Amlodipine Besilate + Atorvastatin interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

  What to do: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.

  9 sources

  1. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
  2. "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
  3. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
  4. "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
  5. "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals (2002):
  6. "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Cerner Multum, Inc. "Australian Product Information." O 0

  Show all 9 sourcesShow fewer sources

  9. "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):

• alcohol

  Moderate

  Synergy

  Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

  What to do: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

• grapefruit juice

  Moderate

  Metabolism

  Coadministration with grapefruit juice may increase the plasma concentrations of atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

  What to do: Patients receiving therapy with atorvastatin should limit their consumption of grapefruit juice to no more than 1 liter per day. Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, patients should either refrain from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times by at least 2 to 4 hours.

  7 sources

  1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706
  2. McMillan K "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a reductase inhibitors." Am J Health Syst Pharm 53 (1996): 2206-14
  3. "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
  4. 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
  5. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  6. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  7. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74

• grapefruit juice

  Minor

  Metabolism

  The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

  What to do: Concomitant use of Amlodipine with grapefruit or grapefruit juice should generally be avoided.

  6 sources

  1. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  2. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL "Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine." Br J Clin Pharmacol 50 (2000): 455-63
  5. Josefsson M, Ahlner J "Amlodipine and grapefruit juice." Br J Clin Pharmacol 53 (2002): 405; discussion 406
  6. Kane GC, Lipsky JJ "Drug-grapefruit juice interactions." Mayo Clin Proc 75 (2000): 933-42

Conditions

Conditions in which Amlodipine Besilate + Atorvastatin needs care, as documented in this source.

• Coronary Artery Disease

  Major

  Increased frequency, duration, and/or severity of angina, as well as acute myocardial infarction, have rarely developed during initiation or dosage increase of calcium channel blockers (CCBs), particularly in patients with severe obstructive coronary artery disease and those treated with immediate-release formulations. The mechanism of this effect is not established. Therapy with CCBs should be administered cautiously in patients with significant coronary artery disease.

  15 sources

  1. Schanzenbacher P, Deeg P, Liebau G, Kochsiek K "Paradoxical angina after nifedipine: angiographic documentation." Am J Cardiol 53 (1984): 345-6
  2. Manga P, Vythilingum "Unstable angina precipitated by nifedipine." S Afr Med J 66 (1984): 144
  3. Sia STB, MacDonald PS, Triester B, et al. "Aggravation of myocardial ischaemia by nifedipine." Med J Aust 142 (1985): 48-50
  4. Myrhed M, Wiholm B-E "Nifedipine: a survey of adverse effects." Acta Pharmacol Toxicol (Copenh) 58 (1986): 133-6
  5. Lambert CR, Hill JA, Feldman RL, Pepine CJ "Myocardial ischemia during intravenous nicardipine administration." Am J Cardiol 55 (1985): 844-5
  6. Thomassen AR, Bagger JP, Nielsen TT "Hemodynamic and cardiac metabolic changes during nicardipine-induced myocardial ischemia." Cathet Cardiovasc Diagn 14 (1988): 41-3
  7. "Product Information. Norvasc (amlodipine)." Pfizer U.S. Pharmaceuticals (2002):
  8. "Product Information. Cardene (nicardipine)." Syntex Laboratories Inc (2002):

  Show all 15 sourcesShow fewer sources

  9. "Product Information. Procardia (nifedipine)." Pfizer U.S. Pharmaceuticals (2002):
  10. Furberg CD, Psaty BM, Meyer JV "Nifedipine: dose-related increase in mortality in patients with coronary heart disease." Circulation 92 (1995): 1326-31
  11. Kloner RA "Nifedipine in ischemic heart disease." Circulation 92 (1995): 1074-8
  12. Yusuf S "Calcium antagonists in coronary artery disease and hypertension: time for reevaluation?" Circulation 92 (1995): 1079-82
  13. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals (2001):
  14. Oei SG, Oei SK, Brolmann HAM "Myocardial infarction during nifedipine therapy for preterm labor." N Engl J Med 340 (1999): 154
  15. Abernathy DR, Schwrtz JB "Calcium-antagonist drugs." N Engl J Med 341 (1999): 1447-57

• Liver Diseases

  Major

  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.

  42 sources

  1. Pan HY, DeValut AR, Wang-Iverson D, et al. "Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin." J Clin Pharmacol 30 (1990): 1128-35
  2. Arnon R, Eisenberg S "Lovastatin-induced hepatitis." Isr J Med Sci 28 (1992): 101-2
  3. Mauro VF "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet 24 (1993): 195-202
  4. Mauro VF, MacDonald JL "Simvastatin: a review of its pharmacology and clinical use." DICP 25 (1991): 257-64
  5. 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
  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. 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
  8. Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6

  Show all 42 sourcesShow fewer sources

  9. 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
  10. McGovern ME, Mellies MJ "Long-term experience with pravastatin in clinical research trials." Clin Ther 15 (1993): 57-64
  11. "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
  12. Geddes JA "Cholestatic jaundice associated with lovastatin (mevacor) therapy." Can Med Assoc J 143 (1990): 13-4
  13. McQueen MJ "Cholestatic jaundice associated with lovastatin (Mevacor) therapy." Can Med Assoc J 142 (1990): 841-2
  14. Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
  15. 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
  16. "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
  17. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
  18. "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
  19. 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
  20. Dain JG, Fu E, Gorski J, Nicoletti J, Scallen TJ "Biotransformation of fluvastatin sodium in humans." Drug Metab Dispos 21 (1993): 567-72
  21. Tse FL, Jaffe JM, Troendle A "Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers." J Clin Pharmacol 32 (1992): 630-8
  22. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
  23. 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
  24. Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
  25. 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)
  26. Quion JAV, Jones PH "Clinical pharmacokinetics of pravastatin." Clin Pharmacokinet 27 (1994): 94-103
  27. Grimbert S, Pessayre D, Degott C, Benhamou JP "Acute hepatitis induced by HMG-coa reductase inhibitor, lovastatin." Dig Dis Sci 39 (1994): 2032-3
  28. 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
  29. 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
  30. 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
  31. "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
  32. 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
  33. "Product Information. Baycol (cerivastatin)." Bayer (2001):
  34. 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
  35. Lea AP, McTavish D "Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias." Drugs 53 (1997): 828-47
  36. 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
  37. 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
  38. Lennernas H, Fager G "Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences." Clin Pharmacokinet 32 (1997): 403-25
  39. 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
  40. Hartleb M, Rymarczyk G, Januszewski K "Acute cholestatic hepatitis associated with pravastatin." Am J Gastroenterol 94 (1999): 1388-90
  41. 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
  42. "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):

• Liver Diseases

  Major

  Calcium channel blockers (CCBs) are extensively metabolized by the liver. The half-lives of CCBs may be prolonged substantially in patients with severe hepatic impairment, with the potential for significant drug accumulation. In addition, the use of some CCBs has been associated with elevations in serum transaminases, both with and without concomitant elevations in alkaline phosphatase and bilirubin. While these effects may be transient and reversible, some patients have developed cholestasis or hepatocellular injury. Therapy with CCBs should be administered cautiously and often at reduced dosages in patients with significantly impaired hepatic function. Periodic monitoring of liver function is advised.

  54 sources

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  2. Saracheck NS, London RL, Matulewicz TJ, et al. "Diltiazem and granulomatous hepatitis." Gastroenterology 88 (1985): 1260-2
  3. Shallcross H, Padley SP, Glynn MJ, Gibbs DD "Fatal renal and hepatic toxicity after treatment with diltiazem." Br Med J 295 (1987): 1256-7
  4. Colombo G, Zucchella G, Planca E, Grieco A "Intravenous diltiazem in the treatment of unstable angina: a study of efficacy and tolerance." Clin Ther 9 (1987): 536-47
  5. Toft E, Vyberg M, Therkelsen K "Diltiazem-induced granulomatous hepatitis." Histopathology 18 (1991): 474-5
  6. Abramson M, Littlejohn GO "Hepatic reactions to nifedipine." Med J Aust 142 (1985): 47-8
  7. Toner M, White A, Moriarty J, Clancy L "Allergic urticarial eruption, leukocytosis and abnormal liver function tests following nifedipine administration." Chest 93 (1988): 1320-1
  8. Babany G, Uzzan F, Larrey D, et al. "Alcoholic-like liver lesions induced by nifedipine." J Hepatol 9 (1989): 252-5

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  11. Woodcock BG, Rietbrock I, Vohringer HF, Rietbrock N "Verapamil disposition in liver disease and intensive-care patients: kinetics, clearance, and apparent blood flow relationships." Clin Pharmacol Ther 29 (1981): 27-34
  12. Woodcock BG, Rietbrock N "Verapamil bioavailability and dosage in liver disease." Br J Clin Pharmacol 13 (1982): 240-1
  13. Stern EH, Pitchon R, King BD, Wiener I "Possible hepatitis from verapamil." N Engl J Med 306 (1982): 612-3
  14. Stehle G, Buss J, Eibach J, et al. "Cardiogenic shock associated with verapamil in a patient with liver cirrhosis." Lancet 336 (1990): 1079
  15. Hare DL, Horowitz JD "Verapamil hepatotoxicity: a hypersensitivity reaction." Am Heart J 111 (1986): 610-11
  16. Guarascio P, D'Amato C, Sette P, et al. "Liver damage from verapamil." Br Med J 288 (1984): 362-3
  17. Dow RJ, Graham DJM "A reveiw of the human metabolism and pharmacokinetics of nicardipine hydrochloride." Br J Clin Pharmacol 22 (1986): s195-202
  18. McAllister RG Jr, Hamann SR, Blouin RA "Pharmacokinetics of calcium-entry blockers." Am J Cardiol 55 (1985): b30-40
  19. Kates RE "Calcium antagonists: pharmacokinetic properties." Drugs 25 (1983): 113-24
  20. Finucci GF, Padrini R, Piovan D, et al. "Verapamil pharmacokinetics and liver function in patients with cirrhosis." Int J Clin Pharmacol Res 8 (1988): 123-6
  21. Giacomini KM, Massoud N, Wong FM, Giacomini JC "Decreased binding of verapamil to plasma proteins in patients with liver disease." J Cardiovasc Pharmacol 6 (1984): 924-8
  22. Razak TA, McNeil JJ, Sewell RB, Drummer OH, Smallwood RA, Conway EL, Louis WJ "The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine." Clin Pharmacol Ther 47 (1990): 463-9
  23. Rush WR, Alexander O, Hall DJ, Cairncross L, Dow RJ, Graham DJ "The metabolism of nicardipine hydrochloride in healthy male volunteers." Xenobiotica 16 (1986): 341-9
  24. Benet LZ "Pharmacokinetics and metabolism of bepridil." Am J Cardiol 55 (1985): c8-13
  25. Kurosawa S, Kurosawa N, Owada E, et al. "Pharmacokinetics of diltiazem in patients with liver cirrhosis." Int J Clin Pharmacol Res 10 (1990): 311-8
  26. Elliott HL, Meredith PA "The clinical consequences of the absorption, distribution, metabolism and excretion of amlodipine." Postgrad Med J 67 (1991): s20-3
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  28. Kleinbloesem CH, van Harten J, Wilson JP, et al. "Nifedipine: kinetics and hemodynamic effects in patients with liver cirrhosis after intravenous and oral administration." Clin Pharmacol Ther 40 (1986): 21-8
  29. Raemsch KD, Sommer J "Pharmacokinetics and metabolism of nifedipine." Hypertension 5 (1983): 18-24
  30. Ramsch KD, Graefe KH, Scherling D, et al. "Pharmacokinetics and metabolism of calcium-blocking agents nifedipine, nitrendipine, and nimodipine." Am J Nephrol 6 (1986): 73-80
  31. Challenor VF, Waller DG, Renwick AG, et al. "The trans-hepatic extraction of nifedipine." Br J Clin Pharmacol 24 (1987): 473-7
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  33. Regardh CG, Edgar B, Olsson R, Kendall M, Collste P, Shansky C "Pharmacokinetics of felodipine in patients with liver disease." Eur J Clin Pharmacol 36 (1989): 473-9
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  35. Tse FL, Jaffe JM "Pharmacokinetics of PN 200-110 (isradipine), a new calcium antagonist, after oral administration in man." Eur J Clin Pharmacol 32 (1987): 361-5
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  37. Gengo FM, Fagan SC, Krol G, Bernhard H "Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls." Br J Clin Pharmacol 23 (1987): 47-53
  38. Meredith P, Elliott H "Clinical pharmacokinetics of amlodipine." Clin Pharmacokinet 22 (1992): 22-31
  39. "Product Information. Norvasc (amlodipine)." Pfizer U.S. Pharmaceuticals (2002):
  40. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical (2002):
  41. "Product Information. Cardizem (diltiazem)." Hoechst Marion Roussel (2002):
  42. "Product Information. Plendil (felodipine)." Merck & Co., Inc (2002):
  43. "Product Information. Cardene (nicardipine)." Syntex Laboratories Inc (2002):
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  52. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals (2001):
  53. Abernathy DR, Schwrtz JB "Calcium-antagonist drugs." N Engl J Med 341 (1999): 1447-57
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• Rhabdomyolysis

  Major

  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.

  35 sources

  1. Schalke BB, Schmidt B, Toyka K, Hartung H-P "Pravastatin-associated inflammatory myopathy." N Engl J Med 327 (1992): 649-50
  2. Pierce LR, Wysowski DK, Gross TP "Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy." JAMA 264 (1990): 71-5
  3. Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6
  4. 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
  5. McGovern ME, Mellies MJ "Long-term experience with pravastatin in clinical research trials." Clin Ther 15 (1993): 57-64
  6. Reaven P, Witztum JL "Lovastatin, nicotinic acid, and rhabdomyolysis." Ann Intern Med 109 (1988): 597-8
  7. "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
  8. 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

  Show all 35 sourcesShow fewer sources

  9. 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
  10. 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
  11. Wallace CS, Mueller BA "Lovastatin-induced rhabdomyolysis in the absence of concomitant drugs." Ann Pharmacother 26 (1992): 190-2
  12. Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
  13. "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
  14. "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
  15. "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
  16. 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
  17. McDonagh J, Winocour P, Walker DJ "Musculoskeletal manifestations during simvastatin therapy." Br J Rheumatol 32 (1993): 647-8
  18. 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
  19. "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
  20. Fernandezzatarain G, Navarro V, Garcia H, Villatoro J, Calvo C "Rhabdomyolysis and acute renal failure associated with lovastatin." Nephron 66 (1994): 483-4
  21. Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
  22. Lees RS, Lees AM "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med 333 (1995): 664-5
  23. Ahmand S "Lovastatin-induced myopathy in a hypothyroid patient." J Fam Pract 41 (1995): 227-8
  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. 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
  26. "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
  27. 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
  28. "Product Information. Baycol (cerivastatin)." Bayer (2001):
  29. Grunden JW, Fisher KA "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother 31 (1997): 859-63
  30. Iliadis EA, Rosenson RS "Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia." Clin Cardiol 22 (1999): 25-8
  31. 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
  32. 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
  33. Pogson GW, Kindred LH, Carper BG "Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy." Am J Cardiol 83 (1999): 1146
  34. "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
  35. "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):

• Shock, Cardiogenic

  Major

  In general, calcium channel blockers (CCBs) should not be used in patients with hypotension (systolic pressure < 90 mm Hg) or cardiogenic shock. Due to potential negative inotropic and peripheral vasodilating effects, the use of CCBs may further depress cardiac output and blood pressure, which can be detrimental in these patients. The use of verapamil and diltiazem is specifically contraindicated under these circumstances.

  6 sources

  1. Stehle G, Buss J, Eibach J, et al. "Cardiogenic shock associated with verapamil in a patient with liver cirrhosis." Lancet 336 (1990): 1079
  2. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical (2002):
  3. "Product Information. Cardizem (diltiazem)." Hoechst Marion Roussel (2002):
  4. "Product Information. Calan (verapamil)." Searle (2001):
  5. Kubota K, Pearce GL, Inman WHW "Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring." Eur J Clin Pharmacol 48 (1995): 1-7
  6. Pahor M, Manto A, Pedone C, Carosella L, Guralnik JM, Carbonin P "Age and severe adverse drug reactions caused by nifedipine and verapamil." J Clin Epidemiol 49 (1996): 921-8

• Cognitive Dysfunction

  Moderate

  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.

  6 sources

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

• Diabetes Mellitus

  Moderate

  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.

  7 sources

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

• Heart Failure

  Moderate

  Calcium channel blockers (CCBs) may have varying degrees of negative inotropic effect. Congestive heart failure (CHF), worsening of CHF, and pulmonary edema have occurred in some patients treated with a CCB, primarily verapamil. Some CCBs have also caused mild to moderate peripheral edema due to localized vasodilation of dependent arterioles and small blood vessels, which can be confused with the effects of increasing left ventricular dysfunction. Although some CCBs have been used in the treatment of CHF, therapy with CCBs should be administered cautiously in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. Likewise, caution is advised in patients with acute myocardial infarction and pulmonary congestion documented by X-ray on admission, since associated heart failure may be acutely worsened by administration of a CCB.

  29 sources

  1. Gillmer DJ, Kark P "Pulmonary oedema precipitated by nifedipine." Br Med J 280 (1980): 1420-1
  2. Batra AK, Segall PH, Ahmed T "Pulmonary edema with nifedipine in primary pulmonary hypertension." Respiration 47 (1985): 161-3
  3. Myrhed M, Wiholm B-E "Nifedipine: a survey of adverse effects." Acta Pharmacol Toxicol (Copenh) 58 (1986): 133-6
  4. Prigogine T, Waterlot Y, Gottignies P, et al. "Acute nonhemodynamic pulmonary edema with nifedipine in primary pulmonary hypertension." Chest 100 (1991): 563-4
  5. Batlouni M, Armaganijan D, Ghorayeb N, Magliano MF "Clinical efficacy and tolerability of isradipine in the treatment of mild-to-moderate hypertension in young and elderly patients." J Cardiovasc Pharmacol 19 (1992): s53-7
  6. Scheidt S, LeWinter MM, Hermanovich J, Venkataraman K, Freedman D "Efficacy and safety of nicardipine for chronic, stable angina pectoris: a multicenter randomized trial." Am J Cardiol 58 (1986): 715-21
  7. Taylor SH, Frais MA, Lee P, Verma SP, Jackson N, Reynolds G, Silke B "A study of the long-term efficacy and tolerability of oral nicardipine in hypertensive patients." Br J Clin Pharmacol 20 (1985): s139-42
  8. Dubois C, Blanchard D "Efficacy and safety of nicardipine in 29,104 patients with hypertension." Clin Ther 11 (1989): 452-60

  Show all 29 sourcesShow fewer sources

  9. Yedinak KC, Lopez LM "Felodipine: a new dihydropyridine calcium-channel antagonist." DICP 25 (1991): 1193-206
  10. Lorimer AR, Pringle SD "The safety of felodipine." J Cardiovasc Pharmacol 15 (1990): s85-9
  11. Sundstedt CD, Ruegg PC, Keller A, Waite R "A multicenter evaluation of the safety, tolerability, and efficacy of isradipine in the treatment of essential hypertension." Am J Med 86 (1989): 98-102
  12. Ruegg PC, Nelson DJ "Safety and efficacy of isradipine, alone and in combination, in the treatment of angina pectoris." Am J Med 86 (1989): 70-4
  13. "Product Information. Norvasc (amlodipine)." Pfizer U.S. Pharmaceuticals (2002):
  14. "Product Information. Plendil (felodipine)." Merck & Co., Inc (2002):
  15. "Product Information. Cardene (nicardipine)." Syntex Laboratories Inc (2002):
  16. "Product Information. Procardia (nifedipine)." Pfizer U.S. Pharmaceuticals (2002):
  17. "Product Information. Nimotop (nimodipine)." Bayer (2002):
  18. "Product Information. Dynacirc (isradipine)." Sandoz Pharmaceuticals Corporation
  19. Walton T, Symes LR "Felodipine and isradipine: new calcium-channel-blocking agents for the treatment of hypertension." Clin Pharm 12 (1993): 261-75
  20. Fagan TC, Haggert BE, Liss C "Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension." Clin Ther 16 (1994): 634-46
  21. Blecker D "Antihypertensive therapy with isradipine in patients with special safety concerns." Angiology 45 (1994): 997-1008
  22. Brogden RN, Sorkin EM "Isradipine: an update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension." Drugs 49 (1995): 618-49
  23. Kubota K, Pearce GL, Inman WHW "Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring." Eur J Clin Pharmacol 48 (1995): 1-7
  24. Johnson BF, Eisner GM, Mcmahon FG, Jain AK, Rudd P, Sowers JR "A multicenter comparison of adverse reaction profiles of isradipine and enalapril at equipotent doses in patients with essential hypertension." J Clin Pharmacol 35 (1995): 484-92
  25. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals (2001):
  26. Sleight P "Calcium antagonists during and after myocardial infarction." Drugs 51 (1996): 216-25
  27. Elkayam U "Calcium channel blockers in heart failure." Cardiology 89 (1998): 38-46
  28. Schaefer RM, Aldons PM, Burgess ED, Tilvis R, Singh GP, Rehn L, Morgan TO "Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: A randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events." Int J Clin Pract 52 (1998): 381
  29. Abernathy DR, Schwrtz JB "Calcium-antagonist drugs." N Engl J Med 341 (1999): 1447-57

• Kidney Diseases

  Moderate

  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.

  7 sources

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

Therapeutic duplication

Drug classes that overlap with Amlodipine Besilate + Atorvastatin, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.

• calcium channel blockers

  The recommended maximum number of medicines in the 'calcium channel blockers' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'calcium channel blockers' category.

  Example product in the source data (US market): Trandolapril/verapamil

• hmg co-a reductase inhibitors

  The recommended maximum number of medicines in the 'HMG Co-A reductase inhibitors' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'HMG Co-A reductase inhibitors' category.

  Example product in the source data (US market): Lovastatin/niacin

• hmg co-a reductase inhibitors

  The recommended maximum number of medicines in the 'HMG Co-A reductase inhibitors' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'HMG Co-A reductase inhibitors' category.

  Example product in the source data (US market): Vytorin

• hmg co-a reductase inhibitors

  The recommended maximum number of medicines in the 'HMG Co-A reductase inhibitors' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'HMG Co-A reductase inhibitors' category.

  Example product in the source data (US market): Simvastatin/sitagliptin

• hmg co-a reductase inhibitors

  The recommended maximum number of medicines in the 'HMG Co-A reductase inhibitors' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'HMG Co-A reductase inhibitors' category.

  Example product in the source data (US market): Niacin/simvastatin

• hmg co-a reductase inhibitors

  The recommended maximum number of medicines in the 'HMG Co-A reductase inhibitors' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'HMG Co-A reductase inhibitors' category.

  Example product in the source data (US market): Roszet