Available from FDA website. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Kane GC, Lipsky JJ. Eur Heart J. 27. From FDA website (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204882.htm). 1999; 353:1274-5. Civeira F, Cenarro A, Ferrando J et al. 1999; 56(Suppl 71):S113-S116. 1993; 71:1408-14. http://www.ncbi.nlm.nih.gov/pubmed/8517385?dopt=AbstractPlus, 30. The Clinical Use of Drugs. Rockville, MD; 2010 Mar 19. 67. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. The GMRs of of simvastatin coadministered with cilostazol to that of simvastatin alone were 1.64 (90% CI, 1.38-1.95) for simvastatin and 1.31 (1.04-1.66) for simvastatin acid. 1984; 69:1065-90A. [Epub ahead of print] . 2011 May 24;123(20):2292-333. 1991 Sep;80(9):830-4 Table 2 summarizes the pharmacokinetic parameters for simvastatin and simvastatin acid. 1999; 100:230-5. http://www.ncbi.nlm.nih.gov/pubmed/10411845?dopt=AbstractPlus. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy. 1990; 150:341-5. http://www.ncbi.nlm.nih.gov/pubmed/2405804?dopt=AbstractPlus, 46. 1995; 92:2404-10. Efficacy and safety of simvastatin 80 mg/day in hypercholesterolemic patients. There was no significant difference in AUC 0-8 or C max values for either SHA or SIM between groups treated with the active and … Olbricht CJ, Wanner C, Thiery J et al. The MARS Research Group. Available from FDA website. Giannini SD, De Goes JM, Dereviacki BE et al. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Dart A, Jerums G, Nicholson G et al. 127. J Pediatr. MAAS Investigators. Int J Clin Pract. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L et al. 1992; 70:1281-6. http://www.ncbi.nlm.nih.gov/pubmed/1442579?dopt=AbstractPlus, 31. Backes JM, Howard PA, Ruisinger JF et al. 1994; 15:255-69. http://www.ncbi.nlm.nih.gov/pubmed/8005129?dopt=AbstractPlus, 21. Clin Ther. FDA Dosing Recommendations for Simvastatin, posted in 2013: Supplemental Table S8. HHS SN - 1744-6872 . A population pharmacokinetic model for simvastatin and its metabolites in children and adolescents. This was an open-label, sequential, single-center study that evaluated the pharmacokinetics of simvastatin when coadministered with PEX168 in healthy adult subjects. The liver is the target organ for the statins, since it is the major site of cholesterol ⦠2015; 372:2387-97. http://www.ncbi.nlm.nih.gov/pubmed/26039521?dopt=AbstractPlus, 310. 113. Lancet. 1999; 13:520-5. Diabetes care. | No statistically significant association was observed between the SLCO1B1 genotype and the pharmacokinetics of lovastatin lactone. 1997; 80:39-44. http://www.ncbi.nlm.nih.gov/pubmed/9205017?dopt=AbstractPlus, 32. 1995; 91:2528-40. http://www.ncbi.nlm.nih.gov/pubmed/7743614?dopt=AbstractPlus. VL - 16. 1997; 129:231-9. http://www.ncbi.nlm.nih.gov/pubmed/9105566?dopt=AbstractPlus, 39. 2013 Nov 12. 1999; 34:1281-6. http://www.ncbi.nlm.nih.gov/pubmed/10601131?dopt=AbstractPlus, 125. 10. Pharmacol Ther. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. 1998; 352: 321-2. http://www.ncbi.nlm.nih.gov/pubmed/9690435?dopt=AbstractPlus, 63. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Circulation. RESULTS: There were no significant associations between the pharmacokinetic parameters of simvastatin lactone and gender. Mauro VF. Hypertension. Lancet. Raal FJ, Pilcher GJ, Illingworth DR et al. 68. Accessed 2010 Sep 20. 1 2004; 292:1307-16. http://www.ncbi.nlm.nih.gov/pubmed/15337732?dopt=AbstractPlus. JO - Pharmacogenetics and Genomics. 1995; 75:455-9. http://www.ncbi.nlm.nih.gov/pubmed/7863988?dopt=AbstractPlus, 117. Med J Aust. http://www.ncbi.nlm.nih.gov/pubmed/6713610?dopt=AbstractPlus. Chan P, Huang TY, Tomlinson B et al. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. Fluvastatin, lovastatin, pravastatin and simvastatin have similar pharmacodynamic properties; all can reduce LDL-cholesterol by 20 to 35%, a reduction which has been shown to achieve decreases of 30 to 35% in major cardiovascular outcomes. 1 Absolute bioavailability is <5%. Am J Cardiol. ), OATP1B1 inhibitors: Potential pharmacokinetic (increased plasma simvastatin acid concentrations) and pharmacodynamic (increased risk of myopathy) interaction.1 339, Increased simvastatin peak plasma concentration and AUC;1 339 increased risk of myopathy and/or rhabdomyolysis, particularly when used with higher dosages of simvastatin1 90 91 92 93 339, Weigh benefits against risks of concomitant use; if used concomitantly, do not exceed simvastatin dosage of 20 mg daily1 339, Itraconazole, ketoconazole, posaconazole, or voriconazole: Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in substantially increased simvastatin peak plasma concentration and/or AUC and increased risk of myopathy and/or rhabdomyolysis1, Itraconazole, ketoconazole, posaconazole, or voriconazole: Concomitant use contraindicated; if short-term therapy with antifungal is unavoidable, interrupt simvastatin therapy during antifungal treatment1, Calcium-channel