Pamelor (Nortriptyline) Drug Information

Nortriptyline Description, Indications, Side Effects, Warnings, Pharmacology, and Dosage
Antidepressant Basics: Pamelor

 

Generic Name: Nortriptyline
Brand Names: • Pamelor • Aventyl HCl

Class: Antidepressant, Tricyclic (TCA)

Updated: August 2014

Pamelor

What Is It?

Pamelor™ (nortriptyline HCl) is a tricyclic antidepressant (TCA) for oral administration. Pamelor is a trademark of Mallinckrodt LLC.

PAMELOR is indicated for the relief of symptoms of depression. Endogenous depressions are more likely to be alleviated than are other depressive states.

Some people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using PAMELOR. Your family or other caregivers should also be alert to changes in your mood or symptoms.

This medication guide does not take the place of talking to your healthcare provider about your medical condition or treatment. Talk with your healthcare provider if there is something you do not understand or want to learn more about.

This medication is not approved for use in children.

Who Should Not Take Pamelor?

Do not take Pamelor if you: 1) are allergic to Pamelor or any of the ingredients in Pamelor. See the end of this section for a complete list of ingredients in Pamelor; 2) are in the acute phase of recovery from a myocardial infarction (heart attack); 3) are allergic to dibenzazepines or tricyclic drugs; 4) take a monoamine oxidase inhibitor (MAOI) or have taken an MAOI in the past 14 days. Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid. Do not take an MAOI within 2 weeks of stopping Pamelor unless directed to do so by your physician. Do not start Pamelor if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician. MAOIs include Parnate (Tranylcypromine), Nardil (Phenelzine), Emsam (Selegiline transdermal), and Marplan (Isocarboxazid).

Do not give Pamelor to anyone younger than 18 years old without the advice of a doctor.

Before Starting Pamelor

Tell your healthcare provider about: 1) any medical conditions you have, including cardiac, liver, kidney, or blood disease; 2) current pregnancy or plans to become pregnant; 3) current breastfeeding or plans to breastfeed; 4) any and all medications and supplements you are taking; 5) any thoughts or feelings of suicide. Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Patients should be told that the concomitant use of Pamelor and alcohol is not advised. Patients should inform their physician if they are taking, or plan to take, any prescription or over-the-counter drugs, as there is a potential for interactions. Patients should notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should notify their physician if they are breast feeding an infant. While patients may notice improvement with Pamelor therapy, they should be advised to continue therapy as directed.

Ingredients of PAMELOR:

Active ingredient: Active Ingredient: nortriptyline hydrochloride USP. In the 10 mg, 25 mg, and 75 mg Capsules: Inactive Ingredients: D&C Yellow #10, FD&C Yellow #6, gelatin, silicone fluid, starch, and titanium dioxide. In the 50 mg Capsules: Inactive Ingredients: gelatin, silicone fluid, starch, and titanium dioxide. In the Solution: Active Ingredient: nortriptyline hydrochloride USP. Inactive Ingredients: alcohol, benzoic acid, flavoring, purified water, and sorbitol.

Indications and Usage

Nortriptyline is used to treat symptoms of depression. Nortriptyline may also be used for purposes not listed in this medication guide.

Nortriptyline is also sometimes used to treat panic disorders and post-herpetic neuralgia (the burning, stabbing pains, or aches that may last for months or years after a shingles infection). Nortriptyline is also sometimes used as a smoking cessation agent. Talk to your doctor about the possible risks of using this medication for your condition.

The physician who elects to use Nortriptyline for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Contraindications

Monoamine Oxidase Inhibitors (MAOIs)
The use of MAOIs intended to treat psychiatric disorders with Pamelor or within 14 days of stopping treatment with Pamelor is contraindicated because of an increased risk of serotonin syndrome. The use of Pamelor within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. Starting Pamelor in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome.

Hypersensitivity to Tricyclic Antidepressants
Cross-sensitivity between Pamelor and other dibenzazepines is a possibility.

Myocardial Infarction
Pamelor is contraindicated during the acute recovery period after myocardial infarction.

Common Side Effects

Gastrointestinal: Constipation

Serious Side Effects

Cardiovascular: Cardiac dysrhythmia, Heart block, Myocardial infarction, Prolonged QT interval, Sudden cardiac death
Endocrine metabolic: Syndrome of inappropriate antidiuretic hormone secretion
Gastrointestinal: Paralytic ileus
Hematologic: Bone marrow depression
Hepatic: Fulminant hepatic failure, Jaundice (rare )
Neurologic: Cerebrovascular accident, Myoclonus, Seizure
Psychiatric: Depression, worsening, Mania, Psychotic disorder, exacerbation, Suicidal thoughts, Suicide
Other: Angioedema

Get emergency medical help if you have any of these signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of nortriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. 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 in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Nortriptyline hydrochloride is not approved for use in pediatric patients.

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. 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 Pamelor should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.

Overdose

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.

Manifestations
Critical manifestations of overdose include: cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, 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, restlessness, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the acute symptoms. There have been reports of patients recovering from nortriptyline overdoses of up to 525 mg.

Call 911 or visit your nearest hospital for all suspected overdose cases.

Pregnancy

Pregnancy Category N (Not Assigned)
Safe use of Pamelor 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.

Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with SNRIs and SSRIs, including Pamelor, alone but particularly with concomitant use of serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, busipirone, 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 aberrations (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 Pamelor with MAOIs intended to treat psychiatric disorders is contraindicated. Pamelor 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 Pamelor. Pamelor should be discontinued before initiating treatment with the MAOI. If concomitant use of Pamelor 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 Pamelor and any concomitant serotonergic agents, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.

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.

Cardiovascular Disease

Patients with cardiovascular disease should be given Pamelor 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, Pamelor should be used with great caution in patients who have glaucoma or a history of urinary retention. Patients with a history of seizures should be followed closely when Pamelor is administered, inasmuch as this drug is known to lower the convulsive threshold. Great care is required if Pamelor is given to hyperthyroid patients or to those receiving thyroid medication, since cardiac arrhythmias may develop.

Other

Pamelor 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.

Detailed Summary

Pamelor™ (nortriptyline HCl) is 1-propanamine, 3-(10,11-dihydro-5H­-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-, hydrochloride.

Mechanism Of Action

The mechanism of mood elevation by tricyclic antidepressants is at present unknown. Pamelor is not a monoamine oxidase inhibitor. It inhibits the activity of such diverse agents as histamine, 5-hydroxytryptamine, and acetylcholine. It increases the pressor effect of norepinephrine but blocks the pressor response of phenethylamine. Studies suggest that Pamelor interferes with the transport, release, and storage of catecholamines. Operant conditioning techniques in rats and pigeons suggest that Pamelor has a combination of stimulant and depressant properties.

Drug-Drug Interactions Including P450 Interactions

Administration of reserpine during therapy with a tricyclic antidepressant has been shown to produce a “stimulating” effect in some depressed patients. Close supervision and careful adjustment of the dosage are required when Pamelor is used with other anticholinergic drugs and sympathomimetic drugs. Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma concentrations of the tricyclic antidepressant. The patient should be informed that the response to alcohol may be exaggerated. A case of significant hypoglycemia has been reported in a type II diabetic patient maintained on chlorpropamide (250 mg/day), after the addition of nortriptyline (125 mg/day).

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

Dosage and Administration

Dosage Forms and Strengths

Pamelor™ (nortriptyline HCl) Capsules USP, equivalent to 10 mg, 25 mg, 50 mg, and 75 mg base, are available as follows:

• 10 mg: Light orange opaque cap printed “ PAMELOR 10 mg” in black and white opaque body printed “M” in black.
Bottles of 30 ………… NDC 0406-9910-03

• 25 mg: Light orange opaque cap printed “ PAMELOR 25 mg” in black and white opaque body printed “M” in black.
Bottles of 30 ………… NDC 0406-9911-03

• 50 mg: White opaque cap printed “ PAMELOR 50 mg” in black and white opaque body printed “M” in black.
Bottles of 30 ………… NDC 0406-9912-03

• 75 mg: Light orange opaque cap printed “ PAMELOR 75 mg” in black and light orange opaque body printed “M” in black.
Bottles of 30 ………… NDC 0406-9913-03

Pamelor™ (nortriptyline HCl) oral solution USP, equivalent to 10 mg base per 5 mL, is supplied in 16-fluid-ounce bottles (NDC 0406-9918-16). Alcohol content 4%.

Adults
Pamelor is administered orally in the form of capsules or liquid. Lower than usual dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients than for hospitalized patients who will be under close supervision. The physician should initiate dosage at a low level and increase it gradually, noting carefully the clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission. If a patient develops minor side effects, the dosage should be reduced. The drug should be discontinued promptly if adverse effects of a serious nature or allergic manifestations occur. Usual Adult Dose – 25 mg three or four times daily; dosage should begin at a low level and be increased as required. As an alternate regimen, the total daily dosage may be given once a day. When doses above 100 mg daily are administered, plasma levels of nortriptyline should be monitored and maintained in the optimum range of 50 to 150 ng/mL. Doses above 150 mg/day are not recommended.

Pediatric Population (children)
Pamelor is not recommended for children. Safety and effectiveness in the pediatric population have not been established. Anyone considering the use of nortriptyline hydrochloride in a child or adolescent must balance the potential risks with the clinical need.

Elderly and Adolescent Population
30 to 50 mg/day, in divided doses, or the total daily dosage may be given once a day.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders
At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with Pamelor. Conversely, at least 14 days should be allowed after stopping Pamelor before starting an MAOI intended to treat psychiatric disorders.

This dosage information does not include all the information needed to use PAMELOR safely and effectively. See full prescribing information for PAMELOR. The information at DepressionHealth.net is not a substitute for medical advice. ALWAYS consult your doctor or pharmacist.
This medication guide does not act as medical advice and does not replace the advice of a physician.
This guide is meant to be used as an educational tool and supplement to the expert advice and judgement of a physician.
Get emergency medical help or visit your nearest hospital if you have any of the signs of an allergic reaction when taking this medication:
skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
If you overdose, seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of nortriptyline can be fatal.
The above information derives from the following sources: FDA Monograph Citation NDA018013, FDA Label Reference ID 3209061, Micromedex®, MedlinePlus, DailyMed. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. Disclaimer: Every effort has been made to ensure that the information provided by Depression Health Network is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This product’s label may have been updated. For current full prescribing information, please visit www.mallinckrodt.com.