Phenelzine

136.19

136.19

200-117-9

O408N561GF

DTXSID2041094

Liquid

N06AF03|N - Nervous system

2928000090

38

1.1

Solid

1.0161 g/cm³ @ Temp: 20 °C

<25 °C

74 °C

143.7±25.1 °C

1.550

1.11e+01 g/L

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. Protect from heat.

4.85X10-2 mm Hg at 25 deg C (est)

LD50 oral in mouse: 130mg/kg

6.5-8

Henry's Law constant = 3.39X10-9 atm-cu m/mol at 25 °C (est)

6.5-8

White powder; soluble in water /Phenelzine acid sulfate/|Hydroxyl radical reaction rate constant = 7.97X10-11 cu cm/molec-sec at 25 °C (est)

IRRITANT

Xi

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Place material in a thick plastic hazardous waste disposal bag or leakproof container and label it CAUTION: HAZARDOUS CHEMICAL WASTE. Dispose of waste in accordance with all applicable Federal, State and local laws.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including phenelzine sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Engineering controls such as exhaust ventilation are recommended.|Respiratory Protection: Use a NIOSH approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used. Gloves: Chemically compatible. Eye Protection: Safety goggles or glasses. Protective Clothing: Protect exposed skin.

This material is assumed to be combustible.

Water spray, dry chemical, carbon dioxide or foam as appropriate for surrounding fire and materials.|As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.

Wear approved respiratory protection, chemically compatible gloves and protective clothing. Wipe up spillage or collect spillage using a high efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.

As with all dry powders it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.|Avoid exposure to heat and moisture.

Phenelzine, as must of the monoamine oxidase inhibitors, can cause transient, mild and asymptomatic aminotransferase elevations. It has also been reported to be associated with cases of liver injury after 1-3 months of treatment.

Phenelzine, like most monoamine oxidase inhibitors, can cause transient serum aminotransferase elevations in a proportion of patients. These elevations are usually mild, asymptomatic and self-limited and do not require dose modification. Phenelzine has also been associated with cases of acute, clinically apparent liver injury. The liver injury associated with MAO inhibitors typically arises 1 to 3 months after starting therapy and presents with a hepatocellular pattern of serum enzyme elevations. The acute hepatitis-like syndrome can be severe and even fatal. Cholestatic liver injury due to phenelzine has also been described (Case 1). Immunoallergic features (rash, fever, eosinophilia) are uncommon as is autoantibody formation. While few cases of phenelzine liver injury have been published, instances of severe jaundice and fatalities due to liver injury have been reported to the FDA and the sponsor.

MAO inhibitors, including Nardil, are contraindicated in patients receiving guanethidine.|Patients taking Nardil should not undergo elective surgery requiring general anesthesia. Also, they should not be given cocaine or local anesthesia containing sympathomimetic vasoconstrictors. The possible combined hypotensive effects of Nardil and spinal anesthesia should be kept in mind. Nardil should be discontinued at least 10 days prior to elective surgery.|The concurrent administration of an MAO inhibitor and bupropion hydrochloride is contraindicated. At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion hydrochloride. /MAO inhibitors/|The combination of MAO inhibitors and tryptophan has been reported to cause behavioral and neurologic syndromes including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperreflexia, shivering, ocular oscillations, and Babinski signs. /MAO inhibitors/|For more Interactions (Complete) data for Phenelzine (9 total), please visit the HSDB record page.

LD50 Mouse iv 160 mg/kg body weight|LD50 Mouse oral 160 mg/kg body weight|LD50 Mouse ip 135 mg/kg body weight|LD50 Rat oral 210 mg/kg body weight

Because the effect of Nardil on the convulsive threshold may be variable, adequate precautions should be taken when treating epileptic patients.|Nardil should not be used in patients who are hypersensitive to the drug or its ingredients, with pheochromocytoma, congestive heart failure, severe renal impairment or renal disease, a history of liver disease, or abnormal liver function tests.|Nardil should be used with caution in diabetes mellitus; increased insulin sensitivity may occur. Requirements for insulin or oral hypoglycemics may be decreased.|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.|Nardil may cause excessive stimulation in schizophrenic patients; in manic-depressive states it may result in a swing from a depressive to a manic phase.

Unchanged phenelzine presents a high protein binding which reduced its bioavailability.

