Tofranil Information
Tofranil (Imipramine hcl)
Tofranil (Imipramine hcl) Suicidality And Antidepressant Drugs
Tofranil (Imipramine hcl) Description
Tofranil (Imipramine hcl) ™ is supplied in tablet form for oral administration.
Tofranil (Imipramine hcl) , imipramine hydrochloride USP, the original tricyclic antidepressant, is a member of the dibenzazepine group of compounds. It is designated 5-3-(dimethylamino)propyl-10,11-dihydro-5-dibenz []-azepine monohydrochloride. Its structural formula is:
Imipramine hydrochloride USP is a white to off-white, odorless, or practically odorless crystalline powder. It is freely soluble in water and in alcohol, soluble in acetone, and insoluble in ether and in benzene.
Tofranil (Imipramine hcl) Clinical Pharmacology
The mechanism of action of Tofranil (Imipramine hcl) is not definitely known. However, it does not act primarily by stimulation of the central nervous system. The clinical effect is hypothesized as being due to potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings. The mode of action of the drug in controlling childhood enuresis is thought to be apart from its antidepressant effect.
Tofranil (Imipramine hcl) Indications And Usage
Depression –
Childhood Enuresis –
Tofranil (Imipramine hcl) Contraindications
The concomitant use of monoamine oxidase 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 Tofranil (Imipramine hcl) in patients receiving a monoamine oxidase inhibitor, as long an 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.
The drug is contraindicated during the acute recovery period after a myocardial infarction. Patients with a known hypersensitivity to this compound should not be given the drug. The possibility of cross-sensitivity to other dibenzazepine compounds should be kept in mind.
Tofranil (Imipramine hcl) Precautions
An ECG recording should be taken prior to the initiation of larger-than-usual doses of Tofranil (Imipramine hcl) 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 Tofranil (Imipramine hcl) .
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 Tofranil (Imipramine hcl) , 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, Tofranil (Imipramine hcl) 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 Tofranil (Imipramine hcl) 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.
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with imipramine hydrochloride and should counsel them in its appropriate use. A patient Medication Guide about "Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions" is available for imipramine hydrochloride. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking imipramine hydrochloride.
Animal reproduction studies have yielded inconclusive results ( ).
There have been no well-controlled studies conducted with pregnant women to determine the effect of Tofranil (Imipramine hcl) on the fetus. However, there have been clinical reports of congenital malformations associated with the use of the drug. Although a causal relationship between these effects and the drug could not be established, the possibility of fetal risk from the maternal ingestion of Tofranil (Imipramine hcl) cannot be excluded. Therefore, Tofranil (Imipramine hcl) should be used in women who are or might become pregnant only if the clinical condition clearly justifies potential risk to the fetus.
Safety and effectiveness in the pediatric population other than pediatric patients with nocturnal enuresis have not been established ( ). Anyone considering the use of imipramine hydrochloride in a child or adolescent must balance the potential risks with the clinical need.
The safety and effectiveness of the drug as temporary adjunctive therapy for nocturnal enuresis in pediatric patients less than 6 years of age has not been established.
The safety of the drug for long-term, chronic use as adjunctive therapy for nocturnal enuresis in pediatric patients 6 years of age or older has not been established; consideration should be given to instituting a drug-free period following an adequate therapeutic trial with a favorable response.
A dose of 2.5 mg/kg/day should not be exceeded in childhood. ECG changes of unknown significance have been reported in pediatric patients with doses twice this amount.
In the literature, there were four well-controlled, randomized, double-blind, parallel group comparison clinical studies done with Tofranil (Imipramine hcl) in the elderly population. There was a total number of 651 subjects included in these studies. These studies did not provide a comparison to younger subjects. There were no additional adverse experiences identified in the elderly.
Clinical studies of Tofranil (Imipramine hcl) in the original application did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Postmarketing clinical experience has not identified differences in responses between the elderly and younger subjects. In general, dose selection for the elderly should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
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Tofranil (Imipramine hcl) Overdosage
Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic overdose. Therefore, hospital monitoring is required as soon as possible.
Children have been reported to be more sensitive than adults to an acute overdosage of imipramine hydrochloride. An acute overdose of any amount in infants or young children, especially, must be considered serious and potentially fatal.
Tofranil (Imipramine hcl) Dosage And Administration
Initially, an oral dose of 25 mg/day should be tried in children aged 6 and older. Medication should be given one hour before bedtime. If a satisfactory response does not occur within one week, increase the dose to 50 mg nightly in children under 12 years; children over 12 may receive up to 75 mg nightly. A daily dose greater than 75 mg does not enhance efficacy and tends to increase side effects. Evidence suggests that in early night bedwetters, the drug is more effective given earlier and in divided amounts, i.e., 25 mg in midafternoon, repeated at bedtime. Consideration should be given to instituting a drug free period following an adequate therapeutic trial with a favorable response. 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.
A dose of 2.5 mg/kg/day should not be exceeded. ECG changes of unknown significance have been reported in pediatric patients with doses twice this amount.
The safety and effectiveness of Tofranil (Imipramine hcl) as temporary adjunctive therapy for nocturnal enuresis in children less than 6 years of age has not been established.
Tofranil (Imipramine hcl) How Supplied
Bottles of 30 ……………… NDC 0406-9920-03
Bottles of 100 ……………… NDC 0406-9920-01
Bottles of 30 ……………… NDC 0406-9921-03
Bottles of 100 ……………… NDC 0406-9921-01
Bottles of 30 ……………… NDC 0406-9922-03
Bottles of 100 ……………… NDC 0406-9922-01
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Tofranil (Imipramine hcl) Animal Pharmacology & Toxicology
A. Acute:
50
Rat 355 to 682 mg/kg
Dog 100 to 215 mg/kg
Depending on the dosage in both species, toxic signs proceeded progressively from depression, irregular respiration and ataxia to convulsions and death.
B. Reproduction/Teratogenic:
Oral: Independent studies in three species (rat, mouse, and rabbit) revealed that when Tofranil (Imipramine hcl) is administered orally in doses up to approximately 2-1/2 times the maximum human dose in the first 2 species and up to 25 times the maximum human dose in the third species, the drug is essentially free from teratogenic potential. In the three species studied, only one instance of fetal abnormality occurred (in the rabbit) and in that study there was likewise an abnormality in the control group. However, evidence does exist from the rat studies that some systemic and embryotoxic potential is demonstrable. This is manifested by reduced litter size, a slight increase in the stillborn rate, and a reduction in the mean birth weight.
Tofranil (Imipramine hcl) and are trademarks of Mallinckrodt Inc.
Manufactured by:Patheon Inc.Whitby, Ontario, CanadaL1N 5Z5
Manufactured for:Mallinckrodt Inc.Hazelwood, MO 63042 USA
Tofranil (Imipramine hcl) Medication Guideantidepressant Medicines, Depression And Other Serious Mental Illnesses,and Suicidal Thoughts Or Actions
Read the Medication Guide that comes with you or your family member's antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
Mallinckrodt Inc. Hazelwood, MO 63042 USA
[05/2009]
Rev 06/2009
Tofranil (Imipramine hcl) Package Label - Principal Display Panel - Mg Bottle
NDC 0406-9920-03
Each tablet contains:Imipramine Hydrochloride USP . . . . . 10 mg
Tofranil (Imipramine hcl) Package Label - Principal Display Panel - Mg Bottle
NDC 0406-9921-03 Each tablet contains:Imipramine Hydrochloride USP . . . . . 25 mg
Tofranil (Imipramine hcl) Package Label - Principal Display Panel - Mg Bottle
NDC 0406-9922-03 Each tablet contains:Imipramine Hydrochloride USP . . . . . 50 mg
