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lovastatin (Mevacor, Altocor, monacolin-K, Altoprev)

Tradename: Mevacor. Indications: - hypercholesterolemia - arteriosclerosis - coronary artery disease - myocardial infarction - prevention of cardiovascular disease - transient ischemic attack - stroke [11] Contraindications: - pregnancy (potentially teratogenic, risk may be small) Dosage: 1) start 20 mg PO QD with evening meal [8] 2) adjust at 4 week intervals 3) 20-80 mg/day 4) 10 mg QD may be effective in some patients 5) lower dose for severe renal impairment [7] Tabs 10, 20 & 40 mg. Extended release: Altocor [9] 1) do NOT crush, chew or split 2) take at bedtime on empty stomach Tabs: 10, 20, 40, 60 mg Pharmacokinetics: 1) bioavailability of oral dose is 30%; < 5% [13] - protein binding >95% [13] 2) absorption is enhanced by food [7] {except Altocor} 3) time to peak plasma concentrations is 2-4 hours 4) requires lactone hydrolysis for activation 5) metabolized by cyt P450 3A4 - substrate of p-glycoprotein which it also inhibits [13] 6) 1/2 life of 1.5 hours is for active metabolite; 2-3 hours [13] 7) 3 days of therapy required for effect on serum cholesterol 8) good penetration of blood brain barrier 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: 1) infrequent (1-10%) a) gastrointestinal - increased serum transaminases - flatus - abdominal cramps - diarrhea - constipation - nausea - dyspepsia - heartburn b) musculoskeletal - myalgias - increased serum creatine kinase - rhabdomyolysis 3) headache 2) uncommon (< 1%) - renal failure, dysgeusia, lenticular opacities, blurred vision 3) potentially teratogenic Drug interactions: 1) avoid combination of lovastatin with: - conivaptan, cyclosporine, tacrolimus, everolimus, sirolimus, gemfibrozil [13] 2) do not exceed lovastatin dose of 10 mg QD in combination with dronedarone [13] 3) do not exceed lovastatin dose of 20 mg QD in combination with amlodipine, diltiazem, verapamil, ranolazine [13] 4) do not exceed lovastatin dose of 40 mg QD in combination with amiodarone, ticagrelor [13] 5) any drug which inhibits cyt P450 3A4 can increase lovastatin levels (see cyt P450 3A4) a) erythromycin, ketoconazole, ritonavir-boosted HIV protease inhibitors, some Ca+2 channel blockers, amiodarone, grapefruit juice (etc) b) probably should not exceed lovastatin dose of 20-40 mg/day if used in combination (see simvastatin) [9] 6) any drug which induces cyt P450 3A4 can diminish lovastatin levels 7) inbibits p-glycoprotein 8) gemfibrozil & niacin may result in: a) myalgia & muscle weakness b) increased serum creatine kinase c) rash & pruritus 9) ritonavir-boosted protease inhibitors used in HIV therapy may slow metabolism of lovastatin [4] 10) close monitoring for myalgia when used in combination with colchicine [13] Test interactions: -> may alter AST, ALT, CPK, ALP, thyroid function studies [6] Mechanism of action: 1) inhibition of HMG CoA reductase 2) maximal effect (80 mg/day) a) total cholesterol: decrease of 30% b) LDL cholesterol: decrease of 40% (30-48% [7]) c) HDL cholesterol: increase of 8% d) triglycerides: decrease of 15% 3) induces inositol-3-phosphate synthase

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 1/2life 1.5 HOURS protein-binding 95% pregnancy-category X safety in lactation -

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1990. pg 882
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Prescriber's Letter 7(8):45 2000
  5. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  6. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  7. Prescriber's Letter 9(1):1 2002
  8. Do All Statins Need to be Taken in the Evening? Prescriber's Letter 10(12):70 2003 Detail-Document#: 191206 (subscription needed) http://www.prescribersletter.com
  9. Prescriber's Letter 15(10): 2008 Rhabdomyolysis with Combined Use of Amiodarone and Simvastatin Detail-Document#: 241002 (subscription needed) http://www.prescribersletter.com
  10. Prescriber's Letter 17(6): 2010 CHART: Characteristics of the Various Statins CHART: Clinically Significant Statin Drug Interactions Detail-Document#: 260611 (subscription needed) http://www.prescribersletter.com
  11. Deprecated Reference
  12. Department of Veterans Affairs, VA National Formulary
  13. 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 PMID: 27754879 http://circ.ahajournals.org/content/circulationaha/early/2016/10/17/CIR.0000000000000456.full.pdf

Component-of

lovastatin/nicotinic acid (Advicor, Nicostatin)