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Zocor Disease Interactions

There are 6 disease interactions with Zocor (simvastatin).

Major

HMG-CoA reductase inhibitors (applies to Zocor) liver disease

Major Potential Hazard, High plausibility. Applicable conditions: 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. Pan HY, DeValut AR, Wang-Iverson D, et al. (1990) "Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin." J Clin Pharmacol, 30, p. 1128-35
  2. Arnon R, Eisenberg S (1992) "Lovastatin-induced hepatitis." Isr J Med Sci, 28, p. 101-2
  3. Mauro VF (1993) "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet, 24, p. 195-202
  4. Mauro VF, MacDonald JL (1991) "Simvastatin: a review of its pharmacology and clinical use." DICP, 25, p. 257-64
  5. Duggan DE, Chen IW, Bayne WF, Halpin RA, Duncan CA, Schwartz MS, Stubbs RJ, Vickers S (1989) "The physiological disposition of lovastatin." Drug Metab Dispos, 17, p. 166-73
  6. Pentikainen PJ, Saraheimo M, Schwartz JI, Amin RD, Schwartz MS, Brunner-Ferber F, Rogers JD (1992) "Comparative pharmacokinetics of lovastatin, simvastatin and pravastatin in humans." J Clin Pharmacol, 32, p. 136-40
  7. Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH (1991) "Biotransformation of pravastatin sodium in humans." Drug Metab Dispos, 19, p. 740-8
  8. Walker JF (1989) "Simvastatin: the clinical profile." Am J Med, 87, s44-6
  9. Simons LA (1993) "Simvastatin in severe primary hypercholesterolemia: efficacy, safety, and tolerability in 595 patients over 18 weeks. The Principal Investigators." Clin Cardiol, 16, p. 317-22
  10. McGovern ME, Mellies MJ (1993) "Long-term experience with pravastatin in clinical research trials." Clin Ther, 15, p. 57-64
  11. (1993) "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med, 153, p. 1079-87
  12. Geddes JA (1990) "Cholestatic jaundice associated with lovastatin (mevacor) therapy." Can Med Assoc J, 143, p. 13-4
  13. McQueen MJ (1990) "Cholestatic jaundice associated with lovastatin (Mevacor) therapy." Can Med Assoc J, 142, p. 841-2
  14. Bilheimer DW (1990) "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology, 77, p. 58-65
  15. Pan HY, Morrison RA, Singhvi SM, Frantz BM, Waclawski AP, Willard DA (1988) "Disposition of pravastatin sodium (SQ 31,000), a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects." Clin Res, 36, a368
  16. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  17. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  18. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  19. Levy RI, Troendle AJ, Fattu JM (1993) "A quarter century of drug treatment of dyslipoproteinemia, with a focus on the new HMG-CoA reductase inhibitor fluvastatin." Circulation, 87, i45-53
  20. Dain JG, Fu E, Gorski J, Nicoletti J, Scallen TJ (1993) "Biotransformation of fluvastatin sodium in humans." Drug Metab Dispos, 21, p. 567-72
  21. Tse FL, Jaffe JM, Troendle A (1992) "Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers." J Clin Pharmacol, 32, p. 630-8
