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Atorvastatin calcium is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammation and other mechanisms. Like all statins, Atorvastatin calcium works by inhibiting HMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body. As with other statins, Atorvastatin calcium is a competitive inhibitor of HMG-CoA reductase. Unlike most others, however, it is a completely synthetic compound. HMG-CoA reductase catalyzes the reduction of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate, which is the rate-limiting step in hepatic cholesterol biosynthesis. Inhibition of the enzyme decreases de novo cholesterol synthesis, increasing expression of low-density lipoprotein receptors (LDL receptors) on hepatocytes. This increases LDL uptake by the hepatocytes, decreasing the amount of LDL-cholesterol in the blood. Like other statins, Atorvastatin calcium also reduces blood levels of triglycerides and slightly increases levels of HDL-cholesterol. In clinical trials, drugs that block cholesterol uptake like ezetimibe combine with and complement those that block biosynthesis like Atorvastatin calcium or simvastatin in lowering cholesterol or targeting levels of LDL. Interactions with clofibrate, fenofibrate, gemfibrozil, which are fibrates used in accessory therapy in many forms of hypercholesterolemia, usually in combination with statins, increase the risk of myopathy and rhabdomyolysis. Co-administration of Atorvastatin calcium with one of CYP3A4 inhibitors such as itraconazole, telithromycin, and voriconazole, may increase serum concentrations of Atorvastatin calcium, which may lead to adverse reactions. This is less likely to happen with other CYP3A4 inhibitors such as diltiazem, erythromycin, fluconazole, ketoconazole, clarithromycin, cyclosporine, protease inhibitors, or verapamil, and only rarely with other CYP3A4 inhibitors, such as amiodarone and aprepitant. Often, bosentan, fosphenytoin, and phenytoin, which are CYP3A4 inducers, can decrease the plasma concentrations of Atorvastatin calcium. Only rarely, though, barbiturates, carbamazepine, efavirenz, nevirapine, oxcarbazepine, rifampin, and rifamycin, which are also CYP3A4 inducers, can decrease the plasma concentrations of Atorvastatin calcium. Oral contraceptives increased AUC values for norethindrone and ethinyl estradiol; these increases should be considered when selecting an oral contraceptive for a woman taking Atorvastatin calcium. Antacids can rarely decrease the plasma concentrations of Atorvastatin calcium, but do not affect the LDL-C-lowering efficacy. Niacin also is proved to increase the risk of myopathy or rhabdomyolysis. Statins may also alter the concentrations of other drugs, such as warfarin or digoxin, leading to alterations in effect or a requirement for clinical monitoring. Vitamin D supplementation lowers Atorvastatin calcium and active metabolite concentrations, yet synergistically reduces LDL and total cholesterol concentrations. Grapefruit juice components are known inhibitors of intestinal CYP3A4. Co-administration of grapefruit juice with Atorvastatin calcium may cause an increase in Cmax and AUC, which can lead to adverse reactions or overdose toxicity.
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