Each tablet contains
imipramine hydrochloride 25 mg
Imipramine is a tricyclic antidepressant with general Pharmacological properties similar to those of structurally related tricyclic antidepressant drugs such as amitriptyline and doxepin. The mechanism of action of imipramine and other tricyclic antidepressant is not well established, but it is thought that it might be related to their action on the transmitter- uptake mechanism of monoaminergic neurons. The mechanism of action in childhood nocturnal enuresis is not fully known.
For the relief of symptoms of depression.
Imipramine may also be useful as temporary adjunctive therapy in
reducing enuresis in children aged 5 years and older after possible
organic causes have been excluded by appropriate tests. In patients
having daytime symptoms of frequency and urgency, examination
should include voiding cystourethrogaphy and cytoscopy, as necessary. The effectiveness of treatment may decrease with continued drug administration. Also useful in treatment of panic attacks, chronic painful condition and pavor continues.
Imipramine should not be given in conjunction with, or within 14 days of treatrmmtwtth AG-4Abibi~ ed therapy of.Jh@..type could
lead to the appearance of serious interactions such as hypenensl
crises, hyperactivity, hyperpyrexia, spasticity, severe Convulsions or coma and death may occur.
Imipramine is contraindicated in patients with existing severs hepatic or renal damage, and those with a history of blood dyscrasias Imipramine is contraindicated in patients who have shown hypersensitivity to the drug or hypersensitivity to tricyclic antidepressants belonging to the dibenzazepine group. Imipramine is contraindicated for use during the acute recovery phase following a myocardial infarction. It should not be used in patients with convulsive disorders or glaucoma.
Warnings and precautions :
Extreme caution should be used when Imipramine is given to patients with know cardiovascular disease including a history of myocarction, atrioventricular- Block (grades I-III) and I or ischemic heart disease. These patients require cardiac surveillance at all dosage levels of the drug.
Imipramine may induce or exacerbate an arrhythmia or lead to a
hypotensive episode, thus making its use hazardous in these
conditions. Imipramine should be used with caution in those on thyroid medication because of the possibility of cardiovascular toxicity. Particularly VIN the elder1y and in hospitalized patients the tricyclic antidepressants may give rise to paralytic ileus and therefore appropriate measures should be taken if constipation occurs.
Imjpramine may produce urinary retention and should be used with
caution in patients with urinary pathology, Particularty in the presence of prostatic hypertrophy caution is called for when employing. Caution is called for when employing Imipramine in
patients with tumors of the adrenal medulla (e.g. pheochromocytoma, neuroblastoma) in whom the drug may provoke hypertensive crisis. Concomitant treatment with Imipramine and electroconvulsive therapy should only be resorted to under careful supervision. Caution is called for when treating patients with low convulsion threshold (e.g., due to baring damage of varying etiology, alcoholism). Since Imipramine may produce sedation and decrease alertness, patients should be cautioned
against driving an automobile, operating heavy machinery or
performing potentially dangerous tasks that require mental alertness, judgment & physical Co-ordination.
Effectiveness in children for conditions other then nocturnal enuresis has not been established. Safety and effectiveness of the drug as temporary adjunctive therapy for nocturnal enuresis in children under 5 years of age has not been established. Safety of Imipramine for long-term chronic use as adjunctive therapy for noctumal enuresis in children 5 years of age or older has not been established; consideration should be given to establishing a drug free period following an adequate therapeutic trial with a favorable response. Recommended doses should not be exceeded in childhood, because ECG Changes of unknown significance have been reported with higher doses in bediatric patients. In order to guard against possible cardio toxic effects, a daily dosage of 5.2 mg , kg should not be exceeded in children. Imipramine should be kept out of the reach of the children.(Orug leaflet) Drug Properties should be known before use
The safety of Imipramine in pregnancy has not been established.
Neonates whose mothers had taken Imipramine up until delivery have shown symptoms such as dyspnea, lethargy, colic, irritability,
hypotension or hypertension, tremor or spasms during the first few
hours or days. Therefore Imipramine should not be administered to
women of childbearing potential, particularty during the first trimester & the last 7 weeks of pregnancy, unless in the opinion of the physician the potential benefit to the patient outweighs the possible hazards to the fetus.
Imipramine passes into the breast milk, in the case of nursing Mothers the infant should be weaned or the drug withdrawn.
