WEST HAVEN, CT -- July 24, 2000 -- The U.S. Food and Drug Administration have just approved the marketing of a new 0.8mg dosage of Bayer's Baycol® (cerivastatin sodium tablets) for the treatment of primary hypercholesterolemia and mixed dyslipidemia, along with an additional indication for the brand for raising HDL cholesterol.

Baycol is one of the latest statins to be released in the United States and the new 0.8mg dosage provides further efficacy as a titration dose for those patients who need additional LDL-C lowering. Baycol now provides even greater LDL-C and triglyceride reductions as well as providing physicians with another choice to raise HDL-C. The new 0.8mg dosage is even more powerful than before and 84 percent of patients impressively achieved their target NCEP (National Cholesterol Education Program) goal in the pivotal trial.(1)

"Baycol 0.8mg greatly increases options for both physicians and patients," said Dr. Evan Stein, Medical Research Laboratories, Kentucky. "With Baycol available in a starting dose of 0.4mg and the new 0.8mg dosage, physicians can appropriately titrate up the dose according to the needs of the specific patient. The 0.4mg is the recommended starting dose for Baycol, however 0.8mg is going to be very valuable for 'hard to treat' patients who require additional LDL-C lowering," Dr. Stein concluded.

Low HDL-C (< 35mg/dl) has now been documented as a significant risk factor for heart disease, independent of LDL-C levels, making the new indication for raising HDL-C very significant for physicians. HDL-C is known as the 'good' cholesterol because it is a reverse cholesterol transporter, carrying excess cholesterol away from blood vessels.

In the pivotal, randomized, double-blind, multicenter North American trial, Professor William Insull, of the Lipid Research Clinic at Houston's Methodist Hospital, and colleagues demonstrated a mean LDL-C reduction of 42 percent after 8 weeks of treatment with Baycol 0.8mg. Overall reductions of LDL-C ranged from 24 - 58 percent in the 6th - 95th percentiles. In patients with elevated baseline triglycerides greater than or equal to 250 - 400mg/dL Baycol reduced triglycerides by a median 30 percent and increased HDL-C by 13 percent. In all patients in the study, Baycol 0.8mg provided a mean HDL-C elevation of 9 percent and a median TG reduction of 22 percent.(1)

Increasingly, physicians are judging efficacy by the number of patients who reach National Cholesterol Education Program (NCEP) targets for their cholesterol. In the pivotal study, Baycol 0.8mg impressively demonstrated that 84 percent of patients overall were able to achieve these goals.(1) Patients receiving Baycol in this study included those with baseline LDL-C > 160mg/dL and <two risk factors without documented cardiovascular disease or those with baseline LDL-C> 130mg/dL and greater than or equal to two risk factors or with documented cardiovascular disease.

"Baycol 0.8mg is a highly effective and safe treatment for patients with primary hypercholesterolemia who need aggressive lipid management in order to achieve NCEP-recommended goals," Professor Insull stated.

With Baycol you get premium power not premium price, making it a very attractive option for both physicians and patients. Bayer expects the new 0.8mg dosage of Baycol to be available to physicians and patients by August 14th. It will be available in bottles of 30 and 90 tablets.

Baycol (cerivastatin sodium tablets) is indicated as an adjunct to diet to reduce elevated Total-C, LDL-C, Apo B, and TG and to increase HDL-C levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb) when the response to dietary restriction of saturated fat and cholesterol and other non-pharmacological measures alone has been inadequate.

The effect of Baycol on cardiovascular morbidity and mortality has not been determined. 

Patients with hypercholesterolemia should be placed on a standard cholesterol-lowering diet. If the response to dietary restrictions of saturated fat and cholesterol and other non-pharmacological measures is inadequate, patients should continue on their diet, and then begin treatment with Baycol. The recommended starting dose of Baycol is 0.4mg once daily in the evening. The dosage range is 0.2mg to 0.8mg. Cerivastatin sodium may be taken with or without food. In patients with significant renal impairment (creatinine clearance less than or equal to 60mL/min/1.73m(2)) the lower doses are recommended.

Mean LDL-C reduction of 38.4 percent was seen with Baycol 0.4mg once daily at 24 weeks in one study of 494 patients with primary hypercholesterolemia.(2) Mean LDL-C reduction with Baycol 0.4mg from 2 large placebo-controlled clinical trials was 34 percent.(3),(4)

Baycol is contraindicated in patients with hypersensitivity to any component of this medication, in patients with active liver disease or unexplained persistent elevations of serum transaminases, in women during pregnancy, and in nursing mothers. The combined use of cerivastatin and gemfibrozil is contraindicated due to the risk for rhabdomyolysis.

Baycol should be temporarily withheld from any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis (acute serious muscle disease), e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine or electrolyte disorders or uncontrolled epilepsy.

Cases of rhabdomyolysis have been reported with cerivastatin and with other drugs in this class. In one clinical study using Baycol 0.8mg as the starting dose, women over 65 years of age, especially those with low body weight, were observed to be at an increased risk of myopathy. Myopathy (a disorder of muscle tissues or muscle) should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of plasma creatine kinase (CK). Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

It is recommended that liver function tests be performed before the initiation of treatment, at six and 12 weeks after initiation of therapy or elevation in dose, and periodically thereafter, e.g. semi-annually.

In pharmacokinetic studies, no drug to drug interactions were observed with warfarin, digoxin, cimetidine, omeprazole and nifedipine. The risk of myopathy is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, azole antifungals or lipid-lowering doses of niacin.

Baycol is generally well tolerated. In the U.S. placebo-controlled clinical studies, discontinuations due to adverse events occurred in 3.1 percent of cerivastatin sodium tablet-treated patients and in 2.0 percent of patients treated with placebo. In worldwide clinical trials with over 5,000 patients, the most common adverse events regardless of causality were pharyngitis, headache, rhinitis, and sinusitis.

References:
1. Insull W, et al "Efficacy and Safety of Cerivastatin 0.8mg in Patients with Hypercholesterolemia: The Pivotal Placebo-controlled Clinical Trial." Journal of International Medical Research 2000; 28: 47-68.

2. Ose L, Luurila O, Eriksson J, Olsson A et al. Efficacy and safety of cerivastatin, 0.2 mg and 0.4 mg, in patients with primary hypercholesterolemia: a multinational, randomised, double-blind study. Curr Med Res Opin 1999;15:228-40.

3. Hanefeld M, Deslypere J-P, Ose L, Durrington PN et al. Efficacy and safety of 300 micrograms and 400 micrograms cerivastatin once daily in patients with primary hypercholesterolaemia: a multicentre, randomized, double-blind, placebo-controlled study. J Int Med Res 1999;27:115-29.

4. Data on file, Bayer Corporation.