Simvastatin interactions
Full monograph for SimvastatinCheck it against another medicine
Medicines
670 documented
| Medicine | Severity | Mechanism | Effect | Sources |
|---|---|---|---|---|
| Amiodarone Hydrochloride | Major | Metabolism | The use of amiodarone with higher dosages of simvastatin or lovastatin may be associated with an increased risk of myopathy. The proposed mechanism is… | 19 sources — open the full entry |
| Amlodipine Besilate | Major | Metabolism | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and… | 9 sources — open the full entry |
| Amlodipine Besilate + Atenolol | Major | Metabolism · Unknown | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 9 sources — open the full entry |
| Amlodipine Besilate + Atorvastatin | Major | Metabolism · Synergy | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 13 sources — open the full entry |
| Amlodipine Besilate + Benazepril Hydrochloride | Major | Metabolism · Unknown | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 9 sources — open the full entry |
| Amlodipine Besilate + Olmesartan Medoxomil | Major | Metabolism | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and… | 9 sources — open the full entry |
| Amlodipine Besilate + Telmisartan | Major | Metabolism · Unknown | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 9 sources — open the full entry |
| Amlodipine Besilate + Valsartan | Major | Metabolism · Unknown | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 9 sources — open the full entry |
| Bempedoic acid | Major | Synergy | Coadministration with bempedoic acid may increase the plasma concentrations of simvastatin and pravastatin and risk of statin-related myopathy. The mechanism… | 11 sources — open the full entry |
| Bempedoic acid + Ezetimibe | Major | Others · Synergy | Coadministration with bempedoic acid may increase the plasma concentrations of simvastatin and pravastatin and risk of statin-related myopathy. The mechanism…2 documented mechanisms | 21 sources — open the full entry |
| Bisoprolol Fumarate + Amlodipine Besilate | Major | Metabolism · Unknown | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 9 sources — open the full entry |
| Ceritinib | Major | Metabolism | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid… | 54 sources — open the full entry |
| Clarithromycin | Major | Metabolism | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid… | 50 sources — open the full entry |
| Colchicine | Major | Metabolism · Synergy | Coadministration of colchicine and HMG-CoA reductase inhibitors may increase the risk of myopathy due to a combination of pharmacodynamic and pharmacokinetic… | 37 sources — open the full entry |
| Cyclosporine (Oral) | Major | Metabolism | Coadministration with cyclosporine may significantly increase the plasma concentrations of some HMG-CoA reductase inhibitors and/or their pharmacologically… | 49 sources — open the full entry |
| Danazol | Major | Metabolism | The use of danazol with higher dosages of certain HMG-CoA reductase inhibitors may be associated with an increased risk of myopathy. The proposed mechanism is… | 13 sources — open the full entry |
| Diltiazem Hydrochloride | Major | Metabolism · Synergy | Coadministration with diltiazem may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and potentiate… | 32 sources — open the full entry |
| ErythromycinLotionOral | Major | Metabolism | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid… | 50 sources — open the full entry |
| Esomeprazole + Amoxicillin + Clarithromycin | Major | Absorption · Metabolism · Unknown | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid…3 documented mechanisms | 63 sources — open the full entry |
| Fenofibrate | Major | Others | Severe myopathy and rhabdomyolysis have been reported during concomitant use of HMG-CoA reductase inhibitors and fibric acid derivatives, especially… | 49 sources — open the full entry |
| FluconazolebaseOphthalmic | Major | Metabolism | Coadministration with potent inhibitors of CYP450 3A4 including azole antifungal agents may significantly increase the plasma concentrations of HMG-CoA… | 21 sources — open the full entry |
| Gemfibrozil | Major | Synergy | Severe myopathy and rhabdomyolysis have been reported during concomitant use of HMG-CoA reductase inhibitors and fibric acid derivatives, especially… | 43 sources — open the full entry |
| Glecaprevir + Pibrentasvir | Major | Absorption · Distribution · Metabolism | Coadministration with glecaprevir-pibrentasvir may significantly increase the plasma concentrations of atorvastatin, simvastatin, and their active acid…2 documented mechanisms | 11 sources — open the full entry |
| Indapamide + Amlodipine | Major | Metabolism · Unknown | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 9 sources — open the full entry |
| Itraconazole | Major | Metabolism | Itraconazole increases the plasma concentrations of some HMG-CoA reductase inhibitors and may increase the risk of rhabdomyolysis. The mechanism has been… | 29 sources — open the full entry |
| Ketoconazole | Major | Metabolism | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of lovastatin and simvastatin as well as their… | 22 sources — open the full entry |
| Ketoconazole + Zinc Pyrithione + Aleovera | Major | Metabolism | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of lovastatin and simvastatin as well as their… | 22 sources — open the full entry |
| Lansoprazole + Amoxicillin + Clarithromycin | Major | Absorption · Metabolism · Unknown | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid…3 documented mechanisms | 63 sources — open the full entry |
| Leflunomide | Major | Synergy | The recent, concomitant, or subsequent use (without the recommended leflunomide washout period or procedure) of other agents known to induce hepatotoxicity may… | 3 sources — open the full entry |
| Lenalidomide | Major | Synergy | The risk of rhabdomyolysis may be increased during coadministration of lenalidomide with HMG-CoA reductase inhibitors (statins). The mechanism is unknown but… | 12 sources — open the full entry |
| Levamlodipine Maleate | Major | Metabolism | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and… | 9 sources — open the full entry |
| Lopinavir + Ritonavir | Major | Metabolism | Protease inhibitors (PIs), particularly ritonavir, may significantly increase the plasma concentrations of certain HMG-CoA reductase inhibitors. The mechanism… | 27 sources — open the full entry |
| Mifepristone | Major | Metabolism | Coadministration with mifepristone may significantly increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme… | 12 sources — open the full entry |
| Mifepristone + Misoprostol | Major | Metabolism · Unknown | Coadministration with mifepristone may significantly increase the plasma concentrations of drugs that are primarily metabolized by the CYP450 3A4 isoenzyme…2 documented mechanisms | 12 sources — open the full entry |
| Nelfinavir | Major | Metabolism | Protease inhibitors (PIs) may significantly increase the plasma concentrations of certain HMG-CoA reductase inhibitors. The mechanism is PI inhibition of… | 27 sources — open the full entry |
| Nicotinic Acid [Niacin] | Major | Synergy | Severe myopathy and rhabdomyolysis have been reported with concomitant use of HMG-CoA reductase inhibitors (i.e., statins) and niacin. The mechanism is… | 20 sources — open the full entry |
| Nirmatrelvir + Ritonavir | Major | Metabolism | Protease inhibitors (PIs), particularly ritonavir, may significantly increase the plasma concentrations of certain HMG-CoA reductase inhibitors. The mechanism… | 27 sources — open the full entry |
| Perindopril Arginine + Amlodipine | Major | Metabolism · Unknown | Coadministration with amlodipine may significantly increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and…2 documented mechanisms | 9 sources — open the full entry |
| Posaconazole | Major | Metabolism | Coadministration with posaconazole may significantly increase the plasma concentrations of HMG-CoA reductase inhibitors that are metabolized by CYP450 3A4 such… | 26 sources — open the full entry |
| Rabeprazole + Amoxicillin + Clarithromycin | Major | Metabolism · Unknown | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid…3 documented mechanisms | 50 sources — open the full entry |
| Ranolazine | Major | Metabolism | Coadministration with ranolazine may increase the plasma concentrations of simvastatin and its active metabolite, simvastatin acid, and potentiate the risk of… | 19 sources — open the full entry |
| Rifampicin | Major | Metabolism | Coadministration with rifampin may significantly decrease the plasma concentrations of lovastatin and simvastatin and their pharmacologically active acid… | 12 sources — open the full entry |
| Rifampicin + Isoniazid | Major | Metabolism · Synergy | Coadministration with rifampin may significantly decrease the plasma concentrations of lovastatin and simvastatin and their pharmacologically active acid…2 documented mechanisms | 16 sources — open the full entry |
| Rifampicin + Isoniazid + Pyrazinamide + Ethambutol | Major | Metabolism · Synergy | Coadministration with rifampin may significantly decrease the plasma concentrations of lovastatin and simvastatin and their pharmacologically active acid…3 documented mechanisms | 16 sources — open the full entry |
| Tucatinib | Major | Metabolism | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid… | 54 sources — open the full entry |
| Verapamil Hydrochloride | Major | Synergy | Coadministration with verapamil may significantly increase the plasma concentrations of simvastatin and lovastatin and potentiate the risk of statin-induced… | 27 sources — open the full entry |
| Vonoprazan + Amoxicillin + Clarithromycin | Major | Metabolism · Unknown | Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid…3 documented mechanisms | 115 sources — open the full entry |
| Voriconazole | Major | Metabolism | Coadministration with voriconazole may significantly increase the plasma concentrations of simvastatin and lovastatin and their active acid metabolites. The… | 52 sources — open the full entry |
| Abametapir | Moderate | Metabolism | Based on in vitro inhibition data, a single topical application of abametapir lotion may increase plasma concentrations of drugs that are substrates of CYP450… | 1 sources — open the full entry |
| Adalimumab | Moderate | Metabolism | Plasma concentrations of drugs that are CYP450 substrates may decrease following the initiation of interleukin (IL) inhibitors, tumor necrosis factor (TNF)… | 19 sources — open the full entry |
Food & lifestyle
grapefruit juice
MajorMetabolism
Coadministration with grapefruit juice may significantly increase the plasma concentrations of lovastatin and simvastatin and their active acid metabolites. 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 lovastatin, simvastatin, or red yeast rice (which contains lovastatin) should be advised to avoid the consumption of grapefruit and grapefruit juice. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are metabolized by other enzymes and may be preferable alternatives in some individuals. All patients receiving statin therapy 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. Also, patients should either refrain from the use of oat bran and pectin, or separate the administration times by at least 2 to 4 hours if concurrent use cannot be avoided. Caution may be advisable when coadministered with green tea or green tea extracts. Dosing reduction of the statin and/or limiting consumption of green tea and green tea products may be required if an interaction is suspected.
12 sources
- Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706
- "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402
- Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
- Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83
- Thompson PD, Clarkson P, Karas RH "Statin-associated myopathy." JAMA 289 (2003): 1681-90
- 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
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- Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L "The effect of green tea on simvastatin tolerability." Ann Intern Med 149 (2008): 286-7
- Werba JP, Misaka S, Giroli MG, et al. "Overview of Green Tea Interaction with Cardiovascular Drugs." Curr Pharm Des (2014):
- Roth M, Timmermann BN, Hagenbuch B "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos 39 (2011): 920-6
- Knop J, Misaka S, Singer K, et al. "Inhibitory effects of green tea and (-)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein." PLoS One 10 (2015): e0139370
alcohol
ModerateSynergy
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
- "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
- "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
- "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals (2002):
- "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
- Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
- Cerner Multum, Inc. "Australian Product Information." O 0
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- "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):
Conditions
Conditions in which Simvastatin needs care, as documented in this source.
Kidney Diseases
MajorAlthough 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.
3 sources
- Mauro VF "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet 24 (1993): 195-202
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- Lennernas H, Fager G "Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences." Clin Pharmacokinet 32 (1997): 403-25
Liver Diseases
MajorThe 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
- Pan HY, DeValut AR, Wang-Iverson D, et al. "Comparative pharmacokinetics and pharmacodynamics of pravastatin and lovastatin." J Clin Pharmacol 30 (1990): 1128-35
- Arnon R, Eisenberg S "Lovastatin-induced hepatitis." Isr J Med Sci 28 (1992): 101-2
- Mauro VF "Clinical pharmacokinetics and practical applications of simvastatin." Clin Pharmacokinet 24 (1993): 195-202
- Mauro VF, MacDonald JL "Simvastatin: a review of its pharmacology and clinical use." DICP 25 (1991): 257-64
- 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
- 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
- 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
- Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6
Show all 42 sourcesShow fewer sources
- 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
- McGovern ME, Mellies MJ "Long-term experience with pravastatin in clinical research trials." Clin Ther 15 (1993): 57-64
- "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
- Geddes JA "Cholestatic jaundice associated with lovastatin (mevacor) therapy." Can Med Assoc J 143 (1990): 13-4
- McQueen MJ "Cholestatic jaundice associated with lovastatin (Mevacor) therapy." Can Med Assoc J 142 (1990): 841-2
- Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
- 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
- "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
- "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- 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
- Dain JG, Fu E, Gorski J, Nicoletti J, Scallen TJ "Biotransformation of fluvastatin sodium in humans." Drug Metab Dispos 21 (1993): 567-72
- Tse FL, Jaffe JM, Troendle A "Pharmacokinetics of fluvastatin after single and multiple doses in normal volunteers." J Clin Pharmacol 32 (1992): 630-8
- "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
- 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
- Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
- 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)
- Quion JAV, Jones PH "Clinical pharmacokinetics of pravastatin." Clin Pharmacokinet 27 (1994): 94-103
- Grimbert S, Pessayre D, Degott C, Benhamou JP "Acute hepatitis induced by HMG-coa reductase inhibitor, lovastatin." Dig Dis Sci 39 (1994): 2032-3
- 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
- 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
- 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
- "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
- 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
- "Product Information. Baycol (cerivastatin)." Bayer (2001):
- 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
- Lea AP, McTavish D "Atorvastatin. A review of its pharmacology and therapeutic potential in the management of hyperlipidaemias." Drugs 53 (1997): 828-47
- 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
- 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
- Lennernas H, Fager G "Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences." Clin Pharmacokinet 32 (1997): 403-25
- 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
- Hartleb M, Rymarczyk G, Januszewski K "Acute cholestatic hepatitis associated with pravastatin." Am J Gastroenterol 94 (1999): 1388-90
- 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
- "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):
Rhabdomyolysis
MajorSevere 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
- Schalke BB, Schmidt B, Toyka K, Hartung H-P "Pravastatin-associated inflammatory myopathy." N Engl J Med 327 (1992): 649-50
- Pierce LR, Wysowski DK, Gross TP "Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy." JAMA 264 (1990): 71-5
- Walker JF "Simvastatin: the clinical profile." Am J Med 87 (1989): s44-6
- 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
- McGovern ME, Mellies MJ "Long-term experience with pravastatin in clinical research trials." Clin Ther 15 (1993): 57-64
- Reaven P, Witztum JL "Lovastatin, nicotinic acid, and rhabdomyolysis." Ann Intern Med 109 (1988): 597-8
- "Lovastatin 5-year safety and efficacy study. Lovastatin Study Groups I through IV." Arch Intern Med 153 (1993): 1079-87
- 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
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- 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
- 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
- Wallace CS, Mueller BA "Lovastatin-induced rhabdomyolysis in the absence of concomitant drugs." Ann Pharmacother 26 (1992): 190-2
- Bilheimer DW "Long-term clinical tolerance of lovastatin and simvastatin." Cardiology 77 (1990): 58-65
- "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
- "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- 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
- McDonagh J, Winocour P, Walker DJ "Musculoskeletal manifestations during simvastatin therapy." Br J Rheumatol 32 (1993): 647-8
- 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
- "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
- Fernandezzatarain G, Navarro V, Garcia H, Villatoro J, Calvo C "Rhabdomyolysis and acute renal failure associated with lovastatin." Nephron 66 (1994): 483-4
- Jokubaitis LA "Updated clinical safety experience with fluvastatin." Am J Cardiol 73 (1994): d18-24
- Lees RS, Lees AM "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med 333 (1995): 664-5
- Ahmand S "Lovastatin-induced myopathy in a hypothyroid patient." J Fam Pract 41 (1995): 227-8
- 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
- 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
- "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
- 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
- "Product Information. Baycol (cerivastatin)." Bayer (2001):
- Grunden JW, Fisher KA "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother 31 (1997): 859-63
- Iliadis EA, Rosenson RS "Long-term safety of pravastatin-gemfibrozil therapy in mixed hyperlipidemia." Clin Cardiol 22 (1999): 25-8
- 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
- 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
- Pogson GW, Kindred LH, Carper BG "Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil combination therapy." Am J Cardiol 83 (1999): 1146
- "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
- "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):
Cognitive Dysfunction
ModerateCognitive 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
- "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
- "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
- "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
- "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
Diabetes Mellitus
ModerateIncreases 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
- "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
- "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
- "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
- "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
- "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):
Kidney Diseases
ModerateSome 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
- "Product Information. Mevacor (lovastatin)." Merck & Co., Inc (2002):
- "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb (2001):
- "Product Information. Zocor (simvastatin)." Merck & Co., Inc (2001):
- "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals (2001):
- "Product Information. Lipitor (atorvastatin)." Parke-Davis (2001):
- "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc (2003):
- "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic) (2010):
Therapeutic duplication
Drug classes that overlap with Simvastatin, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.
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): Lypqozet
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
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): Caduet