Phenelzine's production and administration as an antidepressant(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 900(SRC), determined from a structure estimation method(2), indicates that phenelzine is expected to have low mobility in soil(SRC). Volatilization of phenelzine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.4X10-9 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Phenelzine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.9X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2013).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 900(SRC), determined from a structure estimation method(2), indicates that phenelzine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 3.4X10-9 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 0.97(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2013).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), phenelzine, which has an estimated vapor pressure of 4.8X10-2 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase phenelzine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 0.13 days(SRC), calculated from its rate constant of 7.8X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Phenelzine contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of phenelzine with photochemically-produced hydroxyl radicals has been estimated as 7.8X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 0.13 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Phenelzine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Phenelzine contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for phenelzine(SRC), using an estimated log Kow of 0.97(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of phenelzine can be estimated to be 900(SRC). According to a classification scheme(2), this estimated Koc value suggests that phenelzine is expected to have low mobility in soil.

The Henry's Law constant for phenelzine is estimated as 3.4X10-9 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that phenelzine is expected to be essentially nonvolatile from water and moist soil surfaces(2). Phenelzine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.9X10-2 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to phenelzine may occur through inhalation and dermal contact with this compound at workplaces where phenelzine is produced or used. Exposure to phenelzine among the general population may be limited to those administered the drug. (SRC)

Phenelzine is indicated for the treatment of nonendogenous, neurotic or atypical depression for patients that do not tolerate other forms of therapy. Atypical depression has a high prevalence rate, starts in early life, tends to last longer, is more likely to occur in people with bipolar disorder, has a high comorbidity with anxiety disorder and carries more risk of suicidal behavior. It is important to specify the atypical feature to predict the clinical course of depression and hence generate the best treatment and service. The featuring symptoms of the atypical feature include mood reactivity, two or more of this symptoms: 1) increased appetite, 2) increased sleep, 3) leaden paralysis and 4) interpersonal rejection sensitivity and should not have melancholic or catatonic features of depression. Neurotic depression is a depression of an emotionally unstable person. It is a secondary condition to major personality disorder, neuroses and drug use disorders. Likewise, a primary depression with a family history of depression spectrum disease would fit in this category. A nonendogenous depression is characterized by a disturbance in mood and general outlook. The physical symptoms tend to be less severe and it often occurs in response to stressful life events that keep occurring over a large period of time generating a continuous stress in the daily living.|FDA Label

Phenelzine is a monoamine oxidase inhibitor (MAO inhibitor) used in therapy of moderate-to-severe depression. Phenelzine therapy is associated with rare instances of clinically apparent acute liver injury.

Antidepressant Agents

Antidepressive Agents, Monoamine Oxidase Inhibitors|Phenelzine is used in the treatment of major depressive disorder. /Included in US product label/|Phenelzine has been used with some success in the management of bulimia nervosa. /NOT included in US product label/|Nardil should rarely be the first antidepressant drug used. Rather, it is more suitable for use with patients who have failed to respond to the drugs more commonly used for these conditions.|Nardil has been found to be effective in depressed patients clinically characterized as "atypical," "nonendogenous," or "neurotic." These patients often have mixed anxiety and depression and phobic or hypochondriacal features. There is less conclusive evidence of its usefulness with severely depressed patients with endogenous features.

/BOXED WARNING/ Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of Nardil or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Nardil is not approved for use in pediatric patients.|Safety and efficacy of phenelzine in pediatric patients have not been established. The US Food and Drug Administration (FDA) has determined that antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders. However, FDA also states that depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide. Anyone considering the use of phenelzine in a child or adolescent for any clinical use must balance the potential risk of therapy with the clinical need.|Phenelzine shares the toxic potentials of other MAO inhibitors, and the usual precautions and contraindications associated with these drugs should be observed. Patients should be fully advised about the risks, especially hypertensive crisis and suicidal thinking and behavior (suicidality), associated with MAO inhibitor therapy.|Nardil should not be used in patients who are hypersensitive to the drug or its ingredients, with pheochromocytoma, congestive heart failure, severe renal impairment or renal disease, a history of liver disease, or abnormal liver function tests.|For more Drug Warnings (Complete) data for Phenelzine (19 total), please visit the HSDB record page.

The elimination of monoamine oxidase by phenelzine results in the elevation of brain amines such as 2-phenylethylamine which is a metabolite of phenelzine. These amines have then marked effects on the uptake and release of catecholamines and serotonin in nerve endings. Phenelzine is shown to elevate brain levels of the gamma-aminobutyric acid (GABA) and alanine (ALA) as well as to inhibit the activity of the transaminases that normally metabolize these amino acids. In preclinical studies, it has been shown to be neuroprotective in cerebral ischemia.

A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414) (See all compounds classified as Monoamine Oxidase Inhibitors.)|Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. (See all compounds classified as Antidepressive Agents.)