blocking agents (amlodipine, diltiazem, verapamil), Increased simvastatin peak plasma concentration and AUC;1 339 increased risk of myopathy and/or rhabdomyolysis when used with higher dosages of simvastatin1, Weigh benefits against risks of concomitant use1, Amlodipine: If used concomitantly, do not exceed simvastatin dosage of 20 mg daily1 339, Diltiazem or verapamil: If used concomitantly, do not exceed simvastatin dosage of 10 mg daily1 339, Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in increased simvastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1, Myopathy, including rhabdomyolysis, reported1, Increased risk of myopathy and/or rhabdomyolysis1, Possible increased plasma digoxin concentrations1, Appropriately monitor patients receiving digoxin when simvastatin is initiated1, Increased simvastatin peak plasma concentration and AUC1 339, Weigh benefits against risks of concomitant use; do not exceed simvastatin dosage of 10 mg daily1 339, Fibric acid derivatives (e.g., fenofibrate, gemfibrozil), Fenofibrate: Pharmacokinetic interaction unlikely1, Gemfibrozil: Increased peak plasma concentration and AUC of simvastatin acid1, Gemfibrozil: Concomitant use contraindicated1, Other fibric acid derivatives (e.g., fenofibrate): Use concomitantly with caution; weigh benefits against risks of concomitant use1, Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in increased simvastatin AUC and plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1 378 379, Manufacturer and some clinicians recommend avoiding concomitant use1 379, Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in increased simvastatin peak plasma concentration and AUC and increased risk of myopathy and/or rhabdomyolysis1, Immunosuppressive agents (i.e., cyclosporine, everolimus, sirolimus, tacrolimus), Cyclosporine: Increased simvastatin AUC and increased risk of myopathy and/or rhabdomyolysis1, Everolimus, sirolimus, tacrolimus: Data more limited, but interaction potential expected to be similar to cyclosporine because of similar metabolism339, Cyclosporine: Concomitant use contraindicated1, Everolimus, sirolimus, tacrolimus: Some experts recommend avoiding concomitant use339, Increased peak plasma concentration and AUC of simvastatin and simvastatin acid1, Weigh benefits against risks of concomitant therapy1, When initiating lomitapide, reduce simvastatin dosage by 50%1, Do not exceed simvastatin dosage of 20 mg daily (or 40 mg daily in patients who have received the 80-mg daily dosage for ≥12 months without evidence of adverse muscular effects)1, Macrolides (clarithromycin, erythromycin), Clarithromycin or erythromycin: Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in increased simvastatin plasma concentrations and increased risk of myopathy and/or rhabdomyolysis1, Clarithromycin or erythromycin: Concomitant use contraindicated; if short-term therapy with anti-infective is unavoidable, interrupt simvastatin therapy during anti-infective treatment1, No clinically relevant pharmacokinetic interactions observed375, No dosage adjustment of simvastatin or mipomersen required375, Niacin (antilipemic dosages [≥1 g daily]), Extended-release niacin (2-g single dose): Increased simvastatin peak plasma concentration and AUC1, Extended-release niacin (Niaspan) with fixed-combination simvastatin/ezetimibe: Increased peak plasma concentrations and AUC of niacin and nicotinuric acid; increased peak plasma concentrations of simvastatin acid; increased AUC of total ezetimibe, simvastatin, and simvastatin acid103, Increased risk of myopathy and/or rhabdomyolysis; myopathy, including rhabdomyolysis, reported1, Increased risk of myopathy observed in Chinese versus non-Chinese patients receiving simvastatin 40 mg daily with antilipemic dosages of niacin1 95 103, Increased risk of severe adverse effects (disturbances in glycemic control requiring hospitalization, development of diabetes mellitus, adverse GI effects, myopathy, gout, rash, skin ulceration, infection, bleeding) with concomitant use of niacin (1.5–2 g daily) and simvastatin (40–80 mg daily, with or without ezetimibe)369 371, Use concomitantly with caution; weigh benefits against risks of concomitant therapy1, Extended-release niacin: No dosage adjustments required if used with simvastatin monotherapy1, Patients of Chinese descent: Caution when used concomitantly with simvastatin dosages >20 mg daily; avoid concomitant use with simvastatin 80 mg daily1 103, No effect on rate or extent of exposure to simvastatin or β-hydroxysimvastatin at steady state373, Increased simvastatin peak plasma concentration and AUC; increased risk of myopathy and/or rhabdomyolysis1 339, Inhibition of CYP3A4-dependent metabolism of simvastatin, resulting in substantially increased simvastatin peak plasma concentration and AUC and increased risk of myopathy and/or rhabdomyolysis1, Concomitant use contraindicated; if short-term therapy with telithromycin is unavoidable, interrupt