nded for use in children under 12 years of age.

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 4,400 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 1,000 patients treated) are provided in table 1. table 1 age range drug-placebo difference in number of cases of suicidality per 1,000 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 doxepin 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 doxepin hydrochloride is not approved for use in treating bipolar depression. angle-closure glaucoma the pupillary dilation that occurs following use of many antidepressant drugs including doxepin hydrochloride may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. usage in geriatrics the use of doxepin hydrochloride capsules on a once-a-day dosage regimen in geriatric patients should be adjusted carefully based on the patient’s condition ( see precautions geriatric use ). usage in pregnancy reproduction studies have been performed in rats, rabbits, monkeys and dogs and there was no evidence of harm to the animal fetus. the relevance to humans is not known. since there is no experience in pregnant women who have received this drug, safety in pregnancy has not been established. there has been a report of apnea and drowsiness occurring in a nursing infant whose mother was taking doxepin hydrochloride capsules. usage in children the use of doxepin hydrochloride capsules in children under 12 years of age is not recommended because safe conditions for its use have not been established.

e therapy only and is not recommended for initiation of treatment. anti-anxiety effect is apparent before the antidepressant effect. optimal antidepressant effect may not be evident for two to three weeks.

n, and pruritus have occasionally occurred. hematologic eosinophilia has been reported in a few patients. there have been occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura. gastrointestinal nausea, vomiting, indigestion, taste disturbances, diarrhea, anorexia, and aphthous stomatitis have been reported. ( see anticholinergic effects .) endocrine raised or lowered libido, testicular swelling, gynecomastia in males, enlargement of breasts and galactorrhea in the female, raising or lowering of blood sugar levels, and syndrome of inappropriate antidiuretic hormone secretion have been reported with tricyclic administration other dizziness, tinnitus, weight gain, sweating, chills, fatigue, weakness, flushing, jaundice, alopecia, headache, exacerbation of asthma, angle closure glaucoma, mydriasis and hyperpyrexia (in association with chlorpromazine) have been occasionally observed as adverse effects. withdrawal symptoms the possibility of development of withdrawal symptoms upon abrupt cessation of treatment after prolonged doxepin hydrochloride administration should be borne in mind. these are not indicative of addiction and gradual withdrawal of medication should not cause these symptoms.

e is a #2 capsule with a bright light green opaque cap and bright light green opaque body imprinted with "Є532" in black ink on both the cap and body filled with white powder. they are available as follows: 75 mg– 100 count (ndc 42806-532-01) 75 mg– 1000 count (ndc 42806-532-10) the 100 mg capsule is a #1 capsule with a bright light green opaque cap and white opaque body imprinted with "Є533" in black ink on both the cap and body filled with white powder. they are available as follows: 100 mg– 100 count (ndc 42806-533-01) 100 mg– 1000 count (ndc 42806-533-10) store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] protect from light. dispense in a tight, light-resistant container as defined in the usp, with a child-resistant closure, as required. dispense with medication guide available at: www.epic-pharma.com/medguide/doxepin-hydrochloride-capsule.pdf manufactured by: epic pharma, llc laurelton, ny 11413 rev. 03-2022-00 mf529rev03/22 oe2694

les. 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. patients should be advised that taking doxepin hydrochloride capsules 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. pediatric use safety and effectiveness in the pediatric population have not been established (see box warning and warnings—clinical worsening and suicide risk ). anyone considering the use of doxepin hydrochloride capsules in a child or adolescent must balance the potential risks with the clinical need.