First Approval in Europe of Ezetimibe/Simvastatin for treatment of elevated cholesterol

Merck/Schering-Plough Pharmaceuticals today announced the regulatory approval of INEGY^TM (ezetimibe/simvastatin) in Germany for the treatment of elevated cholesterol (hypercholesterolemia).  INEGY is the first product to reduce low-density lipoprotein cholesterol (LDL-C or ‘bad’ cholesterol), along with diet and exercise, through dual inhibition by inhibiting cholesterol production in the liver and absorption in the intestine.  The approval of INEGY in Germany represents the first approval in Europe for ezetimibe/simvastatin tablets and the first step in seeking marketing approval throughout the European Union (EU) under the EU’s mutual recognition procedure. 

“With this exciting approval in Germany, we have the opportunity to launch an innovative new product into the third largest pharmaceutical market in the world,” said Fred Hassan, chairman and chief executive officer, Schering-Plough Corporation (NYSE: SGP).

“By targeting the two sources of cholesterol, INEGY will provide physicians with another option for the treatment of patients with high cholesterol,” said Raymond V. Gilmartin, chairman, president and chief executive officer, Merck and Co., Inc. (NYSE: MRK).

INEGY will be available in several dosing strengths (ezetimibe/simvastatin): 10/10 mg, 10/20 mg, 10/40 mg and 10/80 mg.

Ezetimibe/simvastatin was approved earlier last month in Mexico.

In the United States, a New Drug Application for ezetimibe/simvastatin was submitted on Sept. 24, 2003.  The filing was accepted by the U.S. Food and Drug Administration on Nov. 23, 2003 and is currently under standard review.  If approved, ezetimibe/simvastatin will be marketed under the name VYTORIN^TM.

Important information about ezetimibe/simvastatin
In clinical trials of ezetimibe co-administered with simvastatin, there was no increased incidence of myopathy or rhabdomyolysis associated with ezetimibe/simvastatin.  However, myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs.  All patients starting therapy with ezetimibe/simvastatin or whose dose of ezetimibe/simvastatin is being increased should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness because they could be signs of serious side effects.  It is recommended that liver function tests be performed before treatment with ezetimibe/simvastatin begins and thereafter as clinically indicated.  Patients titrated to the 10/80 mg dose should receive an additional liver function test prior to titration, three months after titration to the 10/80 mg dose, and periodically thereafter (e.g. semiannually) for the first year of treatment.  Due to the unknown effects of the increased exposure to ezetimibe/simvastatin in patients with moderate or severe hepatic insufficiency, ezetimibe/simvastatin is not recommended in these patients.  The safety and effectiveness of ezetimibe/simvastatin with fibrates have not been established; therefore, co-administration with fibrates is not recommended.

Ezetimibe/simvastatin should not be used in pregnant or nursing women.  In clinical trials, ezetimibe/simvastatin was generally well tolerated.  The most common side effects included headache, dizziness, arthralgia, myalgia and asthenia.

Important information about ezetimibe
When ezetimibe is used with a statin, liver function tests should be performed at the start of therapