N-Ethyl-alpha-methyl-3-(trifluor-methyl)benzolethanamin

Headache, neck stiffness, nausea, and collapse occurred following a single 20 mgdose of fenfluramine hydrochloride in a patient taking a monoamine oxidase inhibitor. In addition, neurologic and circulatory reactions, including hypertensive crises, have been reported in patients who have received sympathomimetic agents concomitantly with monoamine oxidase inhibitors and fatalities have occurred. Fenfluramine is, therefore, contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors. /Fenfluramine hydrochloride/

Fenfluramine should be used with caution in patients taking CNS depressant drugs since the effects may be additive.

'Fen-phen' refers to the off-label combination of the appetite suppressants fenfluramine and phentermine. The rationale for the fen-phen combination was that the two drugs exerted independent actions on brain satiety mechanisms so that it was possible to use lower doses of each drug and yet retain a common action on suppressing appetite while minimizing adverse drug effects. The focus of the present review is to consider whether fenfluramine and phentermine exert actions that are additive in nature or whether these two drugs exhibit drug-drug synergism. The fen-phen combination results in synergism for the suppression of appetite and body weight, the reduction of brain serotonin levels, pulmonary vasoconstriction and valve disease. Fen-phen synergism may reflect changes in the pharmacokinetics of drug distribution, common actions on membrane ion currents, or interactions between neuronal release and reuptake mechanisms with MAO-mediated transmitter degradation. The synergism between fenfluramine and phentermine highlights the need to more completely understand the pharmacology and neurochemistry of appetite suppressants prior to use in combination pharmacotherapy for the treatment of obesity.

... Prior treatment with diethylcarbamazine was found to potentiate the lethality of fenfluramine, while cyproheptadine pretreatment attenuated fenfluramine's toxic effects. Necropsies, conducted 24 hr after fenfluramine administration, revealed widespread alveolar and pulmonary interstitial hemorrhage in the cyproheptadine pretreated animals. The data suggest that high doses of fenfluramine directly result in pulmonary hypertension, which secondarily induces ischemic cardiac injury.

TERRESTRIAL FATE: Based on a classification scheme, an estimated Koc value of 1,600(SRC), determined from a log Kow of 3.36(2) and a regression-derived equation(3), indicates that fenfluramine is expected to have low mobility in soil(SRC). The pKa of fenfluramine is 9.6(4), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(5). Volatilization of fenfluramine from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.7X10-5 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Fenfluramine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.1X10-2 mm Hg(SRC), determined from a fragment constant method(7). Biodegradation data were not available(SRC, 2005).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1,600(SRC), determined from a log Kow of 3.36(2) and a regression-derived equation(3), indicates that fenfluramine is not expected to adsorb to suspended solids and sediment(SRC). The pKa of fenfluramine is 9.6(4), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts and do not volatilize(5). Volatilization of the unionized species from water surfaces is expected(3) based upon an estimated Henry's Law constant of 2.7X10-5 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Using this Henry's Law constant and an estimation method(6), volatilization half-lives for a model river and model lake are 2 days and 20 days, respectively(SRC). According to a classification scheme(7), an estimated BCF of 80(SRC), from its log Kow(2) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data were not available(SRC, 2005).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), fenfluramine, which has an estimated vapor pressure of 4.1X10-2 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 fenfluramine 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 4 hours(SRC), calculated from its rate constant of 3.3X10-11 cu cm/molecule-sec at 25 °C (SRC) that was derived using a structure estimation method(3). Fenfluramine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION: Fenfluramine hydrochloride is a centrally acting amphetamine antiobesity assent. HUMAN EXPOSURE: Main risks and target organs: Acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Summary of clinical effects: Cardiovascular: Palpitation, chest pain, tachycardia, arrhythmias and hypertension are common; cardiovascular collapse can occur in severe poisoning. Myocardial ischaemia, infarction and ventricular dysfunction are described. Central Nervous System (CNS): Stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia are described. Stroke and cerebral vasculitis have been observed. Gastrointestinal: Vomiting, diarrhea and cramps may occur. Acute transient ischemic colitis has occurred with chronic methamphetamine abuse. Genitourinary: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Dermatologic: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Endocrine: Transient hyperthyroxinemia may be noted. Metabolism: Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Fluid/Electrolyte: Hypo- and hyperkalemia have been reported. Dehydration is common. Musculoskeletal: Fasciculations and rigidity may be noted. Rhabdomyolysis is an important consequence of severe amphetamine poisoning. Psychiatric: Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Contraindications: Anorexia, insomnia, psychopathic personality disorders, suicidal tendencies, Gilles de la Tourette syndrome and other disorders, hyperthyroidism, narrow angle glaucoma, diabetes mellitis and cardiovascular diseases such as angina, hypertension and arrythmias. Routes of exposure: Oral: Readily absorbed from the gastro-intestinal tract and buccal mucosa. It is resistant to metabolism by monoamine oxidase. Inhalation: Amphetamine is rapidly absorbed by inhalation and is abused by this route. Parenteral: Frequent route of entry in abuse situations. Absorption by route of exposure: Amphetamine is rapidly absorbed after oral ingestion. Peak plasma levels occur within 1 to 3 hours, varying with the degree of physical activity and the amount of food in the stomach. Absorption is usually complete by 4 to 6 hours. Sustained release preparations are available as resin-bound, rather than soluble, salts. These compounds display reduced peak blood levels compared with standard amphetamine preparations, but total amount absorbed and time to peak levels remain similar. Distribution by route of exposure: Amphetamines are concentrated in the kidney, lungs, cerebrospinal fluid and brain. They are highly lipid soluble and readily cross the blood-brain barrier. Protein binding and volume of distribution varies widely, but the average volume of distribution is 5 L/kg body weight. Biological half-life by route of exposure: Under normal conditions, about 30% of amphetamine is excreted unchanged in the urine but this excretion is highly variable and is dependent on urinary pH. When the urinary pH is acidic (pH 5.5 to 6.0), elimination is predominantly by urinary excretion with approximately 60% of a dose of amphetamine being excreted unchanged by the kidney within 48 hours. When the urinary pH is alkaline (pH 7.5 to 8.0), elimination is predominantly by deamination (less than 7% excreted unchanged in the urine); the half-life ranging from 16 to 31 hours. Metabolism: The major metabolic pathway for amphetamine involves deamination by cytochrome P450 to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidized to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation. Hydroxylation produces an active metabolite, O-hyroxynorephedrine, which acts as a false neurotransmitter and may account for some drug effect, especially in chronic users. Elimination and excretion: Normally 5 to 30% of a therapeutic dose of amphetamine is excreted unchanged in the urine by 24 hours, but the actual amount of urinary excretion and metabolism is highly pH dependent. Mode of action: Toxicodynamics: Amphetamine appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especially norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Adults: The toxic dose varies considerably due to individual variations and the development of tolerance. Children: Children appear to be more susceptible than adults and are less likely to have developed tolerance. Teratogenicity: The use of amphetamine for medical indications does not pose a significant risk to the fetus for congenital anomalies. Amphetamines generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow-up have not shown long-term sequelae. Illicit maternal use or abuse of amphetamine presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. Cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties of amphetamines. Sixty-five children were followed whose mothers were addicted to amphetamine during pregnancy, at least during the first trimester. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. Interactions: Acetazolamide: administration may increase serum concentration of amphetamine. Alcohol: may increase serum concentration of amphetamine. Ascorbic acid: lowering urinary pH, may enhance amphetamine excretion Furazolidone: amphetamines may induce a hypertensive response in patients taking furazolidone. Guanethidine: amphetamine inhibits the antihypertensive response to guanethidine. Haloperidol: limited evidence indicates that haloperidol may inhibit the effects of amphetamine but the clinical importance of this interaction is not established. Lithium carbonate: isolated case reports indicate that lithium may inhibit the effects of amphetamine. Monoamine oxidase inhibitor: severe hypertensive reactions have followed the administration of amphetamines to patients taking monoamine oxidase inhibitors. Noradrenaline: amphetamine abuse may enhance the pressor response to noradrenaline. Phenothiazines: amphetamine may inhibit the antipsychotic effect of phenothiazines, and phenothiazines may inhibit the anorectic effect of amphetamines. Sodium bicarbonate: large doses of sodium bicarbonate inhibit the elimination of amphetamine, thus increasing the amphetamine effect. Tricyclic antidepressants - theoretically increases the effect of amphetamine, but clinical evidence is lacking. Clinical effects: Acute poisoning: Ingestion: Effects are most marked on the central nervous system, cardiovascular system, and muscles. The triad of hyperactivity, hyperpyrexia, and hypertension is characteristic of acute amphetamine overdosage. Agitation, confusion, headache, delirium, and hallucination, can be followed by coma, intracranial hemorrhage, stroke, and death. Chest pain, palpitation, hypertension, tachycardia, atrial and ventricular arrhythmia, and myocardial infarction can occur. Muscle contraction, bruxism (jaw-grinding), trismus (jaw clenching), fasciculation, rhabdomyolysis, are seen leading to renal failure; and flushing, sweating, and hyperpyrexia can all occur. Hyperpyrexia can cause disseminated intravascular coagulation. Inhalation: The clinical effects are similar to those after ingestion, but occur more rapidly. Parenteral exposure: Intravenous injection is a common mode of administration of amphetamine by abusers. Other clinical effects are similar to those observed after ingestion, but occur more rapidly. Ingestion: Tolerance to the euphoric effects and CNS stimulation induced by amphetamine develops rapidly, leading abusers to use larger and larger amounts to attain and sustain the desired affect. Habitual use or chronic abuse usually results in toxic psychosis classically characterised by paranoia, delusions and hallucinations, which are usually visual, tactile or olfactory in nature, in contrast to the typical auditory hallucinations of schizophrenia. The individual may act on the delusions, resulting in bizarre violent behavior, hostility and aggression, sometimes leading to suicidal or homicidal actions. Dyskinesia, compulsive behaviour and impaired performance are common in chronic abusers. The chronic abuser presents as a restless, garrulous, tremulous individual who is suspicious and anxious. Course, prognosis, cause of death: Symptoms and signs give a clinical guide to the severity of intoxication as follows: Mild toxicity: restlessness, irritability, insomnia, tremor, hyperreflexia, sweating, dilated pupils, flushing. Moderate toxicity: hyperactivity, confusion, hypertension, tachypnea, tachycardia, mild fever, sweating. Severe toxicity: delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, circulatory collapse. Death can be due to intracranial hemorrhage, acute heart failure or arrhythmia, hyperpyrexia, rhabdomyolysis and consequent hyperkalaemia or renal failure, and to violence related to the psychiatric effects. Systematic description of clinical effects: Cardiovascular: Cardiovascular symptoms of acute poisoning include palpitation and chest pain. Tachycardia and hypertension are common. Severe poisoning can cause acute myocardial ischemia, myocardial infarction and left ventricular failure. Chronic oral amphetamine abuse can cause a chronic cardiomyopathy; an acute cardiomyopathy has also been described. Hypertensive stroke is a well-recognized complication of amphetamine poisoning. Intra-arterial injection of amphetamine can cause severe burning pain, vasospasm, and gangrene. Respiratory: Pulmonary fibrosis, right ventricular hypertrophy and pulmonary hypertension are frequently found at post-mortem examination. Pulmonary function tests usually are normal except for the carbon monoxide diffusing capacity. Respiratory complications are sometimes caused by fillers or adulterants used in injections by chronic users. These can cause multiple microemboli to the lung, which can lead to restrictive lung disease. Pneumomediastinum has been reported after amphetamine inhalation. Neurological: Central nervous system (CNS): Main symptoms include agitation, confusion, delirium, hallucinations, dizziness, dyskinesia, hyperactivity, muscle fasciculation and rigidity, rigors, tics, tremors, seizures and coma. Both occlusive and hemorrhagic strokes have been reported after abuse of amphetamines. Patients with underlying arteriovenous malformations may be at particular risk. Stroke can occur after oral, intravenous, or nasal administration. Severe headache beginning within minutes of ingestion of amphetamine is usually the first symptom. In more than half the cases, hypertension which is sometimes extreme, accompanies other symptoms. A Cerebral vasculitis has also been observed. Dystonia and dyskinesia can occur, even with therapeutic dosages. Psychiatric effects, particularly euphoria and excitement, are the motives for abuse. Paranoia and a psychiatric syndrome indistinguishable from schizophrenia are sequelae of chronic use. Autonomic nervous system: Stimulation of alpha-adrenergic receptors produces mydriasis, increased metabolic rate, diaphoresis, increased sphincter tone, peripheral vasoconstriction and decreased gastrointestinal motility. Stimulation of ß-adrenergic receptors produces increased heart rate and contractility, increased automaticity and dilatation of bronchioles. Skeletal and smooth muscle: Myalgia, muscle tenderness, muscle contractions, and rhabdomyolysis, leading to fever, circulatory collapse, and myoglobinuric renal failure, can occur with amphetamines. Gastrointestinal: Most common symptoms are nausea, vomiting, diarrhea, and abdominal cramps. Anorexia may be severe. Epigastric pain and hematemesis have been described after intravenous amphetamine use. A case of ischemic colitis with normal mesenteric arteriography in a patient taking dexamphetamine has been described. Hepatic: Hepatitis and fatal acute hepatic necrosis have been described. Urinary: Renal: Renal failure, secondary to dehydration or rhabdomyolysis may be observed. Other: Spontaneous rupture of the bladder has been described in a young woman who took alcohol and an amphetamine-containing diet tablet. Endocrine and reproductive systems: Transient hyperthyroxinemia may result from heavy amphetamine use. Dermatological: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Chronic users may display skin lesion, abscesses, ulcers, cellulitis or necrotising angiitis due to physical insult to skin, or dermatologic signs of dietary deficiencies, cheilosis and purpura. Eye, ear, nose, throat: local effects: Mydriasis may be noted. Diffuse hair loss may be noted. Chronic users may display signs of dietary deficiencies. Hematological: Disseminated intravascular coagulation is an important consequence of severe poisoning. Idiopathic thrombocytopenic purpura may occur. Metabolic: Fluid and electrolyte disturbance: Increase metabolic and muscular activity may result in dehydration. /Fenfluramine hydrochloride/