Phenelzine is rapidly absorbed from the gastrointestinal tract. The decay of the drug action is not dependent on the pharmacokinetic parameters but on the rate of protein synthesis which restores the functional levels of monoamine oxidase. The mean Cmax is 19.8 ng/ml and it occurs after 43 minutes of dose administration.|The elimination of the administered dose is mainly composed of the phenelzine metabolites, phenylacetic acid and parahydroxyphenylacetic acid that constitute 79% of the dose found in the urine in the first 96 hours.|The volume of distribution of phenelzine is hard to determine as drugs from this kind penetrate the CNS very well into the tissue where their activity is desired.|Following ip injection of 2.5 mg/kg bw phenelzine-1-(14)C sulfate to rats, 62% of the dose was recovered in the urine within 24 hours.|Following a single 30 mg dose of Nardil (2 X 15 mg tablets), a mean peak plasma concentration (Cmax) of 19.8 ng/mL occurred at a time (Tmax) of 43 minutes post dose.|Phenelzine is readily absorbed from the gastrointestinal tract. There is little excretion in the urine.

For the metabolic studies, it is assumed that phenelzine is acetylated. Some of the metabolites of phenelzine are phenylacetic acid, 2-phenylethylamine and 4-hydroxyphenylacetic acid as major metabolites and N-acetyl-phenelzine as a minor metabolite.|Nardil is extensively metabolized, primarily by oxidation via monoamine oxidase. After oral administration of (13)C6-phenelzine, 73% of the administered dose was recovered in urine as phenylacetic acid and parahydroxyphenylacetic acid within 96 hours. Acetylation to N2-acetylphenelzine is a minor pathway.|Following ip injection of 2.5 mg/kg bw phenelzine-1-(14)C sulfate to rats, 62% of the dose was recovered in the urine within 24 hours. The major excretion product was phenylacetic acid, which is also a metabolite of phenelzine in mice. The first enzyme involved in this elimination process is monoamine oxidase.

After administration phenelzine presents a very short half-life of 11.6 hours in humans.|The mean apparent half-life, estimated from urinary excretion data in patients who received oral doses of 30 mg thrice daily, was 0.87 hours following the initial dose and 3.11 hours after 13 days of treatment.|The mean elimination half-life after a single 30 mg dose is 11.6 hours.

