Parnate

There are many other drugs that can cause serious medical problems if you take them together with tranylcypromine. Do not take tranylcypromine before telling your doctor about all other prescription and over-the-counter medications you use, including vitamins, minerals, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you.

You may have thoughts about suicide when you first start taking an antidepressant, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment.

Call your doctor at once if you have any new or worsening symptoms 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.

While you are taking tranylcypromine, you must not drink alcohol or eat foods that are high in tyramine, listed in the "What should I avoid while taking tranylcypromine?" section of this leaflet. Eating tyramine while you are taking tranylcypromine can raise your blood pressure to dangerous levels, causing life-threatening symptoms such as sudden and severe headache, confusion, blurred vision, problems with speech or balance, nausea, vomiting, chest pain, seizure (convulsions), and sudden numbness or weakness (especially on one side of the body). Call your doctor at once if you have any of these symptoms.

Tranylcypromine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

• Antidepressants
• Depression
• Prescription Anxiety Medications

• Covis Pharmaceuticals, Inc.

Serious side effects have been reported. See "Drug Precautions" section.

Common side effects include:

• dry mouth
• dizziness
• diarrhea
• headaches
• nausea
• stomach pain
• constipation
• insomnia
• drowsiness
• weakness
• low blood pressure when standing or sitting up
• difficulting urinating
• shakiness

This is not a complete list of Parnate side effects. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Parnate including:

• hypertensive crisis, a life threatening increase in blood pressure. This sometimes fatal side effect can result from taking MAO inhibitors like Parnate with certain drugs and foods (see "Drug Interactions" and "Food Interactions" sections). Symptoms include:
  • headaches
  • stiff or sore neck
  • nausea
  • vomiting
  • palpitations
  • sweating, sometimes with fever and cold, clammy skin
  • either fast or slow heart beat
  • chest pain
  • chest tightness
  • dilated pupils

Get medical help right away if you experience these symptoms.

• severe headaches. If you have frequent headaches, talk to your doctor before starting Parnate as headaches are one of the first symptoms of a hypertensive crisis and you may miss this warning sign.
• suicidal thoughts or behavior. Antidepressants may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment.
  • 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.
• low blood pressure, especially when getting up from a lying position.

Parnate can cause drowsiness. Do not drive or operate heavy machinery until you know how it affects you.

Do not take Parnate if you:

• are allergic to any ingredient in Parnate 
• have heart disease
• have high blood pressure
• have a type of adrenal tumor known as pheochromocytoma
• have a history of a stroke
• have had a transient ischemic attack (TIA)
• have had bleeding in the brain
• are going to have surgery 
• have liver disease
• are taking drugs that should not be taken during treatment with Parnate 

Tell your doctor if you are breastfeeding or plan to breastfeed. It is not known if Parnate is excreted in human breast milk or if it will harm your nursing baby.

Major Depressive Disorder

Treatment of major depressive disorder without melancholia.101 102 a d e

Efficacy in major depressive disorder with melancholia (endogenous features) not established.101 a d

MAO inhibitors appear particularly effective in treatment of major depressive disorder with atypical features, although other antidepressants (e.g., SSRIs) may initially be used because of their more favorable adverse effect profile.102 e f

Because of potential for serious adverse effects and necessity of dietary restrictions, MAO inhibitors (e.g., phenelzine, tranylcypromine) generally are not used as initial therapy for major depressive disorder, but are reserved for carefully selected patients who can be closely supervised and who have depression refractory to other antidepressants (e.g., SSRIs, SNRIs, TCAs) or in whom other therapies are contraindicated.101 102 a d e f

Drugs Associated with Serotonin Syndrome

Potential pharmacologic interaction (serotonin syndrome) with serotonergic agents.101 a e o Caution generally advised.e o (See Specific Drugs and Foods under Interactions.)

Specific Drugs and Foods

• Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.101 103 104 105 a FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.101 103 104 105 a

• Risk of serious adverse effects (e.g., hypertensive reactions).101 a e Importance of promptly informing clinicians if headache or other unusual symptoms (e.g., palpitation and/or tachycardia, constriction in throat or chest, sweating, dizziness, neck stiffness, nausea or vomiting) occur.101 a e

• Importance of informing patients to avoid foods and beverages with a high tyramine content.101 a

• Importance of informing patients to avoid excessive use of caffeine in any form.101 a

• Importance of informing patients to avoid alcoholic beverages.101 a

• Risk of hypotension, faintness, and drowsiness.101 a e Importance of considering possible impaired ability to perform hazardous activities (e.g., operating machinery, driving a motor vehicle).101 a

• Importance of patients informing their clinicians and dentist that they are taking tranylcypromine.101 a

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.101 a

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal or nutritional supplements, as well as any concomitant illnesses.101 a

• Importance of informing patients of other important precautionary information.101 a (See Cautions.)

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Fever or chills.
• Chest pain or pressure.
• Very bad problems with how you act.
• Very upset stomach or throwing up.
• A heartbeat that does not feel normal.
• Sweating a lot.
• Neck stiffness.
• If bright lights bother your eyes.
• Change in eyesight, eye pain, or very bad eye irritation.
• Feeling nervous and excitable.
• Grouchy or touchy.
• Mood changes.
• Restlessness.
• Change in sex ability.
• Fast or slow heartbeat.
• Larger pupils.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Parnate is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Parnate or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Parnate. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

In general, the physician should bear in mind the possibility of a lowered margin of safety when Parnate is administered in combination with potent drugs.

1. Parnate should not be used in combination with some central nervous system depressants such as narcotics and alcohol, or with hypotensive agents. A marked potentiating effect on these classes of drugs has been reported.
2. Anti-parkinsonism drugs should be used with caution in patients receiving Parnate since severe reactions have been reported.
3. Parnate should not be used in patients with a history of liver disease or in those with abnormal liver function tests.
4. Excessive use of caffeine in any form should be avoided in patients receiving Parnate.

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 contrasting agents used before myelography. 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 disulfiram tablets. 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 WARNINGSClinical Worsening and Suicide Risk). Anyone considering the use of Parnate in a child or adolescent must balance the potential risks with the clinical need.

Substance Name

Tranylcypromine

CAS Registry Number

155-09-9

Drug Class

Antidepressants

Monoamine Oxidase Inhibitors