Dosing and uses of Silenor (doxepin)
Adult dosage forms and strengths
capsule (generic)
- 10mg
- 25mg
- 50mg
- 75mg
- 100mg
- 150mg
tablet (Silenor)
- 3mg
- 6mg
oral concentrate (generic)
- 10mg/mL
Depression/Anxiety
Initiate at low dose (25 mg/day); gradually titrate upward every 5-7 days
Dosage range: 25-300 mg/day PO, up to 150 mg/day as single dose
If dose exceeds 150 mg/day, divide q12hr
Dosing considerations
- May give qHS to decrease daytime sedation
Insomnia (Silenor)
Sleep maintenance
3-6 mg PO within 30 minutes before bedtime; not to exceed 6 mg/day
Hepatic impairment/debilitated patients: 3 mg PO within 30 minutes before bedtime
Dosing considerations
- To minimize potential for next day drowsiness, do not take within 3 hr of a meal (AUC increased by 41% and Cmax by 15% when taken with high fat meal)
Dosing Modifications
Hepatic impairment: Use lower dose and adjust gradually for depression; initiate Silenor at 3 mg daily for insomnia
Pediatric dosage forms and strengths
<12 years old: Not recommended
Geriatric dosage forms and strengths
Insomnia (Silenor)
Sleep maintenance
Starting dose: 3 mg PO within 30 minutes before bedtime
May increase to 6 mg PO HS if clinically indicated
Depression/Anxiety
Lower initial dose (ie, 10 mg/day) and adjust gradually; 10-25 mg PO qHs
May increase by 10-25 mg increments q3Day for inpatients and weekly for outpatients if tolerated
Dosing considerations
Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)
Consider alternatives; if must use, initiate with lower initial dose
May cause confusion and oversedation in elderly
Silenor (doxepin) adverse (side) effects
Frequency not defined
Sedation, fatigue, weakness, lethargy
Dry mouth
Constipation
Blurred vision
Headache
Agitation
Insomnia
Anxiety
Nausea, vomiting
Sweating
Confusion, extrapyramidal symptoms (EPS), dizziness, paresthesia
Orthostatic hypotension, ECG changes, tachycardia
Increased LFTs
Tinnitus
Sexual dysfunction
Rash
Seizure
Agranulocytosis
Thrombocytopenia
Eosinophilia
Leukopenia
SIADH
Warnings
Black box warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients >24 years; a slight decrease in suicidal thinking was seen in adults >65 years
In children and young adults, risks must be weighed against the benefits of taking antidepressants
Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
The patient’s family should communicate any abrupt changes in behavior to the healthcare provider
Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy
This drug is not approved for use in pediatric patients
Contraindications
Hypersensitivity
Untreated narrow-angle glaucoma
Severe urinary retention
Within 14 days of MAO inhibitors
Cautions
Use caution in BPH, urinary retention, decreased GI motility, hyperthyroidism, seizure disorder, brain tumor, diabetes, hepatic impairment, cardiovascular disease, mania/hypomania, respiratory disease, and seizure disorders
Clinical worsening and suicidal ideation may occur despite medication in adolescents and young adults (aged 18-24 years)
Risk of anticholinergic side effects
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
CNS depressant; can impair alertness and motor coordination; avoid use with other CNS depressants (eg, alcohol)
Overdose may cause EKG QRS widening and risk of dysrhythmias
Protect capsules and oral concentrate from direct sunlight
Prescriptions should be written for smallest quantity consistent with good patient care; patient's family or caregiver should alert healthcare professional about emergence of suicidality and related behaviors including agitation, panic attacks, irritability, impulsivity, mania, and insomnia or if worsening depression or psychosis occurs
Anticholinergic effects including blurred vision, urinary retention, xerostomia, and constipation may occur
Neuropsychiatric symptoms may occur unpredictably including anxiety and psychosis
Bone fracture reported with use of antidepressant therapy; consider possibility of fracture if patient presents with unexplained bone pain, joint tenderness, bruising or swelling
May cause orthostatic hypotension; use caution in patients at risk of this effect or that may not tolerate hypotensive episodes (eg, hypovolemia, cardiovascular or cerebrovascular disease and others)
Sleep related activities including sleep driving, eating food, cooking, making phone calls reported; discontinue therapy if patient reports sleep-related episodes
Possibility of EPS and neuroleptic malignant syndrome (NMS)
May cause confusion in the elderly; avoid doses >6 mg/day
Pregnancy and lactation
Pregnancy category: Not available
Lactation: Enters breast milk; not recommended (AAP states "may be of concern")
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Silenor (doxepin)
Mechanism of action
Exact mechanism for doxepin's sleep maintenance effect is unknown; however, doxepin's action is believed to result from antagonism of the histamine H1 receptor
Mechanism of action for depression is unknown; may increase CNS synaptic concentrations of serotonin and norepinephrine by inhibiting reuptake
Absorption
Peak plasma time: 2 hr
Onset: >2 weeks (depression)
Distribution
Protein bound: 80%
Metabolism
Hepatic CYP2D6, CYP2C19
Metabolites: N-demethyldoxepin
Elimination
Half-life: 6-8 hr
Excretion: Urine
