: Anxiety, Insomnia, Treatment Resistant Depression, Neuropathic Pain, Chronic Idiopathic Urticaria
Prescribing
Forms: 10, 25, 50, 75, 100, 100, 150mg capsule; 3, 6mg Silenor® tab; 5% topical; 10mg/mL po solnDose Range: 75-300 mg/day
Starting: 25 mg qd qhs, ↑ by 25 mg q3-7 days, max dose 300 mg qd
Stopping: ↓ 50% x3 days, then ↓ another 50% x3 days, then D/C entirely.
Monitoring: Suggested plasma level 500-950 nmol/L
Precautions
Contraindications: Concomitant use of MAOIs; patient s/p MI; coadministration of other QT-prolonging agents; h/o QT ↑ or arrhythmia; caution in patients with hypo-K+ or hypo-Mg2+Serious Side Effects: 5HT syndrome; ↓ seizure threshold; QT↑, arrhythmias, tachycardia, orthostatic hypotension
Conditional Risk of TdP
Side Effects: anticholinergic side effects, weight gain, sexual dysfunction
Pharmacokinetics
t½: 15 (8-24)° TMAX: 2-4°Substrate of: 2D6, 2C19; 1A2, 2C9
Inhibits: ∅ ; Induces: ∅
Active Metabolites: Desmethyldoxepin (t½ 28-52°)
DDIs
- - DO NOT CO-PRESCRIBE WITH MAOIs (need a 14-day washout period)
- - caution combining with other CNS depressants & anticholingerics
- - VPA may ↑ levels
Misc
- - low doses may be useful in treating insomnia in the last third of the night, i.e. "late insomnia"
- - the most anti-histaminergic of all the TCAs
Special Populations
Category C—A case-control study showed ∅ ↑ congenital malformations with 1st trimester use & a review (n=209) showed ∅ assoc with congenital malformations or developmental delay.
RID 1.2-3%; contraindicated d/t significant hypotonia & sedation
Avoid due to its anticholinergicity and high sedation, especially when combining with other CNS depressants and/or anticholingerics. Caution regarding orthostatic hypotension (fall risk!). Can impair cognition.
2019 BEE℞S Recommendation: At low doses (≤6 mg/day), safety profile comparable to that of placebo. At doses > 6mg, avoid d/t being highly anticholinergic, sedating, and propensity to cause orthostatic hypotension.
No dosage adjustment necessary.
All TCAs are hepatically metabolzed, highly protein bound and will accumulate, and associated with ↑ LFTs.
References
Applied Clinical Pharmacokinetics And Pharmacodynamics Of Psychopharmacological AgentsConcise Guide To Drug Interaction Principles For Medical Practice
Foye's Principles Of Medicinal Chemistry
Drug Interactions In Psychiatry, 3rd Ed.
De Swiet's Medical Disorders In Obstetric Practice
Antidepressant Use During Pregnancy