On June 27, Andrx Corporation announced that the FDA had granted final marketing approval for its extended-release lovastatin (Altocor) to slow the progression of atherosclerosis in those with coronary heart disease as part of a therapeutic strategy to lower LDL-cholesterol (LDL-C) and total cholesterol (total-C). Extended-release lovastatin is also indicated as an adjunct to diet for the reduction of total-C, LDL-C, Apolipoprotein B, and triglycerides, and to increase HDL-cholesterol (HDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia.
A recent Food & Drug Administration approval has added Altocor, an extended-release lovastatin from Andrx Corp., to the roster of available statin drugs. Altocor is the company's first internally developed brand product. It is indicated in slowing the progression of atherosclerosis in coronary heart disease as part of a therapeutic strategy to lower LDL cholesterol (LDL-C) and total cholesterol (total-C). Extended-release lovastatin is also indicated as an adjunct to diet for the reduction of total C, LDL-C, apolipoprotein B, and triglycerides and to increase HDL-cholesterol (HDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia.
A recent letter from the FDA granted approvable status for an additional indication for extended-release lovastatin: the primary prevention of coronary heart disease in patients with average to moderately elevated total-C and LDL-C and below average HDL-C. Andrx expects to receive approval for this indication when the exclusivity rights of Merck (maker of Mevacor) expire in September of this year.
As an HMG-CoA reductase inhibitor, extended-release lovastatin works in the same way as the other drugs of its class, said John Isaac-sohn, M.D., v.p., Medpace, a clinical research organization in Cincin- nati. According to Evelyn Hermes- DeSantis, Pharm.D., clinical associate professor, Ernest Mario School of Pharmacy, Rutgers University, it inhibits the conversion of HMG-CoA to mevalonatean early step in cholesterol synthesis.
Extended-release lovastatin also increases the number of receptors in the liver that retrieve cholesterol from the plasma, noted Vincent Brett, R.Ph., director, professional services, Andrx Corp.
While lovastatin is the agent common to both Altocor and Mevacor, there is a difference in the mode of drug delivery in the intestinal tract, Isaacsohn explained. "With Altocor, lovastatin is surrounded by a compound that releases the drug slowly in the gut so that it is absorbed in a more sustained manner."
Patients who, by National Cholesterol Education Program guidelines, require pharmacotherapy to lower cholesterol levels are candidates for ER lovastatin therapy, said Isaacsohn. However, noted Brett, women who are pregnant or lactating should not take lovastatin. Cholesterol and other products of the cholesterol biosynthesis pathway are basic precursor molecules for hormones, steroids, cell membranes, etc. If the amount of cholesterol in the body is reduced, he said, it could cause problems in fetal growth and development.
Extended-release lovastatin is metabolized by the 3A4 isoform of the cytochrome P450 enzyme, said Hermes-DeSantis. Drugs that inhibit this pathway may increase the plasma concentration of lovastatin and lovastatin acid and increase the risk of myopathy. Such compounds include cyclosporine, the macrolide antibiotics, the azole antifungals, large quantities of grapefruit juice, HIV protease inhibitors, and the antidepressant nefazodone (Serzone, Bristol-Myers Squibb), she said.
Fibrates or niacin should be used with caution in those taking lovastatin, Isaacsohn said, although low doses of lovastatin have been used in combination with fibrates or niacin without myopathy in small trials with careful monitoring.
ER lovastatin should be used with caution in those with liver disease, a history of the disease, or an unexplained persistent elevation of serum transaminase, said Brett. And it should be used with caution in those who drink large amounts of alcohol.
The customary recommended daily starting dose is a 20-, 40- or 60-mg tablet, given at bedtime. Despite a suggested starting dose, it is really at the discretion of the physician, based on the patient's therapeutic goals, Isaacsohn said.
In those patients taking cyclosporine concomitantly with extended-release lovastatin, therapy should begin at 10 mg q.d. and should not exceed 20 mg/d, as stated in the package insert. If given concomitantly with fibrates or niacin, the dose of extended-release lovastatin should not exceed 20 mg/d.
Charlotte LoBuono. New formulation of lovastatin reduces cholesterol levels. Drug Topics 2002;15:29.