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Niacin / simvastatin Disease Interactions

There are 12 disease interactions with niacin / simvastatin:

Major

Hmg-Coa Reductase Inhibitors (Includes Niacin/simvastatin) ↔ 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. "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
  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. 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
  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. 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
  9. Grimbert S, Pessayre D, Degott C, Benhamou JP "Acute hepatitis induced by HMG-coa reductase inhibitor, lovastatin." Dig Dis Sci 39 (1994): 2032-3
  10. Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6
  11. 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
  12. 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
  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. Arnon R, Eisenberg S "Lovastatin-induced hepatitis." Isr J Med Sci 28 (1992): 101-2
  16. 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
  17. 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
  18. "Product Information. Lipitor (atorvastatin)." Parke-Davis, Morris Plains, NJ.
  19. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals, East Hanover, NJ.
  20. 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)
  21. "Product Information. Zocor (simvastatin)." Merck & Co, Inc, West Point, PA.
  22. 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
  23. McQueen MJ "Cholestatic jaundice associated with lovastatin (Mevacor) therapy." Can Med Assoc J 142 (1990): 841-2
  24. Pan HY, DeValut AR, Wang-Iverson D, et al "Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin." J Clin Pharmacol 30 (1990): 1128-35
  25. "Product Information. Mevacor (lovastatin)." Merck & Co, Inc, West Point, PA.
  26. Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
  27. Mauro VF, MacDonald JL "Simvastatin: a review of its pharmacology and clinical use." DICP 25 (1991): 257-64
  28. Geddes JA "Cholestatic jaundice associated with lovastatin (mevacor) therapy." Can Med Assoc J 143 (1990): 13-4
  29. 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
  30. 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
  31. McGovern ME, Mellies MJ "Long-term experience with pravastatin in clinical research trials." Clin Ther 15 (1993): 57-64
  32. "Product Information. Baycol (cerivastatin)." Bayer, West Haven, CT.
  33. 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
  34. Dain JG, Fu E, Gorski J, Nicoletti J, Scallen TJ "Biotransformation of fluvastatin sodium in humans." Drug Metab Dispos 21 (1993): 567-72
  35. Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
  36. Tse FL, Jaffe JM, Troendle A "Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers." J Clin Pharmacol 32 (1992): 630-8
  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 Niacin/simvastatin) ↔ 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. Ahmand S "Lovastatin-induced myopathy in a hypothyroid patient." J Fam Pract 41 (1995): 227-8
  5. Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6
  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. "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
  9. "Product Information. Baycol (cerivastatin)." Bayer, West Haven, CT.
  10. 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
  11. 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
  12. Wallace CS, Mueller BA "Lovastatin-induced rhabdomyolysis in the absence of concomitant drugs." Ann Pharmacother 26 (1992): 190-2
  13. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb, Princeton, NJ.
  14. 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
  15. Fernandezzatarain G, Navarro V, Garcia H, Villatoro J, Calvo C "Rhabdomyolysis and acute renal failure associated with lovastatin." Nephron 66 (1994): 483-4
  16. Pogson GW, Kindred LH, Carper BG "Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy." Am J Cardiol 83 (1999): 1146
  17. Reaven P, Witztum JL "Lovastatin, nicotinic acid, and rhabdomyolysis." Ann Intern Med 109 (1988): 597-8
  18. Lees RS, Lees AM "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med 333 (1995): 664-5
  19. Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
  20. Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
  21. "Product Information. Lipitor (atorvastatin)." Parke-Davis, Morris Plains, NJ.
  22. Grunden JW, Fisher KA "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother 31 (1997): 859-63
  23. Schalke BB, Schmidt B, Toyka K, Hartung H-P "Pravastatin-associated inflammatory myopathy." N Engl J Med 327 (1992): 649-50
  24. 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
  25. Iliadis EA, Rosenson RS "Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia." Clin Cardiol 22 (1999): 25-8
  26. 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
  27. 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
  28. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals, East Hanover, NJ.
  29. McDonagh J, Winocour P, Walker DJ "Musculoskeletal manifestations during simvastatin therapy." Br J Rheumatol 32 (1993): 647-8
  30. 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
  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
Major