simvastatin therapy during anti-infective treatment1, Possible increased simvastatin plasma concentrations339, Some experts recommend limiting simvastatin dosage to 40 mg daily339, Possible increased PT;1 339 bleeding observed with other statins1, Closely monitor PT until stabilized if simvastatin is initiated or dosage is adjusted in patients receiving warfarin; thereafter, monitor PT at intervals usually recommended for patients receiving warfarin1 339, Rapidly absorbed following oral administration; undergoes extensive first-pass metabolism in the liver.1 Absolute bioavailability is <5%.1 103 Peak plasma concentrations are attained at 4 hours.1, Maximal to near-maximal therapeutic response occurs within 4–6 weeks.1, Simvastatin/ezetimibe fixed-combination preparation (Vytorin) is bioequivalent to corresponding dosages of the individual components.103, Patients with severe renal insufficiency may have higher systemic exposure.1 (See Renal Impairment under Dosage and Administration. From AHA web site. N Engl J Med. Nestel P, Simons L, Barter P et al. Davidson MH, Stein EA, Dujovne CA et al. Lilja JJ, Neuvonen M, Neuvonen PJ. Vigna GB, Donega P, Passaro A et al. Expert Panel on Detection, Evaluation, and Treatment of high Blood Cholesterol in Adults. Circulation. West Point, PA; 1999 Sep. 19. Borghi C, Prandin MG, Costa FV et al. http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3_rpt.htm, 86. NIH Long-term effects of pravastatin on plasma concentration of C-reactive protein. 2008 Aug 8. Accordingly, it is probable that ⦠Like lovastatin, it is an inactive hydrophobic lactone prodrug which is metabolised in vivo to several more polar, pharmacologically active compounds, most notably the corresponding hydroxy acid form, simvastatin acid. 26. Jenkins GH, Grieve LA, Yacoub MH et al. Am J Med. Am J Cardiol. Simvastatin. Effects of extended-release niacin with laropiprant in high-risk patients. 77. 1994; 55:161-71. Kastelein JJ, Akdim F, Stroes ES et al. Lee JW, Morris JK, Wald NJ. Search for more ⦠1995; 29:235-9. http://www.ncbi.nlm.nih.gov/pubmed/7606066?dopt=AbstractPlus, 14. 13. Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. AHFS DI Essentials™. J Cardiovasc Pharmacol. AU - Neuvonen, Pertti J. A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Brown G, Albers JJ, Fisher LD et al. J Intern Med. N Engl J Med. http://www.ncbi.nlm.nih.gov/pubmed/24474185?dopt=AbstractPlus. Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults: Synopsis of the 2013 ACC/AHA Cholesterol Guideline. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol. Similarities and differences. JF - Pharmacogenetics and Genomics. With the concomitant use of simvastatin and pazopanib, an increase in the incidence of ALT elevations has been documented, so simvastatin treatment should be discontinued when these alterations are observed. Transl Clin Pharmacol. A reappraisal of its pharmacology and therapeutic efficacy in hypercholesterolaemia. Am J Med. 339. Clin Pharmacokinet. 1999; 15:394-400. 50. 74. 2019 Sep;75(9):1227-1235. doi: 10.1007/s00228-019-02697-y. Epub 2019 Jun 6. Merck & Co. Zocor (simvastatin) tablets prescribing information. 92. Lancet. Simvastatin and lovastatin are lipophilic, while pravastatin is hydrophilic. Am J Cardiol. (2.2) • Patients who are currently tolerating the 80-mg dose of ZOCOR who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Lancet. Maximal to near-maximal therapeutic response occurs within 4â6 weeks. Wenke K, Meiser B, Thiery J et al. Effect of simvastatin on ejection fraction in cardiac transplant patients. Cannon CP, Blazing MA, Giugliano RP et al. ), Upper respiratory tract infections, headache, abdominal pain, constipation, nausea.1, Metabolized by CYP3A4; does not inhibit CYP3A4.1, Substrate of organic anion transport protein (OATP) 1B1.1, When used in fixed combination with ezetimibe, consider interactions associated with ezetimibe.103 No formal drug interaction studies to date with fixed-combination preparation other than that with extended-release niacin.103 (See Specific Drugs and Foods under Interactions. Rockville, MD; 2012 Feb 27. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Atherosclerosis. J Clin Pharmacol. B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS). Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Short-term safety and efficacy of low-dose simvastatin in elderly patients with hypertensive hypercholesterolemia and fasting hyperinsulinemia. Aggressive lowering of fibrinogen and cholesterol in the prevention of graft vessel disease after heart transplantation. Common side effects include constipation, headaches, and nausea. Stein E, Kreisberg R, Miller V et al. Accessed 2008 Aug 12. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124362.htm. Simvastatin has this effect at doses of about half those of the other 3 statins. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.
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