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Atorvastatin / ezetimibe Disease Interactions

There are 8 disease interactions with atorvastatin / ezetimibe:

Major

Ezetimibe (Includes Atorvastatin/ezetimibe) ↔ Liver Disease

Severe Potential Hazard, High plausibility

Applies to: Liver Disease

Ezetimibe is partially metabolized in the liver. After a single 10 mg dose, the mean area under the plasma concentration-time curve (AUC) for total ezetimibe was increased approximately 1.7-fold, 3- to 4-fold, and 5- to 6-fold, in patients with mild (Child-Pugh score 5 to 6), moderate (Child-Pugh score 7 to 9), and severe hepatic impairment (Child-Pugh score 10 to 15), respectively, compared to healthy subjects. Due to the unknown effects of increased exposure to ezetimibe in patients with moderate or severe hepatic impairment, therapy with ezetimibe is not recommended in these patients. The combination of ezetimibe with a statin is contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminase levels.

References

  1. "Product Information. Zetia (ezetimibe)." Schering-Plough Corporation, Kenilworth, NJ.
Major

Hmg-Coa Reductase Inhibitors (Includes Atorvastatin/ezetimibe) ↔ Liver Disease

Severe Potential Hazard, High plausibility

Applies to: Liver Disease, Alcoholism

The use of HMG-CoA reductase inhibitors is contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases. HMG-CoA reductase inhibitors are extensively metabolized by the liver. Decreased drug metabolism may lead to accumulation and increased risk of toxicity, including biochemical abnormalities of liver function and, rarely, jaundice, hepatitis, cirrhosis, fatty change in the liver, and fulminant hepatic necrosis. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with a history of liver disease and/or heavy alcohol use. A lower initial dosage may be appropriate, and clinical monitoring of liver transaminase levels according to the individual product package labeling is recommended. Patients who develop elevated ALT or AST levels during therapy should be monitored until abnormalities resolve. If an increase above 3 times the upper limit of normal persists, consideration should be given to a reduction in dosage or withdrawal of therapy.

