Considerations for Safe Use of Statins: Liver Enzyme Abnormalities and Muscle Toxicity



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Am Fam Physician. 2011 Mar 15;83(6):711-716.

Statins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice. The risk of hepatic injury caused by statins is estimated to be about 1 percent, similar to that of patients taking a placebo. Patients with transaminase levels no more than three times the upper limit of normal can continue taking statins; often the elevations will resolve spontaneously. Coexisting elevations of transaminase levels from non alcoholic fatty liver disease and stable hepatitis B and C viral infections are not contraindications to statin use. Although myalgias are common with statin use, myositis and rhabdomyolysis are rare. When prescribed at one-half the recommended maximal dosage or less, statins are associated with an incidence of myopathy similar to that of placebo; therefore, routine monitoring of creatine kinase levels in asymptomatic patients is not recommended. Myopathic symptoms usually resolve approximately two months after discontinuing the statin, and the same statin can be restarted at a lower dosage, or patients can try a different statin. Clinically important drugs that interact with statins and increase the risk of adverse effects include fibrates, diltiazem, verapamil, and amiodarone.

The incidence of true liver injury caused by statin therapy is low (about 1 percent). The dose-related elevations of alanine transaminase and aspartate transaminase levels observed in patients taking statins do not exceed those in patients taking placebo at low to moderate dosages (one-half the maximal dosage or less) and are modest at higher dosages. Many preexisting conditions that cause elevations in transaminase levels (e.g., chronic viral hepatitis, nonalcoholic fatty liver disease) were once thought to be contraindications to statin therapy; however, statins do not worsen liver function in most patients with chronic liver disease.17

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References Comments

Elevated transaminase levels and nonalcoholic fatty liver disease are not contraindications to statin use.

C

14

Expert opinion,1 meta-analysis,2 small case-control studies3,4

Stable hepatitis C infection is not an absolute contraindication to statin use.

C

57

Small cohort study5; small prospective, double-blind, placebo-controlled study6; large cohort study7

Statin-induced myopathy is dose-related and may occur with all statins.

C

17

Systematic review of observational studies

Baseline levels of creatine kinase need to be obtained only in patients at high risk of muscle toxicity.

C

1, 16

Consensus guidelines


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

View Table

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendation Evidence rating References Comments

Elevated transaminase levels and nonalcoholic fatty liver disease are not contraindications to statin use.

C

14

Expert opinion,1 meta-analysis,2 small case-control studies3,4

Stable hepatitis C infection is not an absolute contraindication to statin use.

C

57

Small cohort study5; small prospective, double-blind, placebo-controlled study6; large cohort study7

Statin-induced myopathy is dose-related and may occur with all statins.

C

17

Systematic review of observational studies

Baseline levels of creatine kinase need to be obtained only in patients at high risk of muscle toxicity.

C

1, 16

Consensus guidelines


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.

Statins and the Liver

Elevations in transaminase levels do not reflect hepatic injury per se; the best indicator of true liver injury is the serum bilirubin level.1 Meta-analyses of randomized placebocontrolled trials demonstrate that low to moderate dosages of statins are not associated with clinically significant (i.e., greater than three times the upper limit of normal) elevations in transaminase levels.2,8 Maximal recommended dosages of lovastatin (Mevacor), 9 pravastatin (Pravachol),10 simvastatin (Zocor),11 atorvastatin (Lipitor),8 and rosuvastatin (Crestor)8 were associated with modest but notable increases in transaminase levels. Many of these elevations will resolve with continued therapy.1

NONALCOHOLIC FATTY LIVER DISEASE

The presence of nonalcoholic fatty liver disease or nonalcoholic steatohepatitis should not deter physicians from using statins in patients with hyperlipidemia. Some studies even suggest that statins may have a beneficial effect on underlying liver disease.12

