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doxepin hydrochloride

Apo-Doxepin (CA), Novo-Doxepin (CA), Prudoxin, Silenor, Sinepin (UK), Xepin (UK), Zonalon

Pharmacologic class: Tricyclic antidepressant

Therapeutic class: Antidepressant, anxiolytic, antipruritic

Pregnancy risk category C

FDA Box Warning

• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders. Risk must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family and caregivers to observe patient closely and communicate with prescriber as needed.

• Drug isn't approved for use in pediatric patients.


Unknown. May prevent reuptake of norepinephrine, serotonin, or both at presynaptic neurons, increasing levels of these neurotransmitters in CNS. Exact mechanism in pruritus also unknown, but drug is a potent histamine1- and histamine2-blocker.


Capsules: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

Cream (topical): 5% in 30-g tube

Oral concentrate: 10 mg/ml

Tablets: 3 mg, 6 mg

Indications and dosages

Endogenous depression; anxiety

Adults: Initially, 25 mg P.O. t.i.d., increased as needed up to 150 mg daily in outpatients and 300 mg daily in hospitalized patients

Elderly adults: Initially, 25 to 50 mg P.O. daily; may be increased as needed

Short-term relief of histamine-mediated pruritus of moderate severity accompanying such conditions as eczematous dermatitis

Adults: Apply a thin film of cream to skin q.i.d., with 3 to 4 hours between applications, for a maximum of 8 days.


Adults: 6 mg P.O. daily 30 minutes before bedtime

Dosage adjustment

• Elderly patients


• Hypersensitivity to drug or other dibenzoxepins

• Glaucoma

• Predisposition to urinary retention

• MAO inhibitor use within past 14 days


Use cautiously in:

• cardiovascular disease, prostatic enlargement, seizures

• severe sleep apnea (use not recommended)

• elderly patients

• pregnant or breastfeeding patients.


• If desired, mix contents of capsule with food.

• Dilute oral concentrate with 120 ml of water, milk, or juice. Be aware that drug is incompatible with carbonated beverages.

• Know that drug may be given at bedtime to prevent daytime sleepiness. If given for insomnia, avoid giving within 3 hours of a meal.

Don't give within 14 days of MAO inhibitor, because drug interaction may cause cardiovascular instability.

Avoid concurrent use of other CNS depressants, because inadvertent overdose may occur.

• With topical cream, don't apply to broken skin or use occlusive dressings, because doing so increases dermal absorption.

• Be aware that drug is usually given in conjunction with psychotherapy when used for depression.

Adverse reactions

CNS: fatigue, sedation, agitation, confusion, hallucinations, drowsiness, dizziness, extrapyramidal reactions, poor concentration, syncope, seizures, cerebrovascular accident, increased risk of suicide or suicidal ideation (especially in child or adolescent)

CV: hypotension, orthostatic hypotension, hypertension, vasculitis, ECG changes, tachycardia, palpitations, arrhythmias, myocardial infarction, heart block

EENT: blurred vision, increased intraocular pressure, lacrimation, tinnitus, nasal congestion

GI: nausea, constipation, dry mouth, paralytic ileus

GU: urinary retention, delayed voiding, urinary tract dilation, gynecomastia, galactorrhea, menstrual irregularities, testicular swelling, libido changes

Hematologic: purpura, bone marrow depression, eosinophilia, agranulocytosis, thrombocytopenia, leukopenia

Metabolic: hyperglycemia, hypoglycemia

Skin: photosensitivity, rash, urticaria, pruritus, diaphoresis, flushing, petechiae, alopecia, local burning, stinging, tingling, irritation, or rash (with topical use)

Other: increased appetite, weight gain or loss, hyperthermia, chills, edema, drug-induced fever, hypersensitivity reactions


Drug-drug. Barbiturates, CNS depressants (including antihistamines, clonidine, opioids, sedative-hypnotics): additive CNS depression

Carbamazepine, class IC antiarrhythmics (flecainide, propafenone), other antidepressants, other CYP450-2D6 inhibitors (amiodarone, cimetidine, quinidine, ritonavir), phenothiazines: increased doxepin blood level and effects

Clonidine: hypertensive crisis

Guanethidine: antagonism of antihypertensive effects

Levodopa: delayed or decreased levodopa absorption, hypertension

MAO inhibitors: tachycardia, seizures, potentially fatal reactions

Rifamycin: decreased doxepin effects

Selective serotonin reuptake inhibitors: increased risk of toxicity

Drug-diagnostic tests. Bilirubin, hepatic enzymes: increased levels

Glucose: increased or decreased level

Liver function tests: altered results

Drug-herbs. Angel's trumpet, jimsonweed, scopolia: increased anticholinergic effects

Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Evening primrose oil: additive or synergistic effects

S-adenosylmethionine (SAM-e), St. John's wort, yohimbe: serotonin syndrome

Drug-behaviors. Alcohol use: increased CNS depression

Smoking: increased drug metabolism and altered effects

Sun exposure: increased risk of photosensitivity reactions

Patient monitoring

Record mood changes and watch for suicidal tendencies, especially in child or adolescent.

• Assess bowel elimination pattern. Increase fluids and administer stool softeners as ordered to ease constipation.

• Monitor fluid intake and output. Report changes in voiding pattern.

• Monitor liver function test results, CBC with white cell differential, and glucose level.

Patient teaching

• Tell patient to take drug 30 minutes before bedtime and not within 3 hours of a meal when taking for insomnia.

• Advise patient on long-term therapy not to stop taking drug abruptly because this may lead to nausea, headache, and malaise.

Instruct patient and significant other, as appropriate, to monitor mental status carefully and to immediately report increased depression or suicidal thoughts or behavior (especially when used in child or adolescent).

Tell patient to promptly report easy bruising or bleeding.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Instruct patient to move slowly when sitting up or standing, to avoid dizziness or light-headedness from sudden blood pressure decrease.

• Explain that drowsiness and dizziness usually subside after several weeks.

• Tell patient that using topical cream on more than 10% of body surface area may cause drowsiness.

• Caution patient using topical cream not to apply it to broken skin and not to use occlusive dressings. Also tell him to avoid contact with eyes and to rinse eyes thoroughly with warm water if contact occurs.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved


Doxepin, see there.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.