References

  1. Mauro VF "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet 24 (1993): 195-202
  2. Pan HY, Morrison RA, Singhvi SM, Frantz BM, Waclawski AP, Willard DA "Disposition of pravastatin sodium (SQ 31,000), a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects." Clin Res 36 (1988): a368
  3. Smit JWA, Wijnne HJA, Schobben F, Sitsen A, Debruin TWA, Erkelens DW "Effects of alcohol consumption on pharmacokinetics, efficacy, and safety of fluvastatin." Am J Cardiol 76 (1995): a89-96
  4. "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
  5. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb, Princeton, NJ.
  6. Pentikainen PJ, Saraheimo M, Schwartz JI, Amin RD, Schwartz MS, Brunner-Ferber F, Rogers JD "Comparative pharmacokinetics of lovastatin, simvastatin and pravastatin in humans." J Clin Pharmacol 32 (1992): 136-40
  7. Quion JAV, Jones PH "Clinical pharmacokinetics of pravastatin." Clin Pharmacokinet 27 (1994): 94-103
  8. Grimbert S, Pessayre D, Degott C, Benhamou JP "Acute hepatitis induced by HMG-coa reductase inhibitor, lovastatin." Dig Dis Sci 39 (1994): 2032-3
  9. Duggan DE, Chen IW, Bayne WF, Halpin RA, Duncan CA, Schwartz MS, Stubbs RJ, Vickers S "The physiological disposition of lovastatin." Drug Metab Dispos 17 (1989): 166-73
  10. Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6
  11. Smit JW, Wijnne HJ, Schobben F, Sitsen A, Debruin TW, Erkelens DW "Effects of alcohol and fluvastatin on lipid metabolism and hepatic function." Ann Intern Med 122 (1995): 678-80
  12. Cilla DD Jr, Gibson DM, Whitfield LR, Sedman AJ "Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning an evening." J Clin Pharmacol 36 (1996): 604-9
  13. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos 25 (1997): 321-31
  14. Lea AP, McTavish D "Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias." Drugs 53 (1997): 828-47
  15. "Product Information. Lipitor (atorvastatin)." Parke-Davis, Morris Plains, NJ.
  16. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals, East Hanover, NJ.
  17. Davidson MH, on behalf of the FLUENT Investigators Group "Fluvastatin long-term extension trial (FLUENT): summary of efficacy and safety." Am J Med 96 Suppl (1994): 96 (suppl)
  18. Cilla DD Jr, Whitfield LR, Gibson DM, Sedman AJ, Posvar EL "Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects." Clin Pharmacol Ther 60 (1996): 687-95
  19. Halpin RA, Ulm EH, Till AE, Kari PH, Vyas KP, Hunninghake DB, Duggan DE "Biotransformation of lovastatin .5. species differences in invivo metabolite profiles of mouse, rat, dog, and human." Drug Metab Dispos 21 (1993): 1003-11
  20. McQueen MJ "Cholestatic jaundice associated with lovastatin (Mevacor) therapy." Can Med Assoc J 142 (1990): 841-2
  21. Pan HY, DeValut AR, Wang-Iverson D, et al "Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin." J Clin Pharmacol 30 (1990): 1128-35
  22. "Product Information. Mevacor (lovastatin)." Merck & Co, Inc, West Point, PA.
  23. Bakker-Arkema RG, Davidson MH, Goldstein RJ, Davignon J, Isaacsohn JL, Weiss SR, Keilson LM, Brown WV, Miller VT, Shurzinske LJ, Black DM "Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia." JAMA 275 (1996): 128-33
  24. Arnon R, Eisenberg S "Lovastatin-induced hepatitis." Isr J Med Sci 28 (1992): 101-2
  25. Nakad A, Bataille L, Hamoir V, Sempoux C, Horsmans Y "Atorvastatin-induced acute hepatitis with absence of cross-toxicity with simvastatin." Lancet 353 (1999): 1763-4
  26. Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
  27. "Product Information. Baycol (cerivastatin)." Bayer, West Haven, CT.
  28. "Product Information. Zocor (simvastatin)." Merck & Co, Inc, West Point, PA.
  29. Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
  30. Mauro VF, MacDonald JL "Simvastatin: a review of its pharmacology and clinical use." DICP 25 (1991): 257-64
  31. Muck W, Unger S, Kawano K, Ahr G "Inter-ethnic comparisons of the pharmacokinetics of the HMG-CoA reductase inhibitor cerivastatin." Br J Clin Pharmacol 45 (1998): 583-90
  32. Dain JG, Fu E, Gorski J, Nicoletti J, Scallen TJ "Biotransformation of fluvastatin sodium in humans." Drug Metab Dispos 21 (1993): 567-72
  33. Geddes JA "Cholestatic jaundice associated with lovastatin (mevacor) therapy." Can Med Assoc J 143 (1990): 13-4
  34. Tse FL, Jaffe JM, Troendle A "Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers." J Clin Pharmacol 32 (1992): 630-8
  35. McGovern ME, Mellies MJ "Long-term experience with pravastatin in clinical research trials." Clin Ther 15 (1993): 57-64
  36. Simons LA "Simvastatin in severe primary hypercholesterolemia: efficacy, safety, and tolerability in 595 patients over 18 weeks. The Principal Investigators." Clin Cardiol 16 (1993): 317-22
  37. Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH "Biotransformation of pravastatin sodium in humans." Drug Metab Dispos 19 (1991): 740-8
  38. Levy RI, Troendle AJ, Fattu JM "A quarter century of drug treatment of dyslipoproteinemia, with a focus on the new HMG-CoA reductase inhibitor fluvastatin." Circulation 87 (1993): i45-53
  39. Hartleb M, Rymarczyk G, Januszewski K "Acute cholestatic hepatitis associated with pravastatin." Am J Gastroenterol 94 (1999): 1388-90
  40. Posvar EL, Radulovic LL, Cilla DD Jr, Whitfield LR, Sedman AJ "Tolerance and pharmacokinetics of single-dose atorvastatin, a potent inhibitor of HMG-CoA reductase, in healthy subjects." J Clin Pharmacol 36 (1996): 728-31
  41. Lennernas H, Fager G "Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences." Clin Pharmacokinet 32 (1997): 403-25
View all 41 references
Major