Niacin/Niacinamide (Includes Niacin/simvastatin) ↔ Coronary Artery Disease

Severe Potential Hazard, Moderate plausibility

Applies to: Ischemic Heart Disease, Arrhythmias

The Coronary Drug Project (1975) reported a significant increase in cardiac arrhythmias associated with the use of niacin at lipid-lowering dosages. Treatment using pharmacologic dosages of niacin and niacinamide (nicotinamide) should be administered cautiously in patients with coronary heart disease or arrhythmias. Particular caution is advised in the presence of unstable angina or in the acute phase of myocardial infarction, especially if the patient is also receiving vasoactive drugs such as nitrates, calcium channel blockers, or adrenergic blocking agents.

References

  1. DiPalma JR, Thayer WS "Use of niacin as a drug." Annu Rev Nutr 11 (1991): 169-87
  2. Pasternak RC, Kolman BS "Unstable myocardial ischemia after the initiation of niacin therapy." Am J Cardiol 67 (1991): 904-6
  3. "Niacin and myocardial metabolism." Nutr Rev 31 (1973): 80-1
  4. Darby WJ, McNutt KW, Todhunter EN "Niacin." Nutr Rev 33 (1975): 289-97
  5. Figge HL, Figge J, Souney PF, Mutnick AH, Sacks F "Nicotinic acid: a review of its clinical use in the treatment of lipid disorders." Pharmacotherapy 8 (1988): 287-94
  6. Gray DR, Morgan T, Chretien SD, Kashyap ML "Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans." Ann Intern Med 121 (1994): 252-8
  7. Capurso A "Drugs affecting triglycerides." Cardiology 78 (1991): 218-25
  8. Davignon J, Roederer G, Montigny M, Hayden MR, Tan MH, Connelly PW, Hegele R, McPherson R, Lupien PJ, Gagne C, et al "Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia." Am J Cardiol 73 (1994): 339-45
  9. "Product Information. Nicobid (niacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  10. Ranchoff RE, Tomecki KJ "Niacin or niacinamide? Nicotinic acid or nicotinamide? What is the difference?." J Am Acad Dermatol 15 (1986): 116-7
  11. "Product Information. Slo-Niacin (niacin)." Upsher-Smith Laboratories Inc, Minneapolis, MN.
  12. Hunninghake DB "The pharmacology and therapeutics of lipid-lowering drugs." Am Pharm ns27 (1987): s18-25
  13. Coronary Drug Project "Clofibrate and niacin in coronary heart disease." JAMA 231 (1975): 360-81
View all 13 references
Major

Niacin/Niacinamide (Includes Niacin/simvastatin) ↔ Hepatotoxicity

Severe Potential Hazard, High plausibility

Applies to: Liver Disease, Alcoholism, Gallbladder Disease

The use of nicotinic acid and its derivatives at dosages substantially exceeding those for physiologic requirements is contraindicated in patients with active liver disease or unexplained, persistent elevations of serum transaminases. Hepatotoxicity, including biochemical abnormalities of liver function, cholestatic jaundice, increased prothrombin time, and fulminant hepatic necrosis and failure, has been reported during therapy with niacin and niacinamide (nicotinamide), particularly in patients who have substituted sustained-release nicotinic acid products for immediate-release preparations at equivalent dosages. Treatment using pharmacologic dosages (e.g., lipid-lowering dosages) of these agents should be administered cautiously in patients with gallbladder disease or a history of jaundice, liver disease and/or heavy alcohol use. Liver transaminase levels should be evaluated prior to initiation of therapy, every 6 to 12 weeks for the first year, and periodically thereafter (e.g., semiannually). 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, therapy should be withdrawn. Liver biopsy should be considered in patients with elevations that persist beyond cessation of therapy.

