Potential drug-drug interactions with phentermine among long-term phentermine consumers: A retrospective analysis
DOI:
https://doi.org/10.7196/SAMJ.2023.v113i8.428Keywords:
Phentermine, Drug-drug interactions, long-term consumers, South Africa, Anti-obesityAbstract
Background. Phentermine is an internationally recognised amphetamine derivative with significant appetite-suppressing properties. The drug is indicated for the short-term management of obesity, as the long-term (LT) use of phentermine may potentially be associated with severe cardiovascular side-effects, abuse and dependence. The LT use hereinafter describes periods exceeding 12 consecutive weeks. This use may also be associated with potential drug-drug interactions (PDDIs), which may result in adverse drug reactions (ADRs). The literature reports that phentermine is often prescribed LT and for several other off-label indications, increasing the risk for individuals to experience adverse drug events (ADEs) and drug-drug interactions (DDIs). There are, to our knowledge, no South African (SA) studies investigating the prevalence of co-prescribing LT phentermine with drugs that may potentially cause DDIs.
Objective. To determine the prevalence of mild, moderate and severe DDIs with phentermine use when the duration of therapy in private healthcare exceeded 12 consecutive weeks.
Methods. A cross-sectional drug utilisation review (DUR) was done by using data obtained from a SA pharmacy benefit management (PBM) company’s database. Retrospective data of medicine claims for phentermine, from 1 January 2015 to 31 December 2019, were extracted for analysis. The number of days phentermine was supplied was used to identify the study population, in other words, those patients who received the drug LT. A drug interaction checker (Drugs.com) was used to identify potential mild, moderate and severe DDIs when using phentermine and co-prescribed drugs concurrently.
Results. A total of 889 patients received phentermine LT. The top 20 drugs identified as being frequently co-prescribed in this study population demonstrated no mild PDDI, 15 (75%) moderate PDDIs and 5 (25%) severe PDDIs. The most common co-prescribed drug in the moderate group was dextromethorphan (n=282, 31.72%) and the least co-prescribed was formoterol (n=52, 5.85%). Among the drug group ‘severe PDDIs’, tramadol (n=416, 46.79%) was most frequently prescribed, whereas phenylpropanolamine (n=69, 7.76%) was the least prescribed to patients in this group.
Conclusion. There are patients who receive LT phentermine therapy despite the potential severe consequences that may result. These patients may receive concomitant therapy with phentermine and other pharmaceutical constituents, which may potentially cause DDIs, more specifically, moderate and severe DDIs. As such, these patients are not only confronted with the consequences of DDIs but are also at risk to experience ADRs as the residual effect of PDDIs.
References
Truter I. Prescription appetite suppressants: A drug utilisation study using a claims database. J Pharm
Sci 2014;4(8):32-35. https://doi.org/10.7324/japs.2014.40806
Truter I. Dispensing patterns of prescription-only antiobesity preparations in South Africa. S Afr J Clin
Nutr 2016;29(4):139-144. https://doi.org/10.1080/16070658.2016.1217643
Rossiter DP. South African Medicines Formulary. 12th edition. Pretoria: SAMF, 2016:70-71.
Marais A. The pharmacological management of obesity. S Afr Fam Pract 2018;58(4):16-21. https://doi.
org/10.4102/safp.v58i4.4510
Kalyanasundar B, Perez CI, Luna A, et al. The appetite suppressant D-norpseudoephedrine (cathine) acts
via D1/D2-like dopamine receptors in the nucleus accumbens shell. Front Neurosci 2020;14(572328):1-
https://doi.org/10.3389/fnins.2020.572328
Sanchez-Ramos J. Neurologic complications of psychomotor stimulant abuse. Int Rev Neorobiol
;120(2015):131-160. https://doi.org/10.1016/bs.irn.2015.02.003
Rege S. The dopamine hypothesis of schizophrenia – advances in neurobiology and clinical application.
Psych Scene Hub, 2018. https://psychscenehub.com/psychinsights/the-dopamine-hypothesis-ofschizophrenia/ (accessed 14 May 2022).
Perez CI, Kalyanasundar B, Moreno MG, et al. The triple combination phentermine plus 5-htp/
carbidopa leads to greater weight loss, with fewer psychomotor side-effects than each drug alone. Front
Pharmacol 2019;10:1327.
Rothman RB, Baumann MH. Neurochemical mechanisms of phentermine and fenfluramine:
Therapeutic and adverse effects. Drug Devel Res 2000;51(2):52-65. https://doi.org/10.1002/1098-
%28200010%2951%3A2%3C52%3A%3AAID-DDR2%3E3.0.CO%3B2-H
Volkow ND, Wang G, Baler RD. Reward, dopamine and the control of food intake: Implications for
obesity. Trens Cogn Sci 2011;15(1):37-46. https://doi.org/10.1016/j.tics.2010.11.001
McCorry LK. Physiology of the autonomic nervous system. Am J Pharm Educ 2007;71(4):1-11. https://
doi.org/10.5688/aj710478
Sheng JA, Bales NJ, Myers SA, et al. The hypothalamic-pituitary-adrenal axis: Development, programming
actions of hormones, and maternal-fetal interactions. Front Behav Neurosci 2021;14(601939):1-21.
https://doi.org/10.3389/fnbeh.2020.601939
Dutt M, Wehrle CJ, Jialal I. Physiology, adrenal gland. StatPearls, 2021. https://www.ncbi.nlm.nih.gov/
books/NBK537260/ (accessed 22 July 2022).
Paravati S, Rosani A, Warrington SJ. Physiology, catecholamines. StatPearls, 2020. https://www.ncbi.
nlm.nih.gov/books/NBK507716/ (accessed 23 April 2022).
Alhayek S, Preuss CV. Beta 1 receptors. StatPearls, 2022. https://www.ncbi.nlm.nih.gov/books/
NBK532904/ (accessed 23 April 2022).
Bathia A, Lenchner JR, Saadabadi A. Biochemistry, dopamine receptors. StatPearls, 2020. https://www.
ncbi.nlm.nih.gov/books/NBK538242/ (accessed 8 July 2022).
Farzam K, Kidron A, Lakhkar AD. Adrenergic drugs. StatPearls, 2021. https://www.ncbi.nlm.nih.gov/
books/NBK534230/ (accessed 16 August 2022).
Law J, Martin E. Concise Medical Dictionary. 10th edition. Oxford: Oxford University Press, 2020.
https://www-oxfordreference-com.nwulib.nwu.ac.za/view/10.1093/acref/9780198836612.001.0001/
acref-9780198836612-e-9254?rskey=RuBbkp&result=10652 (accessed 13 January 2022).
WebMD. Phentermine HCL – uses, side-effects, and more. New York: WebMD, 2021. https://www.
webmd.com/drugs/2/drug-4151/phentermine-oral/details (accessed 12 May 2022).
Trantrachoti P, Klomjit S, Rassameehiran S, et al. Supraventricular tachycardia associated with phentermine
use. S West Respir Crit Care Chron 2016;4(15):70-74. https://doi.org/10.12746swrccc2016.0415.206
Kim KK, Cho H, Kang H, et al. Effects on weight reduction and safety of short-term phentermine
administration in Korean obese people. Yonsei Med J 2006;47(5):614-625. https://doi.org/10.3349/
ymj.2006.47.5.614
Hampp C, Kang EM, Borders-Hemphill V. Use of prescription anti-obesity drugs in the United States.
Pharmacotherapy 2013;33(12):1299-1307. https://doi.org/10.1002/phar.1342
iNova Pharmaceuticals Pty Ltd. Duromine. Package insert. Bedfordview: iNova Pharmaceuticals, 2000.
Kokkinos J, Levin SR. Possible association of ischemic stroke with phentermine. Stroke 1993;24(2):310-
https://doi.org/10.1161/01STR.24.2.310
Hussain LS, Reddy V, Maani CV. Physiology, noradrenergic synapse. StatPearls, 2021. https://www.
ncbi.nlm.nih.gov/books/NBK540977/ (accessed 26 June 2022).
Alshak MN, Das JM. Neuroanatomy, sympathetic nervous system. StatPearls, 2020. https://www.ncbi.
nlm.nih.gov/books/NBK542195/ (accessed 23 April 2022).
AMBOSS. Sympathomimetic drugs. AMBOSS, 2020. https://www.amboss.com/us/knowledge/
Sympathomimetic_drugs (accessed 1 September 2020).
Drugs.com. Phentermine disease interactions. Drugs.com, 2020. https://www.drugs.com/diseaseinteractions/phentermine.html#seizure_disorders (accessed 3 May 2022)
Goyal A, Robinson KJ, Sanchack KE. Palpitations. StatPearls, 2020. https://www.ncbi.nlm.nih.gov/
books/NBK436016/ (accessed 14 August 2022).
Hermiz C, Sedhai YR. Angina. StatPearls, 2020. https://www.ncbi.nlm.nih.gov/books/NBK557672/
(accessed 16 September 2022).
Ojha N, Dhamoon AS. Myocardial infarction. StatPearls, 2022. https://www.ncbi.nlm.nih.gov/books/
NBK537076/ (accessed 18 May 2022).
Aronne LJ, Wadden TA, Peterson C, et al. Evaluation of phentermine and topiramate versus phentermine/
topiramate extended-release in obese adults. Obesity 2013;21(11):2163-2171. https://doi.org/10.1002/
oby.20584
Wilding JPH. Combination therapy for obesity. J Psychopharmacol 2017;31(11):1503-1508. https://
doi.org/10.1177/0269881117737401
Marsh DES. Severity of adverse drug reactions. Merck Manual, 2018. https://www.merckmanuals.
com/home/drugs/adverse-drug-reactions/severity-of-adverse-drug-reactions (accessed 4 May 2022).
Drugs.com. 2021a. Drug Interactions Checker (Version 2.12.1) Mobile application.
Hendricks J. Pharmacotherapy. In: Steelman GM, Westman EC, eds. Obesity Evaluation and Treatment
Essentials. London: CRC Press, 2016:137-167.
Chooi YC, Ding C, Magkos F. The epidemiology of obesity. Metabolism 2019;92:6-10. https://doi.
org/10.1016/j.metabol.2018.09.005
Shahabudin S, Bharti C, Faizal P. Surveillance of potential drug-drug interactions in the medicine
department of a tertiary care hospital. JCDR 2012;6(7):1258-1261. https://www.jcdr.net/articles/
PDF/2424/35%20-%204118_U.pdf (accessed 3 May 2022).
Maffei ME. 5-Hydroxytryptophan (5-HTP): Natural occurrence, analysis, biosynthesis, biotechnology,
physiology and toxicology. Int J Mol Sci 2021;22(1):1-25. https://doi.org/10.3390/ijms22010181
Simon LV, Keenaghan M. Serotonin syndrome. StatPearls, 2021. https://www.ncbi.nlm.nih.gov/books/
NBK482377/ (accessed 3 May 2022).
Mathew P, Thoppil D. Hypoglycaemia. StatPearls, 2022. https://www.ncbi.nlm.nih.gov/books/
NBK534841/ (accessed 10 May 2022).
Aggarwal S, Mortensen O. Overview of monoamine transporters. Curr Protoc Pharmacol
;79:12.16.1-12.16.17. https://doi.org/10.1002/cpph.32
Patil N, Rehman A, Jialal I. Hypothyroidism. StatPearls, 2022. https://www.ncbi.nlm.nih.gov/books/
NBK519536/ (accessed 10 May 2022).
Dutt M, Wehrle CJ, Jialal I. Physiology, adrenal gland. StatPearls, 2021. https://www.ncbi.nlm.nih.gov/
books/NBK537260 (accessed 10 May 2022).
Teixeira P, dos Santos P, Pazos-Moura CC. The role of thyroid hormone in metabolism and metabolic
syndrome. Ther Adv Endocrinol Metab 2020;11:1-33. https://doi.org/10.1177/2042018820917869
Mayo Clinic. Hyperthyroidism (overactive thyroid). Mayo Clinic, 2020. https://www.mayoclinic.org/
diseases-conditions/hyperthyroidism/symptoms-causes/syc-20373659 (accessed 10 May 2022).
Lewis KH, Fischer H, Ard J, et al. Safety and effectiveness of longer‐term phentermine use: Clinical
outcomes from an electronic health record cohort. Obesity 2019;27(4):591-602. https://doi.
org/10.1002/oby.22430
Lei X, Ruan G, Lai C, et al. Efficacy and safety of phentermine/topiramate in adults with overweight or
obesity: A systematic review and meta-analysis. Obesity 2021;29(6):985-994. https://doi.org/10.1002/
oby.23152
Haslam D. Weight managements in obesity: Past and present. Int J Clin Pract 2016;70(3):206-217.
https://doi.org/10.111/ijcp.12771
Alomar MJ. Factors affecting the development of adverse drug reactions. Saudi Phar J 2013;22(2):83-
https://doi.org/10.1016/j.jsps.2013.02.003
Mayo Clinic. Seizures. Mayo Clinic, 2021. https://www.mayoclinic.org/diseases-conditions/seizure/
symptoms-causes/syc-20365711 (accessed 3 May 2022).
Vilar S, Friedman C, Hripcsak G. Detection of drug-drug interactions through data mining studies
using clinical sources, scientific literature and social media. Brief Bioinformat 2018;19(5):863-877.
https://doi.org/10.1093/bib/bbx010
Hendricks EJ. Off-label drugs for weight management. Diabetes Metab Syndr Obes 2017;10:223-234.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Jesslee M Du Plessis, Ms A Fourie, Dr M Julyan, Ms CS Mostert
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Licensing Information
The SAMJ is published under an Attribution-Non Commercial International Creative Commons Attribution (CC-BY-NC 4.0) License. Under this license, authors agree to make articles available to users, without permission or fees, for any lawful, non-commercial purpose. Users may read, copy, or re-use published content as long as the author and original place of publication are properly cited.
Exceptions to this license model is allowed for UKRI and research funded by organisations requiring that research be published open-access without embargo, under a CC-BY licence. As per the journals archiving policy, authors are permitted to self-archive the author-accepted manuscript (AAM) in a repository.
Publishing Rights
Authors grant the Publisher the exclusive right to publish, display, reproduce and/or distribute the Work in print and electronic format and in any medium known or hereafter developed, including for commercial use. The Author also agrees that the Publisher may retain in print or electronic format more than one copy of the Work for the purpose of preservation, security and back-up.