Doxepin
Doxepin hydrochloride
Also known as: Sinequan · Anten · Aponal · Deptran · Desidoxepin · Doneurin · Doxal · Doxepia · Gilex · Mareen · Quitaxon · Triadapin · Zonalon · Sinepin · doxepini hydrochloridum · NSC-108160 · P3693A · Doxepinum · Doxepin hydrochloride
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of psychogenic dermatoses | 3-5 mg/kg PO q12h; maximum dose is 150 mg (per dog) q12h | PO | q12h | — | 🌎 NA |
| Treatment of psychogenic dermatoses | 3-5 mg/kg, PO q8-12h. Begin at 3 mg/kg PO q12h for 2 weeks, then increase by 1 mg/kg PO q12h for 2 weeks up to the maximum dosage as needed; if no clinical response after at least 3-4 weeks of therapy, decrease dosage by 1 mg/kg PO q12h for 2 weeks until at the initial dosage | PO | q8-12h | Titrated over weeks | 🌎 NA |
| Antihistaminic effects in treatment of atopy | 2.2 mg/kg PO three times daily | PO | TID | — | 🌎 NA |
| Antihistaminic effects in treatment of atopy | 3-5 mg/kg twice daily | PO | BID | — | 🌎 NA |
| Antihistaminic effects in treatment of atopy | 0.5-2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Antihistaminic effects in treatment of atopy | 1-2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Treatment of behavior problems (OCD) | 0.5-1 mg/kg PO twice daily | PO | BID | — | 🌎 NA |
| Treatment of behavior problems (acral lick granulomas) | 3-5 mg/kg PO q12h (up to 150 mg per dog) | PO | q12h | — | 🌎 NA |
- Antihistaminic effects in treatment of atopy: Used especially if dog has anxiety or other behavioral condition
- Antihistaminic effects in treatment of atopy: May be best in nervous or highly strung dogs
- Treatment of behavior problems (acral lick granulomas): Doses as above for psychogenic dermatoses
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of psychogenic dermatoses | 0.5-1 mg/kg PO q12-24h. Up to 25-50 mg (total dose) per cat. | PO | q12-24h | Allow 3-4 weeks for initial trial | 🌎 NA |
| Excessive grooming | 0.5-1 mg/kg PO q12h. | PO | q12h | — | 🌎 NA |
| Treatment of behavior problems (e.g., overgrooming, intercat aggression) | 0.5-1 mg/kg PO once to twice daily. | PO | SID to BID | — | 🌎 NA |
Birds
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of anxiety, pruritus caused feather plucking in psittacines | 1-2 mg/kg PO q12h | PO | q12h | — | 🌎 NA |
| Treatment of anxiety, pruritus caused feather plucking in psittacines | 0.5-1 mg/kg PO twice daily | PO | BID | — | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Doxepin is a dibenzoxazepine-derivative tricyclic antidepressant (TCA) used primarily in veterinary medicine as an adjunctive therapy for psychogenic dermatoses, particularly those with an underlying anxiety component.
While it is classified as an antidepressant, it possesses extremely potent H1-antihistaminic properties, making it a dual-purpose agent for managing pruritus and behavioral conditions. Its efficacy as a standalone antihistamine for atopic dermatitis is debated, but it is highly valuable when pruritus is exacerbated by or leads to anxiety and compulsive behaviors (e.g., acral lick granulomas, overgrooming).
Clinical Pearl: Because of its combined anxiolytic and antihistaminic effects, doxepin is often selected for nervous or highly-strung patients suffering from allergic skin disease.
Mechanism of action
Doxepin exerts its effects through multiple receptor pathways:
- Monoamine Reuptake Inhibition: In the central nervous system, doxepin blocks the presynaptic reuptake of norepinephrine (moderate inhibition) and serotonin (5-HT) (weak inhibition) → increasing their synaptic concentrations and prolonging their activity, which contributes to its antidepressant and anxiolytic effects.
- Receptor Antagonism: It exhibits potent H1-histamine receptor blockade (providing anti-pruritic and sedative effects), as well as anticholinergic (muscarinic) and alpha-1 adrenergic blocking activity. These latter receptor affinities are largely responsible for its side effect profile (e.g., dry mouth, urinary retention, hypotension).
Safety & warnings
Contraindications
- Prior sensitivity to doxepin or other tricyclic antidepressants
- Concomitant use with Monoamine Oxidase Inhibitors (MAOIs) such as selegiline or amitraz (within 14 days)
- Urinary retention
- Glaucoma
- Severe cardiac disease
- History of seizures
- Concurrent use with MAOIs
Adverse effects
- Hyperexcitability (paradoxical)
- Gastrointestinal distress
- Lethargy and sedation
- Ventricular arrhythmias (particularly in overdose)
- Anticholinergic effects (dry mouth, urinary retention, constipation)
- Altered blood glucose levels
- Dry mouth (xerostomia)
- Tachycardia
Precautions
Pregnancy & Nursing: Safety during pregnancy has not been established (FDA Category C). Doxepin and its active metabolite distribute into milk; use with caution in nursing patients as sedation and respiratory depression have been reported in human infants.
Cardiac Effects: Tricyclics can widen QRS complexes, prolong PR intervals, and invert or flatten T-waves on ECG. Use with caution in patients with pre-existing cardiac disease.
Laboratory Alterations: May alter (increase or decrease) blood glucose levels.
Drug interactions
Additive anticholinergic effects; use cautiously.
May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity.
Additive CNS depression; use cautiously.
Increased risk for serotonin syndrome.
Concomitant use (within 14 days) is generally contraindicated due to high risk of serotonin syndrome.
Increased risk for QTc interval prolongation and tricyclic adverse effects.
Increased risk for serotonin syndrome.
May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia).
Risk of fatal serotonin syndrome
Increased risk of serotonin syndrome
Monitoring
- Efficacy (reduction in pruritus, anxiety, or compulsive behaviors)
- Adverse effects (GI distress, lethargy, hyperexcitability)
- ECG (if arrhythmias are suspected or in cases of overdose)
- Heart rate and rhythm
- Resolution of pruritus or behavioral signs
- Signs of excessive sedation or anticholinergic effects
Pharmacokinetics
Half-life
Absorption
Appears to be well absorbed after oral administration.
Distribution
Doxepin and its N-demethylated active metabolite are distributed into milk.
Metabolism
Extensively metabolized in the liver to an active N-demethylated metabolite.
Elimination
Excreted primarily via the kidneys as metabolites.
Overdose
Overdosage with tricyclic antidepressants can be life-threatening.
- Clinical Signs: Severe ventricular arrhythmias, cardiorespiratory collapse, profound CNS depression or seizures.
- Action: Because the toxicities and therapies for treatment are complicated and controversial, it is highly recommended to contact an animal poison control center immediately for further information in any potential overdose situation.
Available products
Formulations
- Capsules: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
- Oral Concentrate: 10 mg/mL
- Oral capsule (25 mg, 50 mg)
- Topical cream
Human-labeled
- Doxepin Capsules: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg & 150 mg (Sinequan, generic)
- Doxepin Oral Concentrate: 10 mg/mL in 120 mL (generic)
- Sinepin capsules (25 mg, 50 mg)
- Sinequan capsules
- Zonalon cream
Regulatory status
POM (Prescription Only Medicine) status.
POM (Prescription Only Medicine) status.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store protected from direct sunlight in tight, light-resistant containers at room temperature.
Client information
- Patience is Key: Several weeks (often 3-4 weeks) may be required before noticeable behavioral or dermatological efficacy is seen. Continue dosing exactly as prescribed.
- Safety First: All tricyclic antidepressants should be dispensed in child-resistant packaging and kept well away from children and pets. Overdoses can be fatal.
- Do Not Stop Abruptly: Consult your veterinarian before discontinuing the medication to avoid potential withdrawal effects.
- Monitor for Side Effects: Contact your veterinarian if your pet exhibits extreme lethargy, unexpected hyperactivity, vomiting, or signs of a rapid/irregular heartbeat.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.