Phenelzine

Clinical Worsening And Suicide Risk

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 (ages 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 analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included 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 within age strata 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.

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 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 health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for Nardil should be written for the smallest quantity of tablets 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 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 Nardil is not approved for use in treating bipolar depression.

It should be noted that NARDIL is not approved for use in treating any indications in the pediatric population.

The most serious reactions to NARDIL involve changes in blood pressure.

Hypertensive Crises

The most important reaction associated with NARDIL administration 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, vomiting, sweating (sometimes with fever and sometimes with cold, clammy skin), dilated pupils, and photophobia. Either tachycardia or bradycardia may be present and can be associated with constricting chest pain.

NOTE: Intracranial bleeding has been reported in association with the increase in blood pressure.

Blood pressure should be observed frequently to detect evidence of any pressor response in all patients receiving NARDIL. Therapy should be discontinued immediately upon the occurrence of palpitation or frequent headaches during therapy.

Recommended Treatment In Hypertensive Crisis

If a hypertensive crisis occurs, NARDIL should be discontinued immediately and therapy to lower blood pressure should be instituted immediately. On the basis of present evidence, phentolamine is recommended. (The dosage reported for phentolamine is 5 mg intravenously.) 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.

Warning To The Patient

All patients should be warned that the following foods, beverages, and medications must be avoided while taking NARDIL, and for two weeks after discontinuing use.

Meat and Fish

Pickled herring
Liver
Dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna)

Broad bean pods (fava bean pods)
Sauerkraut

Cheese (cottage cheese and cream cheese are allowed)
Yogurt

Beer and wine
Alcohol-free and reduced-alcohol beer and wine products

Yeast extract (including brewer's yeast in large quantities)
Meat extract
Excessive amounts of chocolate and caffeine

Also, any spoiled or improperly refrigerated, handled, or stored protein-rich foods such as meats, fish, and dairy products, including foods that may have undergone protein changes by aging, pickling, fermentation, or smoking to improve flavor should be avoided.

Cold and cough preparations (including those containing dextromethorphan)
Nasal decongestants (tablets, drops, or spray)
Hay-fever medications
Sinus medications
Asthma inhalant medications
Antiappetite medicines
Weight-reducing preparations
"Pep" pills
L-tryptophan containing preparations

Also, certain prescription drugs should be avoided. Therefore, patients under the care of another physician or dentist should inform him/her that they are taking NARDIL.

Patients should be warned that the use of the above foods, beverages, or medications may cause a reaction characterized by headache and other serious symptoms due to a rise in blood pressure, with the exception of dextromethorphan which may cause reactions similar to those seen with meperidine. Also, there has been a report of an interaction between NARDIL and dextromethorphan (ingested as a lozenge) causing drowsiness and bizarre behavior.

Patients should be instructed to report promptly the occurrence of headache or other unusual symptoms.

If the decision is made to administer NARDIL concurrently with other antidepressant drugs, or within less than 10 days after discontinuation of antidepressant therapy, the patient should be cautioned by the physician regarding the possibility of adverse drug interaction.

nortriptyline hydrochloride
amitriptyline hydrochloride
perphenazine and amitriptyline hydrochloride
clomipramine hydrochloride
desipramine hydrochloride
imipramine hydrochloride
doxepin
carbamazepine
cyclobenzaprine HCl
amoxapine
maprotiline HCl
trimipramine maleate
protriptyline HCl
mirtazapine

NARDIL should be used with caution in combination with antihypertensive drugs, including thiazide diuretics and β-blockers, since exaggerated hypotensive effects may result.

Use In Pregnancy

The safe use of NARDIL during pregnancy or lactation has not been established. The potential benefit of this drug, if used during pregnancy, lactation, or in women of childbearing age, should be weighed against the possible hazard to the mother or fetus.

Doses of NARDIL in pregnant mice well exceeding the maximum recommended human dose have caused a significant decrease in the number of viable offspring per mouse. In addition, the growth of young dogs and rats has been retarded by doses exceeding the maximum human dose.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Take phenelzine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

phenelzine should come with a medication guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Dosing

The dose of phenelzine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of phenelzine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For depression:
    • Adults—At first, 15 milligrams (mg) three times a day. Your doctor may adjust your dose as needed. However, the dose is usually not more than 90 mg per day.
    • Children—Use is not recommended.

Missed Dose

If you miss a dose of phenelzine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to check for any unwanted effects.

