Abstract
Background
HMG-CoA reductase inhibitors [statins], a widely prescribed cholesterol-lowering therapy, are associated with muscle-related adverse events. While characteristics of such events are well documented in Western countries, little data exists for the Thai population.
Objective
The aim of this study was to determine the characteristics of patients, type and dosing of statin, and to identify patterns of drug use that may be associated with such adverse events using the national pharmacovigilance database known as Thai Vigibase.
Method
Muscle-related adverse events involving statins in the Thai Vigibase from 1996 to December 2009 were identified. For each report, the following information was extracted: patient demographics, co-morbidities, detailed information of adverse event, detailed information of suspected drug, treatment and outcome, as well as causality assessment and quality of reports. Descriptive statistics were performed for all study variables.
Results
A total of 198 cases of statin-associated muscle-related adverse events were identified. Mean age was 61.4 ± 12.4 years of age and 59.6 % were female. Simvastatin, atorvastatin, rosuvastatin and cerivastatin were implicated as the suspected drug in 163 (82.3 %), 24 (12.1 %), 10 (5.1 %) and 1 (0.5 %) cases, respectively. Rhabdomyolysis accounted for 55.6 % of all muscle-related adverse events. Drug interactions known to enhance such toxicity of statins were identified in 40.9 % of the total set of reports. Similar to studies from Western countries, fibrates, HIV protease inhibitors, non-dihydropyridine calcium channel blockers, azole antifungals and macrolides were commonly found in such cases. Interestingly, colchicine has been identified as the second most common drug interaction in our database. Case fatality rates were 0.9, 1.6 and 16.7 %, when there were 0, 1 and ≥2 interacting drugs, respectively.
Conclusions
Characteristics of muscle-related adverse events with statins in the Thai population showed some similarities and differences compared with Western countries. Such similarities included advanced age, female sex, certain co-morbidities and drug interactions. While the majority of interacting drugs are well known, a big proportion of cases of statin-colchicine interaction attributed to long-term use of colchicine in Thailand was noted and should be further investigated. Based on these results, an attempt to avoid dangerous and well-known drug interactions among statin users should be implemented nationwide.
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References
Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL, REACH Registry Investigators, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006;295:180–9.
Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomized controlled trials. BMJ. 2009;338:b2376.
Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of intensive LDL-cholesterol-lowering therapy: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.
Walley T, Folino-Gallo P, Stephens P, et al. Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997–2003. Br J Clin Pharmacol. 2005;60:543–55.
Mann D, Reynolds K, Smith D, Muntner P. Trends in statin use and low-density lipoprotein cholesterol levels among US adults: impact of the 2001 National Cholesterol Education Program guidelines. Ann Pharmacother. 2008;42:1208–15.
Sukonthasarn A, Homsanit M, Prommete B, Chotinaiwattarakul C, Piamsomboon C, Likittanasombat K. Lipid-lowering treatment in hypercholesterolemic patients: the CEPHEUS Thailand survey. J Med Assoc Thai. 2011;94:1424–34.
Pattanaprateep O, Pongcharoensuk P, Suvanakoot P, Kaojarern S. Pattern of statins’ utilization at Ramathobodi Hospital, 2005 to 2007. J Med Assoc Thai. 2010;93:1223–31.
Gotto AM Jr. Safety and statin therapy: reconsidering the risks and benefits. Arch Intern Med. 2003;163:657–9.
McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006;97 Suppl.:89C–94C.
Buettner C, Davis RB, Leveille SG, Mittleman MA, Mukamal KJ. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med. 2008;23:1182–6.
Furberg CD, Pitt B. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med. 2001;2:205–7.
Silva MA, Swanson AC, Gandhi PJ, Tataronis GR. Statin-related adverse events: a meta-analysis. Clin Ther. 2006;28:26–35.
Schech S, Graham D, Staffa J, et al. Risk factors for statin-associated rhabdomyolysis. Pharmacoepidemiol Drug Saf. 2007;16:352–8.
Cziraky MJ, Willey VJ, McKenny JM, et al. Statin safety: an assessment using an administrative claims database. Am J Cardiol. 2006;97 Suppl.:61C–8C.
