POTENTIAL DRUG-DRUG INTERACTIONS IN HEART FAILURE PATIENTS
Objective: The aim of the present study was to assess the prevalence, risk rating and the severity of hazardous pDDIs (potential drug-drug interactions) in the prescribed pharmacotherapy in the hospital discharged heart failure (HF) patients, primarily with co-administered drugs with narrow therapeutic index (statins, anticoagulants, antithrombotic drugs).
Methods: The prescriptions of chronic heart failure patients for one year (January-December 2014) were analyzed for pDDIs through Lexi-interact® software. DDIs belonging to the categories D (Consider therapy modification) and X (Avoid combination) and/or severity of drug interaction-major, were selected for the study.
Results: After reviewing the medical records of 985 patients, 239 patients were selected based on the criteria mentioned above. The average number of prescription drugs at hospital discharge was 7.27 medications (±1.84 SD) per patient. The total number of pDDIs was 1483 or approximately 6.2 (±3.89 SD) pDDIs per patient. With respect to the risk rating, in categories D and X were detected 76 (5.12 %) and 2 (0.13 %) pDDI, respectively. The major pDDIs were 108 (7.28 %).
Conclusion: HF patients are at high risk of pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety.
2. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, et al. ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America. Circulation 2017;136:e137–e161.
3. Mastromarino V, Casenghi M, Testa M, Gabriele E, Coluccia R, Rubattu S, et al. Polypharmacy in heart failure patients. Curr Heart Fail Rep 2014;11:212-9.
4. Vittalrao AM, Thanusubramanian H, Kumari KM, Shaik AB. Pharmacotherapy of heart failure. Asian J Pharm Clin Res 2018;6:78-87.
5. Marushchak M, Krynytska I. Pharmacological treatment of osteoporosis in patients with coronary heart disease complicated by chronic heart failure. Asian J Pharm Clin Res 2019;1:443-6.
6. Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cut off and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol 2012;65:989-95.
7. Bushardt RL, Massey EB, Simpson TW, Ariail JC, Simpson KN. Polypharmacy: misleading, but manageable. Clin Interv Aging 2008;3:383–9.
8. Zhou SF. Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab 2008;9:310-22.
9. Huo X, Liu K. Renal organic anion transporters in drug-drug interactions and diseases. Eur J Pharm Sci 2018;112:8-19.
10. Roberts AG, Gibbs ME. Mechanisms and the clinical relevance of complex drug-drug interactions. Clin Pharmacol 2018;10:123-34.
11. Lexicomp® interaction analyser (Lexicomp® Inc., Ohio, USA). Available from: http://www.uptodate.com [Last accessed on 05 Mar 2019]
12. Kadam UT, Roberts I, White S, Bednall R, Khunti K, Nilsson PM, et al. Conceptualising multiple drug use in patients with comorbidity and multimorbidity: proposal for standard definitions beyond the term polypharmacy. J Clin Epidemiol 2019;106:98-107.
13. Zocor (simvastatin) [prescribing information]. Whitehouse Station NJ: Merck and Co, Inc.; 2011.
14. Norvasc (amlodipine) [prescribing information]. New York, NY: Pfizer Inc; 2015.
15. Zhou YT, Yu LS, Zeng S, Huang YW, Xu HM, Zhou Q. Pharmacokinetic drug-drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors were determining interaction strength and relevant clinical risk management. Ther Clin Risk Manag 2014;10:17-26.
16. Tufan A, Dede DS, Cavus S, Altintas ND, Iskit AB, Topeli A. Rhabdomyolysis in a patient treated with colchicine and atorvastatin. Ann Pharmacother 2006;40:1466–9.
17. Dvorak Z, Modriansky M, Pichard Garcia L, Balaguer P, Vilarem MJ, Ulrichova J, et al. Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Mol Pharmacol 2003;64:160-9.
18. Valiyil R, Christopher Stine L. Drug-related myopathies of which the clinician should be aware. Curr Rheumatol Rep 2010;12:213-20.
19. Verma S, Eikelboom JW, Nidorf SM, Al-Omran M, Gupta N, Teoh H, et al. Colchicine in cardiac disease: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord 2015;15:96.
20. Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006;80:565-81.
21. Pond SM, Graham GG, Wade DN, Sudlow G. The effects of allopurinol and clofibrate on theelimination of coumarin anticoagulants in man. Aust N Z J Med 1975;5:324–8.
22. Hale SF, Lesar TS. Interaction of vitamin K antagonists and trimethoprim-sulfamethoxazole: ignore at your patient's risk. Drug Metabol Drug Interact 2014;29:53-60.
23. Kim KY, Mancano MA. Fenofibrate potentiates warfarin effects. Ann Pharmacother 2003;37:212-5.
24. Howard Thompson A, Luckey A, George C, Choby BA, Self TH. Graves' disease and treatment effects on warfarin anticoagulation. Case Rep Med 2014. http://dx.doi.org/10.1155/2014/292468
25. Pradaxa (Dabigatran etexilate) [prescribing information]. Boehringer Ingelheim Pharmaceuticals Inc; 2018.
26. Chang SH, Chou IJ, Yeh YH, Chiou MJ, Wen MS, Kuo CT, et al. Association between use of non-vitamin k oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation. JAMA 2017;318:1250-9.
27. Xarelto (rivaroxaban) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc.; 2017.
28. Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 2010;38:92-9.
29. Agewall S, Cattaneo M, Collet JP, Andreotti F, Lip GY, Verheugt FW, et al. Expert position paper on the use of proton pump inhibitors in patients with cardiovascular disease and antithrombotic therapy. Eur Heart J 2013;34:1708–1713, 1713a-1713b.
30. Norgard NB, Mathews KD, Wall GC. Drug-drug interaction between clopidogrel and the proton pump inhibitors. Ann Pharmacother 2009;43:1266-74.
31. Sommers De K, Van Wyk M, Moncrieff J, Schoeman HS. Influence of food and reduced gastric acidity on the bioavailability of bacampicillin and cefuroxime axetil. Br J Clin Pharmacol 1984;18:535-9.
This work is licensed under a Creative Commons Attribution 4.0 International License.