Yes

Antidepressant, Tricyclic (Tertiary Amine); Topical Skin Product

Psychoneurotic patients with depression and/or anxiety; depression and/or anxiety associated with alcoholism; depression and/or anxiety associated with organic disease; psychotic depressive disorders with associated anxiety, including involutional depression and manic-depressive disorder

Topical: Short-term (<8 days) management of moderate pruritus in adults with atopic dermatitis or lichen simplex chronicus

C

Hypersensitivity to this drug and similar chemical class; narrow angle glaucoma; urinary retention; use of monoamine oxidase inhibitors within 14 days; use in a patient during the acute recovery phase of MI

Often causes sedation, which may result in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is very high relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May increase the risks associated with electroconvulsive therapy. This agent should be discontinued, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.

Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities). The risk of conduction abnormalities with this agent is moderate relative to other antidepressants. Use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation. Use with caution in patients with hepatic or renal dysfunction and in elderly patients. Use in children <12 years of age has not been established.

Cardiovascular: Hypotension, hypertension, tachycardia

Central nervous system: Drowsiness, dizziness, headache, disorientation, ataxia, confusion, seizure

Dermatologic: Alopecia, photosensitivity, rash, pruritus

Endocrine & metabolic: Breast enlargement, galactorrhea, SIADH, increase or decrease in blood sugar, increased or decreased libido

Gastrointestinal: Xerostomia, constipation, vomiting, indigestion, anorexia, aphthous stomatitis, nausea, unpleasant taste, weight gain, diarrhea, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux

Genitourinary: Urinary retention, testicular edema

Hematologic: Agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, purpura

Neuromuscular & skeletal: Weakness, tremors, numbness, paresthesia, extrapyramidal symptoms, tardive dyskinesia

Ocular: Blurred vision

Otic: Tinnitus

Miscellaneous: Diaphoresis (excessive), allergic reactions

Symptoms of overdose include confusion, hallucinations, seizures, urinary retention, hypothermia, hypotension, tachycardia, cyanosis

Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when QRS interval is >0.10 seconds or QT_c >0.42 seconds. Ventricular arrhythmias often respond to systemic alkalinization with or without phenytoin 15-20 mg/kg (adults) (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion. Physostigmine (1-2 mg I.V. slowly for adults or 0.5 mg I.V. slowly for children) may be indicated in reversing cardiac arrhythmias that are life-threatening. Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.

CYP2D6 enzyme substrate CYP1A2, 2C9, 2C19, 2D6, and 3A3/4 enzyme substrate

Doxepin inhibits the antihypertensive response to bethanidine, clonidine, debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor BP; consider alternate antihypertensive agent

Abrupt discontinuation of clonidine may cause hypertensive crisis, doxepin may enhance the response

Use with altretamine may cause orthostatic hypertension

Doxepin may be additive with or may potentiate the action of other CNS depressants (sedatives, hypnotics, or ethanol); with MAO inhibitors, hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported (serotonin syndrome), this combination should be avoided

Doxepin may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of doxepin

Additive anticholinergic effects seen with other anticholinergic agents

The SSRIs, to varying degrees, inhibit the metabolism of TCAs and clinical toxicity may result

Use of lithium with a TCA may increase the risk for neurotoxicity

Phenothiazines may increase concentration of some TCAs and TCAs may increase concentration of phenothiazines; monitor for altered clinical response

TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or insulin; monitor for changes in blood glucose levels

Cholestyramine and colestipol may bind TCAs and reduce their absorption; monitor for altered response

TCAs may enhance the effect of amphetamines; monitor for adverse CV effects

Verapamil and diltiazem appear to decrease the metabolism of imipramine and potentially other TCAs; monitor for increased TCA concentrations. The pressor response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced in patients receiving TCAs, this combination is best avoided.

Grapefruit juice,amprenavir, indinavir, ritonavir may inhibit the metabolism of clomipramine and potentially other TCAs; monitor for altered effects; a decrease in TCA dosage may be required

Quinidine may inhibit the metabolism of TCAs; monitor for altered effect

Combined use of anticholinergics with TCAs may produce additive anticholinergic effects; combined use of beta-agonists with TCAs may predispose patients to cardiac arrhythmias

Protect from light

Increases the synaptic concentration of serotonin and norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane

Peak effect (antidepressant): Usually more than 2 weeks; anxiolytic effects may occur sooner

Distribution: Crosses the placenta; appears in breast milk

Protein binding: 80% to 85%

Metabolism: Hepatic; metabolites include desmethyldoxepin (active)

