lovastatin (Rx)

>10%

CPK elevation (11%)

1-10%

Flatulence (4-5%)

Abdominal pain (2-3%)

Constipation (2-3%)

Diarrhea (2-3%)

Myalgia (2-3%)

Nausea (2-3%)

Dyspepsia (1-2%)

Weakness (1-2%)

Blurred vision (0.8-1%)

Rash (0.8-1%)

Muscle cramps (0.6-1%)

Dizziness (0.5-1%)

<1%

Dermatomyositis

Increased LFTs

Hepatotoxicity

Myopathy

Rhabdomyolysis

Postmarketing Reports

Interstitial lung disease

Contraindications

Hypersensitivity to lovastatin or other components

Active liver disease, or unexplained elevated transaminases

Pregnancy, lactation

Concomitant administration with strong CYP3A4 inhibitors (eg, itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, cobicistat, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, and nefazodone)

Cautions

Nonserious and reversible cognitive side effects may occur

Increased blood sugar and glycosylated hemoglobin (HbA1c) levels reported with statin intake

Rhabdomyolysis, risk of myopathy: Risk increased by coadministration CYP3A4 inhibitors or other drugs that cause myopathy

Avoid coadministration with cyclosporine or gemfibrozil; caution with other fibrates or lipid-lowering doses of niacin (≥1 g/day) because of increased risk for myopathy

Heavy alcohol use, history of liver disease, renal failure

Discontinue if markedly elevated CPK levels occur or myopathy is diagnosed or suspected; also, temporarily withhold in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis (eg, sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; uncontrolled epilepsy)

Rare reports of immune-mediated necrotizing myopathy (IMNM), characterized by increased serum creatine kinase that persists despite discontinuation of statin

Obtain baseline liver enzyme tests before initiating and then periodically thereafter

Brand Altocor renamed Altoprev due to confusion with Advicor

Mechanism of Action

HMG-CoA reductase inhibitor; inhibits the rate-limiting step in cholesterol biosynthesis by competitively inhibiting HMG-CoA reductase

Absorption

Bioavailability: 5% (Mevacor)

Onset: 3 d (Mevacor)

Duration: 4-6 wk (Mevacor)

Max effect: 4-6 wk (Mevacor)

Peak plasma time: 2-4 hr; 14 hr (ext-rel Altoprev)

Peak plasma concentration: 7.8 ng/mL; 5.5 ng/mL (ext-rel Altoprev)

AUC: 45 ng.hr/mL; 77 ng.hr/mL (ext-rel Altoprev)

Distribution

Protein bound: 95% (Mevacor)

Metabolism

Extensive first pass in liver; activation to beta-hydroxyacid by nonenzymatic/nonspecific hydrolysis; major CYP3A4 substrate

Metabolite: Beta-hydroxyacid derivative (active) and others

Elimination

Half-life: 1.1-1.7 hr (Mevacor)

Excretion (Mevacor): Feces (83%), urine (10% urine)

Pharmacogenomics

SLCO1B1 (OATP1B1) CC genotype significantly increases AUCs of parent drug and metabolites compared with the CT or TT genotypes

This polymorphism is proposed to reduced transport into the liver, the main site of statin metabolism and elimination, resulting in elevated plasma concentrations

SLCO1B1 polymorphism is thought to have a lesser effect on the more hydrophilic statins (eg, rosuvastatin, fluvastatin) compared with those that are more lipophilic (eg, atorvastatin, pravastatin, simvastatin)

Other genetic polymorphisms of elimination (eg, CYP450, P-glycoprotein) for each individual drug must also be considered to explain variability for statin clearance among patients that exhibit SCLO1B1 polymorphism

SLCO1B1 CC genotype is most common in Caucasians and Asians (15%)

Risk of myopathy is 2.6- to 4.3-fold higher if the C allele is present and is 16.9-fold higher in CC homozygotes compared with TT homozygotes