pressive 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 nine 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 healthcare providers. such monitoring should include daily observation by families and caregivers. prescriptions for doxepin 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 doxepin 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 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 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. usage in children: the use of doxepin in children under 12 years of age is not recommended because safe conditions for its use have not been established.

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.

matologic: 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 administration should be borne in mind. these are not indicative of addiction and gradual withdrawal of medication should not cause these symptoms. to report suspected adverse reactions, contact amneal pharmaceuticals at 1-877-835-5472 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

n reported. doxepin is virtually devoid of euphoria as a side effect. characteristic of this type of compound, doxepin has not been demonstrated to produce the physical tolerance or psychological dependence associated with addictive compounds.

of 1000 capsules: doxepin hcl capsules usp, 75 mg are supplied as hard gelatin capsule filled with white to off-white granular powder having “amneal” printed on green opaque cap and “1172” printed on green opaque body with black ink. they are available as follows: bottle of 30 capsules: bottle of 90 capsules: bottle of 1000 capsules: doxepin hcl capsules usp, 100 mg are supplied as hard gelatin capsule filled with white to off-white granular powder having “amneal” printed on green opaque cap and “1173” printed on white opaque body with black ink. they are available as follows: bottle of 30 capsules: bottle of 90 capsules: bottle of 1000 capsules: 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 using a child-resistant closure. pharmacist: dispense a medication guide with each prescription. manufactured by: amneal pharmaceuticals pvt. ltd. ahmedabad 382220, india distributed by: amneal pharmaceuticals llc bridgewater, nj 08807 rev. 09-2017-01