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---------------------------------------------------------------------------- Doxepin / Brand names: Adapin, Sinequan / Drug monograph ---------------------------------------------------------------------------- Pharmacology Antidepressant Doxepin is a psychotropic agent with antidepressant and anxiolytic properties. It also has sedative and anticholinergic effects, and, in the higher dosage range, it produces peripheral adrenergic blocking effects. Studies of electroencephalograms in humans have shown decreases in amplitude, and amplitude variability, also, the delta, theta and 24-35 CPS activities increased. ---------------------------------------------------------------------------- Indications The drug treatment of: 1. Psychoneurotic patients with anxiety and/or depressive reactions. Anxiety neurosis associated with somatic disorders; alcoholic patients with anxiety and/or depression. 2. Psychotic depression, including manic-depressive illness (depressed type) and involutional melancholia. ---------------------------------------------------------------------------- Contraindications Doxepin is contraindicated in individuals who have shown hypersensitivity to the drug or to other dibenzoxepin compounds. Children: It is not recommended for use in children since safety and efficacy in this age group have not been established. Because of its anticholinergic activity doxepin should not be administered to patients with a history of glaucoma, increased intraocular pressure or urinary retention. Tricyclic agents are generally contraindicated during the acute recovery phase following myocardial infarction and in the presence of acute congestive heart failure, as well as in patients with a history of blood dyscrasias and severe liver disease. Doxepin should not be administered concomitantly with MAO inhibitors, since such a combination may cause a syndrome of intensive sympathetic stimulation. Drugs of this type should be discontinued at least 2 weeks before instituting therapy with doxepin. ---------------------------------------------------------------------------- Warnings Tricyclic antidepressant drugs, particularly when given in high doses, can induce sinus tachycardia, changes in conduction time and arrhythmias. A few instances of unexpected death have been reported in patients with cardiovascular disorders. Myocardial infarction and stroke have also been reported with drugs of this class. Therefore, doxepin should be administered with extreme caution to patients with a history of cardiovascular disease, those with circulatory lability and elderly patients. In such cases, treatment should be initiated with low doses with progressive increases only if required and tolerated, and the patients should be under close surveillance at all dosage levels. Since tricylic agents are known to reduce the seizure threshold, doxepin should be used with caution in patients with a history of convulsive disorders. Concurrent administration of ECT and doxepin may be hazardous and, therefore, such treatment should be limited to patients for whom it is essential. Close supervision is required when doxepin is given to hyperthyroid patients or those receiving thyroid medication because of the possibility of cardiovascular toxicity. At doses above 150 mg/day, it may block the antihypertensive effect of guanethidine and related compounds. Pregnancy and Lactation: The safety of doxepin during pregnancy and lactation has not been established and therefore, it should not be used in women of childbearing potential or nursing mothers, unless, in the opinion of the physician, the potential benefits to the patient outweigh the possible hazards to the fetus. ---------------------------------------------------------------------------- Precautions Occupational Hazards: Since drowsiness may occur with the use of this drug, patients should be advised against driving or engaging in activities requiring mental alertness and physical coordination until their response to the drug has been well established. Patients should be warned that the effects of other drugs acting on the central nervous system, such as alcohol, barbiturates and other CNS depressants, may be potentiated by doxepin. The possibility of suicide in seriously depressed patients may remain until significant remission occurs. Such patients should be closely supervised throughout therapy and consideration should be given to the possible need for hospitalization. This type of patient should not have easy access to large quantities of doxepin. Tricyclic antidepressants may precipitate or aggravate psychotic manifestations in schizophrenic patients and hypomanic or manic episodes in manic-depressive patients. This may require a reduction of dosage, discontinuation of the drug, and/or administration of an antipsychotic agent. Tricyclic antidepressants may also give rise to paralytic ileus, particularly in the elderly and in hospitalized patients. Therefore, appropriate measures should be taken if constipation occurs. When doxepin is given concomitantly with anticholinergic or sympathomimetic drugs, close supervision and careful adjustment of dosages are required. Doxepin should be discontinued prior to elective surgery for as long as the clinical situation will allow. Doxepin should be used with caution in patients with impaired liver function or with a history of hepatic damage or blood dyscrasias. Periodic blood counts and liver function tests should be performed when patients receive doxepin in large doses or over prolonged periods. ---------------------------------------------------------------------------- Adverse Effects Although some of the adverse reactions included in the following list have not been reported with doxepin pharmacological similarities among the tricyclic antidepressants require that each of the reactions be considered when prescribing doxepin. Behavioral: Drowsiness, fatigue, excitement, agitation, restlessness, insomnia, nightmares, hypomania, anxiety, confusion, disorientation, disturbed concentration, delusions, hallucinations, activation of latent psychosis. Neurological: Seizures, alteration in EEG patterns, dizziness, tremors, extrapyramidal symptoms, numbness, tingling, paresthesias of the extremities, peripheral neuropathy, tinnitus, syndrome of inappropriate ADH (antidiuretic hormone) secretion. Cardiovascular: Hypotension, hypertension, tachycardia, palpitations. A quinidine-like effect and other reversible ECG changes such as flattening or inversion of T-waves, bundle branch block, depressed S-T segments, prolonged conduction time and asystole, arrhythmias, heart block, fibrillation, myocardial infarction, stroke and unexpected death in patients with cardiovascular disorders have been reported with other tricyclic antidepressants. Autonomic: Dry mouth, blurred vision, disturbances of accommodation, mydriasis, constipation, nasal stuffiness, delayed micturition, sublingual adenitis, paralytic ileus, urinary retention, dilation of the urinary tract, precipitation of latent and aggravation of existing glaucoma, vertigo. Endocrine: Increased or decreased libido, impotence, menstrual irregularity, testicular swelling, breast enlargement and galactorrhea in the female, gynecomastia in the male, elevation and lowering of blood sugar levels. Allergic or Toxic: Pruritus, skin rash, photosensitization, edema, drug fever, leukopenia, urticaria, petechiae, obstructive jaundice and bone marrow depression, including agranulocytosis, eosinophilia, purpura and thrombocytopenia. Gastrointestinal: Nausea, epigastric distress, vomiting, flatulence, abdominal pain, diarrhea, peculiar taste, stomatitis. Miscellaneous: Weakness, headache, weight gain or loss, excessive appetite, anorexia, increased perspiration, urinary frequency, lacrimation, alopecia, parotid swelling, black tongue, hepatitis. Withdrawal Symptoms: Abrupt cessation of treatment with tricyclic antidepressants after prolonged administration may produce nausea, headache and malaise. These symptoms are not indicative of addiction. ---------------------------------------------------------------------------- Overdose Symptoms: Excessive drowsiness leading to minor alterations of consciousness and even unresponsiveness could be an early indication of excessive dosage. However, overdosage with doxepin is more likely to be manifested by increased psychomotor agitation and convulsions leading to apnea and coma. The ECG changes (broadening of QRS and T-wave abnormalities) tend to be a late finding and are not always accompanied by cardiovascular hemodynamic changes. Treatment: In general, treatment of overdosage should be symptomatic and supportive. Cardiac arrhythmias and CNS involvement pose the greatest threat with tricyclic antidepressant overdosage and may occur suddenly even when initial symptoms appear to be mild. Therefore, patients who may have ingested an overdosage of doxepin, particularly children, should be hospitalized and kept under close surveillance. If the patient is conscious, induced emesis followed by gastric lavage, with appropriate precautions to prevent pulmonary aspiration, should be accomplished as soon as possible. Following lavage, activated charcoal may be administered to reduce absorption. An adequate airway should be established in comatose patients and assisted ventilation instituted, if necessary. The possibility of occurrence of seizures should be kept in mind. External stimulation should be minimized to reduce the tendency to convulsions. Convulsions, should they occur, may respond to standard anticonvulsant therapy; however, barbiturates should be avoided since they may potentiate respiratory depression, particularly in children, and aggravate hypotension and coma. ECG monitoring in an intensive care unit is recommended in all patients, particularly in the presence of ECG abnormalities, and should be maintained for several days after the cardiac rhythm has returned to normal. A patient who has ingested a toxic overdose of a tricyclic antidepressant may remain medically and psychiatrically unstable for several days due to sustained excessive drug levels. Unexpected cardiac deaths have occurred up to 6 days after overdosage with other antidepressants. The QRS interval of the electrocardiogram appears to be a reliable correlate of the severity of overdosage. If the QRS interval exceeds 100 milliseconds any time during the first 24 hours after overdosage, cardiac function should be continuously monitored for 5 or 6 days. Because of its effect on cardiac conduction, digitalis should be used only with caution. If rapid digitalization is required for the treatment of congestive heart failure, special care should be exercised in using the drug. Shock should be treated with supportive measures such as i.v. fluids, oxygen and corticosteroids. Pressor agents, such as noradrenaline (but not adrenaline), are rarely indicated and should be given only after careful consideration and under continuous monitoring. The slow i.v. administration of physostigmine salicylate has been reported to reverse most of the cardiovascular and CNS anticholinergic manifestations of tricyclic overdosage. The recommended dosage in adults has been 1 to 2 mg in very slow i.v. injection. In children, the initial dosage should not exceed 0.5 mg and should be adjusted to age and response. Since physostigmine has a short duration of action, administration may have to be repeated at 30 to 60 minute intervals. Deaths by deliberate or accidental overdosage have occurred with this class of drugs. Since the propensity for suicide is high in depressed patients, a suicide attempt by other means may occur during the recovery phase. The possibility of simultaneous ingestion of other drugs should also be considered. ---------------------------------------------------------------------------- Dosage The optimum daily dosage of doxepin depends on the condition which is being treated and the response of the individual. Some patients respond promptly; others may not respond for 2 weeks or longer. An initial dosage of 25 mg 3 times daily may be used in most patients. This dosage should be increased as required by 25 mg increments at appropriate intervals until a therapeutic response is obtained. The usual optimum dosage range is 100 to 150 mg per day. In some patients, up to 300 mg per day may be required, but there is rarely any benefit to be obtained by increasing this dosage. In elderly patients it is advisable to proceed more cautiously with dosage increments and to initiate treatment with a lower dosage. Once a satisfactory therapeutic response has been obtained, it is generally possible to reduce the dosage and still maintain this effect. For maintenance therapy in depressed patients, the total daily dosage, up to 150 mg, may be given on a once a day schedule. This dosage should be established as described above and should preferably be given at bedtime. The 150 mg capsule strength is intended for maintenance therapy only and is not recommended for initiation of treatment. ---------------------------------------------------------------------------- Supplied Each capsule contains: Doxepin HCl equivalent to 10, 25, 50, 75, 100 and 150 mg of doxepin. Also contains cornstarch and magnesium stearate/sodium lauryl sulfate. Capsule shells also contain gelatin, sodium lauryl sulfate, sodium metabisulfate (25, 50, 75, 100 and 150 mg) and dyes FD & C Blue #1 (10, 25, 50, 100 and 150 mg), FD & C Red #2 (10 mg), FD & C Yellow #6 (10 mg), D & C Yellow #10 (10, 50, 75 and 100 mg) and FD & C Red #3. Tartrazine-free. Bottles of 100 and 500. ---------------------------------------------------------------------------- Note: This information is from a Canadian monograph. There can be differences in indications, dosage forms and warnings for this drug in other countries. ---------------------------------------------------------------------------- Internet Mental Health (www.mentalhealth.com) copyright 1995-1998 by Phillip W. Long, M.D. ---------------------------------------------------------------------------- janet paterson - 51 now /41 dx /37 onset - almonte/ontario/canada http://www.newcountry.nu/pd/members/janet/index.htm [log in to unmask]