The Koc of fenfluramine is estimated as 1,600(SRC), using a log Kow of 3.36(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that fenfluramine is expected to have low mobility in soil. The pKa of fenfluramine is 9.6(4), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(5).

/HUMAN EXPOSURE STUDIES/ Not all the risk factors for primary pulmonary hypertension (PPH) are known. Appetite suppressants, including fenfluramine derivatives, are strongly suspected aetiological agents. In a 5 year retrospective study fenfluramine use was evaluated among patients referred to a medical centre specialising in the management of PPH. Fifteen (20%) of 73 patients with PPH had used fenfluramine: all of them were women and in 10 (67%) there was a close temporal relation between fenfluramine use and the development of exertional dyspnoea. Initial right heart catheterisation in the 15 women showed severe resting pulmonary hypertension (mean (SD)) with pulmonary artery pressure (PAP) 57 (9) mm Hg, cardiac index 2.1 (0.5) l/min/sq M, and pulmonary vascular resistance (PVR) 29 (10) U/sq m. Short-term epoprostenol infusion produced a significant vasodilator response in 10 patients (mean fall in PVR 24 (15%) compared with control values). Three fenfluramine users with PPH showed spontaneous clinical and haemodynamic improvement 3, 6 and 12 months after drug withdrawal but there was no significant difference in overall survival (transplant recipients excluded) between fenfluramine users and controls. Histological examination of lung tissue from five women who had used fenfluramine and 22 controls, with PPH showed features typical of advanced plexogenic pulmonary arteriopathy in all. These results do not accord with earlier reports that PPH associated with fenfluramine is less severe and has a better outcome. Fenfluramine may be one aetiological agent that can precipitate or hasten the development of PPH.

/HUMAN EXPOSURE STUDIES/ Three subjects given 240 mg of fenfluramine experienced brief but vivid hallucinogenic episodes characterized by olfactory, visual, & somatic hallucinations, abrupt polar changes in mood, time distortion, fleeting paranoia, & sexual ideation.

/HUMAN EXPOSURE STUDIES/ Fenfluramine doses of less than 5 mg/kg are toxic, and doses of 5-10 mg/kg may produce coma and seizures. ... Single overdoses reported have ranged from 300 mg to 2 g. The lowest reported fatal dose of fenfluramine hydrochloride was 400 mg in a small child and the highest reported nonfatal dose was 1.8 g in an adult.

/SIGNS AND SYMPTOMS/ Emotional instability, cognitive deficits, and depression were reported in 27 patients taking fenfluramine and dexfenfluramine chronically. Psychosis has been reported after use of dexfenfluramine for 2 months. Headache, diarrhea, dizziness, dry mouth, impotence, palpitations , anxiety, insomnia, irritability, lethargy, and CNS excitation at higher doses have been reported with therapeutic use.

