An ECG recording should be taken prior to the initiation of larger-than-usual doses of Tofranil 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. See WARNINGS.)
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.
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, 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 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 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
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
Imipramine hydrochloride should be used with caution in patients with significantly impaired renal or
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.
Information For Patients
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
Patients should be advised of the following issues and asked to alert their prescriber if these occur
while taking imipramine hydrochloride.
Patients should be advised that taking Tofranil can cause mild pupillary dilation, which in susceptible
individuals, can lead to an episode of angle-closure glaucoma. Pre-existing glaucoma is almost always
open-angle glaucoma because angle-closure glaucoma, when diagnosed, can be treated definitively
with iridectomy. Open-angle glaucoma is not a risk factor for angle-closure glaucoma. Patients may
wish to be examined to determine whether they are susceptible to angle closure, and have a
prophylactic procedure (e.g., iridectomy), if they are susceptible.
Clinical Worsening And Suicide Risk
Patients, their families, and their caregivers should be
encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability,
hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other
unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during
antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients
should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes
may be abrupt. Such symptoms should be reported to the patient’s prescriber or health professional,
especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms.
Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and
indicate a need for very close monitoring and possibly changes in the medication.
Animal reproduction studies have yielded inconclusive results (see also Animal Pharmacology).
There have been no well-controlled studies conducted with pregnant women to determine the effect of
Tofranil 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 cannot be excluded.
Therefore, Tofranil should be used in women who are or might become pregnant only if the clinical
condition clearly justifies potential risk to the fetus.
Limited data suggest that Tofranil is likely to be excreted in human breast milk. As a general rule, a
woman taking a drug should not nurse since the possibility exists that the drug may be excreted in breast
milk and be harmful to the child.
Safety and effectiveness in the pediatric population other than pediatric patients with nocturnal enuresis
have not been established (see BOX WARNING and WARNINGS, Clinical Worsening and Suicide
Risk). 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 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 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.
(See also DOSAGE AND ADMINISTRATION, Adolescent and Geriatric Patients .)
(See also PRECAUTIONS, General.)