Surmontil Information
Surmontil (Trimipramine)
Surmontil (Trimipramine) Description
Surmontil (Trimipramine) (trimipramine maleate) is 5-(3-dimethylamino-2-methylpropyl)-10,11-dihydro-5H-dibenz (b,f) azepine acid maleate (racemic form).
Surmontil (Trimipramine) capsules contain trimipramine maleate equivalent to 25 mg, 50 mg, or 100 mg of trimipramine as the base. The inactive ingredients present are black ink, FD&C Blue 1, gelatin, lactose, magnesium stearate, and titanium dioxide. The 25 mg dosage strength also contains benzyl alcohol, D&C Yellow 10, edetate calcium disodium, FD&C Yellow 6, parabens (butyl, propyl and methyl), sodium lauryl sulfate, and sodium propionate; the 50 mg dosage strength also contains benzyl alcohol, D&C Red 28, edetate calcium disodium, FD&C Red 40, FD&C Yellow 6, parabens (butyl, propyl and methyl), sodium lauryl sulfate, and sodium propionate.
Trimipramine maleate is prepared as a racemic mixture which can be resolved into levorotatory and dextrorotatory isomers. The asymmetric center responsible for optical isomerism is marked in the formula by an asterisk. Trimipramine maleate is an almost odorless, white or slightly cream-colored, crystalline substance, melting at 140°-144° C. It is very slightly soluble in ether and water, is slightly soluble in ethyl alcohol and acetone, and freely soluble in chloroform and methanol at 20° C.
Surmontil (Trimipramine) Clinical Pharmacology
Surmontil (Trimipramine) is an antidepressant with an anxiety-reducing sedative component to its action. The mode of action of Surmontil (Trimipramine) on the central nervous system is not known. However, unlike amphetamine-type compounds it does not act primarily by stimulation of the central nervous system. It does not act by inhibition of the monoamine oxidase system.
The single-dose pharmacokinetics of trimipramine were evaluated in a comparative study of 24 elderly subjects and 24 younger subjects; no clinically relevant differences were demonstrated based on age or gender.
Surmontil (Trimipramine) Indications And Usage
Surmontil (Trimipramine) is indicated for the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than other depressive states. In studies with neurotic outpatients, the drug appeared to be equivalent to amitriptyline in the less-depressed patients but somewhat less effective than amitriptyline in the more severely depressed patients. In hospitalized depressed patients, trimipramine and imipramine were equally effective in relieving depression.
Surmontil (Trimipramine) Contraindications
Surmontil (Trimipramine) is contraindicated in cases of known hypersensitivity to the drug. The possibility of cross-sensitivity to other dibenzazepine compounds should be kept in mind. Surmontil (Trimipramine) should not be given in conjunction with drugs of the monoamine oxidase inhibitor class (e.g., tranylcypromine, isocarboxazid or phenelzine sulfate). The concomitant use of monoamine oxidase inhibitors (MAOI) and tricyclic compounds similar to Surmontil (Trimipramine) has caused severe hyperpyretic reactions, convulsive crises, and death in some patients. At least two weeks should elapse after cessation of therapy with MAOI before instituting therapy with Surmontil (Trimipramine) . Initial dosage should be low and increased gradually with caution and careful observation of the patient. The drug is contraindicated during the acute recovery period after a myocardial infarction.
Surmontil (Trimipramine) Warnings
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (aged 18-24) 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 analysis of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders including 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 with age strada 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.
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 non-psychiatric, 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 Surmontil (Trimipramine) 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 depression 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 Surmontil (Trimipramine) is not approved for use in treating bipolar depression.
Extreme caution should be used when this drug is given to patients with any evidence of cardiovascular disease because of the possibility of conduction defects, arrhythmias, myocardial infarction, strokes, and tachycardia.
Caution is advised in 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 or similar agents, since Surmontil (Trimipramine) (trimipramine maleate) may block the pharmacologic effects of these drugs.
Since the drug 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.
Surmontil (Trimipramine) Precautions
The possibility of suicide is inherent in any severely depressed patient and persists until a significant remission occurs. When a patient with a serious suicidal potential is not hospitalized, the prescription should be for the smallest amount feasible.
In schizophrenic patients activation of the psychosis may occur and require reduction of dosage or the addition of a major tranquilizer to the therapeutic regime.
Manic or hypomanic episodes may occur in some patients, in particular those with cyclic-type disorders. In some cases therapy with Surmontil (Trimipramine) must be discontinued until the episode is relieved, after which therapy may be reinstituted at lower dosages if still required.
Concurrent administration of Surmontil (Trimipramine) and electroshock therapy may increase the hazards of therapy. Such treatment should be limited to those patients for whom it is essential. When possible, discontinue the drug for several days prior to elective surgery.
Surmontil (Trimipramine) should be used with caution in patients with impaired liver function.
Chronic animal studies showed occasional occurrence of hepatic congestion, fatty infiltration, or increased serum liver enzymes at the highest dose of 60 mg/kg/day.
