Doxepin

SINEQUAN

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Pronunciation: DOX-e-pin (SIN-e-kwon)

Doxepin ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Doxepin ballicule

Doxepin SINEQUAN, SILENOR mascot mnemonic cartoon — Visual mnemonic: Doxepin mascot
**“Box with pins”**

What it isTricyclic with very high H1 affinity; at low dose an insomnia agent, at high dose an antidepressant.

Why this oneAt 3 to 6 mg it is essentially a pure H1 antagonist, giving sleep maintenance without anticholinergic or dependence effects.

What limits itAt antidepressant doses it becomes a full tricyclic with all the anticholinergic and overdose liability. The dose determines which drug it is.

Doxepin molecular structure (skeletal formula) — Molecular structure: Doxepin

FDA-approved for

depression/anxiety (~1969)
insomnia (2010)

Off-label

chronic urticaria
insomnia

FDA label

Read the full label on DailyMed ↗

FDA dosing	Population	Start	Target	Max
Insomnia (sleep maintenance)	Adults	6 mg QHS	6 mg QHS	6 mg/day
Insomnia (sleep maintenance)	Elderly ≥65 y	3 mg QHS	3–6 mg QHS	6 mg/day

Renal Undefined

Hepatic Initiate at 3 mg; monitor closely for daytime effects

Instructions

Take within 30 minutes of bedtime.
Do not take within 3 hours of a meal.
Total daily dose should not exceed 6 mg.

Available strengths

cap 10, 25, 50, 75, 100, 150 mg
sol 10 mg/mL
tab 3, 6 mg
cream 5 %

Contraindications

MAOIs (concurrently or within 14 days) due to risk of serious side effects and even death
Untreated narrow-angle glaucoma or severe urinary retention

Cautions

Reevaluate if insomnia persists after 7–10 days (possible comorbid disorder)
Abnormal thinking/behavior, complex sleep behaviors incl. sleep-driving, hallucinations
Worsening depression/suicidal thinking
CNS-depressant effects; avoid alcohol and additive CNS depressants
Not recommended in severe sleep apnea

Adverse reactions

Somnolence/sedation
Nausea
Upper respiratory tract infection

Pregnancy No established increased risk of major birth defects/miscarriage; risk of poor neonatal adaptation with third-trimester TCA exposure

Lactation Doxepin/nordoxepin present in milk; reports of sedation, respiratory depression, poor feeding, hypotonia — breastfeeding not recommended

Cost

Doxepin (SINEQUAN)

What pharmacies pay · NADAC 9/30/26

Strength		#/mo	generic $	CostPlus
10 mg	cap	30 qd	$2.34/mo	offered
25 mg	cap	30 qd	$4.25/mo	offered
50 mg	cap	30 qd	$4.71/mo	offered
75 mg	cap	30 qd	$5.90/mo	offered
100 mg	cap	30 qd	$8.70/mo	offered
150 mg	cap	30 qd	$15.29/mo	offered
10 mg/mL	sol	per unit	$0.84/mL	offered

Other forms: Doxepin low-dose (insomnia) (SILENOR)

Generic entry1986

⚠ BOXED WARNING

Suicidal thoughts and behaviors in patients under 25

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger4 / 4

Weight-gain liability2 / 4

Sedation liability3 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism3 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilityTricyclic anticholinergic and cardiac toxicity become life-threatening in overdose.

Serotonicity

This drug is routinely called serotonergic. By Gillman’s human-effect criteria it does not raise serotonin in the synapse.

Predominantly antihistaminic at usual doses; negligible clinically meaningful SRI activity.

Label contraindicationMAOIs (concurrently or within 14 days) due to risk of serious side effects and even death. The label governs prescribing; Gillman’s point concerns serotonin toxicity only.

It binds the serotonin transporter, and its SERT peg is drawn to that textbook affinity. The pale halo around the peg marks binding that, by Gillman’s human-effect criteria, does not produce clinical serotonin reuptake inhibition.

Gillman’s four human testsA measurable SERT affinity that fails all four is not clinical serotonicity.