| Side Effects of Lipitor®, Zocor® and Other Statin Drugs |
[Statin Drug Overview | CoQ10 Use in Conjunction with Statin Drugs]
[Drug Patents Explain CoQ10 Supplementation | Recommendation]
[Other Side Effects of Statin Drugs | Label Warnings for Select Statin Drugs]
[Possible Interactions With Other Medicines | References]Side Effects of Lipitor®, Zocor® and Other Statin Drugs
While statin drugs such as Lipitor®, Zocor® and Lovastatin® are beneficial to lower high blood cholesterol, they also have the effect of blocking the body’s natural production of Coenzyme Q10. Supplementation with CoQ10 is necessary to avoid the very heart disease that Lipitor®, Zocor® and Lovastatin® seek to avoid by reducing cholesterol. In a small number of other cases, the statin drugs depletion of CoenzymeQ10 led to liver disease.
Statin drugs such as Zocor®, Lipitor® and Lovastatin® block cholesterol production in the body by inhibiting the enzyme called HMG-CoA reductase in the early steps of its synthesis in the mevalonate pathway. This same biosynthetic pathway is also shared by CoQ10. Therefore, one unfortunate consequence of statin drugs is the unintentional inhibition of CoQ10 synthesis. Thus, in the long run, Lovastatin®, Zocor® and Lipitor® could predispose the patients to heart disease by lowering their Coenzyme Q10 status, the very condition that these drugs are intended to prevent.
The most common statin drugs include:
- Lescol Fluvastatin (FLOO-va-sta-tin)
- Lipitor Atorvastatin (a-TOR-va-sta-tin)
- Mevacor Lovastatin (LOE-va-sta-tin)
- Pravachol Pravastatin (PRA-va-stat-in)
- Zocor Simvastatin (SIM-va-stat-in)
Coenzyme Q10 Use in Conjunction with Statin Drugs
Reporting in the Italian Journal of Respiratory Science in 1999, researchers said that the reduction of CoenzymeQ10 levels is associated with myopathy, an infrequent adverse effect associated with statin drugs. This metabolic myopathy is related to Coenzyme Q10 deficiency in muscle cell mitochondria, disturbing normal cellular respiration and causing adverse effects such as rhabdomyolysis, exercise intolerance, and recurrent myoglobinuria.1
It is important to note that Coenzyme Q10 supplementation does not interfere with the very important cholesterol-lowering effect of statin drugs such as Lovastatin®, Lipitor® and Zocor®. Therefore, if you are taking a statin drug, (especially for an extended period of time), you may want to consider discussing CoQ10 supplementation with your health care professional.
Common supplementation of Coenzyme Q10 is 50 mg to 100 mg per day for someone who is not taking statin drugs. A dosage of 100 mg to 200 mg per day may be considered for a person taking Lipitor® or Zocor® or other statins based on the recommendation of Dr. Julian Whitaker, M.D.8
In his 2002 petition to the FDA to mandate a warning be included in the package inserts of all statin drugs, Dr. Whitaker recommended the following text: “Warning: HMG CoA reductase inhibitors (statin drugs) block the endogenous biosynthesis of an essential cofactor, coenzyme Q10, required for energy production. A deficiency of coenzyme Q10 is associated with impairment of myocardial function, with liver dysfunction and with myopathies (including cardiomyopathy and congestive heart failure). All patients taking HMG CoA reductase inhibitors should therefore be advised to take 100 to 200 mg per day of supplemental coenzyme Q10.“8
Drug Patents Explain CoQ10 Supplementation
It is interesting that the statin drug manufacturers have patented the combination of statin drug and Coenzyme Q10. We do not know of any formulations being marketed which actually use these patents. Unfortunately, the addition of Coenzyme Q10 to the pharmaceutical statin drugs would significantly increase the cost of these drugs. From patent #4,933,165 awarded to Merck & Co, in 1989, makers of lovastatin, the reasons for the combination of statin drug plus CoenzymeQ10 are as follows:
Coenzyme Q10 is a redox component in the respiratory chain and is found in all cells having mitochondria. It is thus an essential co-factor in the generation of metabolic energy and is particularly important in muscle function. Researchers, led by Dr Karl Folkers, have measured the levels of Coenzyme Q10 in endomyocardial biopsy samples taken from patients with varying stages of cardiomyopathy. These researchers observed decreasing tissue levels of CoQ10 with increasing severity of the symptoms of cardiac disease.2 In subsequent studies, this same research team, in a double-blind study, have reported improved cardiac output for some patients upon receiving an oral administration of CoQ10.3
Relatively low doses of Statin drugs such as Lipitor and Zocor effectively reduce plasma cholesterol levels. These drugs function by inhibiting the chemical transformation HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol. A branch of the mevalonate cholesterol biosynthetic pathway in mammalian cells leads to the formation of CoQ10.4 Furthermore, high levels of statin drugs can reduce CoQ10 in the liver5 and compactin reduces LDL-bound CoQ10 at doses employed in humans6.
The Physician’s Desk Reference7 states that myalgia has been associated with lovastatin therapy. The myopathy is reversible upon discontinuance of lovastatin therapy. Since CoQ10 is of benefit in congestive heart failure patients, the combination with HMG-CoA reductase inhibitors should be of value in such patients who also have the added risk of high cholesterol levels.
Patent #4,929,437, also filed by Merck & Co describes the benefit of CoenzymeQ10 supplementation in the prevention of liver disease.
“In its application to the counteraction of liver damage (caused by statin drugs) and, in particular, elevated transaminase levels, the present invention (CoenzymeQ10 supplementation in combination with the statin drug) is accordingly to be understood as providing for the avoidance of liver damage and elevated transaminase levels where this may otherwise occur as well as the amelioration of said damage and elevated transaminase. The term counteracting is accordingly to be understood as connecting both a precautionary or prophylactic as well as curative or treatmental function.”
Drug Patents Recommend CoQ10 Supplementation
Patent #4,933,165 from Merck & Co. claims:
1. “A pharmaceutical composition comprising an effective antihypercholesterolemic amount of an HMG-CoA reductase inhibitor and an amount of Coenzyme Q10 effective to counteract HMG-CoA reductase inhibitor-associated skeletal muscle myopathy.
2. A composition of claim 1 in which the HMG-CoA reductase inhibitor is selected from: lovastatin, simvastatin, pravastatin and sodium-3,5-dihydroxy-7- [3-(4-fluorophenyl)-1-(methylethyl)-1H-Indole-2yl]- hept-6-enoate.
3. A method of counteracting HMG-CoA reductase inhibitor-associated skeletal muscle myopathy in a subject in need of such treatment which comprises the adjunct administration of a therapeutically effective amount of an HMG-CoA reductase inhibitor and an effective amount of Coenzyme Q10 to counteract said myopathy.
4. A method of claim 3 in which the HMG-CoA reductase inhibitor is selected from the group consisting of: lovastatin, simvastatin, pravastatin and sodium-3,5-dihydroxy-7-[3-(4-fluorophenyl)-1- (methylethyl)-1H-Indole-2yl]- hept-6-enoate.”
Other Side Effects of Statin Drugs
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
- Less common or rare
Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:
- More common
- Rare
Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.
Label Warnings for Select Statin Drugs
Lipitor SIDE EFFECTS that may occur while taking Lipitor (Atorvastatin) include dizziness, headache, nausea, diarrhea, constipation, gas, or stomach upset/pain. If it continues or is bothersome, check with your doctor. Lipitor (Atorvastatin) MAY INFREQUENTLY cause muscle damage (which can rarely lead to a very serious condition called rhabdomyolysis). Stop taking this drug and tell your doctor immediately if you develop muscle pain, tenderness, or weakness (especially with fever or unusual tiredness). CHECK WITH YOUR DOCTOR AS SOON AS POSSIBLE if you experience joint pain, chest pain, or swelling in the arms or legs. CONTACT YOUR DOCTOR IMMEDIATELY if you experience yellowing eyes and skin, dark urine, change in the amount of urine, black stool, or severe stomach pain. IF YOU EXPERIENCE difficulty breathing; tightness of chest; swelling of eyelids, face, or lips; or if you develop a rash or hives, tell your doctor immediately. Do not take any more doses of Lipitor (Atorvastatin) unless your doctor tells you to do so. If you notice other effects not listed above, contact your doctor, nurse, or pharmacist.
Zocor Side Effects: NO COMMON SIDE EFFECTS HAVE BEEN REPORTED with the proper use of Zocor (Simvastatin). CHECK WITH YOUR DOCTOR AS SOON AS POSSIBLE if you experience muscle pain, tenderness, or weakness, especially if associated with fever and a general feeling of discomfort; rash; yellow skin or eyes; or unusual bleeding or bruising. CONTACT YOUR DOCTOR IMMEDIATELY if you experience the following side effects or symptoms of toxicity: swelling of hands, face, lips, eyes, throat, or tongue; difficulty swallowing or breathing; or hoarseness. If you notice other effects not listed above, contact your doctor, nurse, or pharmacist.
Possible Interactions with Other Medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking HMG-CoA reductase inhibitors, it is especially important that your health care professional know if you are taking any of the following.
Use of these medicines with an HMG-CoA reductase inhibitor may increase the risk of developing muscle problems and kidney failure
- Cyclosporine (e.g., Sandimmune)
- Gemfibrozil (e.g., Lopid)
- Clofibrate (e.g., Atromid-S)
- Fenofibrate (e.g., Tricor)
- Niacin
Use with atorvastatin, fluvastatin, or simvastatin may increase blood levels of digoxin, increasing the risk of side effects
- Digoxin (e.g., Lanoxin)
- Oral contraceptives, (birth control tablets)
Use with simvastatin may increase the risk of developing muscle problems and kidney failure
- HIV protease inhibitors (Amprenavir [e.g., Agenerase], Indinavir [e.g., Crixivan], Nelfinavir [e.g., Viracept], Ritonavir [e.g., Norvir], Saquinavir [e.g., Fortovase, Invirase])
- Nefazodone (e.g. Serzone)
- Verapamil (e.g. Calan, Isoptin)
- DiMuro S., Exercise intolerance and the mitochondrial respiratory chain. Ital J Neurol Sci. Dec. 1999;20 (6):387-393
- Folkers et al., Proc. Natl. Acad. Sci., 82: 901 (1985)
- Folkers et al., Proc. Natl. Acad. Sci., 82: 4513 (1985)
- Brown and Goldstein J. Lipid Res., 21, 505 (1980)
- MK-803 NDA report
- H. Mabuchi et al, N. E. J. Med., 478 (August 1981)
- Physician’s Desk Reference, 42d Ed., 1366 (1988)
- Whitaker JM, MD. Citizen petition before the department of health and human services Food and Drug Administration, November 24, 2002.
- Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans Proc Natl Acad Sci USA 1990 Nov: 87(22):8931-4.