  22. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  23. Halpin RA, Ulm EH, Till AE, Kari PH, Vyas KP, Hunninghake DB, Duggan DE (1993) "Biotransformation of lovastatin .5. species differences in invivo metabolite profiles of mouse, rat, dog, and human." Drug Metab Dispos, 21, p. 1003-11
  24. Jokubaitis LA (1994) "Updated clinical safety experience with fluvastatin." Am J Cardiol, 73, d18-24
  25. Davidson MH, on behalf of the FLUENT Investigators Group (1994) "Fluvastatin long-term extension trial (FLUENT): summary of efficacy and safety." Am J Med, 96 Suppl, 96 (suppl)
  26. Quion JAV, Jones PH (1994) "Clinical pharmacokinetics of pravastatin." Clin Pharmacokinet, 27, p. 94-103
  27. Grimbert S, Pessayre D, Degott C, Benhamou JP (1994) "Acute hepatitis induced by HMG-coa reductase inhibitor, lovastatin." Dig Dis Sci, 39, p. 2032-3
  28. Smit JW, Wijnne HJ, Schobben F, Sitsen A, Debruin TW, Erkelens DW (1995) "Effects of alcohol and fluvastatin on lipid metabolism and hepatic function." Ann Intern Med, 122, p. 678-80
  29. Smit JWA, Wijnne HJA, Schobben F, Sitsen A, Debruin TWA, Erkelens DW (1995) "Effects of alcohol consumption on pharmacokinetics, efficacy, and safety of fluvastatin." Am J Cardiol, 76, a89-96
  30. Bakker-Arkema RG, Davidson MH, Goldstein RJ, Davignon J, Isaacsohn JL, Weiss SR, Keilson LM, Brown WV, Miller VT, Shurzinske LJ, Black DM (1996) "Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia." JAMA, 275, p. 128-33
  31. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  32. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M (1997) "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos, 25, p. 321-31
  33. (2001) "Product Information. Baycol (cerivastatin)." Bayer
  34. Cilla DD Jr, Whitfield LR, Gibson DM, Sedman AJ, Posvar EL (1996) "Multiple-dose pharmacokinetics, pharmacodynamics, and safety of atorvastatin, an inhibitor of HMG-CoA reductase, in healthy subjects." Clin Pharmacol Ther, 60, p. 687-95
  35. Lea AP, McTavish D (1997) "Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias." Drugs, 53, p. 828-47
  36. Cilla DD Jr, Gibson DM, Whitfield LR, Sedman AJ (1996) "Pharmacodynamic effects and pharmacokinetics of atorvastatin after administration to normocholesterolemic subjects in the morning an evening." J Clin Pharmacol, 36, p. 604-9
  37. Posvar EL, Radulovic LL, Cilla DD Jr, Whitfield LR, Sedman AJ (1996) "Tolerance and pharmacokinetics of single-dose atorvastatin, a potent inhibitor of HMG-CoA reductase, in healthy subjects." J Clin Pharmacol, 36, p. 728-31
  38. Lennernas H, Fager G (1997) "Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences." Clin Pharmacokinet, 32, p. 403-25
  39. Muck W, Unger S, Kawano K, Ahr G (1998) "Inter-ethnic comparisons of the pharmacokinetics of the HMG-CoA reductase inhibitor cerivastatin." Br J Clin Pharmacol, 45, p. 583-90
  40. Hartleb M, Rymarczyk G, Januszewski K (1999) "Acute cholestatic hepatitis associated with pravastatin." Am J Gastroenterol, 94, p. 1388-90
  41. Nakad A, Bataille L, Hamoir V, Sempoux C, Horsmans Y (1999) "Atorvastatin-induced acute hepatitis with absence of cross-toxicity with simvastatin." Lancet, 353, p. 1763-4
  42. (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
View all 42 references
Major