For more Human Toxicity Excerpts (Complete) data for FENFLURAMINE (19 total), please visit the HSDB record page.

An estimated BCF of 80 was calculated for fenfluramine(SRC), using a log Kow of 3.36(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC), provided the compound is not metabolized by the organism(SRC).

The Henry's Law constant for fenfluramine is estimated as 2.7X10-5 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that fenfluramine is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 2 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 20 days(SRC). Fenfluramine's Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Fenfluramine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.1X10-2 mm Hg(SRC), determined from a fragment constant method(3).

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... Negative teratolgic testing /was reported/ in rats, rabbits and mice. Doses of up to 45 mg per kg /of fenfluramine/ were given subcutaneously to rats on days 5 through 14 of gestation. Postnatal studies of rats whose mothers received 20 mg per kg daily during most of gestation were reported to be different from controls. Locomotor tests (pivoting) were the most altered. Brain weight, but not DNA, was significantly reduced in the pups at 70 days of postnatal life.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Studies in rats showed decreases in the rate of conception and survival rate at weaning and some potential teratogenicity; however, no adverse effects were reported in reproduction studies in other species (rabbits, monkeys, mice, and chickens).

/LABORATORY ANIMALS: Acute Exposure/ Fenfluramine is a potent serotonin releasing drug used primarily as an anorectic agent. The symptomatology of its acute lethality has been well documented in animal models such as the rat. A very prominent feature of this lethality profile is hypoxia, as demonstrated by the onset of severe cyanosis just prior to death. It is not clear in the literature whether this hypoxia is the result of a direct pulmonary effect or is secondary to cardiac injury. To further characterize this aspect of fenfluramine's toxicity, respiratory and electrocardiographic measurements were taken in anesthetized rats subjected to high doses of fenfluramine (129.6 mg/kg, ip). Death occurred in these animals within 15 min of drug administration, apparently as the result of abrupt respiratory cessation, followed by cardiac ischemia. No significant gross or histopathological lesions were evident in these animals.

/GENOTOXICITY/ Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo.

Clinical studies of dexfenfluramine did not include sufficient numbers of patients 65 years of age and older to determine whether geriatric patients respond differently than younger patients. Because geriatric patients generally are more sensitive to drugs that affect the CNS, dexfenfluramine should be used with caution in these patients. The greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly should also be considered. /Dexfenfluramine/

The rate constant for the vapor-phase reaction of fenfluramine with photochemically-produced hydroxyl radicals has been estimated as 3.3X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 4 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Fenfluramine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(2). Fenfluramine does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Occupational exposure to fenfluramine may have occurred through dermal contact with this compound at workplaces where fenfluramine was produced or used. Exposure to fenfluramine among the general population may have been limited to those administered the drug as a treatment for obesity. (SRC)

Fenfluramine used as a anorectic was marketed in the United States in 1973.

Drug products withdrawn or removed from the market for reasons of safety or effectiveness. The following drug products were withdrawn or removed from the market because such drug products or components of such drug products were found to be unsafe or not effective. The following drug products may not be compounded under the exemptions provided by section 503A(a) of the Federal Food, Drug, and Cosmetic Act. Fenfluramine hydrochloride: All drug products containing fenfluramine hydrochloride is included on this list. /Fenfluramine Hydrochloride/

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Any material, compound, mixture, or preparation which contains any quantity of the following substances, including its salts, isomers (whether optical, position, or geometric), and salts of such isomers, whenever the existence of such salts, isomers, and salts of isomers is possible: Fenfluramine, Schedule IV, DEA Code #: 1670.

MEDICATION

Appetite suppressant for the short-term (a few weeks) management of obesity. /Former use/

Preperation of optical isomers: US 3198834 (1965 to Sci. Union et Cie Soc. Franc. Recherche Med.)

Preperation: L.G Beregi et al., FR M1658; eidem US 3198833 (1965 to Sci. Union et Cie Soc. Franc. Recherche Med.)

Fenfluramine is prepared by reductive alkylation of norfenfluramine with acetaldehyde [18]. The nor compound is obtained by catalytic hydrogenation of the oxime made from 3-trifluoromethylphenyl acetone.