Yes: Tablet

Antidepressant, Tricyclic (Secondary Amine)

Treatment of depression

C

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

May cause sedation, resulting 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 low-moderate relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May cause hyponatremia/SIADH. 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.

Cardiovascular: Arrhythmias, hypotension, hypertension, palpitations, heart block, tachycardia

Central nervous system: Dizziness, drowsiness, headache, confusion, delirium, hallucinations, nervousness, restlessness, parkinsonian syndrome, insomnia, disorientation, anxiety, agitation, hypomania, exacerbation of psychosis, incoordination, seizures, extrapyramidal symptoms

Dermatologic: Alopecia, photosensitivity, skin rash, urticaria

Endocrine & metabolic: Breast enlargement, galactorrhea, SIADH

Gastrointestinal: Xerostomia, decreased lower esophageal sphincter tone may cause GE reflux, constipation, nausea, unpleasant taste, weight gain, anorexia, abdominal cramps, weight loss, diarrhea, heartburn

Genitourinary: Difficult urination, sexual dysfunction, testicular edema

Hematologic: Agranulocytosis, eosinophilia, purpura, thrombocytopenia

Hepatic: Cholestatic jaundice, increased liver enzyme

Neuromuscular & skeletal: Fine muscle tremors, weakness, numbness, tingling, paresthesia of extremities, ataxia

Ocular: Blurred vision, disturbances of accommodation, mydriasis, increased intraocular pressure

Miscellaneous: Diaphoresis (excessive), allergic reactions

Symptoms of overdose include severe hypotension, agitation, confusion, hyperthermia, urinary retention, CNS depression (including coma), cyanosis, dry mucous membranes, cardiac arrhythmias, seizures, changes in EKG (particularly in QRS axis and width), transient visual hallucinations, stupor, muscle rigidity

Following GI decontamination, treatment is supportive. Sodium bicarbonate is indicated when QRS interval is greater than or equal to 0.10 seconds or QT_c >0.42 seconds. Ventricular arrhythmias and EKG changes (eg, QRS widening) often respond with concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to phenytoin 15-20 mg/kg (adults) 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.

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

Desipramine 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, desipramine may enhance the response

Use with altretamine may cause orthostatic hypertension

Desipramine 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

Desipramine may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of desipramine

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

Traditionally believed to increase the synaptic concentration of norepinephrine (and to a lesser extent, serotonin) in the central nervous system by inhibition of its reuptake by the presynaptic neuronal membrane. However, additional receptor effects have been found including desensitization of adenyl cyclase, down regulation of beta-adrenergic receptors, and down regulation of serotonin receptors.

Onset of action: 1-3 weeks (maximum antidepressant effects: after >2 weeks)

Absorption: Well absorbed from GI tract

Metabolism: In the liver

Half-life: Adults: 7-60 hours

Peak plasma levels occur within 4-6 hours

Elimination: 70% excreted in urine

Oral:

Adolescents: Initial: 25-50 mg/day; gradually increase to 100 mg/day in single or divided doses; maximum: 150 mg/day

Adults: Initial: 75 mg/day in divided doses; increase gradually to 150-200 mg/day in divided or single dose; maximum: 300 mg/day

Elderly: Initial dose: 10-25 mg/day; increase by 10-25 mg every 3 days for inpatients and every week for outpatients if tolerated; usual maintenance dose: 75-100 mg/day, but doses up to 150 mg/day may be necessary

Hemodialysis/peritoneal dialysis: Supplemental dose is not necessary

Alcohol: Additive CNS effects, avoid use

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

Plasma levels do not always correlate with clinical effectiveness

Timing of serum samples: Draw trough just before next dose

Therapeutic: 50-300 ng/mL

In elderly patients the response rate is greatest with steady-state plasma concentrations >115 ng/mL

Possible toxicity: >300 ng/mL

Toxic: >1000 ng/mL

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

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

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, excess 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; contraceptives may be recommended. Breast-feeding is not recommended.

May increase appetite

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

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

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