Doxepin

Administration

• Type: Insomnia; Tricyclic Antidepressants (TCAs)
• Dosage Forms: 10, 25, 50, 75, 100, 150; 10/mL
• Routes of Administration: PO
• Common Trade Names: Silenor, Zonalon, Prudoxin

Adult Dosing

Depression

• 150-300mg PO QHS
• start 25-75mg PO QHS; max 300mg/day
• taper gradually to discontinue

Anxiety

• 150-300mg PO QHS
• start 25-75mg PO QHS; max 300mg/day
• taper gradually to discontinue

Insomnia

• 10-50mg PO QHS

Pediatric Dosing

Depression and/or anxiety: Oral: Note: Controlled clinical trials have not shown TCAs to be superior to placebo for the treatment of depression in children and adolescents

• Not recommended as first line medication
• May be beneficial for patients with comorbid conditions

• Children 7 to 11 years: Limited data available; efficacy results variable: 1 to 3 mg/kg/day in single or divided doses.

• Children ≥12 years and Adolescents: Initial: 25 to 75 mg/day at bedtime or in 2 to 3 divided doses; begin at the low end of range and gradually titrate; select patients may respond to 25 to 50 mg/day; maximum single dose: 150 mg; maximum daily dose: 300 mg/day.

Special Populations

• Pregnancy Rating: C
• Lactation risk: unsafe

Renal Dosing

• Adult: no adjustment

Hepatic Dosing

• Adult: not defined, caution advised

Contraindications

• Allergy to class/drug
• MI, acute recovery
• glaucoma, increased IOP
• urinary retention, prostatic hypertrophy, GI/GU obstruction
• avoid abrupt withdrawal
• caution if:
  • age <25 years, elderly
  • cardiovascular disease
  • seizure disorder, parkinsons
  • thyroid disease, diabetes
  • asthma
  • hepatic impairment
  • schizophrenia, bipolar disorder, alcohol abuse, electroconvulsive therapy, suicide risk
  • high environmental temperature

Adverse Reactions

Serious

• syncope, orthostatic hypotension
• ventricular arrhythmias, AV block, QT prolongation, torsades de pointes
• seizures
• MI, HTN
• stroke
• extrapyramidal symptoms, tardive dyskinesia
• ataxia
• paralytic ileus
• IOP elevation
• agranulocytosis, leukopenia, thrombocytopenia
• hallucinations, psychosis, worsening depression, hypomania/mania, suicidality
• SIADH
• hepatitis
• angioedema
• hyperthermia, heat stroke
• withdrawal symptoms if abruptly discontinued

Common

• drowsiness, dizziness, confusion, weakness, tremor, paresthesias
• nausea/vomiting, constipation, xerostomia
• blurred vision
• palpitations, tachycardia, diaphoresis, restlessness, insomnia, anxiety
• urinary frequency, incontinence, retention
• increased appetite, weight gain
• libido changes, impotence, gynecomastia, galactorrhea
• hypo/hyperglycemia
• rash/urticarial, pruritus, photosensitivity

Pharmacology

• Half-life: 15.3 hours (doxepin); 31 hours (metabolite)
• Metabolism: liver; CYP450 (1A2, 2C9/19, 2D6 substrate)
• Excretion: urine
• Mechanism of Action: exact MOA unknown; inhibits norepinephrine and serotonin reuptake; antagonizes central H1 receptors