You will also need to have your blood pressure measured before starting phenelzine and while you are using it. If you notice any change to your recommended blood pressure, call your doctor right away. If you have questions about this, talk to your doctor.

When taken with certain foods, drinks, or other medicines, phenelzine can cause very dangerous reactions, such as sudden high blood pressure (also called hypertensive crisis). To avoid such reactions, follow these rules of caution:

• Do not eat foods that have dopamine and a high tyramine content (most common in foods that are aged or fermented to increase their flavor), such as cheese (especially strong or aged kinds), caviar, sour cream, liver, canned figs, soy sauce, sauerkraut, fava beans, yeasts, and yogurt. Avoid smoked or pickled meat, poultry, or fish, such as sausage, pepperoni, salami, anchovies, or herring. Do not eat dried fruit (such as raisins), bananas, avocados, raspberries, or very ripe fruit.
• Do not drink alcoholic beverages. This includes Chianti wine, sherry, beer, non-alcohol or low alcohol beer and wine, and liqueurs.
• Do not eat or drink too much caffeine. Caffeine can be found in coffee, cola, chocolate, tea, and many other foods and drinks. Ask your doctor how much caffeine is safe to use.

Phenelzine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you or your caregiver notice any of these adverse effects, tell your doctor right away.

Call your doctor or hospital emergency room right away if you have a severe headache, stiff or sore neck, chest pains, fast heartbeat, sweating, dizziness, or nausea and vomiting while you are taking phenelzine. These may be symptoms of a serious side effect called hypertensive crisis.

phenelzine may cause blurred vision or make some people drowsy or less alert than they are normally. Make sure you know how you react to phenelzine before you drive, use machines, or do anything else that could be dangerous if you are unable to see well or not alert.

phenelzine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using phenelzine.

Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help. When you get up from lying down, sit on the edge of the bed with your feet dangling for 1 or 2 minutes, then stand up slowly. If the problem continues or gets worse, check with your doctor.

Do not stop taking phenelzine without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely.

Before having any kind of surgery, dental treatment, or emergency treatment, tell the medical doctor or dentist in charge that you are using phenelzine or have used it within the past 10 days. Taking phenelzine together with medicines that are used during surgery, dental, or emergency treatments may increase the risk of serious side effects.

Your doctor may want you to carry an identification card stating that you are using phenelzine.

phenelzine may affect blood sugar levels. If you are diabetic, be especially careful in testing for sugar in your blood or urine. If you have any questions about this, check with your doctor.

After you stop using phenelzine, you must continue to exercise caution for at least 2 weeks with your foods, drinks, and other medicines, since these items may continue to react with phenelzine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Chills
• cold sweats
• confusion
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
• overactive reflexes
• shakiness in the legs, arms, hands, or feet
• sudden jerky movements of the body
• swelling
• trembling or shaking of the hands or feet

• Abdominal or stomach pain
• actions that are out of control
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in consciousness
• clay-colored stools
• dark urine
• decrease in frequency of urination
• decrease in urine volume
• difficult or troubled breathing
• difficulty in passing urine (dribbling)
• disorganized thoughts
• dizziness
• drowsiness
• false or unusual sense of well-being
• fast, pounding, or irregular heartbeat or pulse
• fear or nervousness
• fever
• general feeling of discomfort, illness, or weakness
• headache
• high blood pressure
• increased sweating
• irregular, fast or slow, or shallow breathing
• irritability
• itching
• lack of emotion or feelings
• loss of appetite
• loss of consciousness
• loud or fast speech
• low blood pressure
• muscle tremors
• muscle twitching
• nausea or vomiting
• nervousness
• no emotion or expression in speech
• painful urination
• pale or blue lips, fingernails, or skin
• rapid, deep, or shallow breathing
• rash
• restlessness
• seeing or hearing things that are not there
• seizures
• shakiness and unsteady walk
• shortness of breath
• slow or irregular heartbeat
• stomach cramps
• sweating
• swelling of the feet or lower legs
• talking, feeling, and acting with excitement
• uncontrolled eye movements
• unpleasant breath odor
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual paleness
• unusual tiredness or weakness
• vomiting of blood
• weakness
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Constipation
• decreased interest in sexual intercourse
• diarrhea
• dry mouth
• inability to have or keep an erection
• indigestion
• loss in sexual ability, desire, drive, or performance
• loss of appetite
• not able to have an orgasm
• passing of gas
• sleeplessness
• stomach pain, fullness, or discomfort
• trouble sleeping
• unable to sleep
• unusually deep sleep
• unusually long duration of sleep
• weight gain