References

  1. Witztum JL "Current approaches to drug therapy for the hypercholesterolemic patient." Circulation 80 (1989): 1101-14
  2. Knapp TR, Middleton RK "Adverse effects of sustained-release niacin." DICP 25 (1991): 253-4
  3. Hodis HN "Acute hepatic failure associated with the use of low-dose sustained- release niacin." JAMA 264 (1990): 181
  4. Dearing BD, Lavie CJ, Lohmann TP, Genton E "Niacin-induced clotting factor synthesis deficiency with coagulopathy." Arch Intern Med 152 (1992): 861-3
  5. DiPalma JR, Thayer WS "Use of niacin as a drug." Annu Rev Nutr 11 (1991): 169-87
  6. Reimund E, Ramos A "Niacin-induced hepatitis and thrombocytopenia after 10 years of niacin use." J Clin Gastroenterol 18 (1994): 270-1
  7. Knopp RH "Niacin and hepatic failure." Ann Intern Med 111 (1989): 769
  8. Etchason JA, Miller TD, Squires RW, Allison TG, Gau GT, Marttila JK, Kottke BA "Niacin-induced hepatitis: a potential side effect with low-dose time- release niacin." Mayo Clin Proc 66 (1991): 23-8
  9. Henkin Y, Oberman A, Hurst DC, Segrest JP "Niacin revisited: clinical observations on an important but underutilized drug." Am J Med 91 (1991): 239-46
  10. Malloy MJ, Frost PH, Kane JP "Niacin--the long and the short of it." West J Med 155 (1991): 424-6
  11. Lavie CJ, Milani RV "Safety and side effects of sustained-release niacin." JAMA 272 (1994): 513-4;disc. 514-5
  12. Truswell AS "ABC of nutrition. Vitamins I." Br Med J (Clin Res Ed) 291 (1985): 1033-5
  13. Dalton TA, Berry RS "Hepatotoxicity associated with sustained-release niacin." Am J Med 93 (1992): 102-4
  14. Goldstein MR "Potential problems with the widespread use of niacin." Am J Med 85 (1988): 881
  15. Etchason JA, Miller TD, Squires RW, et al "Niacin-induced hepatitis: a potential side effect with low-dose time-release niacin." Mayo Clin Proc 66 (1991): 23-8
  16. Keenan JM, Ripsin CM, Huang Z, McCaffrey DJ "Safety and side effects of sustained-release niacin." JAMA 272 (1994): d513;isc. 514-5
  17. Alhadeff L, Gualtieri CT, Lipton M "Toxic effects of water-soluble vitamins." Nutr Rev 42 (1984): 33-40
  18. Perry RS "Contemporary recommendations for evaluating and treating hyperlipidemia." Clin Pharm 5 (1986): 113-27
  19. Patterson DJ, Dew EW, Gyorkey F, Graham DY "Niacin hepatitis." South Med J 76 (1983): 239-41
