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cerivastatin; rivastatin (Baycol, Lipobay)
Tradename: Baycol. Removed from US market 2001 [3] Withdrawn from worldwide market Aug 8, 2001 [2].
Indications:
- adjunct to diet in treatment of primary hypercholesterolemia & mixed dyslipidemia
Contraindications:
1) pregnancy or lactation
2) hepatic disease
3) concurrent administration of GEMFIBROZIL (Lopid)
Dosage:
1) 0.4 mg QD in the evening
2) may be given with or without food
Tabs: 0.2, 0.3, 0.4 mg.
store tabs below 77 degrees F; protect from moisture.
Dosage adjustment in renal failure:
- creatinine clearance < 60 mL/min, start 0.2-0.3 mg QD
Pharmacokinetics:
1) absolute bioavailability is 60%
2) metabolized to pharmacologically active metabolites
a) demethylation
b) hydroxylation
c) metabolized by cyt P450 3A4
3) eliminated in the urine & feces as metabolites
4) terminal elimination 1/2life is 2-3 hours
5) effects on cholesterol seen in 1 week
6) maximal effects on cholesterol seen in 4 weeks
7) time to peak serum concentration 2.5 hours
8) peak serum levels: 0.2 mg 2.4 ug/L; 0.3 mg 3.8 ug/L; 0/4 mg 5.5 ug/L
9) linear elimination kinetics 0.04-0.4 mg QD
10) protein-binding > 99%
11) volume of distribution 0.3 L/kg
Monitor:
1) liver function tests: initially, at 6 & 12 weeks, then semiannually
2) creatine kinase as indicated
Adverse effects:
1) similar to other statins
2) common
a) dyspepsia
b) diarrhea
c) arthralgia
d) myalgia
3) cardiovascular (2%)
- chest pain, peripheral edema
4) headache
5) gastrointestinal
- abdominal pain, dyspepsia (6%), diarrhea (4%)
6) genitourinary
- RHABDOMYOLYSIS with acute renal failure (reason for removal from US market) [3]
7) mild elevations in serum transaminases
8) musculoskeletal
a) increases in creatine kinase (5X)
b) rhabdomyolysis 0.05% [4]
Drug interactions:
1) in combination with GEMFIBROZIL increases incidence of RHABDOMYOLYSIS to 9% [4]
2) zidovudine: mild increased in zidovudine level
3) cholestyramine decreases availability of cerivastatin
4) increased risk of rhabdomyolysis with
- cyclosporine, erythromycin, gemfibrozil, fluconazole, itraconazole, ketoconazole, mibefradil, niacin
5) any drug which inhibits cyt P450 3A4 can increase cerivastatin levels
6) any drug which induces cyt P450 3A4 can diminish cerivastatin levels
Mechanism of action:
1) inhibition of HMG CoA reductase
2) maximal effect (0.3 mg/day)
a) total cholesterol: decrease of 19%
b) LDL cholesterol: decrease of 28%
c) HDL cholesterol: increase of 10%
d) triglycerides: decrease of 13%
Interactions
drug interactions
drug adverse effects (more general classes)
monitor with HMG CoA reductase inhibitors (statins)
Related
cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
General
lipophilic statin
Properties
INHIBITS: HMG CoA reductase
MISC-INFO: elimination route LIVER
KIDNEY
protein-binding >99 &
1/2life 2-3 HOURS
pregnancy-category X
safety in lactation -
Database Correlations
PUBCHEM correlations
References
- Micromedex
- http://www.baycol.com/Dear_HealthCare_Letter_Baycol_pull.jpg
http://www.press.bayer.com/News/news.nsf/ID/NT0000E072
- Prescriber's Letter 8(9):50 2001
- Psaty BM, Furberg CD, Ray WA, Weiss NS.
Potential for conflict of interest in the evaluation of
suspected adverse drug reactions: use of cerivastatin and risk
of rhabdomyolysis.
JAMA. 2004 Dec 1;292(21):2622-31. Epub 2004 Nov 22. Review.
PMID: 15572720