• Blindness
• blurred vision
• decreased vision
• eye pain
• redness, swelling, or soreness of the tongue
• tearing

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• 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 phenelzine 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 phenelzine 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 phenelzine. 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

Phenelzine sulfate is a potent inhibitor of monoamine oxidase. Because this enzyme is widely distributed throughout the body, diverse pharmacologic effects can be expected to occur. When they occur, such effects tend to be mild or moderate in severity (see below), often subside as treatment continues, and can be minimized by adjusting dosage; rarely is it necessary to institute counteracting measures or to discontinue Phenelzine sulfate.

Common side effects include:

Nervous SystemDizziness, headache, drowsiness, sleep disturbances (including insomnia and hypersomnia), fatigue, weakness, tremors, twitching, myoclonic movements, hyperreflexia.

GastrointestinalConstipation, dry mouth, gastrointestinal disturbances, elevated serum transaminases (without accompanying signs and symptoms).

MetabolicWeight gain.

CardiovascularPostural hypotension, edema.

GenitourinarySexual disturbances, eg, anorgasmia and ejaculatory disturbances and impotence.

Less common mild to moderate side effects (some of which have been reported in a single patient or by a single physician) include:

Nervous SystemJitteriness, palilalia, euphoria, nystagmus, paresthesias.

GenitourinaryUrinary retention.

MetabolicHypernatremia.

DermatologicPruritus, skin rash, sweating.

Special SensesBlurred vision, glaucoma.

Although reported less frequently, and sometimes only once, additional severe side effects include:

Nervous SystemAtaxia, shock-like coma, toxic delirium, manic reaction, convulsions, acute anxiety reaction, precipitation of schizophrenia, transient respiratory and cardiovascular depression following ECT.

GastrointestinalTo date, fatal progressive necrotizing hepatocellular damage has been reported in very few patients. Reversible jaundice.

HematologicLeukopenia.

ImmunologicLupus-like syndrome

MetabolicHypermetabolic syndrome (which may include, but is not limited to, hyperpyrexia, tachycardia, tachypnea, muscular rigidity, elevated CK levels, metabolic acidosis, hypoxia, coma and may resemble an overdose).

RespiratoryEdema of the glottis.

GeneralFever associated with increased muscle tone.

Withdrawal may be associated with nausea, vomiting, and malaise.

An uncommon withdrawal syndrome following abrupt withdrawal of Phenelzine sulfate has been infrequently reported. Signs and symptoms of this syndrome generally commence 24 to 72 hours after drug discontinuation and may range from vivid nightmares with agitation to frank psychosis and convulsions. This syndrome generally responds to reinstitution of low-dose Phenelzine sulfate therapy followed by cautious downward titration and discontinuation.

Each Phenelzine sulfate tablet is orange, biconvex, film-coated, and engraved with "P-D 270" and contains Phenelzine sulfate equivalent to 15 mg of Phenelzine base.

NDC 59762-0119-1. Bottle of 60

Storage

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

Rx only

LAB-0456-1.0

February 2011

• Phenelzine Sulfate

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Nardil: 15 mg

Generic: 15 mg

• Antidepressant, Monoamine Oxidase Inhibitor

Thought to act by increasing endogenous concentrations of norepinephrine, dopamine, and serotonin through inhibition of the enzyme (monoamine oxidase) responsible for the breakdown of these neurotransmitters (Wimbiscus 2011).

Absorption

Well absorbed

Metabolism

Oxidized via monoamine oxidase (primary pathway) and acetylation (minor pathway)

Excretion

Urine (73% as metabolites)

Hypersensitivity to phenelzine or any component of the formulation; congestive heart failure; pheochromocytoma; abnormal liver function tests or history of hepatic disease; renal disease or severe renal impairment

Concurrent use of bupropion, buspirone, caffeine (excessive use), CNS depressants (eg, alcohol), cocaine or local anesthesia containing sympathomimetic vasoconstrictors, dextromethorphan, elective surgery requiring general anesthesia (discontinue phenelzine ≥10 days prior to elective surgery), guanethidine, meperidine, MAO inhibitors or dibenzazepine derivatives (eg, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline, doxepin, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, perphenazine, trimipramine), ophthalmic agents (eg, apraclonidine), SSRIs or SNRIs, spinal anesthesia, sympathomimetics (including amphetamines, methylphenidate, dopamine, norepinephrine) or related compounds (levodopa, methyldopa, phenylalanine, tryptophan, tyrosine), or foods high in tyramine content (or within 2 weeks of stopping treatment).

