No

Antidepressant, Tricyclic (Tertiary Amine)

Treatment of obsessive-compulsive disorder (OCD)

C

Hypersensitivity to this drug or other tricyclic agents; use of monoamine oxidase inhibitors within 14 days; use in a patient during the acute recovery phase of MI

May cause seizures (relationship to dose and/or duration of therapy) - do not exceed maximum doses. 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. Has been associated with a high incidence of sexual dysfunction. Weight gain may occur. 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 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 high relative to other antidepressants. 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.

>10%:

Central nervous system: Dizziness, drowsiness, headache, insomnia, nervousness

Endocrine & metabolic: Libido changes

Gastrointestinal: Xerostomia, constipation, increased appetite, nausea, weight gain, dyspepsia, anorexia, abdominal pain

Neuromuscular & skeletal: Fatigue, tremor, myoclonus

Miscellaneous: Increased diaphoresis

1% to 10%:

Cardiovascular: Hypotension, palpitations, tachycardia

Central nervous system: Confusion, hypertonia, sleep disorder, yawning, speech disorder, abnormal dreaming, paresthesia, memory impairment, anxiety, twitching, impaired coordination, agitation, migraine, depersonalization, emotional lability, flushing, fever

Dermatologic: Rash, pruritus, dermatitis

Gastrointestinal: Diarrhea, vomiting

Genitourinary: Difficult urination

Ocular: Blurred vision, eye pain

<1%: Seizures, alopecia, photosensitivity, breast enlargement, galactorrhea, SIADH, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux, marrow depression, increased liver enzymes, prostatic disorder, hyperacusis, abnormal accommodation

Symptoms of overdose include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, tachycardia, ventricular tachycardia, seizures, coma

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 and EKG abnormalities (eg, QRS widening) often respond to systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.) and/or phenytoin 15-20 mg/kg (adults). 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.

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

Clomipramine 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, clomipramine may enhance the response

Use with altretamine may cause orthostatic hypertension

Clomipramine 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

Clomipramine may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of clomipramine

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

Diltiazem and verapamil 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

Clomipramine appears to affect serotonin uptake while its active metabolite, desmethylclomipramine, affects norepinephrine uptake

Onset of effect: Usually >2 weeks to therapeutic effect

Absorption: Oral: Rapid

Metabolism: Extensive first-pass metabolism; metabolized to desmethylclomipramine (active) in the liver

Half-life: 20-30 hours

Oral: Initial:

Adults: 25 mg/day and gradually increase, as tolerated, to 100 mg/day the first 2 weeks, may then be increased to a total of 250 mg/day maximum

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 such as clomipramine increases the risk of caries by reducing salivation and salivary buffer capacity

Take multiple dose medication with meals to reduce side effects. Take single daily dose at bedtime to reduce daytime sedation. The effect of this drug may take several weeks to appear. Do not use excessive alcohol, caffeine, and other prescriptive or OTC medications without consulting prescriber. May cause dizziness, drowsiness, headache, or seizures (use caution when driving or engaging in tasks that require alertness until response to drug is known); dry mouth or unpleasant aftertaste (sucking lozenges and frequent mouth care may help); constipation (increased fluids, dietary fiber and fruits, or exercise may help); or orthostatic hypotension (use caution when rising from lying or sitting to standing position or when climbing stairs). Report unresolved constipation or GI upset, unusual muscle weakness, palpitations, or persistent CNS disturbances (hallucinations, delirium, insomnia, or impaired gait). Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Monitor pulse rate and blood pressure prior to and during therapy, evaluate mental status

Capsule, as hydrochloride: 25 mg, 50 mg, 75 mg

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