Parnate, Page 2

For the treatment of Major Depressive Episode Without Melancholia. Parnate should be used in adult patients who can be closely supervised. It should rarely be the first antidepressant drug given. Rather, the drug is suited for patients who have failed to respond to the drugs more commonly administered for depression.

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 PARNATE is not approved for use in treating bipolar depression.

PARNATE is a potent agent with the capability of producing serious side effects. PARNATE is not recommended in those depressive reactions where other antidepressant drugs may be effective. It should be reserved for patients who can be closely supervised and who have not responded satisfactorily to the drugs more commonly administered for depression.

Before prescribing, the physician should be completely familiar with the full material on dosage, side effects, and contraindications on these pages, with the principles of MAO inhibitor therapy and the side effects of this class of drugs. Also, the physician should be familiar with the symptomatology of mental depressions and alternate methods of treatment to aid in the careful selection of patients for therapy with PARNATE.

Pregnancy Warning

Use of any drug in pregnancy, during lactation or in women of childbearing age requires that the potential benefits of the drug be weighed against its possible hazards to mother and child.

Animal reproductive studies show that PARNATE passes through the placental barrier into the fetus of the rat, and into the milk of the lactating dog. The absence of a harmful action of PARNATE on fertility or on postnatal development by either prenatal treatment or from the milk of treated animals has not been demonstrated. Tranylcypromine is excreted in human milk.

WARNING TO THE PATIENT

Patients should be instructed to report promptly the occurrence of headache or other unusual symptoms, i.e., palpitation and/or tachycardia, a sense of constriction in the throat or chest, sweating, dizziness, neck stiffness, nausea, or vomiting.

Patients should be warned against eating the foods listed in Section 11 under Contraindications while on therapy with PARNATE. Also, they should be told not to drink alcoholic beverages. The patient should also be warned about the possibility of hypotension and faintness, as well as drowsiness sufficient to impair performance of potentially hazardous tasks such as driving a car or operating machinery.

Patients should also be cautioned not to take concomitant medications, whether prescription or over-the-counter drugs such as cold, hay fever, or weight-reducing preparations, without the advice of a physician. They should be advised not to consume excessive amounts of caffeine in any form. Likewise, they should inform other physicians, and their dentist, about their use of PARNATE.

See PRECAUTIONS—Information for Patients for information regarding clinical worsening and suicide risk.

WARNINGS

Hypertensive Crisis

The most important reaction associated with PARNATE is the occurrence of hypertensive crises which have sometimes been fatal.

These crises are characterized by some or all of the following symptoms: occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea or vomiting, sweating (sometimes with fever and sometimes with cold, clammy skin), and photophobia. Either tachycardia or bradycardia may be present, and associated constricting chest pain and dilated pupils may occur. Intracranial bleeding, sometimes fatal in outcome, has been reported in association with the paradoxical increase in blood pressure.

In all patients taking PARNATE, blood pressure should be followed closely to detect evidence of any pressor response. It is emphasized that full reliance should not be placed on blood pressure readings, but that the patient should also be observed frequently.

Therapy should be discontinued immediately upon the occurrence of palpitation or frequent headaches during therapy with PARNATE. These signs may be prodromal of a hypertensive crisis.

Important:

Recommended treatment in hypertensive crises

If a hypertensive crisis occurs, PARNATE should be discontinued and therapy to lower blood pressure should be instituted immediately. Headache tends to abate as blood pressure is lowered. On the basis of present evidence, phentolamine is recommended. (The dosage reported for phentolamine is 5 mg I.V.) Care should be taken to administer this drug slowly in order to avoid producing an excessive hypotensive effect. Fever should be managed by means of external cooling. Other symptomatic and supportive measures may be desirable in particular cases. Do not use parenteral reserpine.

PRECAUTIONS

Hypotension

Hypotension has been observed during therapy with PARNATE. Symptoms of postural hypotension are seen most commonly but not exclusively in patients with pre-existent hypertension; blood pressure usually returns rapidly to pretreatment levels upon discontinuation of the drug. At doses above 30 mg daily, postural hypotension is a major side effect and may result in syncope. Dosage increases should be made more gradually in patients showing a tendency toward hypotension at the beginning of therapy. Postural hypotension may be relieved by having the patient lie down until blood pressure returns to normal.

Also, when PARNATE is combined with those phenothiazine derivatives or other compounds known to cause hypotension, the possibility of additive hypotensive effects should be considered.

There have been reports of drug dependency in patients using doses of tranylcypromine significantly in excess of the therapeutic range. Some of these patients had a history of previous substance abuse. The following withdrawal symptoms have been reported: restlessness, anxiety, depression, confusion, hallucinations, headache, weakness, and diarrhea.

