77,000 patients. There was considerable variation in risk of suicidality among drugs, but a Prior to elective surgery, ma p rotiline should be discontinued for as long as clinically feasi- MAPROTILINE HYDROCHLORIDE tendency toward an increase in the younger patients for almost all drugs studied. There were ble, since little is known about the interaction between maprotiline and general anesthetics. TABLETS, USP differences in absolute risk of suicidality across the different indications, with the highest Maprotiline should be ad ministered with caution in pa tients with history of urinary retention, incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable or history of narrow angle glaucoma because of the drug’s anticholinergic properties. 25 mg, 50 mg and 75 mg within age strata and across indications. These risk differences (drug-placebo difference in Information for Patients: Prescribers or other health professionals should inform pa tients, the number of cases of suicidality per 1,000 patients treated) are provided in Table 1. their families, and their caregivers about the benefits and risks associated with treatment with Table 1: maprotiline and should counsel them in its appropriate use. A patient Medication Guide about Age Range Drug-Placebo Difference in “Antidepressant Medicines, Depression and other Serious Mental Illness and Suicidal Suicidality and Antidepressant Drugs Number of Cases of Suicidality Thoughts or Actions” is available for maprotiline. The prescriber or health professional Antidepressants increased the risk compared to placebo of suicidal thinking and Per 1,000 Patients Treated 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 behavior (suicidality) in children, adolescents and young adults in short-term stud- Increases Compared to Placebo ies of major depressive disorder (MDD) and other psychiatric disorders. Anyone con- to discuss the contents of the Medication Guide and to obtain answers to any questions they < 18 14 additional cases sidering the use of maprotiline or any other antidepressant in a child, adolescent, or may have. The complete text of the Medication Guide is reprinted at the end of this document. young adult must balance this risk with the clinical need. Short-term studies did not 18 to 24 5 additional cases Patients should be advised of the following issues and asked to alert their prescriber if show an increase in the risk of suicidality with antidepressants compared to place- Decreases Compared to Placebo these occur while taking maprotiline. bo in adults beyond age 24; there was a reduction in risk with antidepressants com- 25 to 64 1 fewer case Patients should be advised that taking maprotiline can cause mild pupillary dilation, which pared to placebo in adults aged 65 and older. Depression and certain other psychi- ≥ 65 6 fewer cases in susceptible individuals, can lead to an episode of angle-closure glaucoma. Pre-existing atric disorders are themselves associated with increases in the risk of suicide. glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when Patients of all ages who are started on antidepressant therapy should be monitored No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk fac- appropriately and observed closely for clinical worsening, suicidality, or unusual the number was not sufficient to reach any conclusion about drug effect on suicide. tor for angle-closure glaucoma. Patients may wish to be examined to determine whether they changes in behavior. Families and caregivers should be advised of the need for close It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several are susceptible to angle-closure, and have a prophylactic procedure (e.g., iridectomy), if they observation and communication with the prescriber. Maprotiline is not approved for months. However, there is substantial evidence from placebo-controlled maintenance trials are susceptible. MAP:R14mc use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, in adults with depression that the use of antidepressants can delay the recurrence of depres- Clinical Worsening and Suicide Risk: Patients, their families and their caregivers should be PRECAUTIONS: Information for Patients and PRECAUTIONS: Pediatric Use.) sion. encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irri- All patients being treated with antidepressants for any indication should be monitored tability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypo- DESCRIPTION: Maprotiline hy drochloride, USP is a tetracyclic anti depressant, available as appropriately and observed closely for clinical worsening, suicidality and unusual mania, mania, other unusual changes in behavior, worsening of depression, and suicidal 25 mg, 50 mg and 75 mg tab lets for oral administration. Its chemical name is changes in behavior, especially during the initial few months of a course of drug therapy, ideation, especially early during antidepressant treatment and when the dose is adjusted up N-methyl-9,10-ethanoanthra cene-9(10H)-propylamine hydrochloride, and its structural for- or at times of dose changes, either increases or decreases. or down. Families and caregivers of patients should be advised to look for the emergence of mula is: The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, such symptoms on a day to day basis, since changes may be abrupt. Such symptoms should aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have be reported to the patient's prescriber or health professional, especially if they are severe, been reported in adult and pediatric patients being treated with antidepressants for major depres- abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as sive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a these may be associated with an increased risk for suicidal thinking and behavior and indi- causal link between the emergence of such symptoms and either the worsening of depression cate a need for very close monitoring and possibly changes in the medication. and/or the emergence of suicidal impulses has not been established, there is concern that such Laboratory Tests: Maproti line should be discontinued if there is evidence of pathological C20H23N•HCl symptoms may represent precursors to emerging suicidality. neutrophil depression. Leu ko cyte and differential counts should be performed in pa tients who de velop fever and sore throat during therapy. Maprotiline hydrochloride is a fine, white to off-white, practically odorless crystalline pow - Consideration should be given to changing the therapeutic regimen, including possibly dis- der. It is freely soluble in methanol and in chlo roform, slightly soluble in water, and practi- continuing the medication, in patients whose depression is persistently worse, or who are Drug Interactions: Close super vision and careful ad just ment of dosage are re quired when cally insoluble in isooctane. Its molecular weight is 313.87. experiencing emergent suicidality or symptoms that might be precursors to worsening administering maprotiline concomitantly with anticholinergic or sympathomi metic drugs depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were because of the pos sibility of additive atropine like effects. The tablets contain the following inactive ingredients: col loidal silicon dioxide, cros carmel lose not part of the patient's presenting symptoms. sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethyl- Concurrent administration of maprotiline with electro shock therapy should be a voided ene glycol, pregelatinized starch (corn), sodium lauryl sulfate, titanium di ox ide and triacetin. Families and caregivers of patients being treated with antidepressants for major depres- because of the lack of experience in this area. Additionally, the 50 mg tablet contains FD&C Blue No. 1 Aluminum Lake. sive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted Caution should be exercised when administering ma pro tiline to hyperthyroid pa tients or about the need to monitor patients for the emergence of agitation, irritability, unusual those on thyroid medication because of the possibility of en hanced po tential for cardiovas- CLINICAL PHARMACOLOGY: The mechanism of action of maprotiline is not precisely known. changes in behavior, and the other symptoms described above, as well as the emergence cular toxicity of maprotiline. It does not act primarily by stimulation of the central nervous system and is not a monoamine of suicidality, and to report such symptoms immediately to healthcare providers. Such mon- Maprotiline should be used with caution in patients re ceiving guanethidine or similar oxidase inhib itor. The postulated mechanism of maprotiline is that it acts primarily by poten- itoring should include daily observation by families and caregivers. Prescriptions for mapro- agents since it may block the pharmacologic effects of these drugs. tiation of central adrenergic synap ses