Two retrospective studies examining 7,473 patients with mildly elevated transaminase levels found fewer severe increases in transaminase levels in patients using statins than in patients not using them over a 12-month period.3,4 In another matched study of 2,264 patients, those taking statins showed no differences in liver enzyme levels or progression of steatohepatitis compared with patients not taking statins.13 A small study of 68 patients with biopsy-proven nonalcoholic fatty liver disease showed no change in liver enzymes but a statistically significant 46 percent reduction in the quantitative steatosis on repeat biopsy in the 17 patients taking statins at follow-up.14 Two small studies evaluating patients with nonalcoholic steatohepatitis showed no change (seven patients)15 or a reduction (five patients)12 in liver enzymes among those taking statins; both studies also demonstrated some degree of improvement in liver pathology.

CHRONIC VIRAL HEPATITIS

Evidence suggests that patients with chronic hepatitis B and C infections may safely use statins, although supporting data are not as strong as those for patients with nonalcoholic fatty liver disease. A retrospective cohort study of 13,492 patients taking lovastatin5 and a prospective study of 320 patients taking pravastatin6 found no evidence of increased hepatotoxicity among those with chronic liver disease (including hepatitis B and C infections). A cohort study showed that patients with hepatitis C infection who took statins had less severe elevations in transaminase levels than patients with hepatitis C infection who were not on statins or those who took statins but tested negative for hepatitis C infection.7

An expert consensus panel of hepatologists convened by the National Lipid Association concluded that chronic liver disease is not a contraindication to statin use. Although the panel also concluded that routine monitoring of liver function was not supported by the literature, for medicolegal reasons they recommended checking transaminase levels before initiating therapy, 12 weeks after initiating therapy or increasing the dosage, and periodically thereafter.1

Statins and Muscle

Myopathy is a general term describing any disease of the muscles. Myalgia is defined as muscle ache or weakness without elevated creatine kinase (CK) levels, whereas myositis denotes muscle symptoms with elevated CK levels. Rhabdomyolysis indicates muscle symptoms with a CK elevation greater than 10 times the upper limit of normal associated with creatinine elevation (usually with brown urine and urinary myoglobin).16 Myalgias are common with statin use. However, myositis and rhabdomyolysis are far less common, with rates of 5.0 and 1.6 per 100,000 patient-years, respectively; these rates appear to be similar with all statins, although well-designed comparative studies are lacking.17 The mechanism of statininduced muscle injury is uncertain.18

RISK FACTORS FOR MUSCLE TOXICITY

Several factors may increase the likelihood of statin-induced myopathy (Table 1).16 Multiple clinical trials have found that the risk of myopathy is dose-dependent, especially with simvastatin.17,19 The U.S. Food and Drug Administration recently cautioned about the increased risk of muscle injury from the 80-mg dose of simvastatin.20 A systematic review of placebo-controlled trials found that the incidence of statin-related myopathy from low to moderate dosages (40 mg per day or less) is similar to that with placebo (approximately 5 percent).17 High dosages (more than 40 mg per day) are associated with myopathic symptoms in 5 to 18 percent of patients.19

Table 1.

Risk Factors for Statin-Induced Myopathy

Factors associated with increasing statin plasma concentration

Age older than 70 years

Drug-drug interactions

Female sex

High-dose therapy (greater than one-half the maximal recommended dosage)

Impaired liver/renal function (creatinine clearance < 30 mL per minute per 1.73 m2 [0.50 mL per second per m2])

Low body mass

Untreated hypothyroidism

Factors predisposing muscle to injury

Additive drug adverse effects

Alcohol abuse

Substance abuse (e.g., cocaine, amphetamines, heroin)

Untreated hypothyroidism


Information from reference 16.

Table 1.   Risk Factors for Statin-Induced Myopathy

View Table

Table 1.

Risk Factors for Statin-Induced Myopathy

Factors associated with increasing statin plasma concentration

Age older than 70 years

Drug-drug interactions

Female sex

High-dose therapy (greater than one-half the maximal recommended dosage)

Impaired liver/renal function (creatinine clearance < 30 mL per minute per 1.73 m2 [0.50 mL per second per m2])

Low body mass

Untreated hypothyroidism

Factors predisposing muscle to injury

Additive drug adverse effects

Alcohol abuse

Substance abuse (e.g., cocaine, amphetamines, heroin)

Untreated hypothyroidism


Information from reference 16.

Myopathy risk increases when statins are taken with medications known to inhibit their metabolism (Table 2).11,17,18,2132 Serum levels of simvastatin and lovastatin are increased four- to sixfold in conjunction with erythromycin and verapamil therapy, and 10- to 20-fold with itraconazole (Sporanox) and cyclosporine (Sandimmune) therapy.11,21,22,25,27 Simvastatin and lovastatin levels are increased threefold and rosuvastatin levels are increased twofold in patients also taking gemfibrozil (Lopid).11,22,28 The rate of rhabdomyolysis was 0.44 per 10,000 patient-years with statin monotherapy versus 5.98 when the statin was combined with a fibrate. This interaction appears to be more notable with gemfibrozil than fenofibrate (Tricor).32

Table 2.

Summary of the Major Interactions with Statins

Nonstatin drug/substance Statins affected Recommendation

CYP3A4 inhibitors

Azole antifungals

Atorvastatin (Lipitor)

Lovastatin (Mevacor)

Simvastatin (Zocor)

Avoid lovastatin and simvastatin11,21,22

Use caution when exceeding 20 mg per day of atorvastatin23

Itraconazole (Sporanox)

Ketoconazole

Calcium channel blockers

Diltiazem (Cardizem)

Do not exceed 20 mg per day of lovastatin or 10 mg per day of simvastatin11,17,18,22,24

Verapamil

Do not exceed 40 mg per day of lovastatin or 20 mg per day of simvastatin11,17,18,22,24,25

Other

Grapefruit juice (more than 1 quart per day)

Avoid atorvastatin, lovastatin, and simvastatin11,22,26

CYP3A4/organic anion transporting polypeptide inhibitors

Cyclosporine (Sandimmune)

All statins

Do not exceed 10 mg per day of atorvastatin, 20 mg per day of lovastatin, or 5 mg per day of rosuvastatin (Crestor)22,27,28

Use caution with fluvastatin (Lescol)29

Avoid pitavastatin (Livalo)30 and pravastatin (Pravachol)27

Macrolide antibiotics

Atorvastatin

Lovastatin

Pitavastatin

Simvastatin

Avoid lovastatin and simvastatin11,17,18,22,24,25

Do not exceed 1 mg per day of pitavastatin30

Use caution when exceeding 20 mg per day of atorvastatin17,23,27,31

Clarithromycin (Biaxin)

Erythromycin

Protease inhibitors

All statins

Avoid lovastatin, pitavastatin, and simvastatin11,17,18,22,24

Do not exceed 20 mg per day of atorvastatin or 10 mg per day of rosuvastatin11,23,28

Atazanavir (Reyataz)

Ritonavir (Norvir)

Lopinavir/ritonavir (Kaletra)

CYP3A4/CYP2C9 inhibitor

Amiodarone (Cordarone)

Atorvastatin

Fluvastatin

Lovastatin

Simvastatin

Consider limiting atorvastatin dose17,18,23,24

Do not exceed 40 mg per day of lovastatin or 20 mg per day of simvastatin11,17,22,24

Use caution with fluvastatin29

CYP2C9, CYP2C19, glucuronidation, and organic anion transporting polypeptide inhibitors

Gemfibrozil (Lopid)

All statins

Avoid pravastatin unless benefits outweigh risks32

Consider limiting atorvastatin dose

Do not exceed 10 mg per day of rosuvastatin or simvastatin11,28,32

Do not exceed 20 mg per day of lovastatin22

Use caution with fluvastatin29 and pitavastatin30

CYP2C9 inhibitor

Fluconazole (Diflucan)

Fluvastatin

Use caution29


CYP = cytochrome P450.

Information from references 11, 17, 18, and 21 through 32.

Table 2.   Summary of the Major Interactions with Statins

View Table

Table 2.

Summary of the Major Interactions with Statins

Nonstatin drug/substance Statins affected Recommendation

CYP3A4 inhibitors

Azole antifungals

Atorvastatin (Lipitor)

Lovastatin (Mevacor)

Simvastatin (Zocor)

Avoid lovastatin and simvastatin11,21,22

Use caution when exceeding 20 mg per day of atorvastatin23

Itraconazole (Sporanox)

Ketoconazole

Calcium channel blockers

Diltiazem (Cardizem)

Do not exceed 20 mg per day of lovastatin or 10 mg per day of simvastatin11,17,18,22,24

Verapamil

Do not exceed 40 mg per day of lovastatin or 20 mg per day of simvastatin11,17,18,22,24,25

Other

Grapefruit juice (more than 1 quart per day)

Avoid atorvastatin, lovastatin, and simvastatin11,22,26

CYP3A4/organic anion transporting polypeptide inhibitors

Cyclosporine (Sandimmune)

All statins

Do not exceed 10 mg per day of atorvastatin, 20 mg per day of lovastatin, or 5 mg per day of rosuvastatin (Crestor)22,27,28

Use caution with fluvastatin (Lescol)29

Avoid pitavastatin (Livalo)30 and pravastatin (Pravachol)27

Macrolide antibiotics

Atorvastatin

Lovastatin

Pitavastatin

Simvastatin

Avoid lovastatin and simvastatin11,17,18,22,24,25

Do not exceed 1 mg per day of pitavastatin30

Use caution when exceeding 20 mg per day of atorvastatin17,23,27,31

Clarithromycin (Biaxin)

Erythromycin

Protease inhibitors

All statins

Avoid lovastatin, pitavastatin, and simvastatin11,17,18,22,24

Do not exceed 20 mg per day of atorvastatin or 10 mg per day of rosuvastatin11,23,28

Atazanavir (Reyataz)

Ritonavir (Norvir)

Lopinavir/ritonavir (Kaletra)

CYP3A4/CYP2C9 inhibitor

Amiodarone (Cordarone)

Atorvastatin

Fluvastatin

Lovastatin

Simvastatin

Consider limiting atorvastatin dose17,18,23,24

Do not exceed 40 mg per day of lovastatin or 20 mg per day of simvastatin11,17,22,24

Use caution with fluvastatin29

CYP2C9, CYP2C19, glucuronidation, and organic anion transporting polypeptide inhibitors

Gemfibrozil (Lopid)

All statins

Avoid pravastatin unless benefits outweigh risks32

Consider limiting atorvastatin dose

Do not exceed 10 mg per day of rosuvastatin or simvastatin11,28,32

Do not exceed 20 mg per day of lovastatin22

Use caution with fluvastatin29 and pitavastatin30

CYP2C9 inhibitor

Fluconazole (Diflucan)

Fluvastatin

Use caution29


CYP = cytochrome P450.

Information from references 11, 17, 18, and 21 through 32.

Patients who have disease states or are taking concomitant medications known to independently cause myalgias are more likely to experience muscle injury when statin therapy is initiated. Untreated hypothyroidism33 a nd a lcohol a buse34 m ay p redispose patients to myopathic symptoms from statin therapy. Gemfibrozil and niacin, often used in patients taking statins, have their own associated risks of myopathy, 32 a lthough t hese a ppear t o b e r are a nd have not been confirmed by large, welldesigned studies.18,35 Evidence does not support the hypothesis that lipophilic statins (e.g., lovastatin, simvastatin, atorvastatin), which penetrate muscle fibers more easily, are more likely to cause muscle toxicity than hydrophilic statins (e.g., pravastatin, rosuvastatin).18

PREVENTION OF STATIN-INDUCED MUSCLE INJURY

Strategies to reduce the risk of statin-induced myopathy include using the lowest effective dosage, identifying patient risk factors, monitoring adverse effects and CK levels in symptomatic patients, avoiding serious drug interactions, and educating patients. Although the third report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults recommends measuring baseline CK levels in all patients, other experts recommend obtaining baseline CK levels only in patients at high risk of muscle toxicity.1,16,18,36 Asymptomatic patients do not require routine measurement of CK levels. Figure 1 provides an algorithm for the evaluation and treatment of patients with myopathic symptoms. 37 These usually resolve approximately two months after discontinuing statin therapy; patients can then restart the statin at a lower dosage or try a different statin. In a retrospective cohort study, 43 percent of patients remained asymptomatic on statin rechallenge, with 32 percent of patients tolerating a different statin and 11 percent tolerating a lower dosage of the same statin.38

Evaluation and Treatment of Statin-Induced Myopathic Symptoms

Figure 1.

Algorithm for the evaluation and treatment of patients with statin-induced myopathic symptoms.

Adapted with permission from Sathasivam S, Lecky B. Statin induced myopathy. BMJ. 2008;337:a2286.

View Large

Evaluation and Treatment of Statin-Induced Myopathic Symptoms


Figure 1.

Algorithm for the evaluation and treatment of patients with statin-induced myopathic symptoms.

Adapted with permission from Sathasivam S, Lecky B. Statin induced myopathy. BMJ. 2008;337:a2286.

Evaluation and Treatment of Statin-Induced Myopathic Symptoms


Figure 1.

Algorithm for the evaluation and treatment of patients with statin-induced myopathic symptoms.

Adapted with permission from Sathasivam S, Lecky B. Statin induced myopathy. BMJ. 2008;337:a2286.

The Authors

R. CLARK GILLETT, JR., MD, is associate program director of the Family Medicine Residency Program at Columbus (Ga.) Regional Healthcare System, The Medical Center.

ANGELICA NORRELL, PharmD, is an ambulatory care clinical pharmacist at Columbus Regional Healthcare System, The Medical Center.

Address correspondence to R. Clark Gillett, Jr., MD, Columbus Regional Healthcare System, The Medical Center, 1900 10th Ave., Suite 100, Columbus, GA 31902 (e-mail: clark.gillett@gmail.com). Reprints are not available from the authors.

Author disclosure: Nothing to disclose.

REFERENCES

1. McKenney JM, Davidson MH, Jacobson TA, Guyton JR; National Lipid Association Statin Safety Assessment Task Force. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006;97(8A):89C–94C.

2. de Denus S, Spinler SA, Miller K, Peterson AM. Statins and liver toxicity: a meta-analysis. Pharmacotherapy. 2004;24(5):584–591.

3. Vuppalanchi R, Teal E, Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes. Am J Med Sci. 2005;329(2):62–65.

4. Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology. 2004;126(5):1287–1292.

5. Avins AL, Manos MM, Levin TR, et al. Lovastatin is not hepatotoxic to patients with pre-existing liver disease [abstract]. Gastroenterology. 2006;130(4 suppl 2):A595.

6. Lewis JH, Fusco MJ, Medoff JR, Mortensen ME, Zweig S. Safety and efficacy of pravastatin 80 mg in 320 hypercholesterolemic patients with compensated chronic liver disease [abstract]. Gastroenterology. 2006;130(4 suppl 2):A65.

7. Khorashadi S, Hasson NK, Cheung RC. Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol. 2006;4(7):902–907.

8. Wlodarczyk J, Sullivan D, Smith M. Comparison of benefits and risks of rosuvastatin versus atorvastatin from a meta-analysis of head-to-head randomized controlled trials. Am J Cardiol. 2008;102(12):1654–1662.

9. Bradford RH, Shear CL, Chremos AN, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results: two-year efficacy and safety follow-up. Am J Cardiol. 1994;74(7):667–673.

10. Cannon CP, Braunwald E, McCabe CH, et al.; Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes [published correction appears in N Engl J Med. 2006;354(7):778]. N Engl J Med. 2004;350(15):1495–1504.

11. Zocor. In: Physicians' Desk Reference. 64th ed. Montvale, N.J.: Physicians' Desk Reference, Inc.; 2010:2290.

12. Rallidis LS, Drakoulis CK, Parasi AS. Pravastatin in patients with nonalcoholic steatohepatitis: results of a pilot study. Atherosclerosis. 2004;174(1):193–196.

13. Browning JD. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology. 2006;44(2):466–471.

14. Ekstedt M, Franzén LE, Mathiesen UL, Holmqvist M, Bodemar G, Kechagias S. Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes: a histopathological follow-up study. J Hepatol. 2007;47(1):135–141.

15. Hortander JC, Kwo PY, Cummings OW, Koukoulis G. Atorvastatin for the treatment of NASH [abstract]. Gastroenterology. 2001;120(5 suppl 1):A544.

16. Pasternak RC, Smith SC Jr, Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C; American College of Cardiology; American Heart Association; National Heart, Lung and Blood Institute. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002;40(3):567–572.

17. Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006;97(8A):52C–60C.

18. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289(13):1681–1690.

19. Bruckert E, Hayem G, Dejager S, Yau C, Bégaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients—the PRIMO study. Cardiovasc Drugs Ther. 2005;19(6):403–414.

20. FDA drug safety communication. Ongoing safety review of high-dose Zocor (simvastatin) and increased risk of muscle injury. http://www.fda.gov/Drugs/DrugSafety. Accessed July 22, 2010.

21. Neuvonen PJ, Kantola T, Kivistö KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther. 1998;63(3):332–341.

22. Mevacor [package insert]. Whitehouse Station, N.J.: Merck & Co.; 2009.

23. Lipitor. In: Physicians' Desk Reference. 64th ed. Montvale,N.J.: Physicians' Desk Reference, Inc.; 2010:2704.

24. Bellosta S, Paoletti R, Corsini A. Safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation. 2004;109(23 suppl 1):III50–III57.

25. Kantola T, Kivistö KT, Neuvonen PJ. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther. 1998;64(2):177–182.

26. Saito M, Hirata-Koizumi M, Matsumoto M, Urano T, Hasegawa R. Undesirable effects of citrus juice on the pharmacokinetics of drugs: focus on recent studies. Drug Saf. 2005;28(8):677–694.

27. Olbricht C, Wanner C, Eisenhauer T, et al. Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses. Clin Pharmacol Ther. 1997;62(3):311–321.

28. Crestor [package insert]. Wilmington, Del.: AstraZeneca Pharmaceuticals; 2010.

29. Lescol [package insert]. East Hanover, N.J.: Novartis Pharmaceuticals Corp.; 2006.

30. Pitavastatin [package insert] Cincinnati, Ohio: Kowa Pharmaceuticals America, 2009.

31. Reaven P, Witztum JL. Lovastatin, nicotinic acid, and rhabdomyolysis. Ann Intern Med. 1988;109(7):597–598.

32. Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipidlowering drugs. JAMA. 2004;292(21):2585–2590.

33. Lang JE, Wang P, Glueck CJ. Myopathy associated with lipid lowering therapy in patients with previously undiagnosed or undertreated hypothyroidism. Clin Chim Acta. 1996;254(1):65–92.

34. Song SK, Rubin E. Ethanol produces muscle damage in human volunteers. Science. 1972;175(19):327–328.

35. Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacinstatin regimens. Am J Cardiol. 1998;82(12A):82U–84U.

36. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–2497.

37. Sathasivam S, Lecky B. Stain induced myopathy. BMJ. 2008;337:a2286.

38. Hansen KE, Hildebrand JP, Ferguson EE, Stein JH. Outcomes in 45 patients with statin-associated myopathy. Arch Intern Med. 2005;165(22):2671–2676.

This is one in a series of “Clinical Pharmacology” articles coordinated by Allen F. Shaughnessy, PharmD, Tufts University Family Medicine Residency at Cambridge Health Alliance, Malden, Mass.


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