DOXEPIN HYDROCHLORIDE

DOXEPIN HYDROCHLORIDE (dox'e-pin) Adapin, Sinequan, Triadapin , Zonalon Classifications: psychotherapeutic; tricyclic antidepressant; anxiolytic; Therapeutic: tricyclic antidepressant; antianxiety agent Prototype: Imipramine Pregnancy Category: C

Availability

10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg capsules; 10 mg/mL oral concentrate

Action

Dibenzoxepin is one of the most sedating tricyclic antidepressants (TCAs). Inhibits serotonin reuptake from the synaptic gap; also inhibits norepinephrine reuptake to a moderate degree. Recent evidence suggests that the upset of monoamine oxidase output seen in depressed patients may be regulated by long-term treatment with antidepressants due to their action on beta-adrenergic receptors. This action on beta-receptors may be a better explanation than the reuptake theory for TCAs' antidepressant effects.

Therapeutic Effect

Effective for treatment of both depression and anxiety.

Uses

Psychoneurotic anxiety or depressive reactions; mixed symptoms of anxiety and depression; anxiety or depression associated with alcoholism; organic disease; psychotic depressive disorders; topical for treatment of pruritus.

Unlabeled Uses

Peptic ulcer disease, neuralgia.

Contraindications

Prior sensitivity to any TCA; during acute recovery phase following MI; bundle-branch block, cardiac arrhythmias, QT prolongation; ileus; glaucoma; increased intraocular pressure; prostatic hypertrophy; tendency for urinary retention; concurrent use of MAO inhibitors; pregnancy (category C), lactation. Safe use in children <12 y is not established.

Cautious Use

Patients receiving electroconvulsive therapy, patients with suicidal tendency, bipolar disorder, schizophrenia, psychosis; diabetes mellitus; GI disease; GERD; Parkinson's disease; seizure disorders; renal, cardiovascular, or hepatic dysfunction.

Route & Dosage

Antidepressant Adult: PO 30–150 mg/d h.s. or in divided doses, may gradually  increase to 300 mg/d (use lower doses in older adult patients) Geriatric: PO 10–25 mg h.s., may gradually increase to 75 mg/d Child: PO 1–3 mg/kg/d in single or divided doses Pruritus Adult: Topical Apply a thin film q.i.d. with at least 3–4 h between applications, may use up to 8 d

Administration

Oral

• Give oral concentrate diluted with approximately 120 mL water, milk, or fruit juice.
• Empty capsule and swallow contents with fluid or mix with food as necessary if it cannot be swallowed whole.
• Inform physician if daytime sedation is pronounced. Entire daily dose (up to 150 mg) may be prescribed for bedtime administration.

Topical

• Apply a thin film to affected areas; allow 3–4 h between applications.
• Store all forms at 15°–30° C (59°–86° F) in tightly closed, light-resistant container.

Adverse Effects (≥1%)

All: Anticholinergic. CNS: Drowsiness, dizziness, weakness, fatigue, headache, hypomania, confusion, tremors, paresthesias. CV: Orthostatic hypotension, palpitation, hypertension, tachycardia, ECG changes. Special Senses: Mydriasis, blurred vision, photophobia. GI: Dry-mouth, sour or metallic taste, epigastric distress, constipation. Urogenital: Urinary retention, delayed micturition, urinary frequency. Other: Increased perspiration, tinnitus, weight gain, photosensitivity reaction, skin rash, agranulocytosis, burning or stinging at application site, edema.

Interactions

Drug: May decrease some antihypertensive response to antihypertensives; cns depressants, alcohol, hypnotics, barbiturates, sedatives potentiate CNS depression; may increase hypoprothrombinemic effect of oral anticoagulants; ethchlorvynol may cause transient delirium; levodopa, sympathomimetics (e.g., epinephrine, norepinephrine) introduce possibility of sympathetic hyperactivity with hypertension and hyperpyrexia; mao inhibitors introduce possibility of severe reactions, toxic psychosis, cardiovascular instability; methylphenidate increases plasma TCA levels; thyroid agents may increase possibility of arrhythmias; cimetidine may increase plasma TCA levels. Herbal: Ginkgo may decrease seizure threshold; St. John's wort may cause serotonin syndrome.

Pharmacokinetics

Absorption: Rapidly absorbed from GI sites through intact skin. Peak: 2 h. Distribution: Crosses placenta; distributed into breast milk. Metabolism: In liver. Elimination: Primarily in urine. Half-Life: 6–8 h.

Nursing Implications

Assessment & Drug Effects

• Monitor use of other CNS depressants, including alcohol. Danger of overdosage or suicide attempt is increased when patient uses excessive amounts of alcohol.
• Be alert to changes in voiding and evaluate patient for constipation and abdominal distention; drug has moderate to strong anticholinergic effects.

Patient & Family Education

• Maintain established dosage regimen and avoid change of intervals, doubling, reducing, or skipping doses.
• Consult physician about safe amount of alcohol, if any, that can be taken. The actions of both alcohol and doxepin are potentiated when used together and for up to 2 wk after doxepin is discontinued.
• Do not drive or engage in other potentially hazardous activities until response to drug is known.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug