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|Imipramine HCl

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Imipramine HCl

Pronouncation: (im-IPP-ruh-meen HIGH-droe-KLOR-ide)
Class: Tricyclic compound

Trade Names:
Tofranil
- Tablets 10 mg
- Tablets 25 mg
- Tablets 50 mg

Apo-Imipramine (Canada)
Impril (Canada)
Imipramine Pamoate

Trade Names:
Tofranil-PM
- Capsules 75 mg
- Capsules 100 mg
- Capsules 125 mg
- Capsules 150 mg

Mechanism of Action

Pharmacology

Inhibits reuptake of norepinephrine and, to a lesser degree, serotonin in CNS.

Pharmacokinetics

Absorption

T _max is 2 to 4 hr. Steady state is reached in 2 to 5 days.

Distribution

More than 90% is protein bound. Lipid soluble.

Metabolism

Significant first pass effect. Metabolism occurs in liver. Active metabolite is desipramine.

Elimination

The t _1/2 is 11 to 25 hr.

Peak

2 to 4 weeks.

Indications and Usage

Relief of symptoms of depression; treatment of enuresis in children 6 yr and older.

Unlabeled Uses

Treatment of chronic pain, panic disorder, eating disorders (bulimia nervosa), and facilitation of cocaine withdrawal.

Contraindications

Hypersensitivity to any tricyclic antidepressant. Generally not to be given in combination with or within 14 days of treatment with MAO inhibitor or during acute recovery phase of MI; cross-sensitivity may occur among the dibenzazepines.

Dosage and Administration

Depression

Use parenterally only in patients who are not able or not willing to take oral medication. Give via IM route. Do not administer IV. Up to 100 mg/day in divided doses may be given IM. Switch to oral as soon as possible.

Adults

PO 100 to 300 mg/day, in divided doses or once daily at bedtime.

Elderly & Adolescents

PO 30 to 40 mg/day; may increase up to 100 mg/day.

Children

PO 1.5 mg/kg/day in divided doses; up to maximum of 5 mg/kg/day.

Childhood Enuresis (6 yr)

PO 25 mg/day given 1 hr before bedtime; if response unsatisfactory after 1 wk, may increase to 50 mg in children younger than 12 yr. Children older than 12 yr may receive 75 mg/night. Do not exceed 2.5 mg/kg/day.

Drug Interactions

Carbamazepine

Carbamazepine levels may increase; imipramine levels may decrease.

Cimetidine, fluoxetine

May cause increased imipramine blood levels and effects.

Clonidine

May result in hypertensive crisis.

CNS depressants

Depressant effects may be additive.

Dicumarol

Anticoagulant actions may increase.

Guanethidine

Hypotensive action may be inhibited.

MAO inhibitors

May cause hyperpyretic crises, severe convulsions, and death when given with imipramine.

Sympathomimetics

Pressor response may be decreased by indirect-acting sympathomimetics and increased by direct-acting ones.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Orthostatic hypotension; hypertension; tachycardia; palpitations; arrhythmias; ECG changes; stroke; heartblock; CHF.

CNS

Confusion; hallucinations; delusions; nervousness; restlessness; agitation; panic; insomnia; nightmares; mania; exacerbation of psychosis; drowsiness; dizziness; weakness; numbness; extrapyramidal symptoms; emotional lability; seizures; tremors.

Dermatologic

Rash; pruritus; photosensitivity reaction; dry skin; acne; itching.

EENT

Nasal congestion; tinnitus; conjunctivitis; mydriasis; blurred vision; increased IOP.

GI

Nausea; vomiting; anorexia; GI distress; diarrhea; flatulence; peculiar taste in mouth; dry mouth; constipation.

Genitourinary

Impotence; sexual dysfunction; nocturia; urinary frequency; UTI; vaginitis; cystitis; dysmenorrhea; amenorrhea; urinary retention and hesitancy.

Hematologic

Bone marrow depression including agranulocytosis; eosinophilia; purpura; thrombocytopenia; leukopenia.

Hepatic

Hepatitis; jaundice.

Metabolic

Elevation or depression of blood sugar.

Respiratory

Pharyngitis; rhinitis; sinusitis; laryngitis; coughing.

Miscellaneous

Breast enlargement.

Precautions

Pregnancy

Category D .

Lactation

Excreted in breast milk.

Children

Safety and efficacy of imipramine as temporary adjunctive therapy for nocturnal enuresis in pediatric patients younger than 6 yr have not been established; chronic use in patients 6 yr and older has not been established. Do not exceed 2.5 mg/kg/day.

Special Risk Patients

Use with caution in patients with history of seizures, urinary retention, ureteral spasm, angle-closure glaucoma or increased IOP, conduction disorders, with hyperthyroid or those receiving thyroid medication, hepatic or renal impairment, schizophrenia or paranoia.

Hazardous Tasks

Patients should use caution while performing tasks requiring alertness.

Cardiovascular disorders

Use with extreme caution in patients with cardiovascular disorders. These patients require cardiac surveillance at all dose levels of the drug.

Overdosage

Symptoms

Confusion, agitation, hallucinations, seizures, status epilepticus, clonus, choreoathetosis, hyperactive reflexes, positive Babinski sign, coma, cardiac arrhythmias, renal failure, flushing, dry mouth, dilated pupils, hyperpyrexia.

Patient Information

Warn patient of risk of seizure.
Tell female patient to inform health care provider if becoming or intending to become pregnant.
Explain that it may be several weeks before a response is noticed.
Instruct patient to avoid intake of alcoholic beverages or other CNS depressants.
Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.
Teach patient to avoid sudden position changes to prevent orthostatic hypertension.
Inform patient that dizziness, dry mouth (suggest taking frequent sips of water, sucking on ice chips, or sugarless hard candy or chewing sugarless gum), drowsiness, or constipation may occur, but that these side effects often subside with time.
Instruct patient to report all problems to health care provider, including dizziness, drowsiness, dry mouth, constipation, or weight gain.

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