Ronaldson KJ, O’Shea JM, Boyd IW. Risk factors for rhabdomyolysis with simvastatin and atorvastatin. Drug Saf. 2006;29:1061–7.
Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004;292:2585–90.
Chatzizisis YS, Koskinas KC, Misirli G, et al. Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment prevention and treatment. Drug Saf. 2010;33:171–87.
Wysowski DK, Swartz L. Adverse drug event surveillance and drug withdrawals in the United States, 1969–2002: the importance of reporting suspected reactions. Arch Intern Med. 2005;165:1363–9.
Kunac DL, Harrison-Woolrych M, Tatley MV. Pharmacovigilance in New Zealand: the role of the New Zealand Pharmacovigilance Centre in facilitating safer medicines use. N Z Med J. 2008;121:76–89.
Wise L, Parkinson J, Raine J, Breckenridge A. New approaches to drug safety: a pharmacovigilance tool kit. Nat Rev Drug Discov. 2009;8:779–82.
Edwards IR. Pharmacovigilance. Br J Clin Pharmacol. 2012;73:979–82.
Ucar M, Mjorndal T, Dahlqvist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf. 2000;22:441–57.
Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother. 2002;36:288–95.
Lee E, Ryan S, Birmingham B, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmacol Ther. 2005;78:330–41.
Kim K, Johnson JA, Derendorf H. Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol. 2004;44:1083–105.
Wang A, Yu BN, Luo CH, et al. Ile118Val genetic polymorphism of CYP3A4 and its effects on lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients. Eur J Clin Pharmacol. 2005;60:843–8.
Liao JK. Safety and efficacy of statins in Asians. Am J Cardiol. 2007;99:410–4.
Saokaew S, Suwankesawong W, Permsuwan U, et al. Safety of herbal products in Thailand: an analysis of reports in the Thai health product vigilance center database from 2000 to 2008. Drug Saf. 2011;34:339–50.
The Thai Food and Drug Administration, Ministry of Public Health. Pharmacovigilance in Thailand. Pharmacovigilance: partnership for patient safety. Bangkok: Thai Food and Drug Administration, Ministry of Public Health; 2008.
Health Product Vigilance Center. Spontaneous reports of adverse drug reaction, 2008. http://thaihpvc.fda.moph.go.th/thaihvc/Public/News/uploads/hpvc_1_3_4_100322.pdf (Accessed 16 Apr 2013).
Tatro DS, Wickersham RM, editors. Drug interaction facts: the authority on drug interactions, 2009. Missouri: Wolters Kluwer Health; 2009.
Anonymous. The WHO Adverse Reactions Database on-line searches user’s manual; 1997. Uppsala: Uppsala Monitoring Centre.
Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006;368:1155–63.
Itakura H, Kita T, Mabuchi H, et al. Relationship between coronary events and serum cholesterol during 10 years of low-dose simvastatin therapy: long-term efficacy and safety in Japanese patients with hypercholesterolemia in the Japan Lipid Intervention Trial (J-LIT) Extension 10 Study, a prospective large-scale observational cohort study. Circ J. 2008;72:1218–24.
National Drug Committee. The national list of essential drugs, A.D. 2008 [in Thai]. The Royal Gazette (125); 2008. http://www.ratchakitcha.soc.go.th/DATA/PDF/2551/E/051/12.PDF (Accessed 27 Oct 2011).
Holbrook A, Wright M, Sung M, Ribic C, Baker S. Statin-associated rhabdomyolysis: is there a dose-response relationship? Can J Cardiol. 2011;27:146–51.
Armitage J, Baigent C, Chen Z, et al. Treatment of HDL to reduce the incidence of vascular events HPS2-THRIVE ClinicalTrials.gov identifier NCT00461630]. US National Institutes of Health, ClinicalTrials.gov. http://clinicaltrials.gov/ (Accessed 10 Apr 2013).
US FDA. MedWatch: the FDA safety information and adverse event reporting program. http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm208610.htm (Accessed 6 Feb 2012).
Atasoyu EM, Evrenkaya TR, Solmazgul E. Possible colchicine rhabdomyolysis in a fluvastatin-treated patient. Ann Pharmacother. 2005;39:1368–9.
Baker SK, Goodwin S, Sur M, et al. Cytoskeletal myotoxicity from simvastatin and colchicine. Muscle Nerve. 2004;30:799–802.
Bouquie R, Deslandes G, Renaud C, et al. Colchicine-induced rhabdomyolysis in a heart/lung transplant patient with concurrent use of cyclosporin, pravastatin, and azithromycin. J Clin Rheumatol. 2011;17:28–30.
Justiniano M, Dold S, Espinoza LR. Rapid onset of muscle weakness (rhabdomyolysis) associated with the combined use of simvastatin and colchicine. J Clin Rheumatol. 2007;13:266–8.
Sarullo FM, Americo L, Di Franco A, et al. Rhabdomyolysis induced by co-administration of fluvastatin and colchicine. Monaldi Arch Chest Dis. 2010;74:147–9.
Tufan A, Dede DS, Cavus S, et al. Rhabdomyolysis in a patient treated with colchicine and atorvastatin. Ann Pharmacother. 2006;40:1466–9.
Alayli G, Cengiz K, Cantürk F, Durmuş D, Akyol Y, Menekşe EB. Acute myopathy in a patient with concomitant use of pravastatin and colchicine. Ann Pharmacother. 2005;39:1358–61.
Hsu WC, Chen WH, Chang MT, Chiu HC. Colchicine-induced acute myopathy in a patient with concomitant use of simvastatin. Clin Neuropharmacol. 2002;25:266–8.
Wallace SL, Singer JZ, Duncan GJ, et al. Renal function predicts colchicine toxicity: guidelines for the prophylatic use of colchicine in gout. J Rheumatol. 1991;18:264–9.
Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet. 2002;41:343–70.
Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2004;19:117–25.
Holtzman CW, Wiggins BS, Spinler SA. Role of P-glycoprotein in statin drug interactions. Pharmacotherapy. 2006;26:1601–7.
Prueksaritanont T, Subramanian R, Fang X, et al. Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos. 2002;30:505–12.
Goosen TC, Bauman JN, Davis JA, et al. Atorvastatin glucuronidation is minimally and nonselectively inhibited by the fibrates gemfibrozil, fenofibrate, and fenofibric acid. Drug Metab Dispos. 2007;35:1315–24.
Cocco G, Chu DC, Pandolfi S. Colchicine in clinical medicine: a guide for internists. Eur J Intern Med. 2010;21:503–8.
Terkeltaub RA. Gout. N Engl J Med. 2003;349:1647–55.
Jordan KM, Carmeron JS, Snaith M, et al. British Society for Rheumatology and British Health Professionals in Rheumatology guideline for the management of gout. Rheumatology. 2007;46:1372–4.
Akasilp S, Laorenu W, Zungsontiporn C, et al. Clinical practice guidelines for the management of hyperuricemia and gout. Thai Rheumatism Association database. http://www.thairheumatology.org/wecha.php (Accessed 27 Oct 2011).
de Langen JJ, van Puijenbroek EP. HMG CoA reductase inhibitors and neuropathy: reports to the Netherlands Pharmacovigilance Centre. Neth J Med. 2006;64:334–8.
Pariente A, Gregoire F, Fourrier-Reglat A, et al. Impact of safety alerts on measures of disproportionality in spontaneous reporting databases: the notoriety bias. Drug Saf. 2007;30:891–8.
Acknowledgments
No sources of funding were used to conduct this study or prepare this manuscript. The authors declare there are no conflicts of interest associated with this work. We thank the HPVC, Food and Drug Administration, Ministry of Public Health, Thailand, for providing helpful support on data access and their valuable inputs for the manuscript.
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Boonmuang, P., Nathisuwan, S., Chaiyakunapruk, N. et al. Characterization of Statin-Associated Myopathy Case Reports in Thailand Using the Health Product Vigilance Center Database. Drug Saf 36, 779–787 (2013). https://doi.org/10.1007/s40264-013-0055-5
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DOI: https://doi.org/10.1007/s40264-013-0055-5