The basic mechanism of action of phenelzine acts as an inhibitor and substrate of monoamine oxidase which subsequently causes an elevation in brain levels of catecholamines and serotonin. It also presents a similar structure to amphetamine which explains the effect on the uptake and release of dopamine, noradrenaline, and serotonin. Phenelzine has been reported to inhibit tyrosine aminotransferase, aromatic amino acid decarboxylase, and dopamine B-hydroxylase.|The antidepressant phenelzine is a monoamine oxidase inhibitor known to inhibit various other enzymes, among them semicarbazide-sensitive amine oxidase (currently named primary amine oxidase: SSAO/PrAO), absent from neurones but abundant in adipocytes. It has been reported that phenelzine inhibits adipocyte differentiation of cultured preadipocytes. To further explore the involved mechanisms, our aim was to study in vitro the acute effects of phenelzine on de novo lipogenesis in mature fat cells. Therefore, glucose uptake and incorporation into lipid were measured in mouse adipocytes in response to phenelzine, other hydrazine-based SSAO/PrAO-inhibitors, and reference agents. None of the inhibitors was able to impair the sevenfold activation of 2-deoxyglucose uptake induced by insulin. Phenelzine did not hamper the effect of lower doses of insulin. However, insulin-stimulated glucose incorporation into lipids was dose-dependently inhibited by phenelzine and pentamidine, but not by semicarbazide or BTT2052. In contrast, all these SSAO/PrAO inhibitors abolished the transport and lipogenesis stimulation induced by benzylamine. These data indicate that phenelzine does not inhibit glucose transport, the first step of lipogenesis, but inhibits at 100 uM the intracellular triacylglycerol assembly, consistently with its long-term anti-adipogenic effect and such rapid action was not found with all the hydrazine derivatives tested. Therefore, the alterations of body weight control consecutive to the use of this antidepressant drug might be not only related to central effects on food intake/energy expenditure, but could also depend on its direct action in adipocytes. Nonetheless, phenelzine antilipogenic action is not merely dependent on SSAO/PrAO inhibition.|Phenelzine (PZ) is a scavenger of the lipid peroxidation (LP)-derived reactive aldehyde 4-hydroxynonenal (4-HNE) due to its hydrazine functional group, which can covalently react with 4-HNE. In this study, /the researchers/ first examined the ability of PZ to prevent the respiratory depressant effects of 4-HNE on normal isolated brain cortical mitochondria. Second, in rats subjected to controlled cortical impact traumatic brain injury (CCI-TBI), /the researchers/ evaluated PZ (10 mg/kg subcutaneously at 15 minutes after CCI-TBI) to attenuate 3-hour post-TBI mitochondrial respiratory dysfunction, and in separate animals, to improve cortical tissue sparing at 14 days. While 4-HNE exposure inhibited mitochondrial complex I and II respiration in a concentration-dependent manner, pretreatment with equimolar concentrations of PZ antagonized these effects. Western blot analysis demonstrated a PZ decrease in 4-HNE in mitochondrial proteins. Mitochondria isolated from peri-contusional brain tissue of CCI-TBI rats treated with vehicle at 15 minutes after injury showed a 37% decrease in the respiratory control ratio (RCR) relative to noninjured mitochondria. In PZ-treated rats, RCR suppression was prevented (P<0.05 versus vehicle). In another cohort, PZ administration increased spared cortical tissue from 86% to 97% (P<0.03). These results suggest that PZ's neuroprotective effect is due to mitochondrial protection by scavenging of LP-derived 4-HNE.|Phenelzine is a monoamine oxidase (MAO) inhibitor used in treatment of depression and anxiety disorders. It also elevates brain levels of gamma-aminobutyric acid (GABA) and inhibits primary amine oxidase (PrAO), an enzyme whose activity and/or expression has been reported to be increased in diabetes mellitus, Alzheimer's disease and cardiovascular disorders. Phenelzine is not only an inhibitor of, but also a substrate for, MAO and it has been suggested that an active metabolite, namely beta-phenylethylidenehydrazine (PEH), is responsible for phenelzine's effects on amino acids. PEH is also a strong inhibitor of PrAO but has weak effects on MAO. PEH has a double bond and can thus exist as (E)- and (Z)-geometric isomers, but to date the two isomers have not been compared with regard to their neurochemical effects. /The researchers/ have investigated the effects of phenelzine, (E)- and (Z)-PEH on rat whole brain levels of amino acids, biogenic amine neurotransmitters and methylamine (an endogenous substrate of PrAO). Under the conditions used in the study, (E)- and (Z)-PEH appear to be equivalent in their neurochemical properties. Both PEH isomers and phenelzine produced marked increases in rat brain levels of GABA and alanine while decreasing brain levels of glutamine. Phenelzine increased brain levels of biogenic amine neurotransmitters (noradrenaline, dopamine and serotonin), whereas neither PEH isomer altered levels of these neurotransmitters to a considerable extent. All three drugs significantly increased rat brain levels of methylamine, with (E)- and (Z)-PEH causing a greater increase than phenelzine. These results are discussed in relation to the possible therapeutic applications of these drugs.|Multiple sclerosis (MS) and the animal model, experimental autoimmune encephalomyelitis (EAE), are both accompanied by motor and non-motor symptoms. Pathological changes in the activities of key neurotransmitters likely underlie many of these symptoms. We have previously described disturbances in the levels of 5-hydroxytryptamine (5-HT/serotonin), noradrenaline (NE) and ?-aminobutyric acid (GABA) in a mouse model of EAE. The potential therapeutic effect of a drug that targets these three neurotransmitters, the antidepressant and anti-panic drug phenelzine (PLZ), was assessed in mice with MOG(35-55) induced EAE. The neurotransmitter content of EAE and control tissue after PLZ administration was first evaluated by HPLC. The ability of PLZ treatment to modulate EAE disease course and clinical signs was then assessed. Daily PLZ treatment, starting seven days after disease induction, delayed EAE onset, reduced disease severity in the chronic phase and was associated with substantial improvements in exploratory behavior and a novel measure of sickness and/or depression. Upon completion of the experiment, PLZ's effects on histopathological markers of the disease were examined. No differences were observed in T cell infiltration, microglia/macrophage reactivity, demyelination or axonal injury in PLZ-treated spinal cords. However, EAE mice treated with PLZ showed a normalization of 5-HT levels in the ventral horn of the spinal cord that might account for the improvements in behavioral outcomes. These results demonstrate the therapeutic potential of MAO inhibitors such as PLZ in MS. Additionally, the behavioral changes observed in EAE mice indicate that alterations in non-motor or 'affective' measures may be valuable to consider in addition to traditional measures of gross locomotor function.|For more Mechanism of Action (Complete) data for Phenelzine (11 total), please visit the HSDB record page.

