Synopsis Ezetimibe/simvastatin (v...

Synopsis

Ezetimibe/simvastatin (vytorin) is a combination of ezetimibe (Zetia), which inhibits the absorption of cholesterol by means of the small intestine, and simvastatin (Zocor), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, or statin. Ezetimibe/simvastatin, in conjunction with diet changes, is indicated for patients with hypercholesterolemia. (1)

Safety Adverse reactions to ezetimibe/simvastatin include elevated transaminase plains myopathy, and rhabdomyolysis; they are related to the dose of simvastatin and almost always are reversible. (1) Myopathy and rhabdomyolysis are the greatest in quantity serious known adverse reactions to statins. In clinical trials of the combination, rhabdomyolysis did not come to pass (1-6) and there was simply one reported occurrence of myopathy, (4) which resolv after discontinuation. The rate of myopathy was approximately single in kind per 2,800 persons. (2-6) Elevation of liver enzyme to more than three times the normal flush occurred in 1.7 percent of patients receiving ezetimibe/simvastatin. (1) The fruit labeling for simvastatin states that in clinical trials, elevated liver function occurr in 1 percent of patients. (7)

Simvastatin serum flats may be increased when simvastatin is given concomitantly with medications that affect the cytochrome P450 (CYP450) 3A4 enzyme hypothesis increasing the risk of myopathy and rhabdomyolysis. To avoid this risk, physicians may consider temporarily discontinuing ezetimibe/simvastatin for the duration of therapy with macrolide antibiotics and azole antifungals. Ezetimibe does not interact with unsalable articles metabolized by the CYP450 hypothesis It is pregnancy category X and must not be given to women who may be pregnant. (1)

Tolerability

Ezetimibe/simvastatin generally is well tolerated. The addition of ezetimibe to simvastatin did not affect tolerability through the whole extent of 40 weeks' administration; no subject of attention has assessed ezetimibe/simvastatin for a longer duration. (5) Adverse general intents of ezetimibe/ simvastatin are similar to those of statin monotherapy. (1-5) Headache, upper respiratory infection, influenza, myalgia, and pain in extremities were the solely adverse effects more common than with placebo, and these occurr in les than 4 percent of patients receiving ezetimibe/simvastatin. (1)

Effectiveness

sum of two units studies, (3,5) with a total of 1555 participants, demonstrated ezetimibe/simvastatin to be more effective in lowering low-density lipoprotein (LDL) cholesterol evens than simvastatin monotherapy, with a mean reduction of 51 to 53 percent compared with 37 to 39 percent with simvastatin alone. Another couple studies, (2,6) with a total of 2690 participants, showed ezetimibe/simvastatin to be more effective than atorvastatin (lipitor) in lowering LDL cholesterol resulting in an average reduction of 52 to 53 percent compared with 45 percent in the two studies with atorvastatin alone. no studies of ezetimibe alone or the combination of ezetimibe and simvastatin have examined cardiovascular morbidity or mortality or all-cause mortality.

Price

The price of ezetimibe/simvastatin (approximately $80 for month for all doses) is generally lower than that of other statins. Generic lovastatin richnesss less ($30 to $60 through month). The ezetimibe/simvastatin combination is more cost-effective than taking ezetimibe and a statin separately.

Simplicity

The commended starting dosage for ezetimibe/ simvastatin is 10 mg ezetimibe and 20 mg simvastatin daily in the evening, taken with or without feed Patients who need a smaller reduction in LDL cholesterol on a levels can start with a dosage of 10/10 mg daily, and those requiring a larger reduction in lDl flushs (greater than 55 percent) may start with a dosage of 10/40 mg daily. no dosage adjustments are necessary in older patients, those with mild hepatic insufficiency, or those with mild to moderate renal insufficiency. (1)

Bottom Line

soft doses of ezetimibe/simvastatin provide greater improvements in lipid profile than simvastatin or atorvastatin monotherapy. Ezetimibe/simvastatin may be useful in patients who are unable to tolerate highdose statin therapy. Combination ezetimibe-simvastatin is les expensive than adding ezetimibe to a statin and more convenient than taking pair separate medicines. no trials have been performed to determine the drift of ezetimibe/simvastatin on stroke, myocardial infarction, or mortality rate.

REFERENCES

(1) Vytorin (ezetimibe/simvastatin). Package insert. North Wales, Pa. Merck/Schering-Plough Pharmaceuticals. March 2005 Accessed online August 22 2005 at: http://www.vytorin.com/vytorin/shared/documents/vytorin_pi.pdf.

(2) Ballantyne CM Blazing MA, King TR Brady WE, Palmisano J Efficacy and safety of ezetimibe co-administered with simvastatin compared with atorvastatin in adults with hypercholesterolemia. Am J Cardiol 2004;93:1487-94

(3) Davidson MH McGarry T Bettis R Melani L Lipka LJ LeBeaut AP, et al. Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia. J Am Coll Cardiol 2002;40:2125-34