pravastatin (Pravachol)
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Introduction
Tradename: Pravachol.
Indications
- hyperlipidemia
- arteriosclerosis
- may reduce risk of stroke in women[7]
- may reduce all-cause mortality in women[7]
- treatment of proteinuria in conjunction with ACE inhibitor[6]
- statin of choice for use with HIV protease inhibitors or to avoid cytochrome P450 interactions[8]
Contraindications
- pregnancy (potentially teratogenic, risk may be small)
Dosage
- start 10 mg QHS
- usual dose 20-40 mg QHS
- maximum: 80 mg/day; 40 mg in elderly
- lower dose recommended for moderate renal impairment[5] Tabs 10, 20 & 40 mg.
Pharmacokinetics
- oral absorption is poor, bioavailability is 17%
- extensive 1st pass metabolism in liver;
- extraction ratio 0.66[4]
- transported into hepatocytes (primary site of action), less so into other cells
- maximum plasma levels in 1-1.5 hours[12]
- metabolized in the liver
- isomerization to inactive 3-alpha hydroxy isomer (major metabolite)
- oxidation (not metabolized by cyt P450)[12]
- conjugation
- does not require activation via lactone hydrolysis as do lovastatin, simvastatin, & mevastatin
- protein binding is 50%
- elimination 1/2life is 2-3 hours; 1.8 hours[12]; 77 hours for metabolites
- no active metabolites[12]
- 8% excreted unchanged in the urine
- according to ref[9], pravastatin metabolized by kidney
elimination via liver
protein binding = 50 %
1/2life = 1.6-3 hours
Monitor
(see HMG CoA reductase inhibitor)
Adverse effects
- gastrointestinal
- musculoskeletal
- CNS: headache, dizziness,
- ocular: lens opacity, blurred vision
- skin: rash
- Respiratory: cough
- potentially teratogenic
- risk for diabetes mellitus may be lowest among statins
- pravastatin improves insulin sensitivity & inhibits gluconeogenesis
- drug adverse effects of HMG CoA reductase inhibitors
- drug adverse effects of anti-hyperlipidemic agents
Drug interactions
- avoid use in combination with gemfibrozil[12]
- limit dose of pravastatin to 40 mg QD with coadministration of cyclosporine, tacrolimus, everolimus, sirolimus[12]
- drugs that inhibit cyt P450 3A4 do not increase pravastatin levels significantly[5]
- any drug which induces cyt P450 3A4 can diminish pravastatin levels
- may NOT interact with warfarin as do other HMG CoA reductase inhibitors
- increased effect with cholestyramine
- increased effect of warfarin
- concurrent use may increase risk of rhabdomyolysis
- close monitoring for myalgia with coadministration of colchicine[12]
- drug interaction(s) anticonvulsants with statins
- drug interaction(s) of statins with vitamin D
- drug interaction(s) of statins with SSRIs
- drug interaction(s) of statins with influenza virus vaccines
- drug interaction(s) of statins with macrolide
- drug interaction(s) of statins with antiviral protease inhibitors
- drug interaction(s) of statins with fibrates
Mechanism of action
- inhibition of HMG CoA reductase
- maximal effect (40 mg/day)
- total cholesterol: decrease of 25%
- LDL cholesterol: decrease of 34%
- HDL cholesterol: increase of 8%
- triglycerides: decrease of 25%
- reduces proteinuria in patients with controlled hypertension[6]
More general terms
Additional terms
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
- Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (Mega Study)
- Prospective Study of Pravastatin in Elderly People at Risk (PROSPER)
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1990. pg 882
- ↑ Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 4.0 4.1 Physician's Desk Reference (PDR) 54th edition, Medical Economics, 2000
- ↑ 5.0 5.1 5.2 Prescriber's Letter 9(1):1 2002
- ↑ 6.0 6.1 6.2 Prescriber's Letter 9(9):49 2002
- ↑ 7.0 7.1 7.2 Mizuno K et al. Usefulness of pravastatin in primary prevention of cardiovascular events in women: Analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA study). Circulation 2008 Jan 29; 117:494. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18172039
- ↑ 8.0 8.1 Prescriber's Letter 16(8): 2009 Clinically Significant Statin Drug Interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250812&pb=PRL
- ↑ 9.0 9.1 Medical Knowledge Self Assessment Program (MKSAP) 16, American College of Physicians, Philadelphia 2012
- ↑ Carter AA et al. Risk of incident diabetes among patients treated with statins: Population based study. BMJ 2013 May 23; 346:f2610. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23704171
Huupponen R and Viikari J. Statins and the risk of developing diabetes. BMJ 2013 May 23; 346:f3156 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23709567 - ↑ Deprecated Reference
- ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7 Wiggins BS, Saseen JJ, Page RL 2nd et al Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease. A Scientific Statement From the American Heart Association. Circulation. 2016;134:00-00 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27754879 <Internet> http://circ.ahajournals.org/content/circulationaha/early/2016/10/17/CIR.0000000000000456.full.pdf