Phentermine

Phentermine is used for a short period of time to promote weight loss, if exercise and calorie reduction are not sufficient, and in addition to exercise and calorie reduction.

Phentermine is approved for up to 12 weeks of use and most weight loss occurs in the first weeks. However, significant loss continues through the sixth month and has been shown to continue at a slower rate through the ninth month.{{cite journal | vauthors = Glazer G | title = Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety | journal = Archives of Internal Medicine | volume = 161 | issue = 15 | pages = 1814–1824 | date = August 2001 | pmid = 11493122 | doi = 10.1001/archinte.161.15.1814 | doi-access = free }}

Use is not recommended during pregnancy or breastfeeding,{{cite web |title=Phentermine Use During Pregnancy |url=https://www.drugs.com/pregnancy/phentermine.html |access-date=13 April 2019 |website=Drugs.com}} or with selective serotonin reuptake inhibitors (SSRIs) or monoamine oxidase inhibitors (MAOIs).

Phentermine is contraindicated for users who:

• have a history of drug abuse
• are allergic to sympathomimetic amine drugs
• are taking a monoamine oxidase inhibitor (MAOI) or have taken one within the last 14 days
• have cardiovascular disease, hyperthyroidism, or glaucoma
• are pregnant, planning to become pregnant, or breastfeeding.

Tolerance usually occurs; however, risks of dependence and addiction are considered negligible.{{cite journal | vauthors = Haslam D | title = Weight management in obesity - past and present | journal = International Journal of Clinical Practice | volume = 70 | issue = 3 | pages = 206–217 | date = March 2016 | pmid = 26811245 | pmc = 4832440 | doi = 10.1111/ijcp.12771 }} People taking phentermine may be impaired when driving or operating machinery. Consumption of alcohol with phentermine may produce adverse effects.

There is currently no evidence regarding whether or not phentermine is safe for pregnant women.

Other adverse effects include:{{cite web|title=METERMINE (Phentermine)|date=22 July 2013|access-date=16 November 2013|work=TGA eBusiness Services|publisher=iNova Pharmaceuticals (Australia) Pty Limited|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-06558-3|format=PDF}}{{cite web|title=Phentermine label at FDA|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/085128s065lbl.pdf|archive-url=https://web.archive.org/web/20130823215214/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/085128s065lbl.pdf|url-status=dead|archive-date=23 August 2013|publisher=FDA|access-date=13 October 2016|format=Last updated: January 2012}}

• Cardiovascular effects like palpitations, tachycardia, high blood pressure, precordial pain; rare cases of stroke, angina, myocardial infarction, cardiac failure and cardiac arrest have been reported.
• Central nervous system effects like overstimulation, restlessness, nervousness, insomnia, tremor, dizziness and headache; there are rare reports of euphoria followed by fatigue and depression, and very rarely, psychotic episodes and hallucinations.
• Gastrointestinal effects include nausea, vomiting, dry mouth, cramps, unpleasant taste, diarrhea, and constipation.
• Other adverse effects include trouble urinating, rash, impotence, changes in libido, and facial swelling.

Phentermine may decrease the effect of drugs like clonidine, methyldopa, and guanethidine. Drugs to treat hypothyroidism may increase the effect of phentermine.

Phentermine is a substrate of the monoamine transporters (MATs) and acts as a monoamine releasing agent (MRA), specifically as a norepinephrine–dopamine releasing agent (NDRA).{{cite journal | vauthors = Rothman RB, Baumann MH | title = Monoamine transporters and psychostimulant drugs | journal = Eur J Pharmacol | volume = 479 | issue = 1–3 | pages = 23–40 | date = October 2003 | pmid = 14612135 | doi = 10.1016/j.ejphar.2003.08.054 | url = }}{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Curr Top Med Chem | volume = 6 | issue = 17 | pages = 1845–1859 | date = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = }}{{cite journal | vauthors = Rothman RB, Baumann MH | title=Neurochemical mechanisms of phentermine and fenfluramine: Therapeutic and adverse effects | journal=Drug Development Research | volume=51 | issue=2 | date=2000 | issn=0272-4391 | doi=10.1002/1098-2299(200010)51:2<52::AID-DDR2>3.0.CO;2-H | pages=52–65}} It also acts as a norepinephrine–dopamine reuptake inhibitor (NDRI) to a lesser extent. The drug robustly and dose-dependently elevates brain norepinephrine and dopamine levels in animals. Phentermine is more potent in its effects on norepinephrine than on dopamine and the drug shows only weak effects on serotonin. Unlike many other amphetamines and MRAs, phentermine is completely inactive at the vesicular monoamine transporter 2 (VMAT2).{{cite journal | vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL | title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter | journal = Drug Alcohol Depend | volume = 147 | issue = | pages = 1–19 | date = February 2015 | pmid = 25548026 | pmc = 4297708 | doi = 10.1016/j.drugalcdep.2014.12.005 | url = }}{{cite journal | vauthors = Partilla JS, Dempsey AG, Nagpal AS, Blough BE, Baumann MH, Rothman RB | title = Interaction of amphetamines and related compounds at the vesicular monoamine transporter | journal = J Pharmacol Exp Ther | volume = 319 | issue = 1 | pages = 237–246 | date = October 2006 | pmid = 16835371 | doi = 10.1124/jpet.106.103622 | url = }} Due to its actions on the catecholamines, phentermine produces effects including stimulation, rewarding effects, appetite suppression, and sympathomimetic effects in animals and humans.

In terms of monoamine release in vitro using rat brain synaptosomes, phentermine is about 6-fold less potent than dextroamphetamine in the case of norepinephrine release, 11-fold less potent than dextroamphetamine in the case of dopamine release, and has a ratio of norepinephrine release versus dopamine release of about 6.6:1 compared to dextroamphetamine's ratio of about 3.5:1. It is more than 3-fold less potent than amphetamine in elevating brain dopamine and serotonin levels in rodents in vivo, is about 10-fold less potent than amphetamine in terms of self-administration in monkeys, and is a relatively weak reinforcer in rodents.{{cite book | vauthors = Rothman RB, Blough BE, Baumann MH | chapter = Dopamine/serotonin releasers as medications for stimulant addictions | title = Progress in Brain Research | volume = 172 | pages = 385–406 | date = 2008 | pmid = 18772043 | doi = 10.1016/S0079-6123(08)00919-9 | isbn = 978-0-444-53235-0 | url = }} Although phentermine induces the release of dopamine at sufficiently high concentrations in vitro and at sufficiently high doses in rodents and monkeys in vivo, it may result in only weak or negligible brain dopamine release in humans at typical clinical doses. This may be due to its selectivity for induction of norepinephrine over dopamine release and may be analogous to the case of ephedrine (which is at least 10-fold selective for induction of norepinephrine over dopamine release). The effects of phentermine may be more related to noradrenergic activation rather than dopaminergic activity. However, more research is needed to assess the preceding notions.

As with other MRAs, phentermine produces dopaminergic neurotoxicity in rodents at high doses. It can also produce serotonergic neurotoxicity at very high doses in rodents. The clinical significance of these findings for humans, in which employed doses may be much lower, are unclear.

The combination of phentermine with a serotonin releasing agent (SRA) like fenfluramine results in suppression of brain dopamine release by phentermine and marked attenuation or abolition of phentermine's stimulant and rewarding effects in animals and humans.{{cite journal | vauthors = Rothman RB, Blough BE, Baumann MH | title = Dual dopamine-5-HT releasers: potential treatment agents for cocaine addiction | journal = Trends Pharmacol Sci | volume = 27 | issue = 12 | pages = 612–618 | date = December 2006 | pmid = 17056126 | doi = 10.1016/j.tips.2006.10.006 | url = }}{{cite journal | vauthors = Rothman RB, Baumann MH | title = Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs | journal = Ann N Y Acad Sci | volume = 1074 | issue = 1| pages = 245–260 | date = August 2006 | pmid = 17105921 | doi = 10.1196/annals.1369.064 | bibcode = 2006NYASA1074..245R | url = }}{{cite journal | vauthors = Rothman RB, Blough BE, Baumann MH | title = Dual dopamine/serotonin releasers as potential medications for stimulant and alcohol addictions | journal = AAPS J | volume = 9 | issue = 1 | pages = E1–10 | date = January 2007 | pmid = 17408232 | pmc = 2751297 | doi = 10.1208/aapsj0901001 | url = }}{{cite journal | vauthors = Brauer LH, Johanson CE, Schuster CR, Rothman RB, de Wit H | title = Evaluation of phentermine and fenfluramine, alone and in combination, in normal, healthy volunteers | journal = Neuropsychopharmacology | volume = 14 | issue = 4 | pages = 233–241 | date = April 1996 | pmid = 8924191 | doi = 10.1016/0893-133X(95)00113-R | url = }} Conversely, combined phentermine and fenfluramine administration synergistically enhances the appetite suppression of these drugs in animals and results in greater weight loss than either drug alone in humans. Fenfluramine produces serotonergic neurotoxicity in animals and addition of phentermine results in either no change or augmentation of this neurotoxicity.

Phentermine has been found to be completely inactive as a ligand or agonist of the serotonin 5-HT₂ receptors, including of the serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptors. This is in contrast to the serotonin releasing agents (SRAs) fenfluramine, norfenfluramine, and to a lesser extent chlorphentermine. However, another study found that phentermine was a weak human serotonin 5-HT_2C receptor partial agonist ({{Abbrlink|EC₅₀|half-maximal effective concentration}} = 1,394{{nbsp}}nM, V_max = 66%). In accordance with its lack of serotonin release and serotonin 5-HT_2B receptor agonism, phentermine appears to show no risk of primary pulmonary hypertension (PPH) or valvular heart disease (VHD) in humans.{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic and adverse actions of serotonin transporter substrates | journal = Pharmacol Ther | volume = 95 | issue = 1 | pages = 73–88 | date = July 2002 | pmid = 12163129 | doi = 10.1016/s0163-7258(02)00234-6 | url = https://www.researchgate.net/publication/11223882 }}

Phentermine has been found to be active as an agonist of the rat and human trace amine-associated receptor 1 (TAAR1).{{cite journal | vauthors = Barak LS, Salahpour A, Zhang X, Masri B, Sotnikova TD, Ramsey AJ, Violin JD, Lefkowitz RJ, Caron MG, Gainetdinov RR | title = Pharmacological characterization of membrane-expressed human trace amine-associated receptor 1 (TAAR1) by a bioluminescence resonance energy transfer cAMP biosensor | journal = Molecular Pharmacology | volume = 74 | issue = 3 | pages = 585–594 | date = September 2008 | pmid = 18524885 | pmc = 3766527 | doi = 10.1124/mol.108.048884 | quote = we confirmed agonistic activity at human TAAR1 of several other compounds, including the trace amines octopamine and tryptamine, the amphetamine derivatives l-amphetamine, d-methamphetamine, (+)-MDMA, and phentermine, and the catecholamine metabolites 3-MT and 4-MT (Bunzow et al., 2001; Lindemann and Hoener, 2005; Reese et al., 2007; Wainscott et al., 2007; Wolinsky et al., 2007; Xie and Miller, 2007; Xie et al., 2007). }}{{cite journal | vauthors = Lewin AH, Navarro HA, Mascarella SW | title = Structure-activity correlations for beta-phenethylamines at human trace amine receptor 1 | journal = Bioorg Med Chem | volume = 16 | issue = 15 | pages = 7415–7423 | date = August 2008 | pmid = 18602830 | pmc = 2601700 | doi = 10.1016/j.bmc.2008.06.009 | url = }}{{cite journal | vauthors = Kim N, Shin S, Bae SW | title = cAMP Biosensors Based on Genetically Encoded Fluorescent/Luminescent Proteins | journal = Biosensors | volume = 11 | issue = 2 | date = January 2021 | page = 39 | pmid = 33572585 | pmc = 7911721 | doi = 10.3390/bios11020039 | doi-access = free | url = }}{{cite journal | vauthors = Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Mol Pharmacol | volume = 60 | issue = 6 | pages = 1181–1188 | date = December 2001 | pmid = 11723224 | doi = 10.1124/mol.60.6.1181 | url = }} It appears to be a weak human TAAR1 partial agonist ({{Abbr|EC₅₀|half-maximal effective concentration}} = 5,470{{nbsp}}nM and {{Abbrlink|E_max|maximal efficacy}} = 68% in one study). The drug shows reduced activity as a TAAR1 agonist compared to amphetamine. TAAR1 agonism by amphetamines that possess this action may serve to auto-inhibit and constrain their effects.{{cite book | vauthors = Espinoza S, Gainetdinov RR | title=Taste and Smell | chapter=Neuronal Functions and Emerging Pharmacology of TAAR1 | series=Topics in Medicinal Chemistry | publisher=Springer International Publishing | publication-place=Cham | volume=23 | date=2014 | isbn=978-3-319-48925-4 | doi=10.1007/7355_2014_78 | pages=175–194 | quote = Interestingly, the concentrations of amphetamine found to be necessary to activate TAAR1 are in line with what was found in drug abusers [3, 51, 52]. Thus, it is likely that some of the effects produced by amphetamines could be mediated by TAAR1. Indeed, in a study in mice, MDMA effects were found to be mediated in part by TAAR1, in a sense that MDMA auto-inhibits its neurochemical and functional actions [46]. Based on this and other studies (see other section), it has been suggested that TAAR1 could play a role in reward mechanisms and that amphetamine activity on TAAR1 counteracts their known behavioral and neurochemical effects mediated via dopamine neurotransmission. }}{{cite journal | vauthors = Kuropka P, Zawadzki M, Szpot P | title = A narrative review of the neuropharmacology of synthetic cathinones-Popular alternatives to classical drugs of abuse | journal = Hum Psychopharmacol | volume = 38 | issue = 3 | pages = e2866 | date = May 2023 | pmid = 36866677 | doi = 10.1002/hup.2866 | url = | quote = Another feature that distinguishes [synthetic cathinones (SCs)] from amphetamines is their negligible interaction with the trace amine associated receptor 1 (TAAR1). Activation of this receptor reduces the activity of dopaminergic neurones, thereby reducing psychostimulatory effects and addictive potential (Miller, 2011; Simmler et al., 2016). Amphetamines are potent agonists of this receptor, making them likely to self‐inhibit their stimulating effects. In contrast, SCs show negligible activity towards TAAR1 (Kolaczynska et al., 2021; Rickli et al., 2015; Simmler et al., 2014, 2016). [...] It is worth noting, however, that for TAAR1 there is considerable species variability in its interaction with ligands, and it is possible that the in vitro activity of [rodent TAAR1 agonists] may not translate into activity in the human body (Simmler et al., 2016). The lack of self‐regulation by TAAR1 may partly explain the higher addictive potential of SCs compared to amphetamines (Miller, 2011; Simmler et al., 2013). }}{{cite journal | vauthors = Simmler LD, Buser TA, Donzelli M, Schramm Y, Dieu LH, Huwyler J, Chaboz S, Hoener MC, Liechti ME | title = Pharmacological characterization of designer cathinones in vitro | journal = Br J Pharmacol | volume = 168 | issue = 2 | pages = 458–470 | date = January 2013 | pmid = 22897747 | pmc = 3572571 | doi = 10.1111/j.1476-5381.2012.02145.x | url = | quote = β-Keto-analogue cathinones also exhibited approximately 10-fold lower affinity for the TA1 receptor compared with their respective non-β-keto amphetamines. [...] Activation of TA1 receptors negatively modulates dopaminergic neurotransmission. Importantly, methamphetamine decreased DAT surface expression via a TA1 receptor-mediated mechanism and thereby reduced the presence of its own pharmacological target (Xie and Miller, 2009). MDMA and amphetamine have been shown to produce enhanced DA and 5-HT release and locomotor activity in TA1 receptor knockout mice compared with wild-type mice (Lindemann et al., 2008; Di Cara et al., 2011). Because methamphetamine and MDMA auto-inhibit their neurochemical and functional effects via TA1 receptors, low affinity for these receptors may result in stronger effects on monoamine systems by cathinones compared with the classic amphetamines. }}{{cite journal | vauthors = Di Cara B, Maggio R, Aloisi G, Rivet JM, Lundius EG, Yoshitake T, Svenningsson P, Brocco M, Gobert A, De Groote L, Cistarelli L, Veiga S, De Montrion C, Rodriguez M, Galizzi JP, Lockhart BP, Cogé F, Boutin JA, Vayer P, Verdouw PM, Groenink L, Millan MJ | title = Genetic deletion of trace amine 1 receptors reveals their role in auto-inhibiting the actions of ecstasy (MDMA) | journal = J Neurosci | volume = 31 | issue = 47 | pages = 16928–16940 | date = November 2011 | pmid = 22114263 | pmc = 6623861 | doi = 10.1523/JNEUROSCI.2502-11.2011 | url = }}

Phentermine is a very weak monoamine oxidase inhibitor (MAOI) in vitro.{{cite journal | vauthors = Reyes-Parada M, Iturriaga-Vasquez P, Cassels BK | title = Amphetamine Derivatives as Monoamine Oxidase Inhibitors | journal = Front Pharmacol | volume = 10 | issue = | pages = 1590 | date = 2019 | pmid = 32038257 | pmc = 6989591 | doi = 10.3389/fphar.2019.01590 | doi-access = free | url = }}{{cite journal | vauthors = Ulus IH, Maher TJ, Wurtman RJ | title = Characterization of phentermine and related compounds as monoamine oxidase (MAO) inhibitors | journal = Biochem Pharmacol | volume = 59 | issue = 12 | pages = 1611–1621 | date = June 2000 | pmid = 10799660 | doi = 10.1016/s0006-2952(00)00306-3 | url = }} It specifically inhibits monoamine oxidase A (MAO-A) ({{Abbrlink|IC₅₀|half-maximal inhibitory concentration}} = 85,000–143,000{{nbsp}}nM) and monoamine oxidase B (MAO-B) ({{Abbr|IC₅₀|half-maximal inhibitory concentration}} = 285,000{{nbsp}}nM). However, its potency as a MAOI is far below its potency as a monoamine releasing agent. Relatedly, phentermine does not show neurochemical signs of MAOI activity in rodents in vivo. As such, the significance of phentermine as an MAOI in humans is questionable.

The pharmacokinetics of phentermine are dose-dependent.{{cite web | title=Phentermine: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=4 May 1959 | url=https://go.drugbank.com/drugs/DB00191 | access-date=8 January 2025}} Peak concentrations of phentermine are reached 6{{nbsp}}hours following oral administration of a dose of 15{{nbsp}}mg. The steady-state levels of phentermine with continuous administration have been found to be around 200{{nbsp}}ng/mL in clinical studies. The oral bioavailability of phentermine is not affected by intake of a high-fat meal.

The volume of distribution of phentermine is 5{{nbsp}}L/kg. Its plasma protein binding is approximately 17.5%.

Phentermine undergoes minimal metabolism. Only about 6% of an administered dose of phentermine is metabolized. It is metabolized to a minor extent by para-hydroxylation, N-oxidation, and N-hydroxylation, followed by conjugation.

The drug is eliminated mainly in urine. It is excreted 62 to 85% unchanged in urine. The elimination half-life of phentermine is 20 to 25{{nbsp}}hours. The elimination of phentermine is modified by urine acidicity or pH. In the case of acidic urine (pH < 5), the elimination half-life of phentermine has been found to be 7 to 8{{nbsp}}hours. The clearance of phentermine is 8.79{{nbsp}}L/h.

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In 1959, phentermine first received approval from the US Food and Drug Administration (FDA) as an appetite suppressant.{{cite book| vauthors = Ryan DA, Bray GA | veditors = Bray GA, Bouchard C |title=Handbook of Obesity - Volume 2 Clinical Applications | edition = Fourth |date=2014|publisher=Taylor and Francis|location=Hoboken|isbn=9781841849829|page=234|chapter-url=https://books.google.com/books?id=64XOBQAAQBAJ&pg=PA234|chapter=Sibutramine, Phentermine, and Diethylproprion: Sympathomimetic Drugs in the Management of Obesity}} Eventually a hydrochloride salt and a resin form became available.

Phentermine was marketed with fenfluramine or dexfenfluramine as a combination appetite suppressant and fat burning agent under the popular name fen-phen.{{cite news | vauthors = Kolata G |date=23 September 1997 |title=How Fen-Phen, A Diet 'Miracle,' Rose and Fell |url=https://www.nytimes.com/1997/09/23/science/how-fen-phen-a-diet-miracle-rose-and-fell.html |work=New York Times |location=NY, NY, USA |access-date=}} In 1997, after 24 cases of heart valve disease in fen-phen users, fenfluramine and dexfenfluramine were voluntarily taken off the market at the request of the FDA.{{cite web|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm |archive-url=https://web.archive.org/web/20090827064123/http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm |url-status=dead |archive-date=27 August 2009 |title=FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen) |publisher=Fda.gov |access-date=12 July 2013}} Studies later showed nearly 30% of people taking fenfluramine or dexfenfluramine for up to 24 months had abnormal valve findings.{{cite journal | vauthors = Weigle DS | title = Pharmacological therapy of obesity: past, present, and future | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 6 | pages = 2462–2469 | date = June 2003 | pmid = 12788841 | doi = 10.1210/jc.2003-030151 | doi-access = free }}

