Overview
11 DESCRIPTION Doxepin is available in 3 mg and 6 mg strength tablets for oral administration. Each tablet contains 3.39 mg or 6.78 mg doxepin hydrochloride, USP equivalent to 3 mg and 6 mg of doxepin, respectively. Chemically, doxepin hydrochloride, USP is an (E) and (Z) geometric, isomeric mixture of 1-propanamine, 3-dibenz[ b ,e]oxepin-11(6 H )ylidene- N,N -dimethyl-hydrochloride.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of doxepin in sleep maintenance is unclear; however, doxepin’s effect could be mediated through antagonism of the H1 receptor. 12.2 Pharmacodynamics Doxepin has high binding affinity to the H1 receptor (Ki
Indications
- 1 INDICATIONS AND USAGE Doxepin tablets are indicated for the treatment of insomnia characterized by difficulty with sleep maintenance. The clinical trials performed in support of efficacy were up to 3 months in duration. Doxepin tablets are indicated for the treatment of insomnia characterized by difficulties with sleep maintenance. ( 1 , 14 )
Common Doses
- 6 mg
- 3 mg
Dosage
2 DOSAGE AND ADMINISTRATION The dose of doxepin tablets should be individualized. Initial dose: 6 mg, once daily for adults ( 2.1 ) and 3 mg, once daily for the elderly. ( 2.1 , 2.2 ) Take within 30 minutes of bedtime. Total daily dose should not exceed 6 mg. ( 2.3 ) Should not be taken within 3 hours of a meal. ( 2.3 , 12.3 ) 2.1 Dosing in Adults The recommended dose of doxepin tablets for adults is 6 mg once daily. A 3 mg once daily dose may be appropriate for some patients, if clinically indicated. 2.
Contraindications
- 4 CONTRAINDICATIONS Hypersensitivity to doxepin hydrochloride, inactive ingredients, or other dibenzoxepines. ( 4.1 ) Co-administration with Monoamine Oxidase Inhibitors (MAOIs): Do not administer if patient is taking MAOIs or has used MAOIs within the past two weeks. ( 4.2 ) Untreated narrow angle glaucoma or severe urinary retention. ( 4.3 ) 4.1 Hypersensitivity Doxepin is contraindicated in individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines. 4.
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of labeling: Abnormal thinking and behavioral changes [see Warnings and Precautions (5.2)] . Suicide risk and worsening of depression [ see Warnings and Precautions (5.3) ] . CNS Depressant effects [ see Warnings and Precautions (5.4) ] . The most common treatment-emergent adverse reactions, reported in ≥ 2% of patients treated with doxepin, and more commonly than in patients treated with placebo, were somnolence/sedation, nausea, and upper respiratory tract infection. ( 6.
Interactions
- 7 DRUG INTERACTIONS MAO inhibitors: Doxepin should not be administered in patients on MAOIs within the past two weeks. ( 4.2 ) Cimetidine: Increases exposure to doxepin. ( 7.2 ) Alcohol: Sedative effects may be increased with doxepin. ( 7.3 , 5.4 ) CNS Depressants and Sedating Antihistamines: Sedative effects may be increased with doxepin ( 7.4 , 5.4 ) Tolazamide: A case of severe hypoglycemia has been reported. ( 7.5 ) 7.1 Cytochrome P450 Isozymes Doxepin is primarily metabolized by hepatic cytochrome P450 isozymes CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9.