AA Pharma Imipramine

Imipramine hydrochloride.

Each brown, film-coated tablet contains Imipramine HCl 10 or 25mg. Imprinted 10 and 25 respectively.

Pharmacology: The mechanism of antidepressant action of imipramine is not clear although it has been shown to block the reuptake of various neurotransmitters at the neuronal membrane. As a result, the actions of norepinephrine and serotonin may be potentiated. Imipramine has strong anticholinergic actions as well. Imipramine is not an MAO inhibitor. Imipramine's mechanism of action in the treatment of enuresis may involve inhibition of urination due to anticholinergic activity, arousal by the stimulus of a full bladder due to CNS stimulant activity, or other unknown mechanisms.
Imipramine is absorbed after oral administration with peak plasma levels occurring within 1 to 2 hours. It is extensively metabolised by the liver and the metabolites are excreted primarily by the kidney. One metabolite, desipramine, is active. The half-life of imipramine ranges from 8 to 16 hours.

Depression: Neurotic or psychotic depressive states of diverse psychopathology and varying degree, including depression associated with organic diseases, endogenous and reactive depression, involutional melancholia, senile depressions, the depressive phase of manic-depressive psychosis and certain cases of depression for which a psychiatric basis has been established (i.e., schizophrenia, alcoholism, mental deficiency). In many cases, imipramine may be used in place of electroconvulsive therapy, or may be employed as a supplement to ECT to prevent recurrent attacks.
Persistent functional nocturnal enuresis: Also employed in children to treat persistent functional enuresis when organic causes have been excluded.

Dosage: Depression: Except in elderly patients, adolescents or children: 25mg 3 times daily, initially increased up to 150mg, if necessary. Dosage in excess of 200mg daily is not recommended for office patients. More severe, hospitalised cases may require up to 300mg daily. In elderly patients and adolescents: 30 to 40mg daily, initially increased by 10mg daily to maximum of 100mg in the elderly.
In suitable subjects, the maintenance dose may be administered in a single dose before bedtime.
For persistent, functional enuresis which has not responded to other forms of management, a therapeutic trial with imipramine may be considered for children between 5 and 15 years old, who are not mentally defective, and in whom organic causes of enuresis have been excluded. The recommended dosage for such a trial is 10 to 25mg 1 hour before bedtime for children 5 years or over. If there is no response, the dosage may be increased up to 50mg, in children 12 to 15 years old. The trial period should be 2 to 4 weeks.
If there is a relapse, the treatment can be repeated but the drug should not be given for more than 2 months without discontinuing its administration and assessing the need for further drug therapy.
Because the margin of safety is lower in children, the recommended dose should not be exceeded and the minimum effective dose should be used at all times.

Symptoms: High doses may cause temporary confusion, disturbed concentration, transient visual hallucinations, agitation, hyperactive reflexes, muscle rigidity, vomiting, or hyperpyrexia, in addition to anything listed under Adverse Reactions. Based on imipramine's known pharmacologic actions, overdosage may cause drowsiness, hypothermia, tachycardia and other arrhythmic abnormalities such as bundle branch block, ECG evidence of impaired conduction and congestive heart failure. Other manifestations may be dilated pupils, convulsions, severe hypotension, stupor and coma. All patients suspected of having taken an overdose should be admitted to a hospital as soon as possible.
Treatment: is symptomatic and supportive.
Empty the stomach as quickly as possible by emesis followed by gastric lavage. Following gastric lavage activated charcoal (30g) may be administered every four to six hours during the first 24 hours after ingestion.
Monitor cardiac function for any signs of dysrhythmia.
Maintain an open airway and adequate fluid intake; regulate body temperature.
Use standard medical measures to manage circulatory shock and metabolic acidosis. Cardiac arrhythmias may be treated with neostigmine, pyridostigmine, or propranolol. If signs of cardiac failure occur, consider the use of a short acting digitalis preparation. Close monitoring of cardiac function for not less than 5 days is advisable.
Anticonvulsants may be given to control seizures.
Dialysis is of no value because of low plasma concentrations of the drug.
Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Deaths by deliberate or accidental overdosage have occurred with this class of drugs.
Pyridostigmine given i.v. can be used to reverse the symptoms of tricyclic antidepressant poisoning.
Give physostigmine 1 to 3 mg slow i.v. (over 2 minutes). If no clinical changes or cholinergic signs occur within 15 to 30 minutes, an additional 1 to 2 mg may be administered. Repeated doses of 1 to 2 mg i.v. every 30 minutes up to two hours.
Physostigmine is not innocuous and carries the risk of inducing seizures and cholinergic crisis. It should not be used routinely. If excessive sweating, nausea or vomiting occur, reduce dosage of physostigmine. Atropine in a dose of 50% of the amount of injected physostigmine should be kept on hand and administered if excessive cholinergic symptoms develop.