Half-life: Adults: 6-8 hours

Elimination: Renal

Oral (entire daily dose may be given at bedtime):

Adolescents: Initial: 25-50 mg/day in single or divided doses; gradually increase to 100 mg/day

Adults: Initial: 30-150 mg/day at bedtime or in 2-3 divided doses; may gradually increase up to 300 mg/day; single dose should not exceed 150 mg; select patients may respond to 25-50 mg/day

Dosing adjustment in hepatic impairment: Use a lower dose and adjust gradually

Topical: Adults: Apply a thin film 4 times/day with at least 3- to 4-hour interval between applications

Alcohol: Additive CNS effect, avoid use

Monitor blood pressure and pulse rate prior to and during initial therapy; monitor mental status, weight

Therapeutic: 30-150 ng/mL; Toxic: >500 ng/mL; utility of serum level monitoring is controversial

glucose

Use with caution; epinephrine, norepinephrine and levonordefrin have been shown to have an increased pressor response in combination with TCAs

>10% of patients experience dry mouth; long-term treatment with TCAs increases the risk of caries by reducing salivation and salivary buffer capacity

Oral: Take exactly as directed (do not increase dose or frequency); may take several weeks to achieve desired results; may cause physical and/or psychological dependence. Avoid excessive alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); constipation (increased exercise, fluids, or dietary fruit and fiber may help); urinary retention (void before taking medication); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); altered sexual drive or ability (reversible); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (eg, nervousness, restlessness, insomnia, anxiety, excitation, headache, agitation, impaired coordination, changes in cognition); muscle cramping, weakness, tremors, or rigidity; chest pain, palpitations, or irregular heartbeat; blurred vision or eye pain; yellowing of skin or eyes; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Topical: Use as directed. Apply in thin layer; do not overuse. Report increased skin irritation, worsening of condition or lack of improvement.

May increase appetite; may cause drowsiness, raise bed rails, institute safety precautions

Capsule, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

Concentrate, oral, as hydrochloride: 10 mg/mL (120 mL)

Cream: 5% (30 g)

Boakes AJ, Laurence DR, Teoh PC, et al, "Interactions Between Sympathomimetic Amines and Antidepressant Agents in Man," Br Med J, 1973, 1(849):311-5.

Galynker II, Rosenthal RN, Perkel C, et al, "Doxepin Withdrawal Mania," J Clin Psychiatry, 1995, 56(3):122-3.

Jastak JT and Yagiela JA, "Vasoconstrictors and Local Anesthesia: A Review and Rationale for Use," J Am Dent Assoc, 1983, 107(4):623-30.

Jefferson JW, "Tamoxifen-Associated Reduction in Tricyclic Antidepressant Levels in Blood," J Clin Psychopharmacol, 1995, 15(3):223-4.

Lakshmanan M, Mion LC, and Frengley JD, "Effective Low-Dose Tricyclic Antidepressant Treatment for Depressed Geriatric Rehabilitation Patients. A Double-Blind Study," J Am Geriatr Soc, 1986, 34(6):421-6.

Larochelle P, Hamet P, and Enjalbert M, "Responses to Tyramine and Norepinephrine After Imipramine and Trazodone," Clin Pharmacol Ther, 1979, 26(1):24-30.

Levy HB, Harper CR, and Weinberg WA, " A Practical Approach to Children Failing in School," Pediatr Clin North Am, 1992, 39(4):895-928.

Mitchell JR, "Guanethidine and Related Agents. III Antagonism by Drugs Which Inhibit the Norepinephrine Pump in Man," J Clin Invest, 1970, 49(8):1596-604.

Roose SP, Glassman AH, Attia E, et al, "Comparative Efficacy of Selective Serotonin Reuptake Inhibitors and Tricyclics in the Treatment of Melancholia," Am J Psychiatry, 1994, 151(12):1735-9.

Rundegren J, van Dijken J, Mörnstad H, et al, "Oral Conditions in Patients Receiving Long-Term Treatment With Cyclic Antidepressant Drugs," Swed Dent J, 1985, 9(2):55-64.

Svedmyr N, "The Influence of a Tricyclic Antidepressive Agent (Protriptyline) on Some of the Circulatory Effects of Noradrenaline and Adrenalin® in Man," Life Sci, 1968, 7(1):77-84.

Ware MR, "Tricyclic Antidepressant Overdose: Pharmacology and Treatment," South Med J, 1987, 80(11):1410-5.

Williams JO, "Respiratory Depression in Tricyclic Overdose," Br Med J, 1972, 1(800):631.