  20. Gray DR, Morgan T, Chretien SD, Kashyap ML "Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans." Ann Intern Med 121 (1994): 252-8
  21. Weiner M "Safety and side effects of sustained-release niacin." JAMA 272 (1994): d514;isc. 514-5
  22. "Product Information. Nicobid (niacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  23. Malinow MR "Adverse effects of the treatment for hyperlipidemia." Cardiol Clin 4 (1986): 95-103
  24. Coppola A, Brady PG, Nord HJ "Niacin-induced hepatotoxicity: unusual presentations." South Med J 87 (1994): 30-2
  25. Lawrence SP "Transient focal hepatic defects related to sustained-release niacin." J Clin Gastroenterol 16 (1993): 234-6
  26. Hunninghake DB "The pharmacology and therapeutics of lipid-lowering drugs." Am Pharm ns27 (1987): s18-25
  27. "Product Information. Slo-Niacin (niacin)." Upsher-Smith Laboratories Inc, Minneapolis, MN.
  28. Fischer DJ, Knight LL, Vestal RE "Fulminant hepatic failure following low-dose sustained-release niacin therapy in hospital." West J Med 155 (1991): 410-2
  29. Mullin GE, Greenson JK, Mitchell MC "Fulminant hepatic failure after ingestion of sustained-release nicotinic acid." Ann Intern Med 111 (1989): 253-5
  30. Figge HL, Figge J, Souney PF, Mutnick AH, Sacks F "Nicotinic acid: a review of its clinical use in the treatment of lipid disorders." Pharmacotherapy 8 (1988): 287-94
  31. Henkin Y, Johnson KC, Segrest JP "Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin." JAMA 264 (1990): 241-3
  32. Blum CB, Levy RI "Rational drug therapy of the hyperlipoproteinemias, Part II." Ration Drug Ther 20 (1986): 1-4
  33. Rader JI, Calvert RJ, Hathcock JN "Hepatic toxicity of unmodified and time-release preparations of niacin." Am J Med 92 (1992): 77-81
  34. Frost PH "All niacin is not the same." Ann Intern Med 114 (1991): 1065
  35. Drinka PJ "Alterations in thyroid and hepatic function tests associated with preparations of sustained-release niacin." Mayo Clin Proc 67 (1992): 1206
  36. McKenney JM, Proctor JD, Harris S, Chinchili VM "A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients." JAMA 271 (1994): 672-7
  37. Jungnickel PW, Maloley PA "Comment: adverse-effect profile of sustained-release niacin." DICP 25 (1991): 1014-5
View all 37 references
Major

Niacin/Niacinamide (Includes Niacin/simvastatin) ↔ Hypotension

Severe Potential Hazard, High plausibility

Applies to: Hypotension, Syncope

The use of niacin and niacinamide (nicotinamide) is contraindicated in patients with severe hypotension. These agents have peripheral vasodilating effects and may commonly cause flushing at dosages substantially exceeding those for physiologic requirements (e.g., lipid-lowering dosages).

References

  1. Knapp TR, Middleton RK "Adverse effects of sustained-release niacin." DICP 25 (1991): 253-4
  2. Keenan JM, Fontaine PL, Wenz JB, Myers S, Huang ZQ, Ripsin CM "Niacin revisited. A randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia." Arch Intern Med 151 (1991): 1424-32
  3. Simpson T "Extended-release niacin not problem free." Am J Hosp Pharm 48 (1991): 237-8
  4. Truswell AS "ABC of nutrition. Vitamins I." Br Med J (Clin Res Ed) 291 (1985): 1033-5
  5. Florkowski CM, Cramb R "Approaches to the management of hypercholesterolaemia." J Clin Pharm Ther 17 (1992): 81-9
  6. McKenney JM, Proctor JD, Harris S, Chinchili VM "A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients." JAMA 271 (1994): 672-7
  7. Whelan AM, Price SO, Fowler SF, Hainer BL "The effect of aspirin on niacin-induced cutaneous reactions." J Fam Pract 34 (1992): 165-8
  8. Knopp RH "New approaches to cholesterol lowering: efficacy and safety." Hosp Pract (Off Ed) 23 Suppl 1 (1988): 22-30
  9. Witztum JL "Current approaches to drug therapy for the hypercholesterolemic patient." Circulation 80 (1989): 1101-14
  10. Capurso A "Drugs affecting triglycerides." Cardiology 78 (1991): 218-25
  11. "Product Information. Slo-Niacin (niacin)." Upsher-Smith Laboratories Inc, Minneapolis, MN.
  12. Hoffer A "Niacin reaction." J Fam Pract 34 (1992): 677,680-1
  13. Illingworth DR, Stein EA, Mitchel YB, Dujovne CA, Frost PH, Knopp RH, Tun P, Zupkis RV, Greguski RA "Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial." Arch Intern Med 154 (1994): 1586-95
  14. Blum CB, Levy RI "Rational drug therapy of the hyperlipoproteinemias, Part II." Ration Drug Ther 20 (1986): 1-4
  15. DiPalma JR, Thayer WS "Use of niacin as a drug." Annu Rev Nutr 11 (1991): 169-87
  16. Hunninghake DB "The pharmacology and therapeutics of lipid-lowering drugs." Am Pharm ns27 (1987): s18-25
  17. Hoeg JM, Maher MB, Bailey KR, Brewer HB Jr "Comparison of six pharmacologic regimens for hypercholesterolemia." Am J Cardiol 59 (1987): 812-5
  18. "Product Information. Nicobid (niacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  19. Malloy MJ, Frost PH, Kane JP "Niacin--the long and the short of it." West J Med 155 (1991): 424-6
  20. Malinow MR "Adverse effects of the treatment for hyperlipidemia." Cardiol Clin 4 (1986): 95-103
  21. Perry RS "Contemporary recommendations for evaluating and treating hyperlipidemia." Clin Pharm 5 (1986): 113-27
  22. Davignon J, Roederer G, Montigny M, Hayden MR, Tan MH, Connelly PW, Hegele R, McPherson R, Lupien PJ, Gagne C, et al "Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia." Am J Cardiol 73 (1994): 339-45
  23. Tornvall P, Walldius G "A comparison between nicotinic acid and acipimox in hypertriglyceridaemia--effects on serum lipids, lipoproteins, glucose tolerance and tolerability." J Intern Med 230 (1991): 415-21
  24. Ranchoff RE, Tomecki KJ "Niacin or niacinamide? Nicotinic acid or nicotinamide? What is the difference?." J Am Acad Dermatol 15 (1986): 116-7
  25. Weiner M "Safety and side effects of sustained-release niacin." JAMA 272 (1994): d514;isc. 514-5
View all 25 references
Major

Niacin/Niacinamide (Includes Niacin/simvastatin) ↔ Peptic Ulcer Disease

Severe Potential Hazard, High plausibility

Applies to: Peptic Ulcer, History - Peptic Ulcer

The use of niacin and niacinamide (nicotinamide) at dosages substantially exceeding those for physiologic requirements is contraindicated in patients with active peptic ulcer disease. These agents have been reported to activate peptic ulcer. Treatment using pharmacologic dosages (e.g., lipid-lowering dosages) should be administered cautiously in patients with a history of peptic ulcer disease.

