cents, and young adults (ages 18 to 24) with 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 health care providers. such monitoring should include daily observation by families and caregivers. prescriptions for desipramine hydrochloride should be written for the smallest quantity of tablets 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 desipramine hydrochloride is not approved for use in treating bipolar depression. serotonin syndrome: the development of a potentially life-threatening serotonin syndrome has been reported with serotonin norepinephrine re-uptake inhibitors (snris) and ssris, including desipramine hydrochloride, 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 desipramine hydrochloride with maois intended to treat psychiatric disorders is contraindicated. desipramine hydrochloride 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 desipramine hydrochloride. desipramine hydrochloride should be discontinued before initiating treatment with the maoi (see contraindications and dosage and administration ). if concomitant use of desipramine hydrochloride 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 desipramine hydrochloride 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 desipramine hydrochloride may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. general extreme caution should be used when this drug is given in the following situations: in patients with cardiovascular disease, because of the possibility of conduction defects, arrhythmias, tachycardias, strokes, and acute myocardial infarction. in patients who have a family history of sudden death, cardiac dysrhythmias, or cardiac conduction disturbances. in patients with a history of urinary retention or glaucoma, because of the anticholinergic properties of the drug. in patients with thyroid disease or those taking thyroid medication, because of the possibility of cardiovascular toxicity, including arrhythmias. in patients with a history of seizure disorder, because this drug has been shown to lower the seizure threshold. seizures precede cardiac dysrhythmias and death in some patients. this drug is capable of blocking the antihypertensive effect of guanethidine and similarly acting compounds. the patient should be cautioned that this drug may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. in patients who may use alcohol excessively, it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage. pregnancy safe use of desipramine hydrochloride during pregnancy and lactation has not been established; therefore, if it is to be given to pregnant patients, nursing mothers, or women of childbearing potential, the possible benefits must be weighed against the possible hazards to mother and child. animal reproductive studies have been inconclusive. geriatric use clinical studies of desipramine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. lower doses are recommended for elderly patients (see dosage and administration ). the ratio of 2-hydroxydesipramine to desipramine may be increased in the elderly, most likely due to decreased renal elimination with aging. this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. desipramine hydrochloride use in the elderly has been associated with a proneness to falling as well as confusional states (see adverse reactions ).

should be discontinued if there is evidence of pathologic neutrophil depression. clinical experience in the concurrent administration of ect and antidepressant drugs is limited. thus, if such treatment is essential, the possibility of increased risk relative to benefits should be considered. this drug should be discontinued as soon as possible prior to elective surgery because of possible cardiovascular effects. hypertensive episodes have been observed during surgery in patients taking desipramine hydrochloride.

d frequent electrocardiograms (ecgs) are available. the best available evidence of impending toxicity from very high doses of desipramine is prolongation of the qrs or qt intervals on the ecg. prolongation of the pr interval is also significant, but less closely correlated with plasma levels. clinical symptoms of intolerance, especially drowsiness, dizziness, and postural hypotension, should also alert the physician to the need for reduction in dosage. initial therapy may be administered in divided doses or a single daily dose. maintenance therapy may be given on a once-daily schedule for patient convenience and compliance. adolescent and geriatric dose the usual adolescent and geriatric dose is 25 mg to 100 mg daily. dosage should be initiated at a lower level and increased according to tolerance and clinical response to a usual maximum of 100 mg daily. in more severely ill patients, dosage may be further increased to 150 mg/day. doses above 150 mg/day are not recommended in these age groups. initial therapy may be administered in divided doses or a single daily dose. maintenance therapy may be given on a once-daily schedule for patient convenience and compliance. 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 desipramine hydrochloride. conversely, at least 14 days should be allowed after stopping desipramine hydrochloride before starting an maoi intended to treat psychiatric disorders (see contraindications ). use of desipramine hydrochloride with other maoi’s such as linezolid or methylene blue: do not start desipramine hydrochloride 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 desipramine hydrochloride 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, desipramine hydrochloride should be stopped promptly, and linezolid or intravenous methylene blue can be administered. the patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. therapy with desipramine hydrochloride 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 desipramine hydrochloride is unclear. the clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see warnings ).

: numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures; alterations in eeg patterns; tinnitus. symptoms attributed to neuroleptic malignant syndrome have been reported during desipramine use with and without concomitant neuroleptic therapy. anticholinergic: dry mouth, and rarely associated sublingual adenitis; blurred vision, disturbance of accommodation, mydriasis, increased intraocular pressure; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of urinary tract allergic: skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight), edema (of face and tongue or general), drug fever, cross-sensitivity with other tricyclic drugs hematologic: bone marrow depressions including agranulocytosis, eosinophilia, purpura, thrombocytopenia gastrointestinal: anorexia, nausea and vomiting, epigastric distress, peculiar taste, abdominal cramps, diarrhea, stomatitis, black tongue, hepatitis, jaundice (simulating obstructive), altered liver function, elevated liver function tests, increased pancreatic enzymes endocrine: gynecomastia in the male, breast enlargement and galactorrhea in the female; increased or decreased libido, impotence, painful ejaculation, testicular swelling; elevation or depression of blood sugar levels; syndrome of inappropriate antidiuretic hormone secretion (siadh) other: weight gain or loss; perspiration, flushing; urinary frequency, nocturia; parotid swelling; drowsiness, dizziness, proneness to falling, weakness and fatigue, headache; fever; alopecia; elevated alkaline phosphatase withdrawal symptoms: though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise. to report suspected adverse reactions, contact actavis at 1-800-432-8534 or fda at 1-800-fda-1088 or www.fda.gov/medwatch .

hydrochloride is not a monoamine oxidase inhibitor (maoi) and does not act primarily as a central nervous system stimulant. it has been found in some studies to have a more rapid onset of action than imipramine. earliest therapeutic effects may occasionally be seen in 2 to 5 days, but full treatment benefit usually requires 2 to 3 weeks to obtain. metabolism tricyclic antidepressants, such as desipramine hydrochloride, are rapidly absorbed from the gastrointestinal tract. tricyclic antidepressants or their metabolites are to some extent excreted through the gastric mucosa and reabsorbed from the gastrointestinal tract. desipramine is metabolized in the liver, and approximately 70% is excreted in the urine. the rate of metabolism of tricyclic antidepressants varies widely from individual to individual, chiefly on a genetically determined basis. up to a 36-fold difference in plasma level may be noted among individuals taking the same oral dose of desipramine. the ratio of 2-hydroxydesipramine to desipramine may be increased in the elderly, most likely due to decreased renal elimination with aging. certain drugs, particularly the psychostimulants and the phenothiazines, increase plasma levels of concomitantly administered tricyclic antidepressants through competition for the same metabolic enzyme systems. concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressants. conversely, decreases in plasma levels of the tricyclic antidepressants have been reported upon discontinuation of cimetidine, which may result in the loss of the therapeutic efficacy of the tricyclic antidepressant. other substances, particularly barbiturates and alcohol, induce liver enzyme activity and thereby reduce tricyclic antidepressant plasma levels. similar effects have been reported with tobacco smoke. research on the relationship of plasma level to therapeutic response with the tricyclic antidepressants has produced conflicting results. while some studies report no correlation, many studies cite therapeutic levels for most tricyclics in the range of 50 to 300 nanograms per milliliter. the therapeutic range is different for each tricyclic antidepressant. for desipramine, an optimal range of therapeutic plasma levels has not been established.

in bottles of 100 (ndc 45963-344-02) with a non-child resistant closure. 100 mg – each blue, round, unscored, biconvex with flat edge, film-coated tablet, debossed with over 345 on one side and plain on the other side. tablets are supplied in bottles of 100 (ndc 45963-345-02) with a non-child resistant closure. 150 mg – each white to off-white, round, unscored, biconvex with flat edge, film-coated tablet, debossed with over 346 on one side and plain on the other side. tablets are supplied in bottles of 50 (ndc 45963-346-50) with a non-child resistant closure. dispense in a tight, light-resistant container as defined in the usp. preserve in tight container. protect from excessive heat. storage: store at 20° to 25°c (68° to 77°f) [see usp controlled room temperature]. protect from moisture. manufactured by: epic pharma, llc laurelton, ny 11413 distributed by: actavis pharma, inc. parsippany, nj 07054 usa rev. a 1/2019 9d202fae-figure-02 9d202fae-figure-03 9d202fae-figure-04 9d202fae-figure-05 9d202fae-figure-06 9d202fae-figure-07