Drugs which lower the seizure threshold, including MAO inhibitors, should not be used with Amipaque®*. As with other MAO inhibitors, PARNATE should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.

MAO inhibitors may have the capacity to suppress anginal pain that would otherwise serve as a warning of myocardial ischemia.

The usual precautions should be observed in patients with impaired renal function since there is a possibility of cumulative effects in such patients.

Older patients may suffer more morbidity than younger patients during and following an episode of hypertension or malignant hyperthermia. Older patients have less compensatory reserve to cope with any serious adverse reaction. Therefore, PARNATE should be used with caution in the elderly population.

Although excretion of PARNATE is rapid, inhibition of MAO may persist up to 10 days following discontinuation.

Because the influence of PARNATE on the convulsive threshold is variable in animal experiments, suitable precautions should be taken if epileptic patients are treated.

Some MAO inhibitors have contributed to hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents. Therefore, PARNATE should be used with caution in diabetics using these drugs.

PARNATE may aggravate coexisting symptoms in depression, such as anxiety and agitation.

Use PARNATE with caution in hyperthyroid patients because of their increased sensitivity to pressor amines.

PARNATE should be administered with caution to patients receiving Antabuse®†. In a single study, rats given high intraperitoneal doses of d or l isomers of tranylcypromine sulfate plus disulfiram experienced severe toxicity including convulsions and death. Additional studies in rats given high oral doses of racemic tranylcypromine sulfate (PARNATE) and disulfiram produced no adverse interaction.

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 PARNATE and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions” is available for PARNATE. 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 PARNATE.

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.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS—Clinical Worsening and Suicide Risk). Anyone considering the use of PARNATE in a child or adolescent must balance the potential risks with the clinical need.

ADVERSE REACTIONS

Overstimulation which may include increased anxiety, agitation, and manic symptoms is usually evidence of excessive therapeutic action. Dosage should be reduced, or a phenothiazine tranquilizer should be administered concomitantly.

Patients may experience restlessness or insomnia; may notice some weakness, drowsiness, episodes of dizziness or dry mouth; or may report nausea, diarrhea, abdominal pain, or constipation. Most of these effects can be relieved by lowering the dosage or by giving suitable concomitant medication.

Tachycardia, significant anorexia, edema, palpitation, blurred vision, chills, and impotence have each been reported.

Headaches without blood pressure elevation have occurred.

Rare instances of hepatitis, skin rash, and alopecia have been reported.

Impaired water excretion compatible with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported.

Tinnitus, muscle spasm, tremors, myoclonic jerks, numbness, paresthesia, urinary retention, and retarded ejaculation have been reported.

Hematologic disorders including anemia, leukopenia, agranulocytosis, and thrombocytopenia have been reported.

Post-Introduction Reports

The following are spontaneously reported adverse events temporally associated with use of PARNATE. No clear relationship between PARNATE and these events has been established. Localized scleroderma, flare-up of cystic acne, ataxia, confusion, disorientation, memory loss, urinary frequency, urinary incontinence, urticaria, fissuring in corner of mouth, akinesia.

DOSAGE AND ADMINISTRATION

Dosage should be adjusted to the requirements of the individual patient. Improvement should be seen within 48 hours to 3 weeks after starting therapy.

The usual effective dosage is 30 mg per day, usually given in divided doses. If there are no signs of improvement after a reasonable period (up to 2 weeks), then the dosage may be increased in 10 mg per day increments at intervals of 1 to 3 weeks; the dosage range may be extended to a maximum of 60 mg per day from the usual 30 mg per day.

OVERDOSAGE

Symptoms

The characteristic symptoms that may be caused by overdosage are usually those described above.

However, an intensification of these symptoms and sometimes severe additional manifestations may be seen, depending on the degree of overdosage and on individual susceptibility. Some patients exhibit insomnia, restlessness and anxiety, progressing in severe cases to agitation, mental confusion, and incoherence. Hypotension, dizziness, weakness, and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. A few patients have displayed hypertension with severe headache and other symptoms. Rare instances have been reported in which hypertension was accompanied by twitching or myoclonic fibrillation of skeletal muscles with hyperpyrexia, sometimes progressing to generalized rigidity and coma.

Treatment

Because strategies for the management of overdose are continually evolving, it is advisable to contact a Poison Control Center to determine the latest recommendations for the management of an overdose of any drug. Telephone numbers for the certified Poison Control Centers are listed in the Physicians’ Desk Reference (PDR).

Treatment should normally consist of general supportive measures, close observation of vital signs and steps to counteract specific symptoms as they occur, since MAO inhibition may persist. The management of hypertensive crises is described under WARNINGS in the HYPERTENSIVE CRISES section.

