SILENOR- doxepin hydrochloride tablet
Somaxon Pharmaceuticals, Inc.
1. INDICATIONS AND USAGE
Silenor is 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 [see Clinical Studies (14) ].
2. DOSAGE AND ADMINISTRATION
The dose of Silenor should be individualized.
2.1. Dosing in Adults
The recommended dose of Silenor for adults is 6 mg once daily. A 3 mg once daily dose may be appropriate for some patients, if clinically indicated.
2.2. Dosing in the Elderly
The recommended starting dose of Silenor in elderly patients (≥ 65 years old) is 3 mg once daily. The daily dose can be increased to 6 mg, if clinically indicated.
Silenor should be taken within 30 minutes of bedtime.
To minimize the potential for next day effects, Silenor should not be taken within 3 hours of a meal [see Clinical Pharmacology (12.3) ].
The total Silenor dose should not exceed 6 mg per day.
3. DOSAGE FORMS AND STRENGTHS
Silenor is an immediate-release, oval-shaped, tablet for oral administration available in strengths of 3 mg and 6 mg. The tablets are blue (3 mg) or green (6 mg) and are debossed with 3 or 6, respectively, on one side and SP on the other. Silenor tablets are not scored.
Silenor is contraindicated in individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines.
4.2. Co-administration with Monoamine Oxidase Inhibitors (MAOIs)
Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Do not administer Silenor if patient is currently on MAOIs or has used MAOIs within the past two weeks. The exact length of time may vary depending on the particular MAOI dosage and duration of treatment.
4.3. Glaucoma and Urinary Retention
Silenor is contraindicated in individuals with untreated narrow angle glaucoma or severe urinary retention.
5. WARNINGS AND PRECAUTIONS
5.1. Need to Evaluate for Comorbid Diagnoses
Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Exacerbation of insomnia or the emergence of new cognitive or behavioral abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with hypnotic drugs.
Silenor (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, equivalent to 3 mg and 6mg of doxepin, respectively.
Chemically, doxepin hydrochloride is an (E) and (Z) geometric, isomeric mixture of 1 propanamine, 3-dibenz[b,e ]oxepin-11(6H)ylidene-N,N -dimethyl-hydrochloride.
Doxepin hydrochloride is a white crystalline powder, with a slight amine-like odor, that is readily soluble in water. It has a molecular weight of 315.84 and molecular formula of C19 H21 NO�HCl.
Each Silenor tablet includes the following inactive ingredients: microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. The 3 mg tablet also contains FD&C Blue No.1. The 6 mg tablet also contains D&C Yellow No. 10 and FD&C Blue No. 1.
12. CLINICAL PHARMACOLOGY
12.1. Mechanism of Action
Doxepin binds with high affinity to the histamine H1 receptor (Ki < 1 nM) where it functions as an antagonist. The exact mechanism by which doxepin exerts its sleep maintenance effect is unknown but is believed due to its antagonism of the H1 receptor.