Yes: Tablet

Antidepressant, Tricyclic (Tertiary Amine)

Treatment of various forms of depression

D

Hypersensitivity to imipramine (cross-reactivity with other dibenzodiazepines may occur); 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 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. EKG monitoring is recommended if high dosages are used. 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. Has been associated with photosensitization.

Cardiovascular: Orthostatic hypotension, arrhythmias, tachycardia, hypertension, palpitations, myocardial infarction, heart block, EKG changes, CHF, stroke

Central nervous system: Dizziness, drowsiness, headache, agitation, insomnia, nightmares, hypomania, psychosis, fatigue, confusion, hallucinations, disorientation, delusions, anxiety, restlessness, seizures

Endocrine & metabolic: Gynecomastia, breast enlargement, galactorrhea, increase or decrease in libido, increase or decrease in blood sugar, SIADH

Gastrointestinal: Nausea, unpleasant taste, weight gain, xerostomia, constipation, ileus, stomatitis, abdominal cramps, vomiting, anorexia, epigastric disorders, diarrhea, black tongue, weight loss

Genitourinary: Urinary retention, impotence

Neuromuscular & skeletal: Weakness, numbness, tingling, paresthesias, incoordination, ataxia, tremor, peripheral neuropathy, extrapyramidal symptoms

Ocular: Blurred vision, disturbances of accommodation, mydriasis

Otic: Tinnitus

Miscellaneous: Diaphoresis

<1%: Alopecia, photosensitivity, rash, petechiae, urticaria, itching, eosinophilia, agranulocytosis, purpura, thrombocytopenia, increased liver enzymes, cholestatic jaundice

Symptoms of overdose include confusion, hallucinations, constipation, cyanosis, tachycardia, urinary retention, ventricular tachycardia, seizures

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 concurrent systemic alkalinization (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.

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

Imipramine 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, imipramine may enhance the response

Use with altretamine may cause orthostatic hypertension

Imipramine 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; imipramine may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of imipramine

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

Solutions stable at a pH of 4-5; turns yellowish or reddish on exposure to light. Slight discoloration does not affect potency; marked discoloration is associated with loss of potency. Capsules stable for 3 years following date of manufacture.

Traditionally believed to increase the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their 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.

Peak antidepressant effect: Usually after greater than or equal to 2 weeks

Absorption: Oral: Well absorbed

Distribution: Crosses the placenta

Metabolism: In the liver by microsomal enzymes to desipramine (active) and other metabolites; significant first-pass metabolism

Half-life: 6-18 hours

Elimination: Almost all compounds following metabolism are excreted in urine

Maximum antidepressant effect may not be seen for 2 or more weeks after initiation of therapy.

Depression: 1.5 mg/kg/day with dosage increments of 1 mg/kg every 3-4 days to a maximum dose of 5 mg/kg/day in 1-4 divided doses; monitor carefully especially with doses greater than or equal to 3.5 mg/kg/day

Enuresis: greater than or equal to 6 years: Initial: 10-25 mg at bedtime, if inadequate response still seen after 1 week of therapy, increase by 25 mg/day; dose should not exceed 2.5 mg/kg/day or 50 mg at bedtime if 6-12 years of age or 75 mg at bedtime if greater than or equal to 12 years of age

Adjunct in the treatment of cancer pain: Initial: 0.2-0.4 mg/kg at bedtime; dose may be increased by 50% every 2-3 days up to 1-3 mg/kg/dose at bedtime

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

Adults:

Oral: Initial: 25 mg 3-4 times/day, increase dose gradually, total dose may be given at bedtime; maximum: 300 mg/day

I.M.: Initial: Up to 100 mg/day in divided doses; change to oral as soon as possible

Elderly: Initial: 10-25 mg at bedtime; increase by 10-25 mg every 3 days for inpatients and weekly for outpatients if tolerated; average daily dose to achieve a therapeutic concentration: 100 mg/day; range: 50-150 mg/day

Alcohol: Additive CNS effect, avoid use

Monitor blood pressure and pulse rate prior to and during initial therapy; EKG, CBC; evaluate mental status

Therapeutic: Imipramine and desipramine: 150-250 ng/mL (SI: 530-890 nmol/L); desipramine: 150-300 ng/mL (SI: 560-1125 nmol/L); Toxic: >500 ng/mL (SI: 446-893 nmol/L); utility of serum level monitoring 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 such as imipramine increases the risk of caries by reducing salivation and salivary buffer capacity. In a study by Rundergren, et al, pathological alterations were observed in the oral mucosa of 72% of 58 patients; 55% had new carious lesions after taking TCAs for a median of 51/2 years. Current research is investigating the use of the salivary stimulant pilocarpine to overcome the xerostomia from imipramine.

Oral: Take exactly as directed (do not increase dose or frequency); may take 2-3 weeks to achieve desired results; may cause physical and/or psychological dependence. Take in the evening. 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); nausea, vomiting, altered taste, dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); diarrhea (buttermilk, yogurt, or boiled milk may help); postural hypotension (use caution when climbing stairs or changing position from lying or sitting to standing); or urinary retention (void before taking medication). Report persistent insomnia; muscle cramping or tremors; chest pain, palpitations, rapid heartbeat, swelling of extremities, or severe dizziness; unresolved urinary retention; rash or skin irritation; yellowing of eyes or skin; pale stools/dark urine; or worsening of condition. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate barrier contraceptive measures. Breast-feeding is not recommended.

Raise bed rails, institute safety measures

Capsule, as pamoate (Tofranil-PM®): 75 mg, 100 mg, 125 mg, 150 mg

Injection, as hydrochloride (Tofranil®): 12.5 mg/mL (2 mL)

Tablet, as hydrochloride (Janimine®, Tofranil®): 10 mg, 25 mg, 50 mg

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