Imipramine information from DrugsUpdate  

Pharmacodynamics

Pharmacokinetics

Imipramine inhibits noradrenaline re-uptake and, to a lesser extent, that of serotonin.

Absorption
Readily absorbed from the GI tract (oral). Peak plasma concentrations are achieved within 1-2 hours after oral admin.

Distribution
Extensively protein-bound and widely distributed with an average volume of distribution of 21 l/kg. Both imipramine and desipramine cross the blood-brain barrier; the placenta and can enter breast milk.

Metabolism
Converted to primary active metabolite desipramine by demethylation during extensive first-pass hepatic metabolism.

Excretion
Via urine (as metabolites), faeces (small amounts); 9-28 hours (elimination half-life).

Imipramine Indications / Imipramine Uses

Information Not Available

Imipramine Adverse Reactions / Imipramine Side Effects

Sinus tachycardia, AV/bundle-branch block, postural hypotension, dry mouth, wt loss/gain, constipation, urinary hesitancy/retention, impotence; blurring of vision, exacerbation of glaucoma, liver dysfunction, tremors.

Potentially Fatal: Rarely, agranulocytosis.

Precautions

An ECG recording should be taken prior to the initiation of larger-than-usual doses of Imipramine hydrochloride and at appropriate intervals thereafter until steady state is achieved. (Patients with any evidence of cardiovascular disease require cardiac surveillance at all dosage levels of the drug. Elderly patients and patients with cardiac disease or a prior history of cardiac disease are at special risk of developing the cardiac abnormalities associated with the use of Imipramine hydrochloride.

It should be kept in mind that the possibility of suicide in seriously depressed patients is inherent in the illness and may persist until significant remission occurs. Such patients should be carefully supervised during the early phase of treatment with Imipramine hydrochloride, and may require hospitalization. Prescriptions should be written for the smallest amount feasible. Hypomanic or manic episodes may occur, particularly in patients with cyclic disorders. Such reactions may necessitate discontinuation of the drug, if needed. Imipramine hydrochloride may be resumed in lower dosage when these episodes are relieved.

Administration of a tranquilizer may be useful in controlling such episodes.

An activation of the psychosis may occasionally be observed in schizophrenic patients and may require reduction of dosage and the addition of a phenothiazine.

Concurrent administration of Imipramine hydrochloride with electroshock therapy may increase the hazards; such treatment should be limited to those patients for whom it is essential, since there is limited clinical experience.

Patients taking Imipramine hydrochloride should avoid excessive exposure to sunlight since there have been reports of photosensitization.

Both elevation and lowering of blood sugar levels have been reported with Imipramine hydrochloride use.

Imipramine hydrochloride should be used with caution in patients with significantly impaired renal or hepatic function.

Patients who develop a fever and a sore throat during therapy with Imipramine hydrochloride should have leukocyte and differential blood counts performed. Imipramine hydrochloride should be discontinued if there is evidence of pathological neutrophil depression.

Prior to elective surgery, Imipramine hydrochloride should be discontinued for as long as the clinical situation will allow.

Overdosage
Symptoms include CNS stimulation followed by severe CNS depression; tachycardia and conduction disturbances; peripheral anticholinergic effects and seizures.

Special Precautions

Epilepsy; children, elderly, pregnancy and lactation; cardiac disease; DM; prostatic hyperplasia; angle-closure glaucoma; phaeochromocytoma. Monitor for increased suicidality during early treatment. Withdraw gradually.

Other Drug Interactions

Increased plasma levels and effects with quinidine, cimetidine, SSRIs, propafenone, flecainide. Reduced plasma levels with barbiturates, phenytoin. May increase effects of anticholinergic drugs. Severe orthostatic hypotension with altretamine. Causes drowsiness and impaired performance in combination with alcohol.

Potentially Fatal: Severe hypertension with adrenaline, noradrenaline and methylphenidate. Reduces hypotensive effects of guanethidine, bethanidine, debrisoquine, bretylium, methyldopa and clonidine. Possible serotonin syndrome with MAOIs, separate admin by 3 weeks.

Other Interactions

Information Not Available

Dosage

Oral
Depression
Adult: As hydrochloride: Initially, 75 mg daily in divided doses increased gradually to 150-200 mg daily if necessary; 300 mg daily given in severely depressed patients.
Elderly: As hydrochloride: Initially, 10 mg at night gradually increased to 30-50 mg daily.

Oral
Nocturnal enuresis
Child: As hydrochloride: 6-7 years (20-25 kg): 25 mg; 8-11 years (25-35 kg): 25-50 mg; >11 years (35-54 kg): 50-75 mg. Dose to be taken once daily before bedtime for up to 3 months.

Food(before/after)

May be taken with or without food

Imipramine and Pregnancy

Caution when used during pregnancy

Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Imipramine and Lactation

Caution when used during lactation

Imipramine and Children

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

Imipramine and Geriatic

Information Not Available

Imipramine and Other Contraindications

Post MI, heart block/arrhythmias; mania; porphyria; severe hepatic impairment.

Storage

Information Not Available

Lab interference

Information Not Available