Nortriptyline Hydrochloride (Page 2 of 5)

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 nortriptyline hydrochloride is not approved for use in treating bipolar depression.

Patients with cardiovascular disease should be given nortriptyline hydrochloride only under close supervision because of the tendency of the drug to produce sinus tachycardia and to prolong the conduction time. Myocardial infarction, arrhythmia, and strokes have occurred. The antihypertensive action of guanethidine and similar agents may be blocked. Because of its anticholinergic activity, nortriptyline should be used with great caution in patients who have a history of urinary retention. Patients with a history of seizures should be followed closely when nortriptyline is administered, inasmuch as this drug is known to lower the convulsive threshold. Great care is required if nortriptyline is given to hyperthyroid patients or to those receiving thyroid medication, since cardiac arrhythmias may develop.

Nortriptyline may impair the mental and/or physical abilities required for the performance of hazardous tasks, such as operating machinery or driving a car; therefore, the patient should be warned accordingly.

Excessive consumption of alcohol in combination with nortriptyline therapy may have a potentiating effect, which may lead to the danger of increased suicidal attempts or overdosage, especially in patients with histories of emotional disturbances or suicidal ideation.

The concomitant administration of quinidine and nortriptyline may result in a significantly longer plasma half-life, higher AUC, and lower clearance of nortriptyline.

Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including nortriptyline 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 nortriptyline hydrochloride with MAOIs intended to treat psychiatric disorders is contraindicated. Nortriptyline hydrochloride oral solution 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 nortriptyline hydrochloride oral solution. Nortriptyline hydrochloride oral solution should be discontinued before initiating treatment with the MAOI (See CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION).

If concomitant use of nortriptyline hydrochloride oral solution 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 nortriptyline hydrochloride oral solution and any concomitant serotonergic agents should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

Unmasking of Brugada Syndrome

There have been postmarketing reports of an association between treatment with nortriptyline hydrochloride and the unmasking of Brugada syndrome. Brugada syndrome is a disorder characterized by syncope, abnormal electrocardiographic (ECG) findings, and a risk of sudden death. Nortriptyline hydrochloride should generally be avoided in patients with Brugada syndrome or those suspected of having Brugada syndrome.

Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs including nortriptyline hydrochloride oral solution may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Use in Pregnancy

Safe use of nortriptyline hydrochloride oral solution during pregnancy and lactation has not been established; therefore, when the drug is administered to pregnant patients, nursing mothers, or women of childbearing potential, the potential benefits must be weighed against the possible hazards. Animal reproduction studies have yielded inconclusive results.

PRECAUTIONS

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with nortriptyline hydrochloride 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 nortriptyline hydrochloride. 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 prescribers if these occur while taking nortriptyline hydrochloride.

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.

The use of nortriptyline hydrochloride in schizophrenic patients may result in an exacerbation of the psychosis or may activate latent schizophrenic symptoms. If the drug is given to overactive or agitated patients, increased anxiety and agitation may occur. In manic-depressive patients, nortriptyline hydrochloride may cause symptoms of the manic phase to emerge.

Troublesome patient hostility may be aroused by the use of nortriptyline hydrochloride. Epileptiform seizures may accompany its administration, as is true of other drugs of its class.

When it is essential, the drug may be administered with electroconvulsive therapy, although the hazards may be increased. Discontinue the drug for several days, if possible, prior to elective surgery.

The possibility of a suicidal attempt by a depressed patient remains after the initiation of treatment; in this regard, it is important that the least possible quantity of drug be dispensed at any given time.

Both elevation and lowering of blood sugar levels have been reported.

Patients should be advised that taking nortriptyline hydrochloride 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.