The concomitant use of MAO inhibiting compounds is contraindicated. Hyperpyretic crises or severe convulsive seizures may occur in patients receiving such combinations. The potentiation of adverse effects can be serious, or even fatal. When it is desired to substitute imipramine in patients receiving a MAO inhibitor, as long as interval should elapse as the clinical situation will allow, with a minimum of 14 days. Initial dosage should be low and increases should be gradual and cautiously prescribed.
Patients with a known hypersensitivity to this compound should not be given the drug.

Incompatibilities: Exercise extreme caution when imipramine is used in patients with coronary thrombosis, angina pectoris, congestive heart failure, disorders of cardiac rate or rhythm or conduction, prostatic disorders with potential urinary retention and glaucoma, imipramine should be used cautiously in hyperactive or agitated patients and in epileptics or ambulatory, seriously depressed patients with suicidal tendencies. Elderly patients, children and those with circulatory liability or with cardiovascular disease should receive the drug in low dosage and under careful observation and only when a clear indication for the drug has been established.

Pregnancy: Imipramine should not be used during the first trimester of pregnancy unless the potential benefits outweigh the possible risks. Use of the drug should also be avoided during lactation.

Although the listing which follows includes a few adverse reactions which have not been reported with this specific drug, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when imipramine is administered.
Cardiovascular: Hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, stroke, falls. A few instances of unexpected death have occurred in patients with cardiovascular disorders.
Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions, anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis.
Neurological: Numbness, tingling, paresthesias of extremities, incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms, seizures, alterations in EEG patterns; tinnitus.
Anticholinergic: Dry mouth, and rarely, associated sublingual adenitis, blurred vision, disturbances of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract.
Allergic: skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (general or of face and tongue), drug fever, cross-sensitivity with desipramine.
Hematologic: Bone marrow depression including agranulocytosis; eosinophilia, purpura, thrombocytopenia. Leukocyte and differential counts should be performed in any patient who develops fever and sore throat during therapy; the drug should be discontinued if there is evidence of pathological neutrophil depression.
Gastrointestinal: Nausea and vomiting, anorexia, epigastric distress, diarrhoea; peculiar taste, stomatitis, abdominal cramps, black tongue.
Endocrine: Gynecomastia in the male, breast enlargement and galactorrhea in the female, increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels.
Other: Jaundice (simulating obstructive); urinary frequency, drowsiness, dizziness, weakness and fatigue, headache; parotid swelling, alopecia.
Withdrawal symptoms: Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache and malaise.

Since imipramine may block the pharmacologic effects of guanethidine or similar agents, extreme caution is indicated when these drugs are used concomitantly. The possibility of suicide in depressed patients remains during treatment and until significant remission occurs, this type of patient should not have access to large quantities of the drug.

Store in a cool place. Protect from light.

Antidepressants

N06AA02 - imipramine ; Belongs to the class of non-selective monoamine reuptake inhibitors. Used in the management of depression.

POM