Bupropion: At least 14 days should elapse between phenelzine discontinuation and bupropion initiation.

Buspirone: At least 14 days (10 days in the Canadian labeling) should elapse between phenelzine discontinuation and buspirone initiation.

SSRIs or SNRIs: At least 2 weeks should elapse between the discontinuation of SNRIs and SSRIs and the initiation of phenelzine. At least 5 weeks should elapse between the discontinuation of fluoxetine and the initiation of phenelzine. At least 2 weeks (10 days in the Canadian labeling) should elapse between the discontinuation of phenelzine and the initiation of SNRIs and SSRIs.

At least 2 weeks should elapse between the discontinuation of phenelzine and the initiation of the following agents: Serotoninergic agents (including SNRIs, SSRIs, fluoxetine, and tricyclics), bupropion, buspirone, and other antidepressants.

General anesthesia, spinal anesthesia (hypotension may be exaggerated). Use caution with local anesthetics containing sympathomimetic agents. Phenelzine should be discontinued at least 10 days prior to elective surgery.

Foods high in tyramine or dopamine content; foods and/or supplements containing tyrosine, phenylalanine, tryptophan, or caffeine

Documentation of allergenic cross-reactivity for monoamine oxidase inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with reserpine

Store at 15°C to 30°C (59°F to 86°F).

Canadian labeling: Protect from heat and moisture.

Frequency not defined.

Cardiovascular: Edema, orthostatic hypotension

Central nervous system: Anxiety (acute), ataxia, cardiac insufficiency (following ECT; transient), coma, delirium, dizziness, drowsiness, euphoria, fatigue, headache, hyperreflexia, hypersomnia, insomnia, mania, myoclonus, paresthesia, schizophrenia, seizure, twitching, withdrawal syndrome (nausea, vomiting, malaise)

Dermatologic: Diaphoresis, pruritus, skin rash

Endocrine & metabolic: Hypernatremia, weight gain

Gastrointestinal: Constipation, glottis edema, xerostomia

Genitourinary: Sexual disorder (anorgasmia, ejaculatory disorder, impotence), urinary retention

Hematologic & oncologic: Leukopenia

Hepatic: Increased serum transaminases, jaundice

Neuromuscular & skeletal: Lupus-like syndrome, tremor, weakness

Ophthalmic: Blurred vision, glaucoma, nystagmus

Respiratory: Respiratory depression (following ECT; transient)

Miscellaneous: Fever

<1% (Limited to important or life-threatening): Hepatic necrosis

Major psychiatric warnings:

• Suicidal thinking/behavior: [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1-2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription.Phenelzine is not FDA approved for the treatment of depression in children ≤18 years of age.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Hypertensive crisis: Cases of hypertensive crisis (sometimes fatal) have occurred; symptoms include occipital headache which may radiate frontally, palpitations, nausea/vomiting, neck stiffness/soreness, photophobia, and sweating. Tachycardia and bradycardia may be present, and associated constricting chest pain and dilated pupils may occur. Monitor blood pressure closely in all patients; discontinue treatment immediately upon occurrence of palpitations or frequent headaches. May occur with foods/supplements high in tyramine, tryptophan, dopamine, phenylalanine, or tyrosine content. Treatment with phentolamine is recommended for hypertensive crisis.

• Hypotension: May cause postural hypotension and may result in syncope; use with caution in patients at risk of this effect, patients with preexisting hypertension or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Increase dosage more gradually in patients showing a tendency toward hypotension.

• Intracranial bleeding: Intracranial bleeding has been reported in association with the increase in blood pressure.

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes mellitus; sensitization to the effects of insulin may occur, monitor blood glucose closely.

• Glaucoma: Glaucoma: Use with caution in patients with angle-closure glaucoma

• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Avoid monotherapy in patients with bipolar disorder. Patients presenting with depressive symptoms should be screened for bipolar disorder. Phenelzine is not FDA approved for the treatment of bipolar depression.

• Seizure disorder: Use with caution in patients at risk for seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.

