Simvastatin is a HMG-CoA reductase inhibitor, commonly known as a statin. It is available with a doctor's prescription only and is used to reduce the levels of bad LDL cholesterol, triglycerides and total cholesterol. It may also raise HDL cholesterol, the good cholesterol. The metabolism of this medication may affect the occurrence of side effects and cause drug interactions.
Metabolism
Simvastatin is metabolized in the liver by enzymes called the cytochrome P450 enzymes. These enzymes are found in the body but are in the highest concentration in the liver. The major enzyme involved in simvastatin breakdown is the cytochrome P450 3A4 enzyme, or CYP 3A4. The metabolized components are excreted mainly in the feces.
Drug Interactions
Simvastatin may interact with medications that act on CYP 3A4. CYP 3A4 inhibitors block the actions of the enzymes and lead to an increase in the level of simvastatin in your body. Some examples of CYP 3A4 inhibitors are clarithromycin, diclofenac, diltiazem, doxycycline, erythromycin, isoniazid, nefazodone and verapamil. Azole anti-fungal medications, such as ketoconazole and econazole, and protease inhibitors, such as saquinavir and indinavir, also inhibit CYP 3A4. CYP 3A4 inducers increase the actions of the enzymes, resulting in a decreased level of simvastatin. Inducers include barbiturates, fosphenytoin, nevirapine, oxcarbazepine and rifampin.
Food and Herbal Interactions
Grapefruit juice contains chemicals called furancoumarins, such as quercetin, naringin and bergamottin. They are potent inhibitors of CYP 3A4 and increase levels of simvastatin in the blood, according to "Pharmacotherapy: A Pathophysiologic Approach." St. John's wort induces CYP 3A4 can decrease simvastatin levels.
Consequences
Increased levels of simvastatin can lead to a worsening of side effects. Common side effects include gas, stomach pain and constipation. However, increased levels can place you at risk for muscle breakdown, known as rhabdomyolysis. Rhabdomyolysis is characterized by muscle pain and weakness. If you experience these adverse reactions, stop the medication and contact your physician. Decreased levels of simvastatin prevent the medication from working effectively. This may put you at risk for complications of high cholesterol, such heart attack and stroke.
Prevention
Inform your physician of all the medications you take, including over-the-counter medications and herbal products, to avoid interactions. If you must be placed on a medication that interacts with simvastatin, your physician will lower or raise the dose of the medication. Take the medication as directed by your physician, and do not take more than the recommended daily dose. Any questions or concerns should be discussed with a pharmacist or physician.
References
- Merck Manuals Online Medical Library: Simvastatin
- "Pharmacotherapy: A Pathophysiologic Approach"; Joseph T. DiPiro, Robert L. Talbert, et al.; 2008
- "Drug Information Handbook"; Charles F. Lacy, Lora L. Armstrong, et al.; 2009
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