References

  1. Goldstein MR "Potential problems with the widespread use of niacin." Am J Med 85 (1988): 881
  2. Gray DR, Morgan T, Chretien SD, Kashyap ML "Efficacy and safety of controlled-release niacin in dyslipoproteinemic veterans." Ann Intern Med 121 (1994): 252-8
  3. Blum CB, Levy RI "Rational drug therapy of the hyperlipoproteinemias, Part II." Ration Drug Ther 20 (1986): 1-4
  4. Illingworth DR, Stein EA, Mitchel YB, Dujovne CA, Frost PH, Knopp RH, Tun P, Zupkis RV, Greguski RA "Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial." Arch Intern Med 154 (1994): 1586-95
  5. "Product Information. Slo-Niacin (niacin)." Upsher-Smith Laboratories Inc, Minneapolis, MN.
  6. Davignon J, Roederer G, Montigny M, Hayden MR, Tan MH, Connelly PW, Hegele R, McPherson R, Lupien PJ, Gagne C, et al "Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia." Am J Cardiol 73 (1994): 339-45
  7. Hunninghake DB "The pharmacology and therapeutics of lipid-lowering drugs." Am Pharm ns27 (1987): s18-25
  8. McKenney JM, Proctor JD, Harris S, Chinchili VM "A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients." JAMA 271 (1994): 672-7
  9. Figge HL, Figge J, Souney PF, Mutnick AH, Sacks F "Nicotinic acid: a review of its clinical use in the treatment of lipid disorders." Pharmacotherapy 8 (1988): 287-94
  10. DiPalma JR, Thayer WS "Use of niacin as a drug." Annu Rev Nutr 11 (1991): 169-87
  11. Witztum JL "Current approaches to drug therapy for the hypercholesterolemic patient." Circulation 80 (1989): 1101-14
  12. Henkin Y, Oberman A, Hurst DC, Segrest JP "Niacin revisited: clinical observations on an important but underutilized drug." Am J Med 91 (1991): 239-46
  13. Capurso A "Drugs affecting triglycerides." Cardiology 78 (1991): 218-25
  14. Truswell AS "ABC of nutrition. Vitamins I." Br Med J (Clin Res Ed) 291 (1985): 1033-5
  15. Keenan JM, Fontaine PL, Wenz JB, Myers S, Huang ZQ, Ripsin CM "Niacin revisited. A randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia." Arch Intern Med 151 (1991): 1424-32
  16. Darby WJ, McNutt KW, Todhunter EN "Niacin." Nutr Rev 33 (1975): 289-97
  17. Ranchoff RE, Tomecki KJ "Niacin or niacinamide? Nicotinic acid or nicotinamide? What is the difference?." J Am Acad Dermatol 15 (1986): 116-7
  18. Malloy MJ, Frost PH, Kane JP "Niacin--the long and the short of it." West J Med 155 (1991): 424-6
  19. Knopp RH "New approaches to cholesterol lowering: efficacy and safety." Hosp Pract (Off Ed) 23 Suppl 1 (1988): 22-30
  20. "Product Information. Nicobid (niacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  21. Knapp TR, Middleton RK "Adverse effects of sustained-release niacin." DICP 25 (1991): 253-4
  22. Hoeg JM, Maher MB, Bailey KR, Brewer HB Jr "Comparison of six pharmacologic regimens for hypercholesterolemia." Am J Cardiol 59 (1987): 812-5
View all 22 references
Major

Simvastatin (Includes Niacin/simvastatin) ↔ Renal Dysfunction

Severe Potential Hazard, High plausibility

Applies to: Renal Dysfunction

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

Hmg-Coa Reductase Inhibitors (Includes Niacin/simvastatin) ↔ 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 Niacin/simvastatin) ↔ 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 Niacin/simvastatin) ↔ 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.

Moderate

Niacin/Niacinamide (Includes Niacin/simvastatin) ↔ Hyperglycemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Diabetes Mellitus

Elevated fasting blood sugars and decreased glucose tolerance have been reported during niacin and niacinamide (nicotinamide) therapy at dosages substantially exceeding those for physiologic requirements. Patients with diabetes mellitus should be monitored more closely during therapy with these agents, and adjustments made accordingly in their antidiabetic regimen.