Phentermine is still available by itself in most countries, including the US. However, because it is similar to amphetamine, it is classified as a controlled substance in many countries. Internationally, phentermine is a schedule IV drug under the Convention on Psychotropic Substances.[http://filofetch.com/pdf/Convention-on-Psychotropic-Substances.pdf Convention on Psychotropic Substances] {{webarchive|url=https://web.archive.org/web/20140314174538/http://filofetch.com/pdf/Convention-on-Psychotropic-Substances.pdf |date=14 March 2014 }} In the United States, it is classified as a Schedule IV controlled substance under the Controlled Substances Act. In contrast, amphetamine preparations are classified as Schedule II controlled substances.{{cite journal | vauthors = Rueda-Clausen CF, Padwal RS, Sharma AM | title = New pharmacological approaches for obesity management | journal = Nature Reviews. Endocrinology | volume = 9 | issue = 8 | pages = 467–478 | date = August 2013 | pmid = 23752772 | doi = 10.1038/nrendo.2013.113 | s2cid = 20072687 | url = https://zenodo.org/record/997601 }}

A company called Vivus developed a combination drug, phentermine/topiramate that it originally called Qnexa and then called Qsymia, which was invented and used off-label by Thomas Najarian, who opened a weight-clinic in Los Osos, California in 2001; Najarian had previously worked at Interneuron Pharmaceuticals, which had developed one of the fen-phen drugs previously withdrawn from the market.{{cite news| vauthors = Pollack A |title=Diet Treatment, Already in Use, to Get F.D.A. Review |url=https://www.nytimes.com/2012/02/17/business/diet-treatment-already-in-use-to-get-fda-review.html|work=The New York Times|date=16 February 2012}} The FDA rejected the combination drug in 2010 due to concerns over its safety. In 2012 the FDA approved it after Vivus re-applied with further safety data.{{cite news| url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm | archive-url=https://web.archive.org/web/20120719085042/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm | url-status=dead | archive-date=19 July 2012 | work=FDA | title=FDA approves weight-management drug Qsymia | date=17 July 2012}} At the time, one obesity specialist estimated that around 70% of his colleagues were already prescribing the combination off-label.

Phentermine, also known as α,α-dimethylphenethylamine or as α-methylamphetamine, is a substituted phenethylamine and amphetamine.{{cite web | title=Phentermine | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/4771 | access-date=9 January 2025}}{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA968 | access-date=9 January 2025 | page=968}}{{cite book | author=Schweizerischer Apotheker-Verein | title=Index Nominum 2000: International Drug Directory | publisher=Medpharm Scientific Publishers | year=2000 | isbn=978-3-88763-075-1 | url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA824 | access-date=9 January 2025 | page=824}} It is the derivative of amphetamine in which a second methyl group is present at the alpha carbon. The drug is a positional isomer of methamphetamine (N-methylamphetamine) and of other methylamphetamines such as 4-methylamphetamine.

A number of derivatives of phentermine exist, including cericlamine, chlorphentermine, cloforex, clortermine, etolorex, mephentermine, 3,4-methylenedioxyphentermine (MDPH), 3,4-methylenedioxy-N-methylphentermine (MDMP or MDMPH), and pentorex, among others. Some of these drugs, including chlorphentermine, cloforex, clortermine, and mephentermine, have been marketed as pharmaceutical drugs similarly to phentermine, for instance as appetite suppressants.

The term ‘phentermine' is contracted from phenyl-tertiary-butyl amine.

Phentermine is marketed under many brand names and formulations worldwide, including Acxion, Adipex, Adipex-P, Duromine, Elvenir, Fastin, Ionamin, Lomaira (phentermine hydrochloride), Panbesy, Qsymia (phentermine and topiramate), Razin, Redusa, Sentis, Suprenza, and Terfamex.{{cite web|title=International brands for phentermine|url=https://www.drugs.com/international/phentermine.html|publisher=Drugs.com|access-date=13 October 2016}}

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