Precautions : Activation of latent schizophrenia or aggravation of existing psychotic manifestations in schizophrenic patients may occur; hyperactive or agitated patients become over-stimulated; and patients with manic-depressive tendencies may experience hypomanic or manic shifts. Discontinuation of Imipramine should be considered under these circumstances. In predisposed and elderty patients, Imipramine may, particularty at night, provoke pharmacogenic ( delirious) psychoses which disappear without treatment within a few dates of withdrawing the drug. Before initiating treatment, it is advisable to check the patient’s blood pressure, because individuals with hypotension or a labile
circulation may react to the drug with a fall in blood pressure. Regular measurements of the blood pressure should be performed in patients susceptible to postural hypotension. Posturalhypotension may be controlled by reducing the dosage or administering Circulatory stimulants. Particularly in patients with heart diseases. Especially those who have a history of conduction disorders. As well as in elderly subjects, cardiac function should be monitored and ECG examinations performed during long-term treatment. Periodic blood cell. Counts & liver function tests recommended with prolonged therapy. An abrupt discontinuation ofJreatment should be avoided as it may give rise to withdrawal symptoms.
Drug interaction :
Patients should be warned that, while laking Imipramine their responses to alcoholic beverages, other CNS depressants (e.g., barbiturates, benzodiazepines or general anesthetics) or anticholinergic agents (e.g., atropine, biperiden, levodopa) may be exaggerated. When tricyclic antidepressants are given in combinations with anticholinergics or neuroleptics with an anticholinergic action, hyper excitation states or delirium may occur, as well as attacks of glaucoma. Tricyclic antidepressants should not be employed in combination with anti-arrhythmic agents of the quinidine type. Since Imipramine may diminish or abolish the antihypertensive effects of guanethidine, clonidine, reserpine, methyldopa, patients requiring concomitant treatment for hypertension patients requiring concomitant treatment for
hypertension should be given antihypertensive of a different type. Since Imipramine may diminish or abolish the antihypertensive effects of guanethidine, clonidine, reserpine, methyldopa, patients requiring concomitant treatment for hypertension should be given antihyperten- sive of a different type (e.g., diuretics, beta-blockers).lmipramine may potentiate the cardiovascular effects of noradrenalin or adrenaline, amphetarniJw, as well as nasal drops-and local anesthetics containing sympathomimetics Methylphenidate may increase the activity and plasma concentrations of tricyclic antidepressants. Caution should be exercised if Imipramine is administered together with cimetidine since cimetidine has been shown to inhibit the metabolism of
several tricyclic antidepressants and clinically significant increases in plasma levels of Imipramine may occur; ranitidine was not observed to alter the kinetics of Imipramine.
Substances which activate the hepatic mono-oxygenase enzyme
system (e.g., barbiturates, phenytoin, nicotine) may lower plasma
concentrations of tricyclic antidepressants and so reduce their
antidepressive effects. Neuroleptic agents (e.g., phenothiazines) may increase the plasma concentration of Imipramine. No such effects are known to occur in combination with diazepam but it might be necessary to lower the dosage of Imipramine if administered concomitantly with alprazolam or disulfiram. If administered concomitantly with estrogens, the dose of Imipramine should be reduced since steroid hormones inriibit the metabolism of Imipramine.
Frequently: Tremors. Occasionally: drowsiness, fatigue, Insomnia.
Dizziness. Headache. Parenthesis (numbness. TIngling sensation
symptoms. Symptoms suggestive of peripheral neuropathy.
Rarely: Epileptic seizures. In isolated cases:
Occasionally: Confessional states (especially in the elder1y) with
hallucinations. Disorientation. Delusions. Anxiety, agitation, resUeeness. Nightmares hypomania mania. exacerbation of psychosis, decrease in memory. feefing of unreality. In isolated cases: Feeling of weakness, aggressiveness.
Frequently: Dry mouth and rarely associated sublingual adenitis, blurred vision, disturbances of accommodation, constipation, perspiration flushing. Occasionally: decayed maturation. Dilation of the urinary tract. In isolated cases; mydriasis, glaucoma. Paralytic ileums. urinary frequency.
Frequently: Hypotension, particularly orthostatic hypotension with
associated vertigo, tachycardia, ECG changes (including flattening or inversion of T wave). Occasionally: Arrtlythmia disturbances in cardiac conduction, palpitation synoope. In isolated cases: hypertension , congestive heart failure, myocardial infarction, heart block , a systole, stroke, peripheral vasospastic reactions.
In isolated cases: agranulocytosis eosinophilia. leucopenia purport and thrombocytopenia may occur as an idiosyncratic response.
Occasionally: Nausea vomiting, anorexia and black tongue.
Frequently: weight gain occasionally: Increased or Decreased libido,
impotence. In isolated cases: gynecomastia in the male. breast
enlargement and galactorrhea in the female, testicular swelling, elevation or depression of blood sugar levels, weight loss. inappropriate antidiuretic hormone (AOH) secretion syndrome.
If treatment is terminated abruptly, withdrawal symptoms, such as
gastrointestinal upsets, nervousness, anxiety, and muscle twitching may occur.
Overdose Symptoms :
Children have been reported to be more sensitive then adults to an acute over dosage of Imipramine. An acute overdose in infants or young children must be considered serious and potentially fatal. Symptoms may vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient and the interval between drug ingeslion and the start of treatment. Blood and urine levels of Imipramine may not reflect the severity of poisoning; they have chiefly a qualitative rather than quantitative value, and are unreliable indicators in the clinical management of the patient Drowsiness, stupor, ataxia, vomiting, cyanosis, restlessness, agitation. delirium, severe perspiration, hyperactive reflexes, muscle rigidity, athetoid movements, conwlsions, respiratory depression, hyperpyrexia, hypothermia, mydriasis and bowel and bladder paralysis may occur. Serious carcHovascular disturbances
are frequently present, including tachycardia, cardiac arrhythmia
(flutter, atriofibrillation, ventricular premature beats, and ventricular tachycardia) as well as impaired myocardial conduction, atrioventricular and intraventricular block. ECG abnormalities ( such as widened QRS complexes and marked S-T shifts and signs of congestive heart failure and cardiac arrest ). Hypotension and initial hypertension may occur. However, the usual finding is increasing hypotension which may lead eventually to shock .Coma may ensue.
Symptomatic and supportive. Cardiac arrhythmias and CNS involvement pose the greatest threat with tricycles antidepressant over dosage and may occur suddenly even when initial symptoms appear to be mild. Therefore, patients who may have ingested an over dosage of imipramine, particularty children, should be hospitalizes and kept under dose surveillance.
If the patient is conscious, induced emesis followed by gastric lavage, with appropriate precautions to prevent pulmonary aspiration, should be accomplished as soon as possible. Following lavage. activated charcoal may be administered to reduce absorption. An adequate airway should be established in comatose patients and assisted-yentilation instituted, if necessary, but respiratory stimulants should not be used. Hyperpyrexia should be controlled by external measures, such as ice packs and cooling
sponge baths. Acidosis may be treated by cautious administration of
sodium bicarbonate. Adequate renal function should be maintained.
External stimulation should be minimized to reduce the tendency to
convulsions. If convulsions occur, anticonvulsants (preferably. i .v.
diazepam) should be administered.
The dosage should be individualized according to the requirements of each patient. Treatment should be initiated at the lowest recommended dose and increased gradually noting carefully the dintcal response and any evidence of intolerance, particularty when treating ekjerfy and adolescent patients. It should be kept in mind that a log in therapeutic response usually occurs at the onset of therapy, lasting from several days to a few weeks. Increasing the dosage does not normally shorten this latent period and may increase the incidence of side effects.
25 mg 3 times daily. This should be increased gradually as required & tolerated up to 150 mg/day. Dosages over 200 mg/day are not
recommended. In severely ill, hospitalized patients, initially 100 mg/day in divided doses, gradually increasing to 200 m/g, if required. If no significant response is observed after 3 weeks, dosage may be increased up to 250 to 300 mg/day.
Elderly and debilitated patients:
30 to 40 mg/day, in divided doses, gradually increasing dosage if
necessary, and tolerated; it is generally not necessary to exceed 100
Maintenance dosage :
Dosage during maintenance therapy should be kept at the lowest
effective level. Medication should be continued for the expected duration of the depressive episode in order to minimize the possibility of relapse following clinical improvement. When a maintenance dosage has been established as described above, Imipramine may be administered in a single daily dose at bedtime, provided such a dosage regimen is wen tolerated.
Childhood enuresis :
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 of age, who are not mentally defective & in whom organic causes of enuresis have been excluded, the recommended dosage is 10 to 25 mglday for children 5 years of age & older, if a satisfactory response does not occur within one week, the dosage may be increased up to 75mg/day in children over 12 years of age. A daily dose greater than 75mg does not enhance efficacy & tends to increase side effects. ECG changes of unknown significance have been reported with doses h~her than those recommended in pediatric patients.
The trial period should be 2 to 4 weeks. Medication should be given in a single dose one hour before bedtime however, in children subject to enuresis early on in the night; part of the dose should be taken between 15 and 17 h. Consideration should be given to instituting a drug free period following an adequate therapeutic trial with a favorable response, in order to assess the need for further drug treatment. Dosage should be tapered off gradually rather than abruptly discontinued; this may reduce the tendency to relapse. Children who relapse when the drug is discontinued do not always respond to a subsequent course of treatment.
Safety and effectiveness of Imipramine as temporary adjunctive
treatment for nocturnal enuresis in children less than 5 years of age has not been established.
Panic attack :
The daily dosage required varies from patient to patient between 75mg and 150mg and if necessary it can be increased to 200mg, it is advisable not discontinue treatment for 6 months, during this period the maintenance dose should be decreased slowly.
Chronic painful conditions :
The dosage must be individualized (25 – 300mg daily) a daily dose of 25 – 75mg is generally sufficient.
Store bejow 30′ C, protect from moisture & heat.
Box containing 5 stripes, each of 10 tablets & inner leaflet.
Manufactured by :
for gelatin and pharmaceutical products (Arab Caps)
For Acdima international trading