The Case of the Patient With Myalgia on Every Statin

Douglas S. Paauw, MD

Disclosures

June 02, 2015

Restarting Statins

An alternative option for patients who have tried several statins and experienced recurrent myalgia is to initiate a more potent statin, such as atorvastatin or rosuvastatin, on an every-other-day or twice-weekly schedule. A few studies have looked at this issue.

A retrospective chart review of previously statin-intolerant patients seen in a lipid clinic examined response to rosuvastatin.[8] Thirty patients received rosuvastatin 5 mg twice weekly; an additional 10 patients received 10 mg, also twice weekly. The mean reduction in low-density lipoprotein cholesterol was 43 mg/dL, with 54% of patients reaching the appropriate National Cholesterol Education Program goal. Only eight patients out of 40 had to stop taking rosuvastatin owing to side effects.

It is remarkable that in this study, 80% of patients with multiple episodes of statin-related myalgia who were distrustful of this class of medication were able to tolerate intermittent dosing with this potent statin.

Another retrospective study[9] also examined the tolerability of every-other-day dosing of rosuvastatin in patients treated at two lipid specialty clinics. After over 2000 charts were reviewed, 51 patients were identified who were receiving rosuvastatin every other day and who previously had experienced statin intolerance. Fully three quarters (76.5%) had reported myalgia, and one in five (19.5%) had elevated aminotransferase levels with previous trials of statins. However, 72% were able to tolerate every-other-day dosing, and the mean reduction in low-density lipoprotein cholesterol (LDL-C) in these patients was 34.5% (P < .001), enabling approximately 50% to achieve their LDL-C goal.

What we don't have is an outcome study examining this dosing regimen. We all know that statins do more than just lower LDL-C; they have cardioprotective effects that go beyond pure LDL-C reduction. The unanswered question is, is every other day enough? For now, we know that we need to get high-risk patients back on a statin. For the highest-risk patients who truly need to be on a statin, every-other-day dosing of a more potent statin, and observing for tolerance, is a reasonable option.

So what do we do for people with myalgia who are on statins? In addition to checking vitamin D levels, as previously discussed, a CK value should be obtained to rule out rhabdomyolysis or other causes of myalgia. It is also important to check thyroid-stimulating hormone, because hypothyroidism is associated with a higher incidence of statin-related myalgia. Remember, hypothyroidism is inherently associated with muscle ache. Assess for drug interactions. Several drugs[10] increase the risk for statin toxicity, including rhabdomyolysis:

  • Fibrates: Interactions between statins and drugs in the fibrate class occur much more frequently with gemfibrozil than with fenofibrate.[11] However, even with gemfibrozil, less than 1% of patients on the combination of gemfibrozil and a statin drug will experience rhabdomyolysis.

  • Azole antifungals: All drugs in this class are known to increase the potential for statin toxicity.

  • Amiodarone: An interaction with this drug is more likely with simvastatin and lovastatin.

  • Macrolide antibiotics: This effect is most pronounced with erythromycin and clarithromycin. The other drug in this antibiotic class, azithromycin, is not known to increase risk for statin toxicity.

  • Protease inhibitors: Protease inhibitors, especially ritonavir, have an important effect.

  • Calcium-channel blockers: Verapamil and diltiazem have significant interactions with statins. Amlodipine and nifedipine, although still presenting some risk for interaction, are less likely than the other drugs in this class to have major interactions with statins.

If use of a drug that has a potential interaction with a statin is unavoidable, nonconcurrent dosing can help to minimize interactions. Giving the drug doses 12 hours apart, if possible, will prevent peak levels of the two agents from occurring at the same time.

Which statins are the least likely to cause interactions with other drugs? The fewest drug interactions occur with pravastatin, because it is metabolized differently from the other statins, which are metabolized by the cytochrome P450 3A4 isoenzyme.[10] The most interactions are found with simvastatin and lovastatin.

After assessing vitamin D and CK levels; potentially, thyroid status; and the possibility of drug interactions that may lead to elevated statin levels, the next step is to stop the statin. If the symptoms disappear, the same statin can be restarted at the same or a lower dose. The rationale for this recommendation is to confirm that it is really the statin that is causing the problem.

Some statins are less likely to cause myalgia. Every-other-day dosing, as discussed, is one option for statin-intolerant patients. Another option is fluvastatin 80 mg/day, although this drug is very expensive and not as effective as some other drugs in this class. Finally, ezetimibe is an option, although as noted previously, studies to date have only assessed the efficacy of this drug in combination with a statin.

Red yeast rice, a fermented rice product that has statin-like properties, has been suggested as an alternative to statins.[12] Monacolin K, the active ingredient in red yeast rice, is chemically identical to the active ingredient in lovastatin. These products may lower LDL-C but can cause the same types of side effects and drug interactions as lovastatin. Consumers have no way of knowing how much monacolin K is present in most red yeast rice products, and the US Food and Drug Administration has determined that red yeast rice products that contain a substantial amount of monacolin K are an unapproved new drug, not a dietary supplement, and cannot be sold in the United States.

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