SILENOR (Doxepin)

What is SILENOR (doxepin tablets) and how is it used?

SILENOR (doxepin tablets) is a hypnotic (sleep) medicine that is used to treat people who have trouble staying asleep.

What are the possible side effects of SILENOR (doxepin tablets)?

SILENOR (doxepin tablets) can cause serious side effects including:

• See “What is the most important information I should know about SILENOR (doxepin tablets) ?”

The most common side effect of SILENOR (doxepin tablets) is drowsiness or tiredness.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

INDICATIONS

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.

DOSAGE AND ADMINISTRATION

The dose of SILENOR should be individualized.

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.

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.

Administration

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].

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of labeling:

• Abnormal thinking and behavioral changes
• Suicide risk and worsening of depression

The total SILENOR dose should not exceed 6 mg per day.

Studies Pertinent To Safety Concerns For Sleep-promoting Drugs

Residual Pharmacological Effect In Insomnia Trials

Five randomized, placebo-controlled studies in adults and the elderly assessed next-day psychomotor function within 1 hour of awakening utilizing the digit-symbol substitution test (DSST), symbol copying test (SCT), and visual analog scale (VAS) for sleepiness, following night time administration of SILENOR.

In a one-night, double-blind study conducted in 565 healthy adult subjects experiencing transient insomnia, SILENOR 6 mg showed modest negative changes in SCT and VAS.

In a 35-day, double-blind, placebo-controlled, parallel group study of SILENOR 3 and 6 mg in 221 adults with chronic insomnia, small decreases in the DSST and SCT occurred in the 6 mg group.

In a 3-month, double-blind, placebo-controlled, parallel group study in 240 elderly subjects with chronic insomnia, SILENOR 1 mg and 3 mg was comparable to placebo on DSST, SCT, and VAS.

Other Reactions Observed During The Pre-marketing Evaluation Of SILENOR

SILENOR was administered to 1017 subjects in clinical trials in the United States. Treatment-emergent adverse reactions recorded by clinical investigators were standardized using a modified MedDRA dictionary of preferred terms. The following is a list of MedDRA terms that reflect treatment-emergent adverse reactions reported by subjects treated with SILENOR.

Adverse reactions are further categorized by body system and listed in order of decreasing frequency according to the following definitions: Frequent adverse reactions are those that occurred on one or more occasions in at least 1/100 subjects; Infrequent adverse reactions are those that occurred in fewer than 1/100 subjects and more than 1/1000 subjects. Rare adverse reactions are those that occurred in fewer than 1/1000 subjects. Adverse reactions that are listed in Table 1 are not included in the following listing of frequent, infrequent, and rare AEs.

Blood and Lymphatic System Disorders: Infrequent: anemia; Rare: thrombocythemia.

Cardiac Disorders: Rare: atrioventricular block, palpitations, tachycardia, ventricular extrasystoles.

Ear and Labyrinth Disorders: Rare: ear pain, hypoacusis, motion sickness, tinnitus, tympanic membrane perforation.

Eye Disorders: Infrequent: eye redness, vision blurred; Rare: blepharospasm, diplopia, eye pain, lacrimation decreased.

Gastrointestinal Disorders: Infrequent: abdominal pain, dry mouth, gastroesophageal reflux disease, vomiting; Rare: dyspepsia, constipation, gingival recession, haematochezia, lip blister.

General Disorders and Administration Site Conditions: Infrequent: asthenia, chest pain, fatigue; Rare: chills, gait abnormal, edema peripheral.

Hepatobiliary Disorders: Rare: hyperbilirubinemia.

Immune System Disorders: Rare: hypersensitivity.

Infections and Infestations: Infrequent: bronchitis, fungal infection, laryngitis, sinusitis, tooth infection, urinary tract infection, viral infection; Rare: cellulitis staphylococcal, eye infection, folliculitis, gastroenteritis viral, herpes zoster, infective tenosynovitis, influenza, lower respiratory tract infection, onychomycosis, pharyngitis, pneumonia.

Injury, Poisoning and Procedural Complications: Infrequent: back injury, fall, joint sprain; Rare: bone fracture, skin laceration.

Investigations: Infrequent: blood glucose increased; Rare: alanine aminotransferase increased, blood pressure decreased, blood pressure increased, electrocardiogram ST-T segment abnormal, electrocardiogram QRS complex abnormal, heart rate decreased, neutrophil count decreased, QRS axis abnormal, transaminases increased.

Metabolism and Nutrition Disorders: Infrequent: anorexia, decreased appetite, hyperkalemia, hypermagnesemia, increased appetite; Rare: hypokalemia.

Musculoskeletal and Connective Tissue Disorders: Infrequent: arthralgia, back pain, myalgia, neck pain, pain in extremity; Rare: joint range of motion decreased, muscle cramp, sensation of heaviness.

Neoplasms Benign, Malignant and Unspecified (Including Cysts and Polyps): Rare: lung adenocarcinoma stage I, malignant melanoma.

Nervous System Disorders: Frequent: dizziness; Infrequent: dysgeusia, lethargy, parasthesia, syncope; Rare: ageusia, ataxia, cerebrovascular accident, disturbance in attention, migraine, sleep paralysis, syncope vasovagal, tremor.

Psychiatric Disorders: Infrequent: abnormal dreams, adjustment disorder, anxiety, depression; Rare: confusional state, elevated mood, insomnia, libido decreased, nightmare.

Reproductive System and Breast Disorders: Rare: breast cyst, dysmenorrhea.

Renal and Urinary Disorders: Rare: dysuria, enuresis, hemoglobinuria, nocturia.

Respiratory, Thoracic and Mediastinal Disorders: Infrequent: nasal congestion, pharyngolaryngeal pain, sinus congestion, wheezing; Rare: cough, crackles lung, nasopharyngeal disorder, rhinorrhea, dyspnea.

Skin and Subcutaneous Tissue Disorders: Infrequent: skin irritation; Rare: cold sweat, dermatitis, erythema, hyperhidrosis, pruritis, rash, rosacea.

Surgical and Medical Procedures: Rare: arthrodesis.

Vascular Disorders: Infrequent: pallor; Rare: blood pressure inadequately controlled, hematoma, hot flush. In addition, the reactions below have been reported for other tricyclics and may be idiosyncratic (not related to dose).

Allergic: photosensitization, skin rash.

Hematologic: agranulocytosis, eosinophilia, leukopenia, purpura, thrombocytopenia.

EXPERT ADVICE FOR DOXEPIN