h major depressive disorder (mdd) and other psychiatric disorders. short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. the pooled analyses of placebo-controlled trials in children and adolescents with mdd, obsessive compulsive disorder (ocd), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. the pooled analyses of placebo-controlled trials in adults with mdd or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. there was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. there were differences in absolute risk of suicidality across the different indications, with the highest incidence in mdd. the risk differences (drug vs placebo), however, were relatively stable within age strata and across indications. these risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in table 1 . table 1 age range drug-placebo difference in number of cases of suicidality per 1000 patients treated increases compared to placebo <18 14 additional cases 18 to 24 5 additional cases decreases compared to placebo 25 to 64 1 fewer case ≥65 6 fewer cases no suicides occurred in any of the pediatric trials. there were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. it is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. however, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression. all patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. the following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. such monitoring should include daily observation by families and caregivers. prescriptions for imipramine pamoate should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. screening patients for bipolar disorder: a major depressive episode may be the initial presentation of bipolar disorder. it is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. whether any of the symptoms described above represent such a conversion is unknown. however, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. it should be noted that imipramine pamoate is not approved for use in treating bipolar depression. extreme caution should be used when this drug is given to patients with cardiovascular disease because of the possibility of conduction defects, arrhythmias, congestive heart failure, myocardial infarction, strokes, and tachycardia. these patients require cardiac surveillance at all dosage levels of the drug; patients with increased intraocular pressure, history of urinary retention, or history of narrow-angle glaucoma because of the drug’s anticholinergic properties; hyperthyroid patients or those on thyroid medication because of the possibility of cardiovascular toxicity; patients with a history of seizure disorder because this drug has been shown to lower the seizure threshold; patients receiving guanethidine, clonidine, or similar agents, since imipramine pamoate may block the pharmacologic effects of these drugs; patients receiving methylphenidate hydrochloride. since methylphenidate hydrochloride may inhibit the metabolism of imipramine pamoate, downward dosage adjustment of imipramine pamoate may be required when given concomitantly with methylphenidate hydrochloride. since imipramine pamoate may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as operating an automobile or machinery, the patient should be cautioned accordingly. imipramine pamoate capsules may enhance the cns depressant effects of alcohol. therefore, it should be borne in mind that the dangers inherent in a suicide attempt or accidental overdosage with the drug may be increased for the patient who uses excessive amounts of alcohol. (see precautions .) serotonin syndrome the development of a potentially life-threatening serotonin syndrome has been reported with snris and ssris, including imipramine pamoate capsules, alone but particularly with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and st. john’s wort) and with drugs that impair metabolism of serotonin (in particular, maois, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular changes (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). patients should be monitored for the emergence of serotonin syndrome. the concomitant use of imipramine pamoate capsules with maois intended to treat psychiatric disorders is contraindicated. imipramine pamoate should also not be started in a patient who is being treated with maois such as linezolid or intravenous methylene blue. all reports with methylene blue that provided information on the route of administration involved intravenous administration in the dose range of 1 mg/kg to 8 mg/kg. no reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection) or at lower doses. there may be circumstances when it is necessary to initiate treatment with an maoi such as linezolid or intravenous methylene blue in a patient taking imipramine pamoate. imipramine pamoate should be discontinued before initiating treatment with the maoi (see contraindications and dosage and administration ). if concomitant use of imipramine pamoate with other serotonergic drugs, including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, tryptophan, and st. john’s wort is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases. treatment with imipramine pamoate and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated. angle-closure glaucoma the pupillary dilation that occurs following use of many antidepressant drugs including imipramine pamoate may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

itate discontinuation of the drug. if needed, imipramine pamoate 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 pamoate 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 pamoate 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 pamoate use. imipramine pamoate 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 pamoate should have leukocyte and differential blood counts performed. imipramine pamoate should be discontinued if there is evidence of pathological neutrophil depression. prior to elective surgery, imipramine pamoate should be discontinued for as long as the clinical situation will allow.

an 150 mg/day may also be administered on a once-a-day basis after the optimum dosage and tolerance have been determined. the daily dosage may be given at bedtime. in some patients it may be necessary to employ a divided-dose schedule. as with all tricyclics, the antidepressant effect of imipramine may not be evident for one to three weeks in some patients. adult maintenance dosage: following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission after which the dosage should gradually be decreased. the usual maintenance dosage is 75 to 150 mg/day. the total daily dosage can be administered on a once-a-day basis, preferably at bedtime. in some patients it may be necessary to employ a divided-dose schedule. in cases of relapse due to premature withdrawal of the drug, the effective dosage of imipramine should be reinstituted. adolescent and geriatric patients: therapy in these age groups should be initiated with imipramine pamoate tablets at a total daily dosage of 25 to 50 mg, since imipramine pamoate capsules are not available in these strengths. dosage may be increased according to response and tolerance, but it is generally unnecessary to exceed 100 mg/day in these patients. imipramine pamoate capsules may be used when total daily dosage is established at 75 mg or higher. the total daily dosage can be administered on a once-a-day basis, preferably at bedtime. in some patients it may be necessary to employ a divided-dose schedule. as with all tricyclics, the antidepressant effect of imipramine may not be evident for one to three weeks in some patients. adolescent and geriatric patients can usually be maintained at lower dosage. following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission after which the dosage should gradually be decreased. the total daily maintenance dosage can be administered on a once-a-day basis, preferably at bedtime. in some patients it may be necessary to employ a divided-dose schedule. in cases of relapse due to premature withdrawal of the drug, the effective dosage of imipramine should be reinstituted. switching a patient to or from a monoamine oxidase inhibitor (maoi) intended to treat psychiatric disorders at least 14 days should elapse between discontinuation of an maoi intended to treat psychiatric disorders and initiation of therapy with imipramine pamoate. conversely, at least 14 days should be allowed after stopping imipramine pamoate before starting an maoi intended to treat psychiatric disorders (see contraindications ). use of imipramine pamoate with other maois, such as linezolid or methylene blue do not start imipramine pamoate in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. in a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see contraindications ). in some cases, a patient already receiving imipramine pamoate therapy may require urgent treatment with linezolid or intravenous methylene blue. if acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, imipramine pamoate should be stopped promptly, and linezolid or intravenous methylene blue can be administered. the patient should be monitored for symptoms of serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. therapy with imipramine pamoate may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see warnings ). the risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with imipramine pamoate is unclear. the clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see warnings ).

ccommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract. allergic: skin rash, petechiae, urticaria, itching, photosensitization; edema (general or of face and tongue); drug fever; cross-sensitivity with desipramine. hematologic: bone marrow depression including agranulocytosis; eosinophilia; purpura; thrombocytopenia. gastrointestinal: nausea and vomiting, anorexia, epigastric distress, diarrhea; 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; inappropriate antidiuretic hormone (adh) secretion syndrome. other: jaundice (simulating obstructive); altered liver function; weight gain or loss; perspiration; flushing; urinary frequency; drowsiness, dizziness, weakness and fatigue; headache; parotid swelling; alopecia; proneness to falling. withdrawal symptoms: though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache and malaise. postmarketing experience the following adverse drug reaction has been reported during post-approval use of imipramine pamoate. because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency. eye disorders: angle-closure glaucoma

30 capsules ndc 0054-0276-25: bottle of 100 capsules storage store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] dispense in a tight, child-resistant container as defined in the usp/nf.

ening 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. patients should be advised that taking imipramine pamoate 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.