lovastatin (Mevacor, Altocor, monacolin-K, Altoprev)
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Introduction
Tradename: Mevacor.
Indications
Contraindications
- pregnancy (potentially teratogenic, risk may be small)
Dosage
- start 20 mg PO QD with evening meal[8]
- adjust at 4 week intervals
- 20-80 mg/day
- 10 mg QD may be effective in some patients
- lower dose for severe renal impairment[7] Tabs 10, 20 & 40 mg.
Extended release: Altocor[9]
- do NOT crush, chew or split
- take at bedtime on empty stomach
Tabs: 10, 20, 40, 60 mg
Pharmacokinetics
- bioavailability of oral dose is 30%; < 5%[13]
- protein binding >95%[13]
- absorption is enhanced by food[7] {except Altocor}
- time to peak plasma concentrations is 2-4 hours
- requires lactone hydrolysis for activation
- metabolized by cyt P450 3A4
- substrate of p-glycoprotein which it also inhibits[13]
- 1/2 life of 1.5 hours is for active metabolite; 2-3 hours[13]
- 3 days of therapy required for effect on serum cholesterol
- good penetration of blood brain barrier
elimination via liver
1/2life = 1.5 hours
protein binding = 95 %
Monitor
- see HMG CoA reductase inhibitor
- additional liver function test at 6 weeks, i.e. at baseline, 6 & 12 weeks, then periodically (yearly)[10]
Adverse effects
- infrequent (1-10%)
- headache
- uncommon (< 1%)
- renal failure, dysgeusia, lenticular opacities, blurred vision
- potentially teratogenic
- drug adverse effects of HMG CoA reductase inhibitors
- drug adverse effects of anti-hyperlipidemic agents
Drug interactions
- avoid combination of lovastatin with:
- do not exceed lovastatin dose of 10 mg QD in combination with dronedarone[13]
- do not exceed lovastatin dose of 20 mg QD in combination with amlodipine, diltiazem, verapamil, ranolazine[13]
- do not exceed lovastatin dose of 40 mg QD in combination with amiodarone, ticagrelor[13]
- any drug which inhibits cyt P450 3A4 can increase lovastatin levels (see cyt P450 3A4)
- erythromycin, ketoconazole, ritonavir-boosted HIV protease inhibitors, some Ca+2 channel blockers, amiodarone, grapefruit juice (etc)
- probably should not exceed lovastatin dose of 20-40 mg/day if used in combination (see simvastatin)[9]
- any drug which induces cyt P450 3A4 can diminish lovastatin levels
- inbibits p-glycoprotein
- gemfibrozil & niacin may result in:
- myalgia & muscle weakness
- increased serum creatine kinase
- rash & pruritus
- ritonavir-boosted protease inhibitors used in HIV therapy may slow metabolism of lovastatin[4]
- close monitoring for myalgia when used in combination with colchicine[13]
- 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
Test interactions
Mechanism of action
- inhibition of HMG CoA reductase
- maximal effect (80 mg/day)
- total cholesterol: decrease of 30%
- LDL cholesterol: decrease of 40% (30-48%[7])
- HDL cholesterol: increase of 8%
- triglycerides: decrease of 15%
- induces inositol-3-phosphate synthase
More general terms
Additional terms
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
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 4.0 4.1 Prescriber's Letter 7(8):45 2000
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 7.0 7.1 7.2 7.3 Prescriber's Letter 9(1):1 2002
- ↑ 8.0 8.1 Do All Statins Need to be Taken in the Evening? Prescriber's Letter 10(12):70 2003 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=191206&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 9.2 Prescriber's Letter 15(10): 2008 Rhabdomyolysis with Combined Use of Amiodarone and Simvastatin Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=241002&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 10.0 10.1 Prescriber's Letter 17(6): 2010 CHART: Characteristics of the Various Statins CHART: 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=260611&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 11.0 11.1 Deprecated Reference
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 13.9 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