"Today, the U.S. Food and Drug Administration approved Kanuma (sebelipase alfa) as the first treatment for patients with a rare disease known as lysosomal acid lipase (LAL) deficiency.
Patients with LAL deficiency (also known as Wolman disea"...
(Generic versions may still be available.)
Cerivastatin sodium has been evaluated for adverse events in more than 5,000 patients worldwide. In the U.S. placebo-controlled clinical studies, discontinuations due to adverse events occurred in 3.1% of cerivastatin sodium treated patients and in 2.0% of patients treated with placebo. Adverse reactions have usually been mild and transient.
Clinical Adverse Experiences
Adverse experiences occurring with a frequency ≥ 2% for marketed doses of cerivastatin sodium, regardless of causality assessment, in U.S. placebo-controlled clinical studies, are shown in Table 5 below:
Table 5: Adverse Experiences occurring in ≥ 2% Patients
in U.S. Placebo Controlled Clinical Studies
|Adverse Event|| BAYCOL®
(n = 2231)
(n = 702)
The following effects have been reported with drugs in this class; not all effects listed below have necessarily been associated with cerivastatin therapy.
Neurological: dysfunction of certain cranial nerves (including alteration of taste, impairment of extra-ocular movement, facial paresis), tremor, dizziness, memory loss, vertigo, paresthesia, peripheral neuropathy, peripheral nerve palsy, anxiety, insomnia, depression, psychic disturbances.
Hypersensitivity Reactions: An apparent hypersensitivity syndrome has been reported that included one or more of the following features: anaphylaxis, angioedema, lupus erythematosus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.
Skin: alopecia, pruritus. A variety of skin changes, (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), have been reported. Reproductive: gynecomastia, loss of libido, erectile dysfunction.
Eye: progression of cataracts (lens opacities), ophthalmoplegia.
Post-Marketing Adverse Event Reports
The following events have been reported since market introduction. While these events were generally associated with the use of BAYCOL® (cerivastatin (removed from market 8/2001)) , a casual relationship to the use of BAYCOL® (cerivastatin (removed from market 8/2001)) cannot be readily determined due to the spontaneous nature of reporting of medical events, and the lack of controls.
Hemolytic and Lymphatic System: Anemia, leukopenia.
Hypersensitivity Reaction: Allergic reaction, anaphylactoid reaction, angioedema, urticaria.
Respiratory System: Cough increase.
Urogenital System: Acute renal failure secondary to myoglobinuria.
In studies where cerivastatin sodium has been administered concomitantly with cholestyramine, no adverse reactions unique to this combination or in addition to those previously reported for this class of drugs were reported. Myopathy and rhabdomyolysis (with or without acute renal failure) have been reported when HMG-CoA reductase inhibitors are used in combination with immunosuppressive drugs, fibric acid derivatives, erythromycin, azole antifungals or lipid-lowering doses of nicotinic acid. Concomitant therapy with HMG-CoA reductase inhibitors and these agents is generally not recommended (see WARNINGS: Skeletal Muscle). Concurrent treatment with gemfibrozil is contraindicated (see CONTRAINDICATIONS and WARNINGS: Skeletal Muscle).
Read the Baycol (cerivastatin (removed from market 8/2001)) Side Effects Center for a complete guide to possible side effects
Immunosuppressive Drugs, Fibric Acid Derivatives, Niacin (Nicotinic Acid), Erythromycin, Azole Antifungals: see WARNINGS: Skeletal Muscle.
ANTACID (Magnesium-Aluminum Hydroxide): Cerivastatin plasma concentrations were not affected by co-administration of antacid.
CIMETIDINE: Cerivastatin plasma concentrations were not affected by co-administration of cimetidine.
CHOLESTYRAMINE: The influence of the bile-acid-sequestering agent cholestyramine on the pharmacokinetics of cerivastatin sodium was evaluated in 12 healthy males in 2 separate randomized crossover studies. In the first study, concomitant administration of 0.2 mg cerivastatin sodium and 12 g cholestyramine resulted in decreases of more than 22% for AUC and 40% for Cmax when compared to dosing cerivastatin sodium alone. However, in the second study, administration of 12 g cholestyramine 1 hour before the evening meal and 0.3 mg cerivastatin sodium approximately 4 hours after the same evening meal resulted in a decrease in the cerivastatin AUC of less than 8%, and a decrease in Cmax of about 30% when compared to dosing cerivastatin sodium alone. Therefore, it would be expected that a dosing schedule of cerivastatin sodium given at bedtime and cholestyramine given before the evening meal would not result in a significant decrease in the clinical effect of cerivastatin sodium.