• Thyroid dysfunction: Use with caution in patients with hyperthyroidism.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: The MAO inhibitors are effective and generally well-tolerated by older patients. It is the potential interactions with tyramine or tryptophan-containing foods and other drugs, and their effects on blood pressure that have limited their use (Volz 1998).

• Surgical patients: According to the manufacturer, phenelzine use within 10 days prior to elective surgery is contraindicated. The decision to continue or withhold MAO inhibitors must be done in collaboration with the patient's psychiatrist. Currently, an MAO-safe anesthetic technique which excludes the use of meperidine and indirect-acting adrenergic agonists is recommended for patients requiring continued MAO inhibitor therapy (Huyse 2006).

Other warnings/precautions:

• Appropriate use: Phenelzine is not generally considered a first-line agent for the treatment of depression; phenelzine is typically used in patients who have failed to respond to other treatments. There is less conclusive evidence of the usefulness of phenelzine in severely depressed patients with endogenous features.

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. More severe symptoms have also been associated with MAO inhibitors. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2-5 days after treatment discontinuation and last 7-14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).

• Myelography: Discontinue at least 48 hours prior to myelography; do not resume therapy until at least 24 hours after procedure.

• Pyridoxine deficiency: Pyridoxine deficiency has occurred; symptoms include numbness and edema of hands; may respond to supplementation (Stewart 1984).

Applies to phenelzine: oral tablet

Along with its needed effects, phenelzine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking phenelzine:

• Chills
• cold sweats
• confusion
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
• overactive reflexes
• shakiness in the legs, arms, hands, or feet
• sudden jerky movements of the body
• swelling
• trembling or shaking of the hands or feet

• Abdominal or stomach pain
• actions that are out of control
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in consciousness
• clay-colored stools
• dark urine
• decrease in frequency of urination
• decrease in urine volume
• difficult or troubled breathing
• difficulty in passing urine (dribbling)
• disorganized thoughts
• dizziness
• drowsiness
• false or unusual sense of well-being
• fast, pounding, or irregular heartbeat or pulse
• fear or nervousness
• fever
• general feeling of discomfort, illness, or weakness
• headache
• high blood pressure
• increased sweating
• irregular, fast or slow, or shallow breathing
• irritability
• itching
• lack of emotion or feelings
• loss of appetite
• loss of consciousness
• loud or fast speech
• low blood pressure
• muscle tremors
• muscle twitching
• nausea or vomiting
• nervousness
• no emotion or expression in speech
• painful urination
• pale or blue lips, fingernails, or skin
• rapid, deep, or shallow breathing
• rash
• restlessness
• seeing or hearing things that are not there
• seizures
• shakiness and unsteady walk
• shortness of breath
• slow or irregular heartbeat
• stomach cramps
• sweating
• swelling of the feet or lower legs
• talking, feeling, and acting with excitement
• uncontrolled eye movements
• unpleasant breath odor
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual paleness
• unusual tiredness or weakness
• vomiting of blood
• weakness
• yellow eyes or skin

Some side effects of phenelzine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Constipation
• decreased interest in sexual intercourse
• diarrhea
• dry mouth
• inability to have or keep an erection
• indigestion
• loss in sexual ability, desire, drive, or performance
• loss of appetite
• not able to have an orgasm
• passing of gas
• sleeplessness
• stomach pain, fullness, or discomfort
• trouble sleeping
• unable to sleep
• unusually deep sleep
• unusually long duration of sleep
• weight gain

• Blindness
• blurred vision
• decreased vision
• eye pain
• redness, swelling, or soreness of the tongue
• tearing

Initial dose: 15 mg, orally, 3 times a day
Early phase treatment: Increase to at least 60 mg per day fairly rapidly, as tolerated
-90 mg per day may be needed for sufficient MAO inhibition
-Clinical response may not be seen until at least 4 weeks at 60 mg per day dosing
Maintenance dose: After maximal benefit is achieved, reduce dose slowly over several weeks.
-Maintenance dose may be as low as 15 mg once a day or 15 mg every other day
Duration of therapy: As long as required

Comments:
-This drug should rarely be the first antidepressant used; it is more suitable for patients unresponsive to more commonly used medications.
-This drug is effective in depressed patients characterized as atypical, nonendogenous, or neurotic, who often have mixed anxiety and depression and phobic or hypochondriacal features.
-Evidence of usefulness in severely depressed patients with endogenous features is less conclusive.