SILENOR

5 Missed dose 2025-02 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. 1 Pediatrics ...............................................................................................................

2 Geriatrics ............................................................................................................... 1 Dosing Considerations ...........................................................................................

2 Recommended Dose and Dosage Adjustment ....................................................... 5 Missed dose ........................................................................................................... 5

1 Adverse reaction overview The most common reported adverse drug reactions with SILENOR were somnolence, sedation and nausea. There was no apparent overall relationship to dose for any adverse reaction other than for the combined adverse events of somnolence and sedation.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful for identifying and approximating rates of adverse drug reactions in real-world use. During the SILENOR clinical development program, a total of 1,017 subjects were exposed to doses of 1 mg to 6 mg of doxepin.

The safety of SILENOR has been evaluated in three Phase 3 long-term placebo-controlled clinical trials (ranging from 28 to 85 days) conducted in adults (n = 221) and elderly (n = 494) subjects with chronic insomnia. 8 % in the SILENOR 1 mg, 3 mg, and 6 mg groups, respectively.

5 %. Table 2 lists the treatment-emergent adverse events, regardless of causality, reported by at least 1% of subjects who received SILENOR (3 mg or 6 mg) in the three long-term chronic insomnia studies (n = 221 for adult; and n = 417 for elderly).

5) 0 Table 3 lists the treatment-emergent adverse events, regardless of causality, by age group reported by at least 2 % of subjects who received SILENOR in the three long-term chronic insomnia studies. 0 %) 0 0 0 *includes SILENOR doses ranging from 3 mg to 6 mg.

5 % in elderly). 3 Less Common Clinical Trial Adverse Reactions The following adverse events were reported in the administration of SILENOR at a frequency < 1 % in the three long-term chronic insomnia safety and efficacy studies. Cardiac disorders: atrioventricular block, tachycardia Ear and labyrinth disorders: hypoacusis, motion sickness, tinnitus Eye disorders: blepharospasm, diplopia, eye pain, vision blurred, visual disturbance Gastrointestinal disorders: abdominal pain upper, diarrhoea, gastroesophageal reflux disease, gingival recession, toothache, tooth fracture General disorders: fatigue, feeling abnormal, hangover, oedema peripheral, pitting oedema, sluggishness Infections and infestations: bronchitis, eye infection, fungal infection, gastroenteritis viral, herpes zoster, infective tenosynovitis, influenza, laryngitis, lower respiratory tract infection, onychomycosis, sinusitis, tooth abscess, urinary tract infection, viral infection Injury, poisoning and procedural complications: back injury, excoriation, foot fracture, hand fracture, skin laceration, upper limb fracture Investigations: blood pressure decreased, electrocardiogram abnormal Metabolism and nutrition disorders: decreased appetite, hypokalemia, increased appetite Musculoskeletal and connective tissue disorders: joint range of motion decreased, muscle cramp, myalgia, neck pain, pain in extremity Neoplasm benign, malignant and unspecified (including cysts and polyps): lung adenocarcinoma stage I, malignant melanoma Nervous system disorders: ageusia, ataxia, disturbance in attention, lethargy, migraine, sleep paralysis, tremor SILENOR® (doxepin tablets) Page 13 of 27 Psychiatric disorders: depression, elevated mood, libido decreased, nightmare Renal and […]

4 Drug- Drug Interactions). 4 Drug-Drug Interactions). Patients should be cautioned about potential additive effects of SILENOR used in combination with CNS depressants or sedating antihistamines. , driving while not fully awake after ingestion of a hypnotic, with amnesia for the event) have been reported with hypnotics.

Other potentially dangerous behaviours have been reported in patients who got out of bed after taking a sedative-hypnotic and were not fully awake, including preparing and eating food, making phone calls, leaving the house, etc. As with “sleep-driving”, patients usually do not remember these events.

These events can occur in hypnotic-naive as well as in hypnotic-experienced persons. Although behaviours such as “sleep-driving” may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviours, as does the use of hypnotics at doses exceeding the maximum recommended dose.

Due to the risk to the patient and the community, discontinuation of SILENOR should be strongly considered for patients who report a “sleep- driving” episode or other complex behaviours episode. Dependence/Tolerance Potential withdrawal effects were assessed in a 35-day double blind study of adults with chronic insomnia who were randomized to placebo, SILENOR 3 mg, or SILENOR 6 mg.

There was no indication of a withdrawal syndrome after discontinuation of SILENOR treatment (3 mg or 6 mg), as measured by the Tyrer’s Symptom Checklist. Discontinuation-period emergent nausea and vomiting occurred in 5 % of subjects treated with 6 mg SILENOR, versus 0 % in 3 mg and placebo subjects.

SILENOR has not been demonstrated to produce tolerance or physical 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.

SILENOR is contraindicated in patients: • with known intolerance or hypersensitivity to doxepin hydrochloride, other dibenzoxepine compounds or to any ingredient in the formulation or component of the container. For a complete listing, see the 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

• with untreated narrow angle glaucoma. • with severe urinary retention. • currently taking monoamine oxidase inhibitors (MAOIs) or who have used MAOIs within the past two weeks. Serious side effects and even death have been reported following the concomitant use of certain drugs with MAOIs.