References

  1. Capurso A "Drugs affecting triglycerides." Cardiology 78 (1991): 218-25
  2. Witztum JL "Current approaches to drug therapy for the hypercholesterolemic patient." Circulation 80 (1989): 1101-14
  3. Schwartz ML "Severe reversible hyperglycemia as a consequence of niacin therapy." Arch Intern Med 153 (1993): 2050-2
  4. "Product Information. Nicobid (niacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  5. Truswell AS "ABC of nutrition. Vitamins I." Br Med J (Clin Res Ed) 291 (1985): 1033-5
  6. Tornvall P, Walldius G "A comparison between nicotinic acid and acipimox in hypertriglyceridaemia--effects on serum lipids, lipoproteins, glucose tolerance and tolerability." J Intern Med 230 (1991): 415-21
  7. Darby WJ, McNutt KW, Todhunter EN "Niacin." Nutr Rev 33 (1975): 289-97
  8. Henkin Y, Oberman A, Hurst DC, Segrest JP "Niacin revisited: clinical observations on an important but underutilized drug." Am J Med 91 (1991): 239-46
  9. Malinow MR "Adverse effects of the treatment for hyperlipidemia." Cardiol Clin 4 (1986): 95-103
  10. Perry RS "Contemporary recommendations for evaluating and treating hyperlipidemia." Clin Pharm 5 (1986): 113-27
  11. Blum CB, Levy RI "Rational drug therapy of the hyperlipoproteinemias, Part II." Ration Drug Ther 20 (1986): 1-4
  12. McKenney JM, Proctor JD, Harris S, Chinchili VM "A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients." JAMA 271 (1994): 672-7
  13. Gorrell RL "Niacin caution." Postgrad Med 89 (1991): 262
  14. Figge HL, Figge J, Souney PF, Mutnick AH, Sacks F "Nicotinic acid: a review of its clinical use in the treatment of lipid disorders." Pharmacotherapy 8 (1988): 287-94
  15. "Product Information. Slo-Niacin (niacin)." Upsher-Smith Laboratories Inc, Minneapolis, MN.
  16. Hunninghake DB "The pharmacology and therapeutics of lipid-lowering drugs." Am Pharm ns27 (1987): s18-25
View all 16 references
Moderate

Niacin/Niacinamide (Includes Niacin/simvastatin) ↔ Hyperuricemia

Moderate Potential Hazard, Moderate plausibility

Applies to: Gout

Large doses of niacin and niacinamide (nicotinamide) can compete with uric acid for excretion by the kidney. Hyperuricemia and precipitation of gout have been reported during long-term therapy. Treatment using pharmacologic dosages (e.g., lipid-lowering dosages) of these agents should be administered cautiously in patients with or predisposed to gout.

References

  1. Hunninghake DB "The pharmacology and therapeutics of lipid-lowering drugs." Am Pharm ns27 (1987): s18-25
  2. "Product Information. Slo-Niacin (niacin)." Upsher-Smith Laboratories Inc, Minneapolis, MN.
  3. Blum CB, Levy RI "Rational drug therapy of the hyperlipoproteinemias, Part II." Ration Drug Ther 20 (1986): 1-4
  4. Perry RS "Contemporary recommendations for evaluating and treating hyperlipidemia." Clin Pharm 5 (1986): 113-27
  5. Gorrell RL "Niacin caution." Postgrad Med 89 (1991): 262
  6. Figge HL, Figge J, Souney PF, Mutnick AH, Sacks F "Nicotinic acid: a review of its clinical use in the treatment of lipid disorders." Pharmacotherapy 8 (1988): 287-94
  7. Witztum JL "Current approaches to drug therapy for the hypercholesterolemic patient." Circulation 80 (1989): 1101-14
  8. Capurso A "Drugs affecting triglycerides." Cardiology 78 (1991): 218-25
  9. McKenney JM, Proctor JD, Harris S, Chinchili VM "A comparison of the efficacy and toxic effects of sustained- vs immediate-release niacin in hypercholesterolemic patients." JAMA 271 (1994): 672-7
  10. Henkin Y, Oberman A, Hurst DC, Segrest JP "Niacin revisited: clinical observations on an important but underutilized drug." Am J Med 91 (1991): 239-46
  11. Malinow MR "Adverse effects of the treatment for hyperlipidemia." Cardiol Clin 4 (1986): 95-103
  12. "Product Information. Nicobid (niacin)." Rhone-Poulenc Rorer, Collegeville, PA.
  13. Darby WJ, McNutt KW, Todhunter EN "Niacin." Nutr Rev 33 (1975): 289-97
  14. Truswell AS "ABC of nutrition. Vitamins I." Br Med J (Clin Res Ed) 291 (1985): 1033-5
View all 14 references

niacin / simvastatin drug Interactions

There are 408 drug interactions with niacin / simvastatin

niacin / simvastatin alcohol/food Interactions

There are 3 alcohol/food interactions with niacin / simvastatin

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.

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