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Baycol

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Baycol

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Warnings
Precautions

WARNINGS

Liver Enzymes: HMG-CoA reductase inhibitors have been associated with biochemical abnormalities of liver function. Persistent increases of serum transaminase (ALT, AST) values to more than 3 times the upper limit of normal (occurring on two or more not necessarily sequential occasions, regardless of baseline status) have been reported in 0.5% of patients treated with cerivastatin sodium in the US over an average period of 11 months. The incidence of these abnormalities was 0.1%, 0.4%, 0.9% and 0.6% for BAYCOL® (cerivastatin (removed from market 8/2001)) 0.2, 0.3, 0.4, and 0.8 mg respectively. These abnormalities usually occurred within the first 6 months of treatment, usually resolved after discontinuation of the drug, and were not associated with cholestasis. In most cases, these biochemical abnormalities were asymptomatic.

It is recommended that liver function tests be performed before the initiation of treatment, at 6 and 12 weeks after initiation of therapy or elevation in dose, and periodically thereafter, e.g., semiannually. Patients who develop increased transaminase levels should be monitored with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormality(ies) return to normal. Should an increase in AST or ALT of three times the upper limit of normal or greater persist, withdrawal of cerivastatin sodium therapy is recommended.

Active liver disease or unexplained transaminase elevations are contraindications to the use of BAYCOL® (cerivastatin sodium tablets) (see CONTRAINDICATIONS). Caution should be exercised when cerivastatin sodium is administered to patients with a history of liver disease or heavy alcohol ingestion (see CLINICAL PHARMACOLOGY: Pharmacokinetics/Metabolism). Such patients should be started at the low end of the recommended dosing range and closely monitored.

Skeletal Muscle: Cases of rhabdomyolysis, some with acute renal failure secondary to myoglobinuria, have been reported with cerivastatin and other drugs in this class. Beginning therapy above the 0.4 mg starting dose increases the risk of myopathy and rhabdomyolysis. Myopathy, defined as muscle aching or muscle weakness, associated with increases in plasma creatine kinase (CK) values to greater than 10 times the upper limit of normal, was seen in 0.4% of patients in U.S. cerivastatin clinical trials. In one clinical study using BAYCOL (cerivastatin (removed from market 8/2001)) 0.8 mg 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 should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CK. Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. BAYCOL® (cerivastatin sodium tablets) therapy should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected. BAYCOL® (cerivastatin sodium tablets) should be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine or electrolyte disorders; or uncontrolled epilepsy.

The risk of myopathy during treatment with HMG-CoA reductase inhibitors is increased with concurrent administration of cyclosporine, fibric acid derivatives, erythromycin, azole antifungals or lipid-lowering doses of niacin.

The combined use of HMG-CoA inhibitors and fibrates generally should be avoided. The use of fibrates alone may be associated with myopathy including rhabdomyolysis and associated renal failure. The combined use of cerivastatin and gemfibrozil is contraindicated due to a risk for rhabdomyolysis (see CONTRAINDICATIONS).

PRECAUTIONS

General

Before instituting therapy with BAYCOL® (cerivastatin sodium tablets), an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, weight reduction in obese patients, and treatment of underlying medical problems (see INDICATIONS).

Cerivastatin sodium may elevate creatine kinase and transaminase levels (see ADVERSE REACTIONS). This should be considered in the differential diagnosis of chest pain in a patient on therapy with cerivastatin sodium.

Homozygous Familial Hypercholesterolemia: Cerivastatin sodium has not been evaluated in patients with rare homozygous familial hypercholesterolemia. HMG-CoA reductase inhibitors have been reported to be less effective in these patients because they lack functional LDL receptors.

Information for Patients

Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 2-year study was conducted in rats with dietary administration resulting in average daily doses of cerivastatin of 0.007, 0.034, or 0.158 mg/kg. The high dosage level corresponded to plasma free drug levels (AUC) of approximately 2 times those in humans following a 0.8-mg oral dose. Tumor incidences of treated rats were comparable to controls in all treatment groups. In a 2-year carcinogenicity study conducted in mice with dietary administration resulting in average daily doses of cerivastatin of 0.4, 1.8, 9.1, or 55 mg/kg hepatocellular adenomas were significantly increased in male and female mice at ≥ 9.1 mg/kg (AUCfree values about 3 times human at 0.8 mg/day). Hepatocellular carcinomas were significantly increased in male mice at ≥ 1.8 mg/k (AUCfree values in the range of human exposure at 0.8 mg/day).

No evidence of genotoxicity was observed in vitro with or without metabolic activation in the following assays: microbial mutagen tests using mutant strains of S. typhimurium or E. coli, Chinese Hamster Ovary Forward Mutation Assay, Unscheduled DNA Synthesis in rat primary hepatocytes, chromosome aberrations in Chinese Hamster Ovary cells, and spindle inhibition in human lymphocytes. In addition, there was no evidence of genotoxicity in vivo in a mouse Micronucleus Test; there was equivocal evidence of mutagenicity in a mouse Dominant Lethal Test.

In a combined male and female rat fertility study, cerivastatin had no adverse effects on fertility or reproductive performance at doses up to 0.1 mg/kg/day (in the range of human Cmax free drug levels). At a dose of 0.3 mg/kg/day (about 3 times human Cmax free drug levels), the length of gestation was marginally prolonged, stillbirths were increased, and the survival rate up to day 4 postpartum was decreased. In the fetuses (F1), a marginal reduction in fetal weight and delay in bone development was observed. In the mating of the F1 generation, there was a reduced number of female rats that littered. In the testicles of dogs treated chronically with cerivastatin at a dose of 0.008 mg/kg/day (in the range of human Cmax free drug levels), atrophy, vacuolization of the germinal epithelium, spermatidic giant cells, and focal oligospermia were observed. In another 1-year study in dogs treated with 0.1 mg/kg/day (approximately 17-fold the human exposure at doses of 0.8 mg based on Cmax free), ejaculate volume was small and libido was decreased. Semen analysis revealed an increased number of morphologically altered spermatozoa indicating disturbances of epididymal sperm maturation that was reversible when drug administration was discontinued.

Pregnancy

Pregnancy Category X: (See CONTRAINDICATIONS): Cerivastatin caused a significant increase in incomplete ossification of the lumbar center of the vertebrae in rats at an oral dose of 0.72 mg/kg. Cerivastatin did not cause any anomalies or malformations in rabbits at oral doses up to 0.75 mg/kg. These doses resulted in plasma levels about 6 times the human exposure (Cmax free) for rats and 3 times the human exposure for rabbits (Cmax free) at a human dose of 0.8 mg. Cerivastatin crossed the placenta and was found in fetal liver, gastrointestinal tract, and kidneys when pregnant rats were given a single oral dose of 2 mg/kg.

Safety in pregnant women has not been established. Cerivastatin should be administered to women of child-bearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards. Rare reports of congenital anomalies have been received following intrauterine exposure to other HMG-CoA reductase inhibitors. In a review of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or lovastatin, the incidences of congenital anomalies, spontaneous abortions and fetal deaths/stillbirths did not exceed what would be expected in the general population. The number of cases is adequate only to exclude a three- to four-fold increase in congenital anomalies over the background incidence. In 89% of the prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. As safety in pregnant women has not been established and there is no apparent benefit to therapy with BAYCOL® during pregnancy (see CONTRAINDICATIONS), treatment should be immediately discontinued as soon as pregnancy is recognized. If a women becomes pregnant while taking cerivastatin, the drug should be discontinued and the patient advised again as to potential hazards to the fetus.

Nursing Mothers

Based on preclinical data, cerivastatin is present in breast milk in a 1.3:1 ratio (milk:plasma). Because of the potential for serious adverse reactions in nursing infants, nursing women should not take cerivastatin (see CONTRAINDICATIONS).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

In clinical pharmacology studies, there were no clinically relevant effects of age on the pharmacokinetics of cerivastatin sodium. In one clinical study using BAYCOL (cerivastatin (removed from market 8/2001)) 0.8 mg 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. Caution should be exercised when titrating such patients to the 0.8 mg dose of BAYCOL (cerivastatin (removed from market 8/2001)) .

Renal Insufficiency

Patients with significant renal impairment (Clcr ≤ 60 mL/min/1.73m2) have increased AUC (up to 60%) and Cmax (up to 23%) and should be administered BAYCOL® (cerivastatin (removed from market 8/2001)) with caution.

Hepatic Insufficiency

Safety and effectiveness in hepatically impaired patients have not been established. Cerivastatin should be used with caution in patients who have a history of liver disease and/or consume substantial quantities of alcohol (see CONTRAINDICATIONS and WARNINGS).

Last reviewed on RxList: 4/17/2009
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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