Doxepin Hydrochloride

Pronouncation: (DOX-uh-pin HIGH-droe-KLOR-ide)
Class: Antianxiety agent, Tricyclic compound, Topical antihistamine preparation

Trade Names:
Sinequan
- Capsules 10 mg
- Capsules 25 mg
- Capsules 50 mg
- Capsules 75 mg
- Capsules 100 mg
- Capsules 150 mg

Trade Names:
Zonalon
- Cream 5%

Apo-Doxepin (Canada)
Novo-Doxepin (Canada)

Pharmacology

Moderately blocks reuptake of norepinephrine and weakly blocks reuptake of serotonin; also produces antihistaminic and anticholinergic activity.

Pharmacokinetics

Absorption

T max is 2 to 8 days (steady-state).

Metabolism

Metabolized in the liver to desmethyldoxepin (active).

Elimination

Urinary excretion; t ½ is 8 to 24 h (oral), 28 to 52 h (topical).

Indications and Usage

Treatment of psychoneurotic patients with depression and/or anxiety; depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol); depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly); psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders; moderate pruritus with atopic dermatitis or lichen simplex chronicus (topical).

Unlabeled Uses

Neurogenic pain, peptic ulcer disease.

Contraindications

Hypersensitivity to tricyclic antidepressants; use during acute recovery phase after MI; glaucoma; risk of urinary retention; concomitant use with MAOI; dibenzoxepines may produce cross-sensitivity.

Dosage and Administration

Depression and/or Anxiety
Adults

PO Initial dose 75 mg/day, increasing as tolerated (max, 300 mg/day). May be given every day or on a divided dosage schedule. If given every day, the max recommended dose is 150 mg/day.

For Mild Cases with Organic Diseases

PO 25ߙto 50ߙmg/day.

Pruritus
Adults

Topical Apply thin film 4 times daily with at least 3 to 4 h between applications. Not recommended for more than 8 days.

Storage/Stability

Store capsules below 86°F.

Drug Interactions

Alcohol/CNS depressants

CNS and respiratory depression may be potentiated.

Cimetidine

May inhibit metabolism of doxepin, leading to increased concentrations.

Clonidine

Concurrent use may lead to loss of BP control and possibly dangerous increases in BP.

Guanethidine

Hypotensive action may be inhibited.

MAOIs

Concurrent use may lead to severe seizures, hyperpyretic crisis, and fatal reactions. Generally, allow 7 to 10 days between discontinuation of 1 drug and start of another.

SSRIs (eg, fluoxetine)

May increase serum concentrations of doxepin; effect may occur up to 5 wk after discontinuation of fluoxetine.

Sympathomimetics (eg, dopamine, epinephrine)

Pressor response may increase or decrease; arrhythmias may occur.

Type IC antiarrhythmics (eg, propafenone, flecainide)

May inhibit metabolism of doxepin, leading to increased concentrations.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Orthostatic hypotension; hypertension; fainting; tachycardia.

CNS

Dizziness; drowsiness; headache; confusion; weakness; tremors; convulsions; fatigue; disorientation; hallucinations; numbness; paresthesias; ataxia; extrapyramidal symptoms; tardive dyskinesia.

Dermatologic

Skin rash; edema; photosensitization; pruritus.

Topical use

Local burning or stinging; dry or tight skin.

EENT

Mydriasis; photophobia; blurred vision; tinnitus.

GI

Nausea; constipation; dry mouth; paralytic ileus; vomiting; indigestion; taste perversion; diarrhea; anorexia; aphthous stomatitis.

Genitourinary

Urinary retention; nocturia; altered libido; testicular swelling, gynecomastia (males); enlargement of breasts, galactorrhea (females).

Hepatic

Jaundice.

Hematologic

Agranulocytosis; eosinophilia; purpura; thrombocytopenia; leukopenia.

Metabolic

Weight gain; syndrome of inappropriate secretion of antidiuretic hormone; raising or lowering of blood sugar levels.

Respiratory

Exacerbation of asthma.

Miscellaneous

Hyperthermia; alopecia; sweating; chills.

Precautions

Pregnancy

Category C (oral); Category B (topical).

Lactation

Excreted in breast milk.

Children

Not recommended for children younger than 12 yr of age.

Special Risk Patients

Use drug with caution in patients with history of seizures, urinary retention, urethral spasm, angle-closure glaucoma or increased IOP, CV disorders, hyperthyroidism (or those receiving thyroid medication), hepatic or renal function impairment, schizophrenia, or paranoia.

Capsule, 150 mg

The 150 mg capsule strength is intended for maintenance therapy only and is not recommended for initiation of treatment.

Contact sensitization

Use of cream can cause Type IV hypersensitivity reactions.

Suicide

Use drug with caution in patients with suicidal tendencies; do not allow access to large quantities of drug.

Topical use

For external use only; do not use ophthalmically, orally, or intravaginally. Because of absorption of drug, drowsiness often occurs.

Withdrawal

If treatment is to be discontinued, or the dose reduced, gradually taper the dose and monitor patient for withdrawal symptoms. If significant withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.

Overdosage

Symptoms

Confusion, agitation, transient visual hallucinations, seizures, hyperactive reflexes, coma, cardiac arrhythmias, dilated pupils, hyperpyrexia, severe hypotension, CNS depression, ECG changes (QRS axis or width), disturbed concentration, stupor, drowsiness, muscle rigidity, vomiting, hypothermia.

Patient Information

  • Advise patient to read patient information leaflet before starting therapy and with each refill.
  • Advise patient that medication is usually started at a low dose and then gradually increased as tolerated until max benefit is obtained.
  • Advise patient to take prescribed dose without regard to meals, but to take with food if stomach upset occurs.
  • Advise patient not to change the dose or stop taking unless advised by health care provider.
  • Inform patient that it may take 2 to 6 wk to note improvement in symptoms and to continue with prescribed therapy once improvement has been noted.
  • Instruct patient to contact health care provider if symptoms do not appear to be getting better, are getting worse, or if bothersome adverse reactions (eg, unusual sweating, urination difficulty, drowsiness, dizziness, constipation, changes in sexual function) occur.
  • Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Advise patient that drug (oral and topical) may cause drowsiness, dizziness, or impair reflexes and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Instruct patient not to take prescription or OTC drugs or dietary supplements without consulting health care provider.
  • Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.
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