Hmg-Coa Reductase Inhibitors (Includes Atorvastatin/ezetimibe) ↔ Rhabdomyolysis

Severe Potential Hazard, Moderate plausibility

Applies to: Myopathy, Myoneural Disorder, Hypothyroidism, Renal Dysfunction

Severe myopathy, including rhabdomyolysis with acute renal failure secondary to myoglobinuria, has been reported rarely with the use of HMG-CoA reductase inhibitors. The myopathy may be dose-related and is characterized by muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values exceeding 10 times the upper limit of normal. Therapy with HMG-CoA reductase inhibitors should be administered cautiously in patients with preexisting myopathy, in those with predisposing factors for myopathy or with a history of myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. Periodic CPK determinations may be considered in some patients, although the value of such monitoring is uncertain. HMG-CoA reductase inhibitor therapy should be withdrawn if markedly elevated CPK levels occur or if drug-related myopathy is diagnosed or suspected.

References

  1. Norman DJ, Illingworth DR, Munson J, Hosenpud J "Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin." N Engl J Med 318 (1988): 46-7
  2. Vanpuijenbroek EP, Dubufvereijken PWG, Spooren PFMJ, Vandoormaal JJ "Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil." J Intern Med 240 (1996): 403-4
  3. "Product Information. Zocor (simvastatin)." Merck & Co, Inc, West Point, PA.
  4. Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6
  5. Ahmand S "Lovastatin-induced myopathy in a hypothyroid patient." J Fam Pract 41 (1995): 227-8
  6. van Puijenbroek EP, Du Buf-Vereijken PW, Spooren PF, van Doormaal JJ "Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil." J Intern Med 240 (1996): 403-4
  7. Pierce LR, Wysowski DK, Gross TP "Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy." JAMA 264 (1990): 71-5
  8. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb, Princeton, NJ.
  9. Bakker-Arkema RG, Davidson MH, Goldstein RJ, Davignon J, Isaacsohn JL, Weiss SR, Keilson LM, Brown WV, Miller VT, Shurzinske LJ, Black DM "Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia." JAMA 275 (1996): 128-33
  10. Pogson GW, Kindred LH, Carper BG "Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy." Am J Cardiol 83 (1999): 1146
  11. Reaven P, Witztum JL "Lovastatin, nicotinic acid, and rhabdomyolysis." Ann Intern Med 109 (1988): 597-8
  12. "Product Information. Baycol (cerivastatin)." Bayer, West Haven, CT.
  13. Wallace CS, Mueller BA "Lovastatin-induced rhabdomyolysis in the absence of concomitant drugs." Ann Pharmacother 26 (1992): 190-2
  14. Lees RS, Lees AM "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med 333 (1995): 664-5
  15. Grunden JW, Fisher KA "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother 31 (1997): 859-63
  16. "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
  17. Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
  18. Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
  19. Corpier CL, Jones PH, Suki WN, et al. "Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients." JAMA 260 (1988): 239-41
  20. Chariot P, Abadia R, Agnus D, Danan C, Charpentier C, Gherardi RK "Simvastatin-induced rhabdomyolysis followed by a MELAS syndrome." Am J Med 94 (1993): 109-10
  21. Simons LA "Simvastatin in severe primary hypercholesterolemia: efficacy, safety, and tolerability in 595 patients over 18 weeks. The Principal Investigators." Clin Cardiol 16 (1993): 317-22
  22. "Product Information. Lipitor (atorvastatin)." Parke-Davis, Morris Plains, NJ.
  23. Schalke BB, Schmidt B, Toyka K, Hartung H-P "Pravastatin-associated inflammatory myopathy." N Engl J Med 327 (1992): 649-50
  24. Fernandezzatarain G, Navarro V, Garcia H, Villatoro J, Calvo C "Rhabdomyolysis and acute renal failure associated with lovastatin." Nephron 66 (1994): 483-4
  25. Pedersen TR, Berg K, Cook TJ, Faergeman O, Haghfelt T, Kjekshus J, Miettinen T, Musliner TA, Olsson AG, Pyorala K, Thorgeirsso "Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the scandinavian simvastatin survival study." Arch Intern Med 156 (1996): 2085-92
  26. McDonagh J, Winocour P, Walker DJ "Musculoskeletal manifestations during simvastatin therapy." Br J Rheumatol 32 (1993): 647-8
  27. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals, East Hanover, NJ.
  28. Levy RI, Troendle AJ, Fattu JM "A quarter century of drug treatment of dyslipoproteinemia, with a focus on the new HMG-CoA reductase inhibitor fluvastatin." Circulation 87 (1993): i45-53
  29. Iliadis EA, Rosenson RS "Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia." Clin Cardiol 22 (1999): 25-8
  30. Alvarez JM, Rawdanowiz TJ, Goldstein J "Rhadbdomyolysis after coronary artery bypass grafting in a patient receiving simvastatin." J Thorac Cardiovasc Surg 116 (1998): 654-5
  31. McGovern ME, Mellies MJ "Long-term experience with pravastatin in clinical research trials." Clin Ther 15 (1993): 57-64
  32. East C, Alivizatos PA, Grundy SM, Jones PH, Farmer JA "Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation." N Engl J Med 318 (1988): 47-8
  33. "Product Information. Mevacor (lovastatin)." Merck & Co, Inc, West Point, PA.
View all 33 references
Moderate