DIGOXIN: Plasma digoxin levels and digoxin clearance at steady-state were not affected by co-administration of 0.2 mg cerivastatin sodium. Cerivastatin plasma concentrations were also not affected by co-administration of digoxin.
WARFARIN: Co-administration of warfarin and cerivastatin to healthy volunteers did not result in any changes in prothrombin time or clotting factor VII when compared to co-administration of warfarin and placebo. The AUC and Cmax of both the (R) and (S) isomers of warfarin were unaffected by concurrent dosing of 0.3 mg cerivastatin sodium. Co-administration of warfarin and cerivastatin did not alter the pharmacokinetics of cerivastatin sodium.
ERYTHROMYCIN: In hypercholesterolemic patients, steady-state cerivastatin AUC and Cmax increased approximately 50% and 24% respectively after 10 days with co-administration of erythromycin, a known inhibitor of cytochrome P450 3A4.
ITRACONAZOLE: In hypercholesterolemic patients, following a 0.3 mg dose of cerivastatin, steady-state cerivastatin AUC and Cmax increased 38% and 12%, respectively after 10 days with co-administration of 200 mg itraconazole, a potent inhibitor of cytochrome P450 3A4. Cerivastatin half-life was approximately 5 hours (a 64% increase) following co-administration with itraconazole, which would not lead to accumulation of cerivastatin upon multiple dosing. The administration of 0.3 mg of cerivastatin concomitantly with itraconazole has no effect on itraconazole pharmacokinetics.
In a single dose crossover study using 0.8 mg cerivastatin, the AUC and Cmax of cerivastatin were increased 27% and 25% respectively during concomitant itraconazole treatment.
OMEPRAZOLE: There were no changes in the pharmacokinetic parameters of either cerivastatin or its major active metabolites, or of omeprazole in healthy young males given single 0.3 mg oral doses of cerivastatin alone or on the fifth day of a five-day omeprazole 20 mg daily pre-treatment.
GEMFIBROZIL: The potential for clinically relevant interaction between gemfibrozil and cerivastatin has not been assessed in clinical trials. However, during postmarketing surveillance, patients on cerivastatin who experienced rhabdomyolysis and associated renal failure, were in most cases also taking gemfibrozil. (See CONTRAINDICATIONS and WARNINGS: Skeletal Muscle).
CYCLOSPORINE: The single dose pharmacokinetics of 0.2 mg of cerivastatin in healthy subjects was compared to the pharmacokinetics of single and multiple doses in renal transplant patients who were at steady-state with respect to cyclosporine. Cyclosporine levels were unaffected by cerivastatin. Plasma concentrations of cerivastatin and its metabolites increased 3- to 5-fold with no change in its elimination. No cerivastatin accumulation occurred with multiple dosing.
Endocrine Function: HMG-CoA reductase inhibitors interfere with cholesterol synthesis and lower cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Clinical studies have shown that cerivastatin sodium has no adverse effect on sperm production and does not reduce basal plasma cortisol concentration, impair adrenal reserve or have an adverse effect on thyroid metabolism as assessed by TSH. Results of clinical trials with drugs in this class have been inconsistent with regard to drug effect on basal and reserve steroid levels. The effects of HMG-CoA reductase inhibitors on male fertility have not been studied in adequate numbers of male patients. The effects, if any, on the pituitary-gonadal axis in pre-menopausal women are unknown.
Patients treated with cerivastatin sodium who develop clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should be exercised if an HMG-CoA reductase inhibitor or other agent used to lower cholesterol levels is administered to patients also receiving other drugs that may decrease the levels or activity of endogenous steroid hormones, e.g., ketoconazole, spironolactone, or cimetidine.
CNS and other Toxicities: Chronic administration of cerivastatin to rodent and non-rodent species demonstrated the principal toxicologic targets and effects observed with other HMG-CoA reductase inhibitors: Hemorrhage and edema in multiple organs and tissues including CNS (dogs); cataracts (dogs); degeneration of muscle fibers (dogs, rats, and mice); hyperkeratosis in the non-glandular stomach (rats and mice, this organ has no human equivalent); liver lesions (dogs, rats, and mice).
CNS lesions were characterized by multifocal bleeding with fibrinoid degeneration of vessel walls in the plexus chorioideus of the brain stem and in the ciliary body of the eye at 0.1 mg/kg/day in the dog. This dose resulted in plasma levels of cerivastatin (Cmax, measured as free drug), that were about 17 times higher than the mean values in humans taking 0.8 mg/day. No CNS lesions were observed after chronic treatment with cerivastatin for up to two years in the mouse (up to 6 times human Cmax free drug levels) and rat (in the range of human Cmax free drug levels).This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 4/17/2009
Additional Baycol Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.