External cooling is recommended if hyperpyrexia occurs. Barbiturates have been reported to help relieve myoclonic reactions, but frequency of administration should be controlled carefully because PARNATE may prolong barbiturate activity. When hypotension requires treatment, the standard measures for managing circulatory shock should be initiated. If pressor agents are used, the rate of infusion should be regulated by careful observation of the patient because an exaggerated pressor response sometimes occurs in the presence of MAO inhibition. Remember that the toxic effect of PARNATE may be delayed or prolonged following the last dose of the drug. Therefore, the patient should be closely observed for at least a week. It is not known if tranylcypromine is dialyzable.

HOW SUPPLIED

PARNATE is supplied as round, rose-red, film-coated tablets debossed with the product name PARNATE and SB and contains tranylcypromine sulfate equivalent to 10 mg of tranylcypromine, in bottles of 100 with a desiccant.

10 mg 100’s: NDC 0007-4471-20

Store between 15° and 30°C (59° and 86°F).

*metrizamide, The Sanofi-Aventis Group.

disulfiram, Odyssey Pharmaceuticals, Inc.

Medication Guide

Antidepressant Medicines, Depression and Other Serious Mental Illnesses, and Suicidal Thoughts or Actions

PARNATE® (PAR-nate) (tranylcypromine sulfate) Tablets

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:

  • All risks and benefits of treatment with antidepressant medicines
  • All treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other serious mental illnesses, and suicidal thoughts or actions?

1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.

2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal thoughts or actions.

3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

  • Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is very important when an antidepressant medicine is started or when the dose is changed.
  • Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings.
  • Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider between visits as needed, especially if you have concerns about symptoms.

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:

  • Thoughts about suicide or dying
  • Attempts to commit suicide
  • New or worse depression
  • New or worse anxiety
  • Feeling very agitated or restless
  • Panic attacks
  • Trouble sleeping (insomnia)
  • New or worse irritability
  • Acting aggressive, being angry, or violent
  • Acting on dangerous impulses
  • An extreme increase in activity and talking (mania)
  • Other unusual changes in behavior or mood

What else do I need to know about antidepressant medicines?

  • Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an antidepressant medicine suddenly can cause other symptoms.
  • Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss all the risks of treating depression and also the risks of not treating it. Patients and their families or other caregivers should discuss all treatment choices with the healthcare provider, not just the use of antidepressants.
  • Antidepressant medicines have other side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
  • Antidepressant medicines can interact with other medicines. Know all of the medicines that you or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start new medicines without first checking with your healthcare provider.
  • Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk to your child’s healthcare provider for more information.

This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.

July 2008 PRT:4MG

GlaxoSmithKline

Research Triangle Park, NC 27709

©2010, GlaxoSmithKline. All rights reserved.

May 2010 PRT:75PI

Principal Display Panel

NDC 0007-4471-20

PARNATE®

TRANYLCYPROMINE SULFATE TABLETS

100 Tablets

Rx only

Federal Law requires dispensing of PARNATE® with the Medication Guide under this label.

Store tablets between 15o and 30oC (59o and 86oF). Dispense in a tight, light-resistant container. Each tablet contains tranylcypromine, 10 mg, as the sulfate.

Usual Dosage: 30 mg per day, usually given in divided doses. See accompanying prescribing information.

Important: Use safety closures when dispensing this product unless otherwise directed by physician or requested by purchaser.

GlaxoSmithKline

RTP, NC 27709

Made in Canada

Rev. 9/ 08

A059715

10 mg, 100-tablet bottle label
(click image for full-size original)
PARNATE
tranylcypromine sulfate tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0007-4471
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
TRANYLCYPROMINE SULFATE (TRANYLCYPROMINE) TRANYLCYPROMINE SULFATE 10 mg
Inactive Ingredients
Ingredient Name Strength
CELLULOSE, MICROCRYSTALLINE
CITRIC ACID
CROSCARMELLOSE SODIUM
D&C RED NO. 7
FD&C BLUE NO. 2
FD&C RED NO. 40
FD&C YELLOW NO. 6
GELATIN
LACTOSE
MAGNESIUM STEARATE
TALC
TITANIUM DIOXIDE
Product Characteristics
Color RED (rose-red) Score no score
Shape ROUND Size 8mm
Flavor Imprint Code PARNATE;SB
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0007-4471-20 100 TABLET, FILM COATED (TABLET) in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA012342 06/23/1989
Labeler — GlaxoSmithKline LLC (167380711)

Revised: 04/2011 GlaxoSmithKline LLC

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