Both elevation and lowering of blood sugar have been reported with tricyclic antidepressants.
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Surmontil (Trimipramine) and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for Surmontil (Trimipramine) . The prescriber or health professional 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 to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Surmontil (Trimipramine) .
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.
Semen studies in man (four schizophrenics and nine normal volunteers) revealed no significant changes in sperm morphology. It is recognized that drugs having a parasympathetic effect, including tricyclic antidepressants, may alter the ejaculatory response.
Chronic animal studies showed occasional evidence of degeneration of seminiferous tubules at the highest dose of 60 mg/kg/day.
Clinical studies of Surmontil (Trimipramine) (trimipramine maleate) were not adequate to determine whether subjects aged 65 and over respond differently from younger subjects.
The pharmacokinetics of trimipramine were not substantially altered in the elderly (see ).
Surmontil (Trimipramine) is known to be substantially excreted by the kidney. Clinical circumstances, some of which may be more common in the elderly, such as hepatic or renal impairment, should be considered (see — ).
Greater sensitivity (e.g., confusional states, sedation) of some older individuals cannot be ruled out (see ). In general, dose selection for an elderly patient should be cautious, usually starting at a lower dose (see ).
Surmontil (Trimipramine) Adverse Reactions
Note: The pharmacological similarities among the tricyclic antidepressants require that each of the reactions be considered when Surmontil (Trimipramine) is administered. Some of the adverse reactions included in this listing have not in fact been reported with Surmontil (Trimipramine) .
Surmontil (Trimipramine) Dosage And Administration
Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.
Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients as compared to hospitalized patients who will be under close supervision. It is not possible to prescribe a single dosage schedule of Surmontil (Trimipramine) that will be therapeutically effective in all patients. The physical psychodynamic factors contributing to depressive symptomatology are very complex; spontaneous remissions or exacerbations of depressive symptoms may occur with or without drug therapy. Consequently, the recommended dosage regimens are furnished as a guide which may be modified by factors such as the age of the patient, chronicity and severity of the disease, medical condition of the patient, and degree of psychotherapeutic support.
Most antidepressant drugs have a lag period of ten days to four weeks before a therapeutic response is noted. Increasing the dose will not shorten this period but rather increase the incidence of adverse reactions.
Surmontil (Trimipramine) Overdosage*
Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose, therefore, hospital monitoring is required as soon as possible.
Critical manifestations of overdose include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.
Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the symptoms listed under .
Surmontil (Trimipramine) How Supplied
Surmontil (Trimipramine) ® (trimipramine maleate) Capsules
25 mg — Opaque blue and yellow capsule in bottles of 100.
Printed OP and 718
50 mg — Opaque blue and orange capsule in bottles of 100.
Printed OP and 719.
100 mg — Opaque blue and white capsule in bottles of 100.
Printed OP and 720
Surmontil (Trimipramine) Medication Guide
Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions
Read the Medication Guide that comes with you or your family member’s antidepressant medicine. This Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk to your, or your family member’s, healthcare provider about:
What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?
Call a healthcare provider right away if you or your family member has any of the following symptoms, especially if they are new, worse, or worry you:
What else do I need to know about antidepressant medicines?
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
DURAMED PHARMACEUTICALS, INC.
Subsidiary of Barr Pharmaceuticals, Inc.Pomona, New York 10970
Revised JUNE 2007Br-718, 719, 720
B08-0718
Surmontil (Trimipramine) Principal Display Panels
NDC 51285-538-02
Surmontil (Trimipramine) Trimiparamine Maleate25 mg
PHARMACIST: PLEASE DISPENSE WITH MEDICATION GUIDE
100 Capsules
SEALED FOR YOU PROTECTION
Each capsule contains trimipramine maleate equivalent to 25 mg trimipramine.
USUAL DOSAGE: One or two capsules 3 times a day.
See accompanying information.
Keep tightly closed.
Store at 20° to 25° C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight container.
R6-07 (v.2)10001434
NDC 51285-539-02
Surmontil (Trimipramine) Trimiparamine Maleate50 mg
PHARMACIST: PLEASE DISPENSE WITH MEDICATION GUIDE
100 Capsules
SEALED FOR YOU PROTECTION
Each capsule contains trimipramine maleate equivalent to 50 mg trimipramine.
USUAL DOSAGE: One capsule 3 times a day.
See accompanying information.
Keep tightly closed.
Store at 20° to 25° C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight container.
R6-07 (v.2)10001435
NDC 51285-554-02
Surmontil (Trimipramine) Trimiparamine Maleate100 mg
PHARMACIST: PLEASE DISPENSE WITH MEDICATION GUIDE
100 Capsules
SEALED FOR YOU PROTECTION
Each capsule contains trimipramine maleate equivalent to 100 mg trimipramine.
USUAL DOSAGE: One capsule 1 to 2 times daily.
See accompanying information.
Keep tightly closed.
Store at 20° to 25° C (68° to 77°F) [See USP Controlled Room Temperature].
Dispense in a tight container.
R6-07 (v.2)10001433