Intensive symptomatic and supportive treatment may be required. Induction of emesis or gastric lavage with instillation of charcoal slurry may be helpful in early poisoning, provided the airway has been protected against aspiration. Signs and symptoms of central nervous system stimulation, including convulsions, should be treated with diazepam, given slowly intravenously. Phenothiazine derivatives and central nervous system stimulants should be avoided. Hypotension and vascular collapse should be treated with intravenous fluids and, if necessary, blood pressure titration with an intravenous infusion of dilute pressor agent. It should be noted that adrenergic agents may produce a markedly increased pressor response. Respiration should be supported by appropriate measures, including management of the airway, use of supplemental oxygen, and mechanical ventilatory assistance, as required. Body temperature should be monitored closely. Intensive management of hyperpyrexia may be required. Maintenance of fluid and electrolyte balance is essential. There are no data on the lethal dose in man. The pathophysiologic effects of massive overdosage may persist for several days, since the drug acts by inhibiting physiologic enzyme systems. With symptomatic and supportive measures, recovery from mild overdosage may be expected within 3 to 4 days. Hemodialysis, peritoneal dialysis, and charcoal hemoperfusion may be of value in massive overdosage, but sufficient data are not available to recommend their routine use in these cases.|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.|Emergency and supportive measures: Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. Treat hypertension, coma, seizures, and hyperthermia if they occur. Use titratable intravenous antihypertensives such as nitroprusside and phentolamine because of the potential for rapid changes in hemodynamics. If hypotension occurs, it may reflect depletion of neuronal catecholamine stores, and in this case the directly acting agent norepinephrine is preferred over the directly acting drug dopamine. Continuously monitor temperature, other vital signs, an ECG for a minium of 6 hours in asymptomatic patients, and admit all symptomatic patients for continuous monitoring for 24 hours /Monoamine Oxidase Inhibitors/.|Specific drugs and antidotes: Since the hypertension /of MAO-reaction/ is catecholamine-mediated, alpha-adrenergic blockers (eg, phentolamine) or combined alpha- and beta-adrenergic blockers (eg, labetalol) and particularly useful. NOTE: Use of nonselective beta blockers without a vasodilator may cause paradoxical worsening of hypertension owing to unopposed alpha-adrenergic effects. Serotonin syndrome should be treated with supportive care, sedation and cooling. Anecdotal reports suggest possible benefit with cyproheptadine (Periactin), ... . Chlorpromazine ... has also been used. /Monoamine Oxidase Inhibitors/.|For more Antidote and Emergency Treatment (Complete) data for Phenelzine (9 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Accidental or intentional overdosage may be more common in patients who are depressed. It should be remembered that multiple drugs and/or alcohol may have been ingested. Depending on the amount of overdosage with Nardil, a varying and mixed clinical picture may develop, including signs and symptoms of central nervous system and cardiovascular stimulation and/or depression. Signs and symptoms may be absent or minimal during the initial 12-hour period following ingestion and may develop slowly thereafter, reaching a maximum in 24-48 hours. Death has been reported following overdosage. Therefore, immediate hospitalization, with continuous patient observation and monitoring throughout this period, is essential. Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonus, rigidity, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension, and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.|/SIGNS AND SYMPTOMS/ Withdrawal may be associated with nausea, vomiting, and malaise. An uncommon withdrawal syndrome following abrupt withdrawal of Nardil 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 Nardil therapy followed by cautious downward titration and discontinuation.|/SIGNS AND SYMPTOMS/ Numerous acute toxic reactions to phenelzine sulphate can occur, including agitation, hallucinations, hyperreflexia, hyperpyrexia and convulsions. Both hypotension and hypertension have been reported. Chronic toxicity may involve the liver, central nervous system and cardiovascular system (orthostatic hypotension).|/SIGNS AND SYMPTOMS/ The combination of MAO inhibitors and tryptophan has been reported to cause behavioral and neurologic syndromes including disorientation, confusion, amnesia, delirium, agitation, hypomanic signs, ataxia, myoclonus, hyperreflexia, shivering, ocular oscillations, and Babinski signs. /MAO inhibitors/|For more Human Toxicity Excerpts (Complete) data for Phenelzine (11 total), please visit the HSDB record page.

2 Phenethylhydrazine

Each Nardil film-coated tablet for oral administration contains phenelzine sulfate equivalent to 15 mg of phenelzine base and the following inactive ingredients: mannitol, USP; croscarmellose sodium, NF; povidone, USP; edetate disodium, USP; magnesium stearate, NF; isopropyl alcohol, USP; purified water, USP; opadry orange Y30-13242A|Oral: Tablets, film-coated: 15 mg (of phenelzine), Nardil (Pfizer). /Phenelzine sulfate/

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals