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2000
Volume 1, Issue 1
  • ISSN: 2949-6632
  • E-ISSN: 2949-6640

Abstract

Introduction

Combinational synthetic medications are a treatment strategy that employs two or more medications to address specific diseases or conditions. This method is particularly prevalent in the management of chronic illnesses, infections, and multifactorial conditions. The use of multiple medications can elevate the risk of side effects due to potential interactions between the drugs. These interactions may result in enhanced or novel adverse effects, complicating the treatment process. This review article aims to enhance awareness and education about the use of combination synthetic medications and the risks linked to combination therapies in medical practice. It emphasizes the potential dangers that may result from the concurrent use of multiple chemicals or individual drugs. The primary focus is on comprehending the consequences of these combinations, which can result in negative health effects. Furthermore, it seeks to address strategies for mitigating risks associated with combination synthetic medications.

Methods

A comprehensive literature analysis was conducted using databases like PubMed and Scopus, focusing on studies published up until April 2025. The investigation focused on analysing the relationship between combination pharmaceutical therapy and adverse effects, exploring innovative strategies to reduce these undesirable outcomes.

Results

This review primarily explored the relationship between combinational drug therapy and its associated undesirable effects, revealing several significant findings. Combination medication therapy is required for the treatment of many complicated disorders, according to a comprehensive study, but it must be used carefully.

Discussion

To prevent hazardous and potentially harmful consequences, pharmacological parameters must be carefully calculated, and a comprehensive understanding must be maintained when combining various drugs. This emphasizes how important it is to carefully arrange medication therapy in order to guarantee both efficacy and safety. The primary areas of focus are the development and use of diverse strategies intended to address specific issues. The most significant insight is that preemptive measures and educated decision-making are necessary to avoid unfavourable outcomes.

Conclusion

This article emphasizes the necessity for increased awareness and comprehensive research in the field of combinational drug therapy. It highlights that a deeper understanding of how different drugs can work together is essential for improving treatment outcomes. The call for more research suggests that current knowledge may be insufficient, indicating a potential gap in the existing literature and clinical practices. Overall, the text advocates for a focused effort to explore the synergies between various medications to enhance therapeutic efficacy and patient care.

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2025-07-31
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References

  1. DasP. DelostM.D. QureshiM.H. SmithD.T. NjardarsonJ.T. A survey of the structures of US FDA approved combination drugs.J. Med. Chem.20196294265431110.1021/acs.jmedchem.8b0161030444362
    [Google Scholar]
  2. MorewitzSJ Chronic diseases and health care: new trends in diabetes, arthritis, osteoporosis, fibromyalgia, low back pain, cardiovascular disease, and cancer.2006
    [Google Scholar]
  3. HeB. LuC. ZhengG. Combination therapeutics in complex diseases.J. Cell. Mol. Med.201620122231224010.1111/jcmm.1293027605177
    [Google Scholar]
  4. BlowerP. de WitR. GoodinS. AaproM. Drug–drug interactions in oncology: Why are they important and can they be minimized?Crit. Rev. Oncol. Hematol.200555211714210.1016/j.critrevonc.2005.03.00715890526
    [Google Scholar]
  5. KratzT. DiefenbacherA. Psychopharmacological treatment in older people: avoiding drug interactions and polypharmacy.Dtsch. Arztebl. Int.201911629-3050851810.3238/arztebl.2019.050831452508
    [Google Scholar]
  6. JiaJ. ZhuF. MaX. Mechanisms of drug combinations: Interaction and network perspectives.Nat. Rev. Drug Discov.20098211112810.1038/nrd268319180105
    [Google Scholar]
  7. PeerigaR. Individualization of Drug Dosage.A Short Guide to Clinical Pharmacokinetics.SingaporeSpringer Nature Singapore20249712010.1007/978‑981‑97‑4283‑7_6
    [Google Scholar]
  8. YuanH. MaQ. YeL. PiaoG. The traditional medicine and modern medicine from natural products.Molecules201621555910.3390/molecules2105055927136524
    [Google Scholar]
  9. TyersM. WrightG.D. Drug combinations: A strategy to extend the life of antibiotics in the 21st century.Nat. Rev. Microbiol.201917314115510.1038/s41579‑018‑0141‑x30683887
    [Google Scholar]
  10. CegielskiJ.P. ChinD.P. EspinalM.A. The global tuberculosis situation: Progress and problems in the 20th century, prospects for the 21st century.Infect. Dis. Clin. North Am.200216115810.1016/S0891‑5520(03)00045‑X11917808
    [Google Scholar]
  11. FalzoneL. SalomoneS. LibraM. Evolution of cancer pharmacological treatments at the turn of the third millennium.Front. Pharmacol.20189130010.3389/fphar.2018.0130030483135
    [Google Scholar]
  12. MayM.T. SterneJ.A. CostagliolaD. HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: A collaborative analysis.Lancet2006368953445145810.1016/S0140‑6736(06)69152‑616890831
    [Google Scholar]
  13. WilkinsC.A. HammanH. HammanJ.H. SteenekampJ.H. Fixed-dose combination formulations in solid oral drug therapy: Advantages, limitations, and design features.Pharmaceutics202416217810.3390/pharmaceutics1602017838399239
    [Google Scholar]
  14. BrownJ.D. Rivera RiveraK.J. HernandezL.Y.C. Natural and synthetic cannabinoids: Pharmacology, uses, adverse drug events, and drug interactions.J. Clin. Pharmacol.202161S2S37S5210.1002/jcph.187134396558
    [Google Scholar]
  15. SunL. MiK. HouY. Pharmacokinetic and pharmacodynamic drug–drug interactions: Research methods and applications.Metabolites202313889710.3390/metabo1308089737623842
    [Google Scholar]
  16. BenedettiM.S. WhomsleyR. PoggesiI. Drug metabolism and pharmacokinetics.Drug Metab. Rev.200941334439010.1080/1083745090289129519601718
    [Google Scholar]
  17. LentineK.L. CostaS.P. WeirM.R. Cardiac disease evaluation and management among kidney and liver transplantation candidates: A scientific statement from the American Heart Association and the American College of Cardiology Foundation.J. Am. Coll. Cardiol.201260543448010.1016/j.jacc.2012.05.00822763103
    [Google Scholar]
  18. DyG.K. AdjeiA.A. Understanding, recognizing, and managing toxicities of targeted anticancer therapies.CA Cancer J. Clin.201363424927910.3322/caac.2118423716430
    [Google Scholar]
  19. MyersS.P. VigarV. The state of the evidence for whole-system, multi-modality naturopathic medicine: a systematic scoping review.J. Altern. Complement. Med.201925214116810.1089/acm.2018.034030785315
    [Google Scholar]
  20. KaurG. RanaP. DwibediV. RathS.K. Herbal or poly-herbal formulations in various viral diseases. in: promising antiviral herbal and medicinal plants.2024799810.1201/9781003329169‑6
    [Google Scholar]
  21. BarcanR. Complementary and alternative medicine: bodies, therapies, senses.Routledge202010.4324/9781003084990
    [Google Scholar]
  22. MatthewsH.B. LucierG.W. FisherK.D. Medicinal herbs in the United States: Research needs.Environ. Health Perspect.19991071077377810.1289/ehp.9910777310504141
    [Google Scholar]
  23. BandaranayakeW.M. Quality control, screening, toxicity, and regulation of herbal drugs.Modern phytomedicine: Turning medicinal plants into drugs.WILEY200625
    [Google Scholar]
  24. WangH. ChenY. WangL. LiuQ. YangS. WangC. Advancing herbal medicine: enhancing product quality and safety through robust quality control practices.Front. Pharmacol.202314126517810.3389/fphar.2023.126517837818188
    [Google Scholar]
  25. MokhtariR.B. HomayouniT.S. BaluchN. Combination therapy in combating cancer.Oncotarget2017823380223804310.18632/oncotarget.1672328410237
    [Google Scholar]
  26. CockI.E. Is the pharmaceutical industry’s preoccupation with the monotherapy drug model stifling the development of effective new drug therapies?Inflammopharmacology201826386187910.1007/s10787‑018‑0488‑729736688
    [Google Scholar]
  27. BakerT.B. McFallR.M. ShohamV. Current status and future prospects of clinical psychology: Toward a scientifically principled approach to mental and behavioral health care.Psychol. Sci. Public Interest2008926710310.1111/j.1539‑6053.2009.01036.x20865146
    [Google Scholar]
  28. OuelletC SaïasT SitV Access to Indigenous and allopathic medicines: A systematic review of barriers and facilitators.Global J Community Psychol Practice20189210.17161/gjcpp.v9i2.20712
    [Google Scholar]
  29. LeopoldJ.A. LoscalzoJ. Emerging role of precision medicine in cardiovascular disease.Circ. Res.201812291302131510.1161/CIRCRESAHA.117.31078229700074
    [Google Scholar]
  30. JacobsenL. WahnU. BiloM.B. Allergen‐specific immunotherapy provides immediate, long‐term and preventive clinical effects in children and adults: The effects of immunotherapy can be categorised by level of benefit ‐the centenary of allergen specific subcutaneous immunotherapy.Clin. Transl. Allergy201221810.1186/2045‑7022‑2‑822500494
    [Google Scholar]
  31. VodovotzY. BarnardN. HuF.B. Prioritized research for the prevention, treatment, and reversal of chronic disease: recommendations from the lifestyle medicine research summit.Front. Med. (Lausanne)2020758574410.3389/fmed.2020.58574433415115
    [Google Scholar]
  32. PayneJ.W. BettmanJ.R. SchkadeD.A. Measuring constructed preferences: Towards a building code.J. Risk Uncertain.1999191/324327010.1023/A:1007843931054
    [Google Scholar]
  33. KalariyaY. KumarA. UllahA. Integrative medicine approaches: Bridging the gap between conventional and renal complementary therapies.Cureus2023159e4603310.7759/cureus.4603337900457
    [Google Scholar]
  34. GoyalM.R. ChauhanA. Holistic Approach of nutrients and traditional natural medicines for human health: A review.Future Integr Med20243319720810.14218/FIM.2023.00089
    [Google Scholar]
  35. MukherjeeP.K. Evidence-based validation of herbal medicine: Translational research on botanicals.Elsevier202210.1016/B978‑0‑323‑85542‑6.00025‑1
    [Google Scholar]
  36. Ulrich-MerzenichG.S. Combination screening of synthetic drugs and plant derived natural products—Potential and challenges for drug development.Synergy201411596910.1016/j.synres.2014.07.011
    [Google Scholar]
  37. MalikM.A. WaniM.Y. HashmiA.A. Combination therapy: Current status and future perspectives.Combination Therapy Against Multidrug Resistance.London, United KingdomAcademic Press202013810.1016/B978‑0‑12‑820576‑1.00001‑9
    [Google Scholar]
  38. LehárJ. KruegerA.S. AveryW. Synergistic drug combinations tend to improve therapeutically relevant selectivity.Nat. Biotechnol.200927765966610.1038/nbt.154919581876
    [Google Scholar]
  39. ShayneP.H. PittsS.R. Severely increased blood pressure in the emergency department.Ann. Emerg. Med.200341451352910.1067/mem.2003.11412658252
    [Google Scholar]
  40. McConnellK. BakerW. Blood pressure management.Kidney Int.20135337414
    [Google Scholar]
  41. HajjarI. Postural blood pressure changes and orthostatic hypotension in the elderly patient: impact of antihypertensive medications.Drugs Aging2005221556810.2165/00002512‑200522010‑0000415663349
    [Google Scholar]
  42. CarrC. NgJ. WigmoreT. The side effects of chemotherapeutic agents.Curr. Anaesth. Crit. Care2008192707910.1016/j.cacc.2008.01.004
    [Google Scholar]
  43. AlhurA. AlhurA.A. Al-RowaisD. Enhancing patient safety through effective interprofessional communication: A focus on medication error prevention.Cureus2024164e5799110.7759/cureus.5799138738027
    [Google Scholar]
  44. SkalliS. ZaidA. SoulaymaniR. Drug interactions with herbal medicines.Ther. Drug Monit.200729667968610.1097/FTD.0b013e31815c17f618043467
    [Google Scholar]
  45. SilvaA. CostaB. CastroI. MourãoJ. ValeN. New perspective for drug–drug interaction in perioperative period.J. Clin. Med.20231214481010.3390/jcm1214481037510925
    [Google Scholar]
  46. KingP.D. PerryM.C. Hepatotoxicity of chemotherapy.Oncologist20016216217610.1634/theoncologist.6‑2‑16211306728
    [Google Scholar]
  47. RhodesT. LillyR. FernándezC. Risk factors associated with drug use: the importance of ‘risk environment’.Drugs Educ. Prev. Policy200310430332910.1080/0968763031000077733
    [Google Scholar]
  48. YeoL.Y. ChangH.C. ChanP.P. FriendJ.R. Microfluidic devices for bioapplications.Small201171124810.1002/smll.201000946
    [Google Scholar]
  49. LiX. ShenX. JiangW. XiY. LiS. Comprehensive review of emerging contaminants: Detection technologies, environmental impact, and management strategies.Ecotoxicol. Environ. Saf.202427811642010.1016/j.ecoenv.2024.11642038701654
    [Google Scholar]
  50. AndreozziL. GiannettiA. CiprianiF. CaffarelliC. MastrorilliC. RicciG. Hypersensitivity reactions to food and drug additives: Problem or myth?Acta Biomed.2019903809030830065
    [Google Scholar]
  51. LamyP.P. Adverse drug effects.Clin. Geriatr. Med.19906229330710.1016/S0749‑0690(18)30618‑92184925
    [Google Scholar]
  52. FriedT.R. TinettiM.E. TowleV. O’LearyJ.R. IannoneL. Effects of benefits and harms on older persons’ willingness to take medication for primary cardiovascular prevention.Arch. Intern. Med.20111711092392810.1001/archinternmed.2011.3221357797
    [Google Scholar]
  53. DaviesE.A. O’MahonyM.S. Adverse drug reactions in special populations – the elderly.Br. J. Clin. Pharmacol.201580479680710.1111/bcp.1259625619317
    [Google Scholar]
  54. HoelR.W. Giddings ConnollyR.M. TakahashiP.Y. Polypharmacy management in older patients.Mayo Clin. Proc.202196124225610.1016/j.mayocp.2020.06.01233413822
    [Google Scholar]
  55. MartinezM.N. AmidonG.L. A mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals.J. Clin. Pharmacol.200242662064310.1177/0097000204200600512043951
    [Google Scholar]
  56. AzmanM. SabriA.H. AnjaniQ.K. MustaffaM.F. HamidK.A. Intestinal absorption study: Challenges and absorption enhancement strategies in improving oral drug delivery.Pharmaceuticals202215897510.3390/ph1508097536015123
    [Google Scholar]
  57. deShazoR.D. KempS.F. Allergic reactions to drugs and biologic agents.JAMA1997278221895190610.1001/jama.1997.035502201010149396651
    [Google Scholar]
  58. VogelW.H. Infusion reactions.Clin. J. Oncol. Nurs.2010142E10E2110.1188/10.CJON.E10‑E2120350882
    [Google Scholar]
  59. ScottI.A. HilmerS.N. ReeveE. Reducing inappropriate polypharmacy: the process of deprescribing.JAMA Intern. Med.2015175582783410.1001/jamainternmed.2015.032425798731
    [Google Scholar]
  60. PlanaD. PalmerA.C. SorgerP.K. Independent drug action in combination therapy: Implications for precision oncology.Cancer Discov.202212360662410.1158/2159‑8290.CD‑21‑021234983746
    [Google Scholar]
  61. VerbeeckR.K. MusuambaF.T. Pharmacokinetics and dosage adjustment in patients with renal dysfunction.Eur. J. Clin. Pharmacol.200965875777310.1007/s00228‑009‑0678‑819543887
    [Google Scholar]
  62. SulashviliN. NimangreR.R. Manifestation of some aspects of cardiovascular diseases, implications, pharmacotherapeutic strategies, effects, impacts and potential hazards in general.Res Jr20253112710.52340/jr.2025.03.01.01
    [Google Scholar]
  63. HatamiH. MojahedianM.M. KesharwaniP. SahebkarA. Advancing personalized medicine with 3D printed combination drug therapies: A comprehensive review of application in various conditions.Eur. Polym. J.202421511324510.1016/j.eurpolymj.2024.113245
    [Google Scholar]
  64. Al-ShammariA.M. The role of clinical pharmacy in the treatment of hypertension in the State of Kuwait.Doctoral dissertation, University of Bradford2012
    [Google Scholar]
  65. NgF. MammenO.K. WiltingI. The International Society for Bipolar Disorders (ISBD) consensus guidelines for the safety monitoring of bipolar disorder treatments.Bipolar Disord.200911655959510.1111/j.1399‑5618.2009.00737.x19689501
    [Google Scholar]
  66. ShirazibeheshtiA. EttefaghianA. KhanizadehF. WilsonG. RadwanT. LucaC. Automated detection of patients at high risk of polypharmacy including anticholinergic and sedative medications.Int. J. Environ. Res. Public Health20232012617810.3390/ijerph2012617837372763
    [Google Scholar]
  67. GresserU. Amoxicillin-clavulanic acid therapy may be associated with severe side effects-review of the literature.Eur. J. Med. Res.20016413914911309226
    [Google Scholar]
  68. HuttnerA. BielickiJ. ClementsM.N. Oral amoxicillin and amoxicillin–clavulanic acid: Properties, indications and usage.Clin. Microbiol. Infect.202026787187910.1016/j.cmi.2019.11.02831811919
    [Google Scholar]
  69. Ciprofloxacin and Dexamethasone OticAvailable From:https://medlineplus.gov/druginfo/meds/a607010.html
  70. Ciprofloxacin/Dexamethasone (Ciprodex) Uses, side effects, and more.2024Available from: https://www.webmd.com/drugs/2/drug-76575/ciprofloxacin-dexamethasone-otic-ear/details
  71. DuPontH.L. EvansD.G. RiosN. CabadaF.J. EvansD.J. DuPontM.W. Prevention of travelers’ diarrhea with trimethoprim-sulfamethoxazole.Clin. Infect. Dis.19824253353910.1093/clinids/4.2.5337051246
    [Google Scholar]
  72. MelinK. Antihypertensives Lippincott Illustrated Reviews: Pharmacology.LWW2014
    [Google Scholar]
  73. AhmedN. MartinelliA. KiruthiC. Antihypertensive drugs.Side Eff Drugs Annu201537227236Elsevier.10.1016/bs.seda.2015.08.003
    [Google Scholar]
  74. NaiduM.U.R. UshaP.R. RaoT.R.K. ShobhaJ.C. Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension.Postgrad. Med. J.20007689635035310.1136/pmj.76.896.35010824049
    [Google Scholar]
  75. DowellD. HaegerichT.M. ChouR. CDC Guideline for prescribing opioids for chronic pain—United States, 2016.JAMA2016315151624164510.1001/jama.2016.146426977696
    [Google Scholar]
  76. PergolizziJ. BögerR.H. BuddK. Opioids and the management of chronic severe pain in the elderly: Consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization Step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone).Pain Pract.20088428731310.1111/j.1533‑2500.2008.00204.x
    [Google Scholar]
  77. DerryC.J. DerryS. MooreR.A. Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.Cochrane Libr.201320195CD01021010.1002/14651858.CD010210.pub223794268
    [Google Scholar]
  78. VolpeD.A. TobinG.A.M.M. MellonR.D. Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs.Regul. Toxicol. Pharmacol.201159338539010.1016/j.yrtph.2010.12.00721215785
    [Google Scholar]
  79. BenyaminR. TrescotA.M. DattaS. Opioid complications and side effects.Pain Physician20082s11S105S12010.36076/ppj.2008/11/S10518443635
    [Google Scholar]
  80. DormandyJ.A. CharbonnelB. EcklandD.J.A. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.Lancet200536694931279128910.1016/S0140‑6736(05)67528‑916214598
    [Google Scholar]
  81. InzucchiS.E. BergenstalR.M. BuseJ.B. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the study of diabetes.Diabetes Care201538114014910.2337/dc14‑244125538310
    [Google Scholar]
  82. CazzolaM. DahlR. Inhaled combination therapy with long-acting β 2-agonists and corticosteroids in stable COPD.Chest2004126122023710.1378/chest.126.1.22015249466
    [Google Scholar]
  83. ZamaniN.F. SjahidA.S. Tuan KamauzamanT.H. LeeY.Y. IslamM.A. Efficacy and safety of domperidone in combination with proton pump inhibitors in gastroesophageal reflux disease: A systematic review and meta-analysis of randomised controlled trials.J. Clin. Med.20221118526810.3390/jcm1118526836142915
    [Google Scholar]
  84. BhattD.L. FoxK.A.A. HackeW. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events.N. Engl. J. Med.2006354161706171710.1056/NEJMoa06098916531616
    [Google Scholar]
  85. BallantyneC.M. BlazingM.A. KingT.R. BradyW.E. PalmisanoJ. Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia.Am. J. Cardiol.200493121487149410.1016/j.amjcard.2004.02.06015194018
    [Google Scholar]
  86. TohenM. VietaE. CalabreseJ. Efficacy of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression.Arch. Gen. Psychiatry200360111079108810.1001/archpsyc.60.11.107914609883
    [Google Scholar]
  87. BlierP. WardH.E. TremblayP. LabergeL. HébertC. BergeronR. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study.Am. J. Psychiatry2010167328128810.1176/appi.ajp.2009.0902018620008946
    [Google Scholar]
  88. CaiJ. XiaoJ. ZhangQ. Side effects and tolerability of post-exposure prophylaxis with zidovudine, lamivudine, and lopinavir/ritonavir: A comparative study with HIV/AIDS patients.Chin. Med. J. (Engl.)2014127142632263625043080
    [Google Scholar]
  89. KowdleyK.V. GordonS.C. ReddyK.R. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.N. Engl. J. Med.2014370201879188810.1056/NEJMoa140235524720702
    [Google Scholar]
  90. SaxP.E. WohlD. YinM.T. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: Two randomised, double-blind, phase 3, non-inferiority trials.Lancet201538599872606261510.1016/S0140‑6736(15)60616‑X25890673
    [Google Scholar]
  91. GreenbergH.L. ShwayderT.A. BieszkN. FivensonD.P. Clotrimazole/betamethasone diproprionate: a review of costs and complications in the treatment of common cutaneous fungal infections.Pediatr. Dermatol.2002191788110.1046/j.1525‑1470.2002.00027.x11860579
    [Google Scholar]
  92. Norethindrone/ethinyl estradiol (Fyavolv, FemHRT, and others).2025Available from:https://www.webmd.com/drugs/2/drug-18857/estradiol-norethindrone-acetate-oral/details
  93. Gemcitabine and cisplatin (GC).Available from:https://www.cancerresearchuk.org/about-cancer/treatment/drugs/gc-gemcis
  94. HuangC.C. LiuH.C. Delirium from valproic acid with lamotrigine.Am. J. Psychiatry200416161128112910.1176/appi.ajp.161.6.1128‑a
    [Google Scholar]
  95. Latanoprost + Timolol.Available from:https://www.truemeds.in/drug-salts/latanoprost-timolol-4800
  96. PolakaS. GomteS.S. PandeyV. Pharmaceutical excipients: Special focus on adverse interactions.Pharmacokinetics and Toxicokinetic Considerations.Academic Press202251354210.1016/B978‑0‑323‑98367‑9.00009‑3
    [Google Scholar]
  97. CorrieK. HardmanJ.G. Mechanisms of drug interactions: Pharmacodynamics and pharmacokinetics.Anaesth. Intensive Care Med.201112415615910.1016/j.mpaic.2010.12.008
    [Google Scholar]
  98. CaballeroM.L. KrantzM.S. QuirceS. PhillipsE.J. StoneC.A. Hidden dangers: Recognizing excipients as potential causes of drug and vaccine hypersensitivity reactions.J. Allergy Clin. Immunol. Pract.2021982968298210.1016/j.jaip.2021.03.00233737254
    [Google Scholar]
  99. GudemanJ. JozwiakowskiM. CholletJ. RandellM. Potential risks of pharmacy compounding.Drugs R D.20131311810.1007/s40268‑013‑0005‑923526368
    [Google Scholar]
  100. DarjiM.A. LalgeR.M. MaratheS.P. Excipient stability in oral solid dosage forms: A review.AAPS PharmSciTech2018191122610.1208/s12249‑017‑0864‑428895106
    [Google Scholar]
  101. PifferiG. RestaniP. The safety of pharmaceutical excipients.Farmaco200358854155010.1016/S0014‑827X(03)00079‑X12875883
    [Google Scholar]
  102. KarriV.V.S.R. KuppusamyG. MulukutlaS. SoodS. MalayandiR. Understanding the implications of pharmaceutical excipients and additives in the treatment of diabetic foot ulcers.Int J Pharm Excipients201661
    [Google Scholar]
  103. UrsinoM.G. PoluzziE. CaramellaC. De PontiF. Excipients in medicinal products used in gastroenterology as a possible cause of side effects.Regul. Toxicol. Pharmacol.20116019310510.1016/j.yrtph.2011.02.01021354240
    [Google Scholar]
  104. ElderD.P. KuentzM. HolmR. Pharmaceutical excipients — quality, regulatory and biopharmaceutical considerations.Eur. J. Pharm. Sci.201687889910.1016/j.ejps.2015.12.01826699228
    [Google Scholar]
  105. AbrantesC.G. DuarteD. ReisC.P. An overview of pharmaceutical excipients: Safe or not safe?J. Pharm. Sci.201610572019202610.1016/j.xphs.2016.03.01927262205
    [Google Scholar]
  106. LockhartH PaineFA PaineFA Packaging of pharmaceuticals and healthcare products.199610.1007/978‑1‑4615‑2125‑9
    [Google Scholar]
  107. DaughtonC.G. TernesT.A. Pharmaceuticals and personal care products in the environment: Agents of subtle change?Environ. Health Perspect.1999107Suppl. 690793810.1289/ehp.99107s690710592150
    [Google Scholar]
  108. GonzalezF.J. TukeyR.H. Drug metabolism. Goodman and Gilman’s.The Pharmacological Basis of Therapeutics.11th edMcGraw-Hill20067191
    [Google Scholar]
  109. CohenM.R. The role of drug packaging and labeling in medication errors.Cohen MR.2nd ed ErrorsM. Washington, DCAmerican Pharmaceutical Association2007111152
    [Google Scholar]
  110. ValliG. GiardinaE.G.V. Benefits, adverse effects and drug interactionsof herbal therapies with cardiovascular effects.J. Am. Coll. Cardiol.20023971083109510.1016/S0735‑1097(02)01749‑711923030
    [Google Scholar]
  111. ChillistoneS. HardmanJ.G. Factors affecting drug absorption and distribution.Anaesth. Intensive Care Med.201718733533910.1016/j.mpaic.2017.04.007
    [Google Scholar]
  112. BenetL.Z. KroetzD. SheinerL. HardmanJ. LimbirdL. Pharmacokinetics: The dynamics of drug absorption, distribution, metabolism, and elimination.Goodman and Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition.McGraw-Hill Education2025
    [Google Scholar]
  113. DuB. DanielsV.R. VaksmanZ. BoydJ.L. CradyC. PutchaL. Evaluation of physical and chemical changes in pharmaceuticals flown on space missions.AAPS J.201113229930810.1208/s12248‑011‑9270‑021479701
    [Google Scholar]
  114. AleeshaR. AugustineT. Vishnu PriyaP.H. XavierS. TomyT. MishraB. Allopolyherbal formulations: A novel symbiotic approach.World J. Pharm. Research199695601
    [Google Scholar]
  115. ZhouX. SetoS.W. ChangD. Synergistic effects of Chinese herbal medicine: A comprehensive review of methodology and current research.Front. Pharmacol.2016720110.3389/fphar.2016.0020127462269
    [Google Scholar]
  116. DasD. M K, Mitra A, Zaky MY, Pathak S, Banerjee A. A review on the efficacy of plant-derived bio-active compounds curcumin and aged garlic extract in modulating cancer and age-related diseases.Curr Rev Clin Exp Pharmacol202419214616210.2174/277243281966623050409322737150987
    [Google Scholar]
  117. SpeersA.B. CabeyK.A. SoumyanathA. WrightK.M. Effects of Withania somnifera (Ashwagandha) on stress and the stress-related neuropsychiatric disorders anxiety, depression, and insomnia.Curr. Neuropharmacol.20211991468149510.2174/1570159X1966621071215155634254920
    [Google Scholar]
  118. RajalekshmiR. AgrawalD.K. Therapeutic efficacy of medicinal plants with allopathic medicine in musculoskeletal diseases.Int J Plant Animal Environ Sci202414410412910.26502/ijpaes.4490170
    [Google Scholar]
  119. MannelM.St. John’s wort drug interactions–review of mechanisms and clinical implications.Drug Saf.2004271177310.2165/00002018‑200427110‑00003
    [Google Scholar]
  120. Francini-PesentiF. PuatoM. PiccoliA. BrocadelloF. Liquorice‐induced hypokalaemia and water retention in the absence of hypertension.Phytother. Res.200822456356510.1002/ptr.240218386259
    [Google Scholar]
  121. TariraiC. ViljoenA.M. HammanJ.H. Herb–drug pharmacokinetic interactions reviewed.Expert Opin. Drug Metab. Toxicol.20106121515153810.1517/17425255.2010.52912921067427
    [Google Scholar]
  122. PatilR.A. PardeshiK.H. ChavanH.P. AmrutkarS.V. Pharmacotherapeutics and pharmacokinetics.Current Advances in Drug Delivery Through Fast Dissolving/Disintegrating Dosage Forms.Sharjah, United Arab EmiratesBentham Science Publishers202215517810.2174/9789815036725122010012
    [Google Scholar]
  123. SaundersP.R. Goldenseal-drug interactions: A concern.Clin. Pharmacol. Ther.202110913421352
    [Google Scholar]
  124. PhamD.Q. PhamA.Q. Interaction potential between cranberry juice and warfarin.Am. J. Health Syst. Pharm.200764549049410.2146/ajhp06037017322161
    [Google Scholar]
  125. MirakianR. EwanP.W. DurhamS.R. BSACI guidelines for the management of drug allergy.Clin. Exp. Allergy2009391436110.1111/j.1365‑2222.2008.03155.x19128352
    [Google Scholar]
  126. RodenD.M. AltmanR.B. BenowitzN.L. Pharmacogenomics: Challenges and opportunities.Ann. Intern. Med.20061451074975710.7326/0003‑4819‑145‑10‑200611210‑0000717116919
    [Google Scholar]
  127. PandeyA. GuptaS.P. Personalized medicine: A comprehensive review.Orient. J. Chem.202440493394410.13005/ojc/400403
    [Google Scholar]
  128. AmbrosioniJ. DíazN.A. MarzoliniC. Outcomes of drug interactions between antiretrovirals and co-medications, including over-the-counter drugs: A real-world study.Infect. Dis. Ther.202413360961710.1007/s40121‑024‑00935‑038372897
    [Google Scholar]
  129. RosenbaumS.E. Basic pharmacokinetics and pharmacodynamics: An integrated textbook and computer simulations2016
    [Google Scholar]
  130. PalleriaC. Di PaoloA. GiofrèC. Pharmacokinetic drug-drug interaction and their implication in clinical management.J. Res. Med. Sci.2013187601
    [Google Scholar]
  131. ChengF. KovácsI.A. BarabásiA.L. Network-based prediction of drug combinations.Nat. Commun.2019101119710.1038/s41467‑019‑09186‑x30867426
    [Google Scholar]
  132. SinghN. YehP.J. Suppressive drug combinations and their potential to combat antibiotic resistance.J. Antibiot. (Tokyo)201770111033104210.1038/ja.2017.10228874848
    [Google Scholar]
  133. LevyH.B. Maybe It’s Your Medications: How to Avoid Unnecessary Drug Therapy and Adverse Drug Reactions.Simon and Schuster2023
    [Google Scholar]
  134. ScarpelloJ.H. Review: Optimal dosing strategies for maximising the clinical response to metformin in type 2 diabetes.Br. J. Diabetes Vasc. Dis.200111283610.1177/14746514010010010501
    [Google Scholar]
  135. Cardona-MorrellM. PrgometM. LakeR. Vital signs monitoring and nurse–patient interaction: A qualitative observational study of hospital practice.Int. J. Nurs. Stud.20165691610.1016/j.ijnurstu.2015.12.00726775214
    [Google Scholar]
  136. BrownM.T. BussellJ.K. Medication adherence: WHO cares?Mayo Clin. Proc.201186430431410.4065/mcp.2010.057521389250
    [Google Scholar]
  137. MuthC. BlomJ.W. SmithS.M. Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: A systematic guideline review and expert consensus.J. Intern. Med.2019285327228810.1111/joim.1284230357955
    [Google Scholar]
  138. DavisE.P. NarayanA.J. Pregnancy as a period of risk, adaptation, and resilience for mothers and infants.Dev Psychopathol202032516253910.1017/S095457942000112133427164
    [Google Scholar]
  139. StepanskiE.J. RybarczykB. Emerging research on the treatment and etiology of secondary or comorbid insomnia.Sleep Med. Rev.200610171810.1016/j.smrv.2005.08.00216376125
    [Google Scholar]
  140. AilabouniN.J. NishtalaP.S. ManginD. TordoffJ.M. Challenges and enablers of deprescribing: A general practitioner perspective.PLoS One2016114e015106610.1371/journal.pone.015106627093289
    [Google Scholar]
  141. MacLaughlinE.J. RaehlC.L. TreadwayA.K. SterlingT.L. ZollerD.P. BondC.A. Assessing medication adherence in the elderly: which tools to use in clinical practice?Drugs Aging200522323125510.2165/00002512‑200522030‑0000515813656
    [Google Scholar]
  142. LiR. CurtisK. ZaidiS.T. VanC. CastelinoR. A new paradigm in adverse drug reaction reporting: consolidating the evidence for an intervention to improve reporting.Expert Opin. Drug Saf.20222191193120410.1080/14740338.2022.211871236031811
    [Google Scholar]
  143. SabatinoJ.M. ADR as litigation lite: Procedural and evidentiary norms embedded within alternative dispute resolution.Emory Law J.1998471289
    [Google Scholar]
  144. KarunarathnaI. GunasenaP. Kapila De AlvisS. Anaphylaxis: The essential guide for healthcare providers.2024Available From: https://www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment
  145. VarnaiP. DavéA. FarlaK. NooijenA. PetrosovaL. The evidence reveal study: Exploring the use of real‐world evidence and complex clinical trial design by the European pharmaceutical industry.Clin. Pharmacol. Ther.202111051180118910.1002/cpt.210333216976
    [Google Scholar]
  146. AppukuttanD. Strategies to manage patients with dental anxiety and dental phobia: literature review.Clin. Cosmet. Investig. Dent.20168355010.2147/CCIDE.S6362627022303
    [Google Scholar]
  147. CoulterA. EllinsJ. Effectiveness of strategies for informing, educating, and involving patients.BMJ20073357609242710.1136/bmj.39246.581169.80
    [Google Scholar]
  148. MatzkeG.R. MoczygembaL.R. WilliamsK.J. CzarM.J. LeeW.T. Impact of a pharmacist–physician collaborative care model on patient outcomes and health services utilization.Am. J. Health Syst. Pharm.201875141039104710.2146/ajhp17078929789318
    [Google Scholar]
  149. AlsharyahI H ZudaidS Multidisciplinary collaboration for enhanced public health response: Insights from pharmacy, epidemiology, emergency care, and social services.JICRCR202472
    [Google Scholar]
  150. AhmedR. Enhancing medication safety: The role of community and hospital pharmacists in modern healthcare systems.Radinka J Health Sci202523328
    [Google Scholar]
  151. MonzonJ. G. DanceyJ. Combination agents versus multi-targeted agents–pros and cons.Drug Discovery Series.The Royal Society of Chemistry201210.1039/9781849734912‑00155
    [Google Scholar]
  152. BickerJ. AlvesG. FalcãoA. FortunaA. Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics.Br. J. Pharmacol.2020177102215223910.1111/bph.1501732056195
    [Google Scholar]
  153. MazharH. The use of complementary and integrative medicines and exploring natural health product-drug interactions in vitro in the management of pediatric attention-deficit hyperactivity disorder.University of Ottawa2020
    [Google Scholar]
  154. HombergJ.R. KyzarE.J. StewartA.M. Improving treatment of neurodevelopmental disorders: Recommendations based on preclinical studies.Expert Opin. Drug Discov.2016111112510.1517/17460441.2016.111583426558752
    [Google Scholar]
  155. SharmaA. KalaS. KumarA. SharmaS. GuptaG. JaiswalV. Deep Learning in Genomics, Personalized Medicine, and Neurodevelopmental Disorders.Intelligent Data Analytics for Bioinformatics and Biomedical Systems.Hoboken, NJ, USAJohn Wiley Sons, Inc.202423526410.1002/9781394247165.ch10
    [Google Scholar]
  156. WalsonP.D. Therapeutic drug monitoring in special populations.Clin. Chem.199844241541910.1093/clinchem/44.2.4159474053
    [Google Scholar]
  157. ElenduC. JeswaniB.M. MadekweC.C. Clinical and electroencephalographic correlates of carbamazepine-associated hiccups in epileptic patients.Ann. Med. Surg. (Lond.)20248674015403410.1097/MS9.000000000000215938989169
    [Google Scholar]
  158. HaddadMJ McComseyG RadixA Natella Rakhmanina WR. Primary care guidance for providers who care for persons with human immunodeficiency virus: 2024 Update by HIVMA/IDSA.2024ciae479.https://www.idsociety.org/practice-guideline/primary-care-management-of-people-with-hiv/
  159. VargasC.M. PrelockP.A. Caring for children with neurodevelopmental disabilities and their families: An innovative approach to interdisciplinary practice.Routledge200410.4324/9781410610980
    [Google Scholar]
  160. Vlahović-PalčevskiV. MentzerD. Postmarketing surveillance.Handb. Exp. Pharmacol.201120533935121882120
    [Google Scholar]
  161. IqubalM.K. SaleemS. ChaudhuriA. Combination therapy: past, present, and future.Nanocarriers for the Delivery of Combination Drugs.Elsevier202114610.1016/B978‑0‑12‑820779‑6.00010‑4
    [Google Scholar]
  162. DemariaS. PikarskyE. KarinM. Cancer and inflammation: Promise for biologic therapy.J. Immunother.201033433535110.1097/CJI.0b013e3181d32e7420386472
    [Google Scholar]
  163. ReligioniU. Barrios-RodríguezR. RequenaP. BorowskaM. OstrowskiJ. Enhancing therapy adherence: Impact on clinical outcomes, healthcare costs, and patient quality of life.Medicina (Kaunas)202561115310.3390/medicina6101015339859135
    [Google Scholar]
  164. ZarrinkamarM. GeranM. GeranM. Patient adherence for oral combination therapies in diabetes management: A scoping review.Health Sci. Rep.202585e7078010.1002/hsr2.7078040309616
    [Google Scholar]
  165. JainN. NagaichU. PandeyM. ChellappanD.K. DuaK. Predictive genomic tools in disease stratification and targeted prevention: a recent update in personalized therapy advancements.EPMA J.202213456158010.1007/s13167‑022‑00304‑236505888
    [Google Scholar]
  166. MeyerL. Drug interactions between HIV-associated lymphoma treatment and antiretroviral therapy.Thesis University of the Free State2019
    [Google Scholar]
  167. WilliamsC.K.O. Therapy of cancer and retroviral diseases.Cancer and AIDS: Part III: Presentation and Management.Springer2019
    [Google Scholar]
  168. FrankJ. Managing hypertension using combination therapy.Am. Fam. Physician20087791279128618540493
    [Google Scholar]
  169. DayD. SiuL.L. Approaches to modernize the combination drug development paradigm.Genome Med.20168111510.1186/s13073‑016‑0369‑x27793177
    [Google Scholar]
  170. GuptaD.K. TiwariA. YadavY. SoniP. JoshiM. Ensuring safety and efficacy in combination products: regulatory challenges and best practices.Front Med Technol20246137744310.3389/fmedt.2024.137744339050909
    [Google Scholar]
  171. KimD.W. WeonK.Y. Pharmaceutical application and development of fixed-dose combination: dosage form review.J. Pharm. Investig.202151555557010.1007/s40005‑021‑00543‑x
    [Google Scholar]
  172. NayanM.U. SultanaA. LeN.T.H. PoluektuvaL.Y. EdagwaB. GendelmanH.E. Advancing long-acting formulations for treating chronic diseases.Neuroimmune Pharmacology and Therapeutics.ChamSpringer Nature Switzerland202463965610.1007/978‑3‑031‑68237‑7_37
    [Google Scholar]
  173. McDonaldH.P. GargA.X. HaynesR.B. Interventions to enhance patient adherence to medication prescriptions: scientific review.JAMA2002288222868287910.1001/jama.288.22.286812472329
    [Google Scholar]
  174. BhandareA. NannorK.M. Bioavailability in drug design and development: A comprehensive review.World J. Pharm. Res.20241317145168
    [Google Scholar]
  175. LiP. ZhaoL. Developing early formulations: Practice and perspective.Int. J. Pharm.20073411-211910.1016/j.ijpharm.2007.05.04917658228
    [Google Scholar]
  176. MbataA.O. SoyegeO.S. NwokediC.N. Preventative medicine and chronic disease management: reducing healthcare costs and improving long-term public health.Int J Multidisciplin Res Growth Evaluation2024561584160010.54660/.IJMRGE.2024.5.6.1584‑1600
    [Google Scholar]
  177. ZhangH. WangG. YangH. Drug delivery systems for differential release in combination therapy.Expert Opin. Drug Deliv.20118217119010.1517/17425247.2011.54747021226651
    [Google Scholar]
  178. SandriG. BonferoniM.C. FerrariF. RossiS. CaramellaC.M. The role of particle size in drug release and absorption.Particulate Products: Tailoring Properties for Optimal Performance. Merkus HenkG. Meesters GabrielM.H. Cham, SwitzerlandSpringer2014323341
    [Google Scholar]
  179. ZiY. YangK. HeJ. WuZ. LiuJ. ZhangW. Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms.Adv. Drug Deliv. Rev.202218811444910.1016/j.addr.2022.11444935835353
    [Google Scholar]
  180. XuL. XuM. SunX. Quantitative comparison of gold nanoparticle delivery via the enhanced permeation and retention (EPR) effect and mesenchymal stem cell (MSC)-based targeting.ACS Nano20231732039205210.1021/acsnano.2c0729536717361
    [Google Scholar]
  181. WangW. SongH. ZhangJ. An injectable, thermosensitive and multicompartment hydrogel for simultaneous encapsulation and independent release of a drug cocktail as an effective combination therapy platform.J. Control. Release2015203576610.1016/j.jconrel.2015.02.01525683618
    [Google Scholar]
  182. ReynoldsT.D. MitchellS.A. BalwinskiK.M. Investigation of the effect of tablet surface area/volume on drug release from hydroxypropylmethylcellulose controlled-release matrix tablets.Drug Dev. Ind. Pharm.200228445746610.1081/DDC‑12000300712056539
    [Google Scholar]
  183. Sousa de AlmeidaM. SusnikE. DraslerB. Taladriz-BlancoP. Petri-FinkA. Rothen-RutishauserB. Understanding nanoparticle endocytosis to improve targeting strategies in nanomedicine.Chem. Soc. Rev.20215095397543410.1039/D0CS01127D33666625
    [Google Scholar]
  184. WangN. ChengX. LiN. WangH. ChenH. Nanocarriers and their loading strategies.Adv. Healthc. Mater.201986180100210.1002/adhm.20180100230450761
    [Google Scholar]
  185. KowalczukA. TrzcinskaR. TrzebickaB. MüllerA.H.E. DworakA. TsvetanovC.B. Loading of polymer nanocarriers: Factors, mechanisms and applications.Prog. Polym. Sci.2014391438610.1016/j.progpolymsci.2013.10.004
    [Google Scholar]
  186. YetisginA.A. CetinelS. ZuvinM. KosarA. KutluO. Therapeutic nanoparticles and their targeted delivery applications.Molecules2020259219310.3390/molecules2509219332397080
    [Google Scholar]
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