Ezetimibe (Includes Atorvastatin/ezetimibe) ↔ Myopathy/Rhabdomyolysis

Moderate Potential Hazard, Moderate plausibility

Applies to: Myopathy

Myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs. In post-marketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin prior to initiating ezetimibe. However, rhabdomyolysis has been reported with ezetimibe monotherapy and with the addition of ezetimibe to agents known to be associated with increased risk of rhabdomyolysis, such as fibrates. In the presence of muscle symptoms and a CPK level >10 × the ULN indicative of myopathy, ezetimibe and any statin or fibrate that the patient is taking concomitantly should be immediately discontinued if myopathy is diagnosed or suspected.

Moderate

Ezetimibe (Includes Atorvastatin/ezetimibe) ↔ Renal Impairment

Moderate Potential Hazard, Moderate plausibility

Applies to: Renal Dysfunction

No dosage adjustment of ezetimibe is necessary in patients with renal impairment. However, when ezetimibe therapy is given in combination with simvastatin in patients with moderate to severe renal impairment (estimated glomerular filtration rate <60 mL/min/1.73 m2), doses of simvastatin exceeding 20 mg should be used with caution and close monitoring is recommended.

Moderate

Hmg-Coa Reductase Inhibitors (Includes Atorvastatin/ezetimibe) ↔ Cognitive Impairment

Moderate Potential Hazard, Moderate plausibility

Applies to: CNS Disorder

Cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been observed in patients receiving statins. The reports are usually not serious, and reversible upon statin discontinuation. Caution is recommended when using these agents in patients with cognitive impairment.

Moderate

Hmg-Coa Reductase Inhibitors (Includes Atorvastatin/ezetimibe) ↔ Diabetes

Moderate Potential Hazard, Moderate plausibility

Applies to: Diabetes Mellitus

Increases in HbA1c and fasting serum glucose levels have been reported with the use of certain HMG-CoA reductase inhibitors. Caution should be exercised when using these agents in diabetic patients and close monitoring is recommended.

Moderate

Hmg-Coa Reductase Inhibitors (Includes Atorvastatin/ezetimibe) ↔ Renal Disease

Moderate Potential Hazard, Moderate plausibility

Applies to: Renal Dysfunction

Some HMG-CoA reductase inhibitors such as fluvastatin, have not been studied in patients with severe renal impairment or end-stage renal disease. Some others such as pitavastatin and simvastatin, require a dose reduction when used in this group of patients. Caution and close monitoring is advised when using these drugs in patients with renal impairment.

atorvastatin / ezetimibe drug Interactions

There are 391 drug interactions with atorvastatin / ezetimibe

atorvastatin / ezetimibe alcohol/food Interactions

There is 1 alcohol/food interaction with atorvastatin / ezetimibe

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the relevance of a particular drug interaction to any individual given the large number of variables.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No information available.

Do not stop taking any medications without consulting your healthcare provider.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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