Silenor

Side Effects
Interactions

SIDE EFFECTS

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

  • Abnormal thinking and behavioral changes [see WARNINGS AND PRECAUTIONS]
  • Suicide risk and worsening of depression [see WARNINGS AND PRECAUTIONS].
  • CNS Depressant effects [see WARNINGS AND PRECAUTIONS].

Clinical Trials Experience

The pre-marketing development program for Silenor included doxepin HCl exposures in 1017 subjects (580 insomnia patients and 437 healthy subjects) from 12 studies conducted in the United States. 863 of these subjects (580 insomnia patients and 283 healthy subjects) participated in six randomized, placebo-controlled efficacy studies with Silenor (doxepin tablets) doses of 1 mg, 3 mg, and 6 mg for up to 3-months in duration.

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. However, data from the Silenor (doxepin tablets) studies provide the physician with a basis for estimating the relative contributions of drug and non-drug factors to adverse reaction incidence rates in the populations studied.

Associated with Discontinuation of Treatment

The percentage of subjects discontinuing Phase 1, 2, and 3 trials for an adverse reaction was 0.6% in the placebo group compared to 0.4%, 1.0%, and 0.7% in the Silenor (doxepin tablets) 1 mg, 3 mg, and 6 mg groups, respectively. No reaction that resulted in discontinuation occurred at a rate greater than 0.5%.

Adverse Reactions Observed at an Incidence of ≥ 2% in Controlled Trials

Table 1 shows the incidence of treatment-emergent adverse reactions from three long-term (28 to 85 days) placebo-controlled studies of Silenor (doxepin tablets) in adult (N=221) and elderly (N=494) subjects with chronic insomnia.

Reactions reported by Investigators were classified using a modified MedDRA dictionary of preferred terms for purposes of establishing incidence. The table includes only reactions that occurred in 2% or more of subjects who received Silenor (doxepin tablets) 3 mg or 6 mg in which the incidence in subjects treated with Silenor (doxepin tablets) was greater than the incidence in placebo-treated subjects.

Table 1: Incidence (%) of Treatment-Emergent Adverse Reactions in Long-term Placebo-Controlled Clinical Trials

System Organ Class Preferred Term* Placebo (N=278) Silenor 3 mg (N=157) Silenor 6 mg (N=203)
Nervous System Disorders
  Somnolence/Sedation 4 6 9
Infections and Infestations
  Upper Respiratory Tract Infection/nasopharyngitis 2 4 2
  Gastroenteritis 0 2 0
Gastrointestinal Disorders
  Nausea 1 2 2
Vascular Disorders
  Hypertension 0 3 < 1
* Includes reactions that occurred at a rate of ≥ 2% in any Silenor-treated group and at a higher rate than placebo.

The most common treatment-emergent adverse reaction in the placebo and each of the Silenor (doxepin tablets) dose groups was somnolence/sedation.

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 (doxepin tablets) .

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

In a 35-day, double-blind, placebo-controlled, parallel group study of Silenor (doxepin tablets) 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 (doxepin tablets) 1 mg and 3 mg was comparable to placebo on DSST, SCT, and VAS.

Other Reactions Observed During the Pre-marketing Evaluation of Silenor (doxepin tablets)

Silenor (doxepin tablets) 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 (doxepin tablets) .

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.

Read the Silenor (doxepin tablets) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Cytochrome P450 Isozymes

Silenor (doxepin tablets) is primarily metabolized by hepatic cytochrome P450 isozymes CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. Inhibitors of these isozymes may increase the exposure of doxepin. Silenor (doxepin tablets) is not an inhibitor of any CYP isozymes at therapeutically relevant concentrations. The ability of Silenor (doxepin tablets) to induce CYP isozymes is not known.

Cimetidine

Silenor (doxepin tablets) exposure is doubled with concomitant administration of cimetidine, a nonspecific inhibitor of CYP isozymes. A maximum dose of 3 mg is recommended in adults and elderly when cimetidine is co-administered with Silenor [see CLINICAL PHARMACOLOGY]

Alcohol

When taken with Silenor (doxepin tablets) , the sedative effects of alcohol may be potentiated [see WARNINGS AND PRECAUTIONS].

CNS Depressants and Sedating Antihistamines

When taken with Silenor (doxepin tablets) , the sedative effects of sedating antihistamines and CNS depressants may be potentiated [see WARNINGS AND PRECAUTIONS].

Tolazamide

A case of severe hypoglycemia has been reported in a type II diabetic patient maintained on tolazamide (1 g/day) 11 days after the addition of oral doxepin (75 mg/day).

Drug Abuse And Dependence

Controlled Substance

Doxepin is not a controlled substance.

Abuse

Doxepin is not associated with abuse potential in animals or in humans. Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of doxepin (e.g., incrementation of dose, drug-seeking behavior).

Dependence

In a brief assessment of adverse events observed during discontinuation of doxepin following chronic administration, no symptoms indicative of a withdrawal syndrome were observed. Thus, doxepin does not appear to produce physical dependence.

Read the Silenor Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 4/2/2010
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
A A A

Silenor - User Reviews

Silenor User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Silenor sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.


NIH talks about Ebola on WebMD