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Archiv Fur Kriminologie 2013According to international surveys, the appetite suppressant phentermine has frequently been seized although its approval has been withdrawn in Germany. Phentermine is... (Review)
Review
According to international surveys, the appetite suppressant phentermine has frequently been seized although its approval has been withdrawn in Germany. Phentermine is an isomer of methamphetamine though is not optically active such as e. g. amphetamine. The drug acts as a potent substrate at the norepinephrine transporter simultaneously promoting its release; it has a weaker activity at the dopamine transporter whereas its activity towards the serotonin transporter is negligible. Overall, its pharmacological action is comparable to that of amphetamine albeit less strong. Due to its declining effect with time and its addiction potential it has been recommended that phentermine should be used for a few weeks only. Phentermine hydrochloride is a readily soluble salt; absorption of the resinate compound is considerably slower. The drug is not extensively biotransformed; p- and N-hydroxyphentermine are the primary metabolites also being excreted as glucuronide conjugates. Gas chromatographic techniques to identify and to quantify phentermine in biological specimens are applicable following derivatization; however, liquid chromatography coupled to mass spectrometry is currently preferred for analysis of urine, serum or hair. Short-term clinical studies having been performed in the 80s and 90s revealed no serious harmful side effects. However, there are case reports proposing that phentermine usage might be associated with severe health risks due to hypertension, vasoconstriction and vasculopathy; in some individuals, mental illness had been observed. Apart from the legal consequences following purchase of drugs that have been withdrawn its user will simultaneously run serious and unpredictable health risks.
Topics: Aged; Biotransformation; Comorbidity; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Approval; Drug Combinations; Drug and Narcotic Control; Female; Fenfluramine; Germany; Half-Life; Humans; Hypertension, Pulmonary; Illicit Drugs; Metabolic Clearance Rate; Obesity; Overweight; Phentermine; Risk Factors; Structure-Activity Relationship; Substance Abuse Detection
PubMed: 23678625
DOI: No ID Found -
Expert Opinion on Pharmacotherapy Jun 2015Losing ≥ 5% of initial weight improves quality of life and risk factors for cardiovascular disease (CVD) in obese individuals. Lifestyle modification, the cornerstone... (Review)
Review
INTRODUCTION
Losing ≥ 5% of initial weight improves quality of life and risk factors for cardiovascular disease (CVD) in obese individuals. Lifestyle modification, the cornerstone of weight reduction, may be complemented by pharmacotherapy. In 2012, the FDA approved the combination of phentermine and topiramate extended release (ER) for chronic weight management, as an adjunct to lifestyle modification.
AREAS COVERED
This review examines the safety and efficacy of phentermine-topiramate ER, as determined by randomized controlled trials (RCTs). A preliminary study confirmed the benefit of combining the two medications for improving weight loss and reducing adverse effects, as compared to using equivalent-dose monotherapy alone.
EXPERT OPINION
Across RCTs, groups prescribed phentermine 15 mg/topiramate ER 92 mg lost an average of 10% of initial weight, ∼ 8% more than placebo and 2% more than phentermine 7.5 mg/topiramate 46 mg. Weight loss reduced the risk of developing type 2 diabetes and improved CVD risk factors. Phentermine-topiramate ER, however, was associated with increased heart rate, the clinical significance of which is being investigated in an FDA-required CVD outcomes study. The medication also must be used with caution in women of child-bearing age because of an increased risk to infants of oral cleft.
Topics: Anti-Obesity Agents; Cardiovascular Diseases; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Diabetes Mellitus, Type 2; Disease Management; Drug Combinations; Fructose; Humans; Life Style; Obesity; Phentermine; Randomized Controlled Trials as Topic; Risk Factors; Topiramate; Weight Loss
PubMed: 25958964
DOI: 10.1517/14656566.2015.1041505 -
Drugs of Today (Barcelona, Spain : 1998) Dec 2011Phentermine hydrochloride is a noradrenergic sympathetic amine approved for decades by the U.S. Food and Drug Administration (FDA) at doses as high as 37.5 mg/day for... (Review)
Review
Phentermine hydrochloride is a noradrenergic sympathetic amine approved for decades by the U.S. Food and Drug Administration (FDA) at doses as high as 37.5 mg/day for the short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide marketed since 1996, and approved by the FDA for seizure disorders at doses up to 400 mg/day and for the prevention of migraine headaches at doses up to 100 mg/day. Clinical trial data suggest topiramate promotes weight loss. The prescribing information of neither agent describes adverse drug interactions with the other. The controlled-release formulation of phentermine and topiramate at low, medium and full doses (with full dose containing 15 mg of phentermine hydrochloride and 92 mg of topiramate) promotes weight reduction, with clinical trial data supporting improvement in adiposopathic consequences leading to metabolic diseases. Reported adverse events with this combination agent are as expected, based upon knowledge of the individual components.
Topics: Animals; Anti-Obesity Agents; Appetite Depressants; Chemistry, Pharmaceutical; Drug Approval; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate; United States; United States Food and Drug Administration
PubMed: 22348915
DOI: 10.1358/dot.2011.47.12.1718738 -
Recent Patents on Cardiovascular Drug... Apr 2013Obesity is a major public health concern associated with increased morbidity and mortality. Its prevalence is rising worldwide mainly due to modern lifestyle habits.... (Review)
Review
Obesity is a major public health concern associated with increased morbidity and mortality. Its prevalence is rising worldwide mainly due to modern lifestyle habits. Several mechanisms like inflammation, endothelial dysfunction, increased sympathetic tone, high leptin and insulin concentrations as well as enhanced thrombogenesis are implicated to the emergence and progress of cardiovascular disease. Although, changes in the lifestyle remain the cornerstone of antiobesity treatment, alone do not always provide the desired weight loss. Often, the addition of pharmacotherapy or bariatric surgery is considered the treating option for patients meeting eligibility criteria. Although, bariatric surgery is limited to patients with a high body mass index due to the risks of the procedures, the effects of anti-obesity medication on cardiovascular outcome are still unclear. Several anti-obesity drugs have been abandoned because of serious adverse events. Qsymia is a combination of phentermine and topiramate used for obesity treatment. Administration of this drug reduces body weight and has favorable effects in various metabolic and anthropometric parameters. However, there are concerns regarding cardiovascular safety of this drug. In this review, we are going to present the history of current antiobesity medication focusing on the combination of phentermine and topiramate and recent patents.
Topics: Animals; Anti-Obesity Agents; Cardiovascular Diseases; Delayed-Action Preparations; Drug Combinations; Fructose; Humans; Obesity; Patents as Topic; Phentermine; Topiramate; Treatment Outcome; Weight Loss
PubMed: 23565717
DOI: 10.2174/15748901112079990012 -
Mayo Clinic Proceedings Jul 2019
Topics: Coronary Angiography; Coronary Vasospasm; Humans; Myocardial Infarction; Phentermine
PubMed: 31272562
DOI: 10.1016/j.mayocp.2019.05.021 -
Expert Review of Cardiovascular Therapy Dec 2010Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to... (Review)
Review
Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of non-surgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide D-fructose approved as a treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl/topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediate-release phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease.
Topics: Adipose Tissue; Adiposity; Animals; Anti-Obesity Agents; Appetite Depressants; Appetite Regulation; Delayed-Action Preparations; Drug Approval; Drug Combinations; Drugs, Investigational; Fructose; Humans; Metabolic Diseases; Obesity; Phentermine; Practice Guidelines as Topic; Sympathomimetics; Topiramate; United States; United States Food and Drug Administration; Weight Loss
PubMed: 20707765
DOI: 10.1586/erc.10.125 -
Mayo Clinic Proceedings Jul 2019Women presenting to the cardiac catheterization laboratory with normal coronary arteries without significant atherosclerotic disease is a common presentation. In such...
Women presenting to the cardiac catheterization laboratory with normal coronary arteries without significant atherosclerotic disease is a common presentation. In such patients, it is important to maintain a wide differential and consider alternate diagnoses. We present two cases of women presenting with chest pain found to have severe coronary vasospasm in the setting of recent initiation of phentermine. Phentermine may have vasospastic proprieties which are important to consider when prescribing to patients.
Topics: Central Nervous System Stimulants; Chest Pain; Coronary Vasospasm; Electrocardiography; Female; Humans; Middle Aged; Myocardial Infarction; Nitroglycerin; Phentermine; Vasodilator Agents
PubMed: 31272579
DOI: 10.1016/j.mayocp.2018.08.029 -
The American Journal of Emergency... Oct 2009
Topics: Appetite Depressants; Coronary Angiography; Electrocardiography; Female; Heart Arrest; Humans; Middle Aged; Phentermine
PubMed: 19857423
DOI: 10.1016/j.ajem.2009.07.014 -
Expert Review of Clinical Pharmacology May 2013The aim of this article is to focus on the fixed-dose combination of phentermine and topiramate, a new antiobesity drug recently approved by the US FDA. The mechanisms... (Review)
Review
The aim of this article is to focus on the fixed-dose combination of phentermine and topiramate, a new antiobesity drug recently approved by the US FDA. The mechanisms of weight loss for each drug in monotherapy is described, followed by the rationale for its use as a combination therapy and a comprehensive review of recently published clinical trials that assessed its efficacy and safety.
Topics: Anti-Obesity Agents; Appetite Depressants; Dose-Response Relationship, Drug; Drug Combinations; Fructose; Humans; Obesity; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Treatment Outcome
PubMed: 23656337
DOI: 10.1586/ecp.13.13 -
Medical Principles and Practice :... 2022Hepatic steatosis is associated with increased surgical complications in bariatric surgery patients. We aimed to evaluate the effect of phentermine in reducing hepatic... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Hepatic steatosis is associated with increased surgical complications in bariatric surgery patients. We aimed to evaluate the effect of phentermine in reducing hepatic steatosis, adipose tissue, and surgical complications in patients undergoing bariatric surgery.
METHODS
This was a two-arm, double-blind, randomized, controlled pilot trial of 64 adult subjects with BMI >35 kg/m2 selected for bariatric surgery randomized into phentermine group (15 mg once daily) or placebo group for 8 weeks. Both groups adhered to a hypocaloric diet (500 calories/day) and an individualized exercise program. The primary endpoint was reducing the frequency of hepatic steatosis measured by ultrasound and reducing adipose tissue through fat mass in total kilograms or percentage. Key secondary points were the prevalence of surgical complications. Baseline and final biochemical parameters and blood pressure too were assessments.
RESULTS
In the phentermine group, the frequency of hepatic steatosis decreased by 19%, and the percentage of patients with a normal ultrasound increased from 9% to 28% (p = 0.05). Likewise, the decrease in fat mass in kilograms was more significant in the phentermine group (56.1 kg vs. 51.8 kg, p = 0.02). A significant reduction in the HOMA-IR index was observed regardless of weight loss. No differences in surgical complications were observed between groups. Phentermine was well-tolerated; no differences were observed in the frequency of adverse events between the groups.
CONCLUSIONS
Phentermine decreased the proportion of individuals with hepatic steatosis by 19% and promoted a more significant fat mass loss in kilograms among candidates for bariatric surgery.
Topics: Adult; Bariatric Surgery; Diet, Reducing; Humans; Obesity; Phentermine; Pilot Projects
PubMed: 35526530
DOI: 10.1159/000524805