HMG-CoA reductase inhibitors (applies to Zocor) rhabdomyolysis

Major Potential Hazard, Moderate plausibility. Applicable conditions: 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. Schalke BB, Schmidt B, Toyka K, Hartung H-P (1992) "Pravastatin-associated inflammatory myopathy." N Engl J Med, 327, p. 649-50
  2. Pierce LR, Wysowski DK, Gross TP (1990) "Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy." JAMA, 264, p. 71-5
  3. Walker JF (1989) "Simvastatin: the clinical profile." Am J Med, 87, s44-6
  4. Simons LA (1993) "Simvastatin in severe primary hypercholesterolemia: efficacy, safety, and tolerability in 595 patients over 18 weeks. The Principal Investigators." Clin Cardiol, 16, p. 317-22
  5. McGovern ME, Mellies MJ (1993) "Long-term experience with pravastatin in clinical research trials." Clin Ther, 15, p. 57-64
  6. Reaven P, Witztum JL (1988) "Lovastatin, nicotinic acid, and rhabdomyolysis." Ann Intern Med, 109, p. 597-8
  7. (1993) "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med, 153, p. 1079-87
  8. Corpier CL, Jones PH, Suki WN, et al. (1988) "Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients." JAMA, 260, p. 239-41
  9. East C, Alivizatos PA, Grundy SM, Jones PH, Farmer JA (1988) "Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation." N Engl J Med, 318, p. 47-8
  10. Norman DJ, Illingworth DR, Munson J, Hosenpud J (1988) "Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin." N Engl J Med, 318, p. 46-7
  11. Wallace CS, Mueller BA (1992) "Lovastatin-induced rhabdomyolysis in the absence of concomitant drugs." Ann Pharmacother, 26, p. 190-2
  12. Bilheimer DW (1990) "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology, 77, p. 58-65
  13. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  14. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  15. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  16. Chariot P, Abadia R, Agnus D, Danan C, Charpentier C, Gherardi RK (1993) "Simvastatin-induced rhabdomyolysis followed by a MELAS syndrome." Am J Med, 94, p. 109-10
  17. McDonagh J, Winocour P, Walker DJ (1993) "Musculoskeletal manifestations during simvastatin therapy." Br J Rheumatol, 32, p. 647-8
  18. Levy RI, Troendle AJ, Fattu JM (1993) "A quarter century of drug treatment of dyslipoproteinemia, with a focus on the new HMG-CoA reductase inhibitor fluvastatin." Circulation, 87, i45-53
  19. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  20. Fernandezzatarain G, Navarro V, Garcia H, Villatoro J, Calvo C (1994) "Rhabdomyolysis and acute renal failure associated with lovastatin." Nephron, 66, p. 483-4
  21. Jokubaitis LA (1994) "Updated clinical safety experience with fluvastatin." Am J Cardiol, 73, d18-24
  22. Lees RS, Lees AM (1995) "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med, 333, p. 664-5
  23. Ahmand S (1995) "Lovastatin-induced myopathy in a hypothyroid patient." J Fam Pract, 41, p. 227-8
  24. Pedersen TR, Berg K, Cook TJ, Faergeman O, Haghfelt T, Kjekshus J, Miettinen T, Musliner TA, Olsson AG, Pyorala K, Thorgeirsso (1996) "Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the scandinavian simvastatin survival study." Arch Intern Med, 156, p. 2085-92
  25. Bakker-Arkema RG, Davidson MH, Goldstein RJ, Davignon J, Isaacsohn JL, Weiss SR, Keilson LM, Brown WV, Miller VT, Shurzinske LJ, Black DM (1996) "Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia." JAMA, 275, p. 128-33
  26. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  27. Vanpuijenbroek EP, Dubufvereijken PWG, Spooren PFMJ, Vandoormaal JJ (1996) "Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil." J Intern Med, 240, p. 403-4
  28. (2001) "Product Information. Baycol (cerivastatin)." Bayer
  29. Grunden JW, Fisher KA (1997) "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother, 31, p. 859-63
  30. Iliadis EA, Rosenson RS (1999) "Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia." Clin Cardiol, 22, p. 25-8
  31. van Puijenbroek EP, Du Buf-Vereijken PW, Spooren PF, van Doormaal JJ (1996) "Possible increased risk of rhabdomyolysis during concomitant use of simvastatin and gemfibrozil." J Intern Med, 240, p. 403-4
  32. Alvarez JM, Rawdanowiz TJ, Goldstein J (1998) "Rhadbdomyolysis after coronary artery bypass grafting in a patient receiving simvastatin." J Thorac Cardiovasc Surg, 116, p. 654-5
  33. Pogson GW, Kindred LH, Carper BG (1999) "Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy." Am J Cardiol, 83, p. 1146
  34. (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
  35. (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
View all 35 references
Major

Simvastatin (applies to Zocor) renal dysfunction

Major Potential Hazard, High plausibility.

Although simvastatin itself is not eliminated by the kidney, the plasma concentrations of total HMG-CoA reductase inhibitors after a single dose of simvastatin may be increased in patients with significant renal impairment, presumably due to the accumulation of active metabolites. Increased HMG-CoA reductase inhibitory activity may be associated with a greater risk of adverse effects, including hepatic and musculoskeletal toxicities. Therapy with simvastatin should be administered cautiously at a reduced dosage in patients with severe renal impairment. Close clinical monitoring is recommended.

References

  1. Mauro VF (1993) "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet, 24, p. 195-202
  2. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  3. Lennernas H, Fager G (1997) "Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences." Clin Pharmacokinet, 32, p. 403-25
Moderate

HMG-CoA reductase inhibitors (applies to Zocor) cognitive impairment

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: 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.

References

  1. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  2. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  3. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  4. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  5. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  6. (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
View all 6 references
Moderate

HMG-CoA reductase inhibitors (applies to Zocor) diabetes

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: 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.

References

  1. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  2. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  3. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  4. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  5. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  6. (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
  7. (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
View all 7 references
Moderate

HMG-CoA reductase inhibitors (applies to Zocor) renal disease

Moderate Potential Hazard, Moderate plausibility. Applicable conditions: 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.

References

  1. (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
  2. (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
  3. (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
  4. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  5. (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
  6. (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
  7. (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
View all 7 references

Zocor drug interactions

There are 311 drug interactions with Zocor (simvastatin).

Zocor alcohol/food interactions

There are 2 alcohol/food interactions with Zocor (simvastatin).


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
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 interaction information available.

Further information

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