SILENOR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SILENOR (SILENOR).
Selective histamine H1 receptor antagonist; promotes sleep by antagonizing central histaminergic neurotransmission.
| Metabolism | Hepatic via multiple CYP450 isoenzymes, including CYP3A4, CYP2D6, CYP1A2, and CYP2C9. |
| Excretion | Primarily renal (approximately 60% as unchanged drug and metabolites), with 30% fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 10 hours (range 8-15 hours) in healthy adults; prolonged in elderly and hepatic impairment. |
| Protein binding | <10% bound to plasma proteins (albumin). |
| Volume of Distribution | 0.8-1.0 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral: approximately 80%. |
| Onset of Action | Oral: 15-30 minutes to sleep onset. |
| Duration of Action | Approximately 6-8 hours; residual sedation may occur in some patients. |
| Molecular Weight | 259.34 |
6 mg orally once daily at bedtime, not to exceed 6 mg/day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <15 mL/min) or ESRD. |
| Liver impairment | Contraindicated in Child-Pugh class C. For Child-Pugh class A or B: use with caution; consider reduced dose of 3 mg once daily. |
| Pediatric use | Not approved for use in pediatric patients <18 years; safety and efficacy not established. |
| Geriatric use | Lower initial dose of 3 mg once daily recommended due to increased risk of impaired motor/cognitive function; maximum dose 6 mg/day. |
| 1st trimester | Avoid use due to potential fetal harm; limited human data, but animal studies show adverse effects. |
| 2nd trimester | Avoid use; may cause fetal respiratory depression or withdrawal if used near term. |
| 3rd trimester | Avoid use; risk of neonatal respiratory depression, hypotonia, and withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for SILENOR (SILENOR).
| Placental transfer | Crosses placenta; human data limited, but animal studies indicate transfer. |
| Breastfeeding | Excreted into breast milk in low amounts; however, due to long half-life and potential for sedation in the infant, use is generally not recommended. Monitor infant for excessive drowsiness. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to doxepin or any componentNarrow-angle glaucomaUrinary retentionConcomitant use with MAOIs within 14 daysSevere hepatic impairment
| Precautions | CNS depressant effects; may impair daytime alertness, Risk of anaphylaxis and angioedema, Use with caution in patients with hepatic impairment, Avoid alcohol and other CNS depressants, Elderly patients may be more sensitive to anticholinergic effects |
| Food/Dietary | High-fat meals significantly increase the absorption of doxepin, leading to higher peak concentrations and increased risk of next-day sedation. Administer SILENOR on an empty stomach, at least 3 hours after a meal. Avoid grapefruit juice, which may inhibit CYP450 metabolism and increase drug levels. |
Loading safety data…
| L4 - Possibly Hazardous |
| Teratogenic Risk | First trimester: limited data; doxylamine succinate (the active ingredient in SILENOR) is an antihistamine with no well-established human teratogenicity; some studies suggest a weak association with oral clefts, but overall risk is low. Second and third trimesters: no known fetal structural risks; avoid near term due to potential for neonatal respiratory depression and withdrawal symptoms. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and sedation level; assess fetal heart rate and uterine activity if used near term. No specific fetal monitoring required for short-term use. |
| Fertility Effects | No known adverse effects on fertility; limited data from animal studies do not indicate impairment. |
| Clinical Pearls | SILENOR (doxepin) is a tricyclic antidepressant used at low doses (3-6 mg) for insomnia. Its high selectivity for histamine H1 receptors reduces anticholinergic and cardiovascular side effects seen at higher doses. Avoid use in patients with severe urinary retention, narrow-angle glaucoma, or recent MI. Onset of action is within 30 minutes; take immediately before bedtime. Do not use within 3 hours of a meal due to food effects on absorption. |
| Patient Advice | Take SILENOR exactly at bedtime, only when you have a full 7-8 hours to dedicate to sleep. · Do not take SILENOR with or right after a meal; take it on an empty stomach, at least 3 hours after eating. · Avoid alcohol and other sedatives while taking SILENOR, as they can increase drowsiness and impair coordination. · SILENOR can cause next-day drowsiness; do not drive or operate heavy machinery until you know how the drug affects you. · Do not increase the dose or stop taking SILENOR without consulting your doctor. |