Phentermine

Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]:；SMALL FIRE: Dry chemical, CO2 or water spray.；LARGE FIRE: Water spray, fog or regular foam. If it can be done safely, move undamaged containers away from the area around the fire. Dike runoff from fire control for later disposal. Avoid aiming straight or solid streams directly onto the product.；FIRE INVOLVING TANKS, RAIL TANK CARS OR HIGHWAY TANKS: Fight fire from maximum distance or use unmanned master stream devices or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks in direct contact with flames. For massive fire, use unmanned master stream devices or monitor nozzles; if this is impossible, withdraw from area and let fire burn. (ERG, 2024)

Phentermine hydrochloride capsules and tablets should be stored in tight and well-closed containers, respectively, at a temperature less than 40 °C, preferably at 15-30 °C. Capsules containing phentermine as a resin complex should be stored in tight containers at 15-30 °C. . /Phentermine hydrochloride/

Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]:；Do not touch damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. Cover with plastic sheet to prevent spreading. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. DO NOT GET WATER INSIDE CONTAINERS. For solids, prevent dust cloud and avoid inhalation of dust. (ERG, 2024)

Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number P046, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste.

A good candidate for liquid injection incineration at a temperature range of 650 to 1,600 °C and a residence time of 0.1 to 2 seconds. A good candidate for rotary kiln incineration at a temperature range of 820 to 1,600 °C and residence times of seconds for liquids and gases, and hours for solids. A good candidate for fluidized bed incineration at a temperature range of 450 to 980 °C and residence times of seconds for liquids and gases, and longer for solids.

Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]:；IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.；SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.；FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

Excerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]:；Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer when there is NO RISK OF FIRE. Structural firefighters' protective clothing provides thermal protection but only limited chemical protection. (ERG, 2024)

Management of acute phentermine intoxication is largely symptomatic and includes lavage and sedation with a barbiturate. Acidification of the urine increases phentermine excretion. Intravenous phentolamine (REGITINE) has been suggested for possible acute, severe hypertension, if this complicates phentermine overdosage. (L1712)

'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.

An increased prevalence of abnormal cardiac valve function, primarily aortic regurgitation, was found on echocardiographic evaluation in patients receiving phentermine in combination with either dexfenfluramine or fenfluramine, both of which act to suppress appetite by increasing serotonergic function; however, an increased prevalence of abnormal cardiac valve function also has been found in patients receiving dexfenfluramine or fenfluramine alone, and the role of phentermine in producing the cardiotoxic effect is uncertain; because of the severity of these cardiovascular effects and because the safety and efficacy of other appetite suppressant combinations have not been established, combined use is not recommended; also, the safety and efficacy of combining as selective serotonin reuptake inhibitor (SSRI), which enhances serotonergic function, with a sympathomimetic appetite suppressant have not been established and combined use is not recommended.

Concurrent use /of other CNS stimulation-producing medications or thyroid hormones with appetite suppressants/ may increase the CNS stimulant effects of either these medications or the appetite suppressant. /Appetite suppressants, sympathomimetic/

Vasopressant effect may be potentiated; if necessary to administer a pressor amine agent to a patient who has recently received an appetite suppressant, initiating pressor therapy in reduced dosage and monitoring blood pressure at frequent intervals are recommended. /Appetite suppressants, sympathomimetic/

For more Interactions (Complete) data for PHENTERMINE (11 total), please visit the HSDB record page.

Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion. Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.

Phentermine has not been linked to an increased rate of serum enzyme elevations during therapy; however, results of ALT monitoring during phentermine therapy have rarely been reported. Despite long term availability and wide use of phentermine, there have been no published reports linking it to clinically apparent acute liver injury.；Likelihood score: E (unlikely cause of clinically apparent liver injury).；Drug Class: Weight Loss Agents, see also Phentermine-Topiramate

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 260(SRC), determined from a log Kow of 1.90(2) and a regression-derived equation(3), indicates that phentermine is expected to have moderate mobility in soil(SRC). The estimated pKa of phentermine is 10.1(4), indicating that this compound will primarily 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 phentermine from moist soil surfaces is expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.4X10-6 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Phentermine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.6X10-2 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 260(SRC), determined from a log Kow of 1.90(2) and a regression-derived equation(3), indicates that phentermine is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 10.1(4) indicates phentermine will exist primarily in the cation form at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process(5). Volatilization from water surfaces is expected(3) based upon an estimated Henry's Law constant of 1.4X10-6 atm-cu m/mole(SRC), developed using a fragment constant estimation method(6). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 31 and 232 days, respectively(SRC). According to a classification scheme(7), an estimated BCF of 6(SRC), from its log Kow(2) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(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), phentermine, which has an estimated vapor pressure of 9.6X10-2 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 phentermine 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 14 hours(SRC), calculated from its rate constant of 2.7X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Phentermine 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: Phentermine hydrochloride is an amphetamine type antiobesity drug. Description: Indications: Used as an appetite suppressant (anorectic). Misuse: Performance enhancement and relief of fatigue. Abuse: Abuse either orally or by injection is extremely common. 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 ischemia, 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 abuse. Genitourinary: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can result 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 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 oc

Phentermine is an amphetamine that stimulates neurons to release or maintain high levels of a particular group of neurotransmitters known as catecholamines; these include dopamine and norepinephrine. High levels of these catecholamines tend to suppress hunger signals and appetite. The drug seems to inhibit reuptake of noradrenaline, dopamine, and seratonin through inhibition or reversal of the reuptake transporters. It may also inhibit MAO enzymes leaving more neurotransmitter available at the synapse.Phentermine (through catecholamine elevation) may also indirectly affect leptin levels in the brain. It is theorized that phentermine can raise levels of leptin which signal satiety. It is also theorized that increased levels of the catecholamines are partially responsible for halting another chemical messenger known as neuropeptide Y. This peptide initiates eating, decreases energy expenditure, and increases fat storage.

The Koc of phentermine is estimated as 260(SRC), using a log Kow of 1.90(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that phentermine is expected to have moderate mobility in soil(SRC). The estimated pKa of phentermine is 10.1(4), indicating that this compound will primarily exist in the cation form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(5).

/CASE REPORTS/ A 47-year-old mildly obese female began a weight reduction program that included anorectic therapy with phentermine and phendimetrazine. A normal urinalysis and serum creatinine were documented at the start of therapy. After three weeks of treatment, the patient felt ill and discontinued her treatment. Subsequently she was found to have leukocyturia, a rash on her face and chest, and a rise in her serum creatinine from 0.8 mg/dl to 2.1 mg/dl. A renal biopsy confirmed the diagnosis of acute interstitial nephritis. The patient was treated with corticosteroids and her renal function returned to normal. Despite the recent withdrawal of two anorectic agents due to data linking them to severe cardiac and pulmonary disease, the appetite suppressants phentermine and phendimetrazine remain in widespread usage for the treatment of obesity. This case represents the first report of acute interstitial nephritis associated with phentermine or phendimetrazine.

/CASE REPORTS/ Psychotic reactions that could easily be mistaken for schizophrenic illness were reported in 20 yr old woman who had been taking phentermine (ionamin), 30 mg/day for 3 mo, beginning 1 mo prior to onset of symptoms.

/CASE REPORTS/ Acutely intoxicated patients exhibit tremor, hyperreflexia, rapid respiration, confusion, assaultive behavior, hallucinations, panic, nausea, vomiting, diarrhea and abdominal cramps. Death may occur following convulsions and coma. A 26-year-old schizophrenic woman developed an acute psychotic disorganization with mydriasis, tachycardia and restlessness after 240 mg, /of/ phentermine. ... Signs of chronic intoxication are severe dermatoses, marked insomnia, irritability, hyperactivity and, in the severe cases, a psychosis resembling schizophrenia. Extreme fatigue, mental depression and changes in the sleep EEG have been observed after abrupt cessation of long-term usage.

/EPIDEMIOLOGY STUDIES/ ...A population-based follow-up study and a nested case-control analysis of 6532 subjects who received dexfenfluramine, 2371 who received fenfluramine, and 862 who received phentermine /was conducted/ to assess the risk of a subsequent clinical diagnosis of a valvular disorder of uncertain origin. For comparison, a group of 9281 obese subjects who had not taken appetite suppressants were matched to the treated subjects for age, sex, and weight. All subjects were free of diagnosed cardiovascular disease at the start of follow-up. The average duration of follow-up for all subjects was about four years. There were 11 cases of newly diagnosed idiopathic valvular disorders, 5 after the use of dexfenfluramine and 6 after the use of fenfluramine. There were six cases of aortic regurgitation, two cases of mitral regurgitation, and three cases of combined aortic and mitral regurgitation. There were no cases of idiopathic cardiac-valve abnormalities among the subjects who had not taken appetite suppressants or among those who took only phentermine. The five-year cumulative incidence of idiopathic cardiac-valve disorders was 0 per 10,000 subjects among those who had not taken appetite suppressants (95 percent confidence interval, 0 to 15.4) and among those who took phentermine alone (95 percent confidence interval, 0 to 76.6), 7.1 per 10,000 subjects among those who took either fenfluramine or dexfenfluramine for less than four months (95 percent confidence interval, 3.6 to 17.8; P=0.02 for the comparison with subjects who had not taken appetite suppressants), and 35.0 per 10,000 subjects among those who received either of these medications for four or more months (95 percent confidence interval, 16.4 to 76.2; P<0.001). The use of fenfluramine or dexfenfluramine, particularly for four months or longer, is associated with an increased risk of newly diagnosed cardiac-valve disorders, particularly aortic regurgitation.

Phentermine's production and use as an appetite suppressant(1) may result in its release to the environment through various waste streams(SRC). It was a component of the popular diet-drug combination of fenfluramine and phnetermine (Fen/phen)(1).

DEA schedule IV controlled substance

Status: Active Update: 11-10-2012 https://echa.europa.eu/registration-dossier/-/registered-dossier/11363

Phentermine: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

Schedules of controlled substances are established by section 202 of the Controlled Substances Act (21 U.S.C. 812). Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: Phentermine, Schedule IV, DEA Code #: 1640.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl phentermine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Phentermine Hydrochloride/

P046; As stipulated in 40 CFR 261.33, when alpha,alpha-dimethylphenethylamine as a commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or a manufacturing chemical intermediate, becomes a waste, it must be managed according to federal and/or state hazardous waste regulations. Also defined as a hazardous waste is any container or inner liner used to hold this waste or any residue, contaminated soil, water, or other debris resulting from the cleanup of a spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (40 CFR 261.5(e)).

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Benzeneethanamine, alpha,alpha-dimethyl- is included on this list.

Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 5000 lb or 2270 kg. The toll free number of the NRC is (800) 424-8802. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b).

Appetite suppressant for the short-term (a few weeks) management of obesity

THERAP CAT: Anorectic agent

MEDICATION

Use (kg) in USA (2002): 4170；Consumption (g per capita) in the USA (2002): 0.0148；Calculated removal (%): 22.8

For the treatment and management of obesity.

Preperation: Shelton, Van Campen, US 2590079 (1952 to Wyeth)

Prepartion: ... Abell et al., US 2408345 (1946 to Wm. S. Merrell)

Grignardization of benzyl alcohol with acetone, reacting the resulting alpha, alpha-dimethylpenethyl alcohol with sodium cyanide in acid to form the corresponding 2-formamido compound, and hydrolyzing this to phentermine.

Phentermine is prepared by converting the condensation product of benzaldehyde and nitropropane to the corresponding aminoalcohol followed by transformation to the chloroamine and then catalytic hydrogenation.

ADIPEX-P, FASTIN, WILPO. /PHENTERMINE HYDROCHLORIDE/

/INGREDIENT OF/ IONAMIN, MIRAPRONT, LINYL, OMNIBEX, DUROMINE /ION EXCHANGE RESIN COMPLEX/

PHENTERMINE IS AVAIL AS HYDROCHLORIDE SALT & AS COMPLEX OF BASE WITH AN ION-EXCHANGE RESIN. ... GENERIC: CAPSULES 15, 18, 75, 30, AND 37.5 MG; TABLETS 8, 30, AND 37.5 MG. ADIPEX-P (LEMMON): CAPSULES AND TABLETS 37.5 MG (EQUIVALENT TO 30 MG OF BASE). FASTIN (BEECHAM), OBERMINE (FOREST): CAPSULES 30 MG (EQUIVALENT TO 24 MG OF BASE). PHENTROL (VORTECH): CAPSULES 30 MG (EQUIVALENT TO 24 MG OF BSE) (PHENTROL 2); CAPSULES (PROLONGED-RELEASE) 15 MG (EQUIVALENT TO 12 MG OF BASE) (PHENTROL 3) AND 30 MG (EQUIVALENT TO 24 MG OF BASE) (PHENTROL 4); TABLETS 8 MG (EQUIVALENT TO 6.4 MG OF BASE) (PHENTROL) PHENTERMINE RESIN: IONAMIN (FISONS), GENERIC. ORAL: CAPSULES 15 AND 30 MG.

Each tablet /of Adipex-P/ contain phentermine hydrochloride, 37.5 mg (equivalent to 30 mg of phentermine base)

For more Formulations/Preparations (Complete) data for PHENTERMINE (6 total), please visit the HSDB record page.

Benzeneethanamine, .alpha.,.alpha.-dimethyl-: ACTIVE

Phentermine is a chemical congener of amphetamine in that it has an additional methyl group on alpha-carbon atom, which is symmetrical & lacks an alpha-hydrogen atom. These differences from amphetamine are reflected in metabolism & pharmacology.

An anorectic drug supplied as a cationic resin complex ... and as the hydrochloride salt.

... has not been marketed in the Federal Republic of Germany since 1968 because of suspected pulmonary hypertension

Fen-phen refers to the off-label combination of the appetite suppressants fenfluramine and phentermine