The P-I-E-N-O Parkinsn's List Drug Database
phenelzine / NardilTM
ANTIDEPRESSANT:
MAOI-TYPE: HIGH RISK
Description: Phenelzine is an oral, MAOI-type antidepressant. It is a derivative of hydrazine and irreversibly inhibits monoamine oxidase. It is used to treat major depression, particularly atypical depressioný, nonendogenous depressioný, double depressioný (in which the patient can have a dysthymic mood and major depression), and psychotic depressioný (in which there are prominent psychotic features), as well as obsessive-compulsive disorderý, panic disorderý, and phobic disorderý. Phenelzine was approved by the FDA in 1959.
Mechanism of Action: Phenelzine inhibits monoamine oxidase by binding to it irreversibly. Isocarboxazid and pargyline are similar; tranylcypromine binds reversibly. Depression is believed to result from dysregulation of CNS neurotransmitter systems. Antidepressant activity arises from the increased availability of monoamines, resulting from the inhibition of the enzyme monoamine oxidase (MAO). Reduction of MAO activity causes an increased concentration of neurotransmitters, such as epinephrine, norepinephrine, and dopamine, at various storage sites in the central nervous system and sympathetic nervous system.
Phenelzine is a nonselective MAOI and desensitizes ›and œadrenergic and serotonin receptors. The delay of up to 4 weeks in therapeutic response to MAOI drugs may be accounted for by alterations in receptor characteristics rather than by increased neurotransmitter concentration. MAOIs also have a variable hypotensive action, probably due to central inhibition of vasomotor centers. Inhibition of MAO in the GI tract and liver can cause systemic absorption of large amounts of tyramine, which can result in severe hypertension because of massive release of norepinephrine. MAOIs also interfere with the hepatic metabolism of many drugs.
Pharmacokinetics: Phenelzine is administered orally and is completely absorbed from the GI tract. There is insufficient evidence on distribution, and dosage is adjusted to suit patient response. Peak plasma concentrations are achieved between 2-4 hours. Onset of antidepressant action can take anywhere from 7 days to 8 weeks.
The drug is rapidly metabolized in the liver and may produce active metabolites. Excretion is mainly as metabolites in the urine. The half-life is fairly short and is unrelated to the length of enzyme inhibition, which is prolonged.
CONTRAINDICATIONS/PRECAUTIONS: Phenelzine should not be used in patients with active alcoholism. The presence of tyramine in alcohol (beer, wine, ale) can precipitate hypertensive crisis if ingested during phenelzine treatment. Alcoholic beverages, such as beer (including reducedalcohol and alcohol-free beer); wine (red and white varieties); sherry; hard liquor; or liqueurs that contain tyramine can precipitate a hypertensive reaction if consumed by patients during therapy with an MAOI. Sudden and severe hypertensive episodes can occur if foods containing high-pressor amines (e.g., tyramine) are consumed during therapy with phenelzine. Foods to avoid include: aged cheese; yeast extract; protein extract; soy sauce; fava bean or broad bean pods; smoked meats; pickled meats;, smoked poultry; pickled poultry; smoked fish (lox, smoked salmon); pickled fish (pickled herring); fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; bananas; avocados; and any over-ripe fruit. Following discontinuation of any MAOI, dietary restrictions should continue for at least 2 weeks.
Patients with hypertension, cardiac arrhythmias, cardiac disease, congestive heart failure, or cerebrovascular disease should be treated with MAOIs cautiously because of possible effects on blood pressure. Blood pressure should be monitored carefully. Hypertensive crisis is the most serious side effect of MAOIs, and if palpitations, neck stiffness, chest pains, or headaches occur, the drug should be discontinued.
Phenelzine should not be used in patients with pheochromocytoma because the tumor secretes norepinephrine that can increase blood pressure, leading to a hypertensive crisis.
Phenelzine should be used with caution in patients with hepatic disease or severe heart failure, and is not recommended for use in patients with severe hepatic disease. Hepatic precoma could occur if phenelzine is administered to patients with cirrhosis.
Phenelzine should be used with caution in patients with renal disease and is not recommended for use in conditions of severe renal impairment because the reduction in renal excretion can increase the cumulative effects of the MAOI.
Phenelzine can change the pattern of seizures and should be used with caution in cases of epilepsy or preexisting seizure disorder.
Phenelzine should be used with caution in patients with asthma or bronchitis because of possible changes in the blockade of sympathetic neurotransmission and dramatic pressor effects from œ-adrenergic bronchodilators.
Phenelzine should be used with caution in patients with diabetes mellitus because requirements of insulin or oral hypoglycemics can be changed.
Phenelzine should be used with caution in patients who have persistent, severe, or frequent headaches because they can mask possible headache associated with hypertensive reactions. Blood pressure should be routinely measured any time a patient receiving phenelzine complains of a headache.
Phenelzine should be used with caution in patients with hyperthyroidism because sensitivity to pressor amines will be further increased.
All effective antidepressants can precipitate mania in patients with major depression. The usual presentation of this switch is the sudden appearance of insomnia. The antidepressant should be held and appropriate therapy to treat the manic symptoms initiated. Therapeutic doses of lithium (and possibly carbamazepine or valproate) are effective in suppressing the switch process.
Phenelzine should be used with caution is patients with schizophrenia. Phenelzine may aggravate psychosis or cause excessive stimulation in these patients.
All antidepressants should be used with caution in depressed patients because of the possibility of suicidal ideation. Close monitoring of the patient is essential during the initial stages of therapy and phenelzine prescribed in the smallest quantity consistent with good management.
Parkinson's disease can be aggravated by phenelzine because of the drug's induction of tremor, muscle spasm, or myoclonic movement. Use of a more selective MAOI, such as selegiline, is indicated in patients with Parkinson's disease.
Phenelzine should be used with caution in the elderly because of the increased possibility of cerebrosclerosis.
Phenelzine is classified as pregnancy category C. There have been no studies carried out in humans to determine safe use during pregnancy. Phenelzine should only be used during pregnancy when benefit to the mother outweighs risk to the fetus.
It is not known whether or not phenelzine is excreted into breast milk. Many drugs are excreted into breast milk and can pose a potetnial threat to the nursing infant. This drug should be used cautiously in women who are breast-feeding.
DRUG INTERACTIONS: Phenelzine should not be used concurrently with other MAOIs (furazolidone, isocarboxazid, pargyline, procarbazine, selegiline, or tranylcypromine) because of the possibility of severe hyperpyretic or hypertensive crises, convulsions, or death. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline, paroxetine, and fluvoxamine, interact with MAOIs, producing possible confusion, seizures, and severe hypertension as well as less severe symptoms. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of therapy with any of the agents listed above, and at least 5 weeks should elapse between the discontinuation of fluoxetine therapy and commencement of MAOI therapy. This 5-week period is needed because of the long half-lives of fluoxetine and its principal metabolite norfluoxetine. For the other SSRIs (sertraline, paroxetine, and fluvoxamine), at least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of SSRI therapy, or vice versa.
Phenelzine used concomitantly with tryptophan can cause "serotonin syndrome" (presenting as agitation, restlessness, aggressive behavior, insomnia, poor concentration, headache, paresthesia, incoordination, worsening of obsessive thoughts or compulsive behaviors, nausea, abdominal cramps, diarrhea, palpitations, or chills). Discontinuation of tryptophan can resolve symptoms, although supportive care is essential.
Beverages such as beer (including reduced-ethanol and ethanol-free beer); wine (red and white varieties); sherry; hard liquor; or liqueurs that contain tyramine can precipitate a hypertensive reaction if consumed by patients during therapy with an MAOI. The following foods can precipitate sudden and severe hypertensive episodes if consumed during therapy with phenelzine: aged cheese; yeast extract; protein extract; soy sauce; fava bean or broad bean pods; smoked meats; pickled meats; smoked poultry; pickled poultry; smoked fish (lox, smoked salmon); pickled fish (pickled herring); fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; bananas; avocados; any over-ripe fruit; or foods containing high-pressor amines such as tyramine. Following discontinuation of any MAOI, dietary restrictions should continue for at least 2 weeks.
Phenelzine used concomitantly with local anesthetics containing epinephrine, levonordefrin, or cocaine can precipitate a severe hypertensive crisis because of synergistic sympathomimetic effects. Cocaine should not be used either concurrently with an MAOI drug or within 14 days of administration.
Phenelzine should be discontinued 10 days before elective surgery. Alternatively, the dosage of spinal anesthetics should be carefully adjusted to avoid potential hypotension.
Phenelzine can increase the anticholinergic effects of anticholinergics, antidyskinetics, or HA-blockers because of secondary anticholinergic effects of the MAOI. Detoxification of anticholinergics can be blocked, resulting in increased effect. Patients should report any adverse GI reactions in case paralytic ileus occurs. Concurrent use with HA-blockers is not recommended because of an increase in the intensity and prolongation of CNS-depressant and anticholinergic effects.
Phenelzine can cause a change in seizure patterns. Dose adjustment of anticonvulsants may be necessary if phenelzine therapy is added.
Phenelzine should not be used with other antidepressants including tricyclic antidepressants; SSRIs (fluoxetine, fluvoxamine, paroxetine, and sertraline); or any other antidepressant class (trazodone, amoxapine, maprotiline, or bupropion). Severe hypertensive crises as well as increased anticholinergic effects can result from concomitant use. Tricyclic antidepressants can, in some cases, be used concomitantly with MAOIs if tricyclic antidepressant therapy is in effect prior to beginning therapy with a MAOI; tricyclic antidepressants should never be added to an existing MAOI regime. Under careful monitoring of the patient for signs or symptoms of hypertension, add the MAOI gradually, starting at a low dose. Patients should observe strict adherence to the diet restrictions and should not be receiving other sympathomimetics. Most references suggest avoiding this drug interaction entirely if clomipramine or imipramine are being administered.
Phenelzine can increase the hypoglycemic response to insulin or oral hypoglycemics. Patient monitoring is required and dose adjustment may be necessary.
Phenelzine can increase serum prolactin concentrations and interfere with the effects of bromocriptine if the drugs are used concurrently.
Concomitant use of phenelzine and buspirone is not recommended because of a possible increase in blood pressure. An interval of at least 10 days is recommended between discontinuation of one drug and initiation of the other.
Phenelzine can produce severe hypertensive crises or dangerous cardiac arrhythmias when caffeine is taken concurrently. All preparations containing caffeine should be used sparingly such as tea, coffee, chocolate, cola, or "stay awake" products. Nonprescription medicines should not be taken without advice and discussion with both the patient's physician and pharmacist.
Phenelzine can react with dextromethorphan to produce excitation, hypertension, and hyperpyrexia.
Diuretics used concomitantly with MAOIs can result in increased hypotensive effects.
The pressor effects of either the MAOI or doxapram can be increased if these agents are used concurrently.
Concurrent use of phenelzine with guanadrel, guanethidine, or reserpine can produce moderate to severe hypertension due to release of catecholamines. At least 2 weeks should elapse between withdrawal of the MAOI and initiation of therapy with any of these agents.
The sedative, hypotensive, and anticholinergic effects of phenelzine can be additive with those of antipsychotics such as clozapine, haloperidol, loxapine, molindone, phenothiazines, pimozide, or thioxanthenes (such as thiothixene).
Phenelzine is not recommended for concurrent use with levodopa. The combination can produce sudden, severe hypertensive crises. Levodopa, a catecholamine precursor, in combination with an MAOI can lead to a relative catecholamine (dopamine, norepinephrine, and epinephrine) excess. An interval of 2-4 weeks is recommended between the discontinuation of the MAOI and initiation of treatment with levodopa.
Phenelzine should not be used concurrently with meperidine. Severe reactions, such as immediate excitation; sweating; rigidity; hypertension; severe respiratory depression; coma; and vasculatory collapse, possibly resulting in death, can occur. These reactions may stem from accumulation of serotonin. Meperidine should be avoided within 2-3 weeks of MAOI therapy. It is unclear if other opiate agonists interact in a similar manner.
Methyldopa used concurrently with MAOIs can produce hyperexcitability. Headaches, hypertension, and hallucinations also can occur.
Phenelzine can increase the CNS-stimulant effects of methylphenidate, which can produce a hypertensive crisis. Methylphenidate should not be used with MAOIs or within 14 days of their use.
Metrizamide used with MAOIs can increase the risk of seizure by lowering the seizure threshold. MAOIs should be discontinued at least 48 hours before myelography and not resumed until 24 hours after the procedure.
Phenylephrine in nasal or ophthalmic products can be absorbed systemically in sufficient amounts that concomitant use of an MAOI drug will potentiate its effects. The cardiac stimulant and vasopressor effects of oral sympathomimetics can be greatly increased by concurrent MAOI therapy. Medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days of their use. Patients should be warned about their possible presence in OTC drugs, such as those used for hay fever, colds, or weight-reducing, or decongestants such as ephedrine, pseudoephedrine, or phenylpropanolamine.
ADVERSE REACTIONS: Phenelzine is a potent inhibitor of monoamine oxidase, an enzyme that has wide distribution throughout the body. Administration of phenelzine can therefore be expected to produce diverse effects. Most adverse effects subside with continued dosage, or respond to dosage reduction. The development of hypertensive crisis is the most serious potential adverse effect of treatment with MAOIs. Symptoms that may be indicative of potential hypertension include sinus tachycardia or sinus bradycardia, angina, palpitations, severe headache, photophobia, mydriasis, fever, diaphoresis, nausea/vomiting, stiff or sore neck. Intracranial hemorrhage can result from increased blood pressure and may be fatal. If a hypertensive crisis develops, the MAOI should be immediately withdrawn and appropriate steps taken to reduce blood pressure. Hypertensive crises also can be precipitated by intake of foods containing tyramine or tryptophan, so patients should be warned of dietary restrictions.
Orthostatic hypotension is a common side effect of MAOIs and is most likely to occur in patients with preexisting hypertension. If hypotension is detected during routine monitoring of initial therapy with phenelzine, the dose should be increased more gradually. Dose reduction can counteract hypotensive effects, but if orthostatic hypotension persists or worsens, the MAOI should be withdrawn. Postural hypotension can be alleviated by lying down until blood pressure returns to normal. Dizziness is often worse if the patient changes positions too rapidly.
Peripheral edema, swelling of the feet and legs, may be only a transient adverse reaction to phenelzine, subsiding within a week. If persistent, then the patient needs to be monitored to ensure that SIADH is not present. If patients have a reduced cardiac reserve, then peripheral edema could progress to overt congestive heart failure.
Anticholinergic effects during therapy with phenelzine can cause a number of adverse reactions such as drowsiness, constipation, confusion, blurred vision or mydriasis, xerostomia, urinary retention, or weakness.
Sexual dysfunction, which can include orgasm dysfunction (anorgasmia or delayed orgasm), ejaculation dysfunction (retarded or no ejaculation), priapism, and possible impotence, can occur during therapy with phenelzine.
Appetite stimulation and weight gain can occur during therapy with phenelzine.
Shaking or tremor can result from action of MAOIs on the vasomotor centers. Other nervous system effects of phenelzine include myoclonia, hyperreflexia, twitching, fatigue, and insomnia (or other sleep disturbance). Nystagmus, paresthesias, euphoria and general jitteriness have been reported infrequently. Depression may obscure hypomania, which may emerge as depression is lifted. Phenelzine can also exacerbate preexisting agitation. Mania and agitation have been reported with high dosage levels of phenelzine.
Elevated hepatic enzymes have been reported during phenelzine therapy. Necrotizing hepatocellular damage secondary to MAOI therapy may be indicated by the presence of jaundice (dark urine, skin rash, yellow eyes or skin).
Hematological adverse reactions that have been reported rarely with phenelzine therapy include anemia, leukopenia, agranulocytosis and thrombocytopenia.
Abrupt discontinuation of phenelzine has been associated with an uncommon withdrawal syndrome. Symptoms become manifest within 24 to 72 hours of drug withdrawal. These symptoms, which can range from agitation to frank psychosis and convulsions, generally respond to reinstitution of therapy, followed by a gradual downward titration before discontinuation. Other withdrawal symptoms include nausea/vomiting and malaise.
PATIENT INFORMATION:
What do phenelzine tablets do?
Phenelzine (NardilTM ) is an antidepressant or mood elevator that helps to lift severe mental depression. Phenelzine belongs to a class of drugs, called monoamine oxidase inhibitors (MAOIs), that block certain enzymes in the brain. This action increases other chemicals in the brain that help fight depression. Phenelzine can interact with certain foods and other medicines to cause unpleasant side effects. You must know what foods and medicines to avoid (see below). Generic phenelzine tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take phenelzine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take phenelzine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking the tablets except on your doctor's advice.
Special precautions for use in children:
This medicine is not for children under 16 years old.
Elderly patients over age 65 years may have a stronger reaction to this medicine and should be treated with extreme caution.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is less than two hours to your next dose, take only that dose and skip the missed dose. Do not take double or extra doses.
What other medicines can interact with phenelzine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking phenelzine?
Serious side effects with phenelzine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with phenelzine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take phenelzine?
Visit your doctor for regular checks on your progress. It can take up to 4 weeks to see the full effects of phenelzine. Do not suddenly stop taking your medicine; this may make your condition worse or give you withdrawal symptoms. Ask your doctor for advice about gradually reducing your dosage. Even after you stop taking phenelzine the effects can last for at least two weeks. Continue to take all precautions and avoid all food and medicine that interact with phenelzine.
Phenelzine can interact with certain foods that contain tyramine to produce severe headaches, a rise in blood pressure, or irregular heart beat. Foods that contain significant amounts of tyramine include aged cheeses; meats and fish (especially aged, smoked, pickled, or processed such as bologna, pepperoni, salami, summer sausage); beer and ale; alcohol-free beer; wine (especially red); sherry; hard liquor; liqueurs; avocados; bananas; figs; raisins; soy sauce; miso soup; yeast/protein extracts; bean curd; fava or broad bean pods; or any over-ripe fruit. Ask your doctor, pharmacist, or nutritionist for a complete listing of tyramine-containing foods. Also, avoid drinks containing caffeine, such as tea, coffee, chocolate, or cola.
Call your doctor as soon as you can if you get frequent headaches or have palpitations.
You may get drowsy, dizzy or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how phenelzine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness or drowsiness; avoid alcoholic drinks.
Phenelzine can make your mouth dry. Chewing sugarless gum, sucking hard candy and drinking plenty of water will help.
Do not treat yourself for coughs, colds, or allergies without asking your doctor or pharmacist for advice. Some ingredients may increase possible side effects.
You should stop taking phenelzine at least 10 days before elective surgery; tell your doctor or dentist that you have been taking phenelzine.
If you are diabetic there is a possibility that phenelzine may affect your blood sugar. Ask your doctor for advice if there is any change in your blood or urine sugar tests.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Keep container tightly closed. Throw away any unused medicine after the expiration date.
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