QuickView for Doxepin (compound)

Summary
General Info

PubChem

PubChem Compound 10039438

Name:	Doxepin
PubChem Compound ID:	10039438
Description:	A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors.
Molecular formula:	C₁₉H₂₁NO
Molecular weight:	282.395 g/mol

DrugBank

Identification

Name:	Doxepin
Name (isomeric):	DB01142
Drug Type:	small molecule
Description:	A dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors.
Synonyms:	Doxepine; Doxepinum [INN-Latin]; Doxepina [INN-Spanish]; Doxepin, Hydrochloride; Doxepin Hcl
Brand:	Adapin, Zonalon, Triadapin, Quitaxon, Sinequan, Curatin, Aponal
Category:	Norepinephrine-Reuptake Inhibitors, Antidepressants, Histamine Antagonists, Anti-anxiety Agents, Antipruritics, Antidepressive Agents, Tricyclic
CAS number:	1668-19-5

Pharmacology

Indication:	Labeled indications: depression and insomnia. Unlabeled indications: chronic and neuropathic pain, anxiety, idiopathic urticaria.
Pharmacology:	Doxepin, a tricyclic antidepressant of the dibenzoxepin type, is used to treat depression and anxiety and, topically, pruritus associated with eczema. Doxepin has substantial anticholinergic and sedative effects.
Mechanism of Action:	The mechanism of action of doxepin is not completely understood. It is thought that Like amitriptyline, doxepin enhances the actions of norepinephrine and serotonin by blocking their reuptake at the neuronal membrane. Doxepin may also act on histamine H₁-receptors, resulting in sedative effects, and β-adrenergic receptors.
Absorption:	Well-absorbed from the GI tract. Peak plasma concentrations occur within 2 hours of oral administration.
Protein binding:	Highly bound to plasma proteins.
Biotransformation:	Extensively metabolized in the liver via the same pathways as other TCAs. N-demethylation produces an active metabolite, N-desmethyldoxepin.
Half Life:	6 - 24.5 hours
Toxicity:	LD₅₀=26 (mg/kg) (in mice, iv); LD₅₀=16 (mg/kg) (in rats, iv); Cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Avoid St.John's Wort.

Avoid alcohol.

Take with food to reduce irritation.

Avoid excessive quantities of coffee or tea (caffeine).

Drug interaction:

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Butalbital	Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as doxepin. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Fenoterol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of fenoterol.
Ritonavir	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if ritonavir if initiated, discontinued or dose changed.
Butabarbital	Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like doxepin. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.

Grepafloxacin	Increased risk of cardiotoxicity and arrhythmias
Butalbital	Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as doxepin. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Fenoterol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of fenoterol.
Ritonavir	Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if ritonavir if initiated, discontinued or dose changed.
Butabarbital	Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like doxepin. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Sparfloxacin	Increased risk of cardiotoxicity and arrhythmias
Isoproterenol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of isoproterenol.
Tranylcypromine	Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Salbutamol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of salbutamol.
Trospium	Trospium and Doxepin, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Lumefantrine	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Norepinephrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of norepinephrine.
Procaterol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of procaterol.
Voriconazole	Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may also increase the serum concentration of doxepin by decreasing its metabolism. Consider alternate therapy or monitor for QTc prolongation and changes in the therapeutic and adverse effects of doxepin if voriconazole is initiated, discontinued or dose changed.
Triprolidine	Triprolidine and Doxepin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Rifabutin	The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifabutin is initiated, discontinued or dose changed.
Epinephrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of epinephrine.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Quinidine	Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Phenelzine	Possibility of severe adverse effects
Thioridazine	Increased risk of cardiotoxicity and arrhythmias
Terbinafine	Terbinafine may reduce the metabolism and clearance of Doxepin. Consider alternate therapy or monitor for therapeutic/adverse effects of Amytriptyline if Doxepin is initiated, discontinued or dose changed.
Tacrine	The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Doxepin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Moclobemide	Possible severe adverse reaction with this combination
Galantamine	Possible antagonism of action
Artemether	Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus	Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Zolmitriptan	Use of two serotonin modulators, such as zolmitriptan and doxepin, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Toremifene	Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Atazanavir	Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if atazanavir if initiated, discontinued or dose changed.
Mephentermine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of mephentermine.
Fluvoxamine	The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of doxepin if fluvoxamine is initiated, discontinued or dose changed.
Metaraminol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of metaraminol.
Isocarboxazid	Possibility of severe adverse effects
Rivastigmine	Possible antagonism of action
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Phenylephrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of phenylephrine.
Ephedra	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of ephedra.
Guanethidine	The tricyclic antidepressant, doxepin, decreases the effect of guanethidine.
Sibutramine	Increased risk of CNS adverse effects
Trimethobenzamide	Trimethobenzamide and Doxepin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Dihydroquinidine barbiturate	Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, doxepin.
Pseudoephedrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of pseudoephedrine.
Terbutaline	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of terbutaline.
Dobutamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of dobutamine.
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Donepezil	Possible antagonism of action
Zuclopenthixol	Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Tramadol	Tramadol increases the risk of serotonin syndrome and seizures.
Pirbuterol	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of pirbuterol.
Altretamine	Risk of severe hypotension
Cimetidine	Cimetidine may increase the effect of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if cimetidine is initiated, discontinued or dose changed.
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Mesoridazine	Increased risk of cardiotoxicity and arrhythmias
Thiothixene	May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Vorinostat	Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Thiabendazole	The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Doxepin by decreasing Doxepin metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Doxepin if Thiabendazole is initiated, discontinued or dose changed.
Rifampin	The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if rifampin is initiated, discontinued or dose changed.
Terfenadine	Increased risk of cardiotoxicity and arrhythmias
Dopamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of dopamine.
Methoxamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of methoxamine.
Telithromycin	Telithromycin may reduce clearance of Doxepin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Doxepin if Telithromycin is initiated, discontinued or dose changed.
Phenylpropanolamine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of phenylpropanolamine.
Ziprasidone	Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Fluoxetine	The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, doxepin, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of doxepin if fluoxetine is initiated, discontinued or dose changed.
Clonidine	The tricyclic antidepressant, doxepin, decreases the effect of clonidine.
Ephedrine	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of ephedrine.
Carbamazepine	Carbamazepine may decrease the serum concentration of the tricyclic antidepressant, doxepin, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of doxepin if carbamazepine is initiated, discontinued or dose changed.
Orciprenaline	The tricyclic antidepressant, doxepin, increases the sympathomimetic effect of orciprenaline.
Cisapride	Increased risk of cardiotoxicity and arrhythmias
Rasagiline	Possibility of severe adverse effects
Quinidine barbiturate	Quinidine barbiturate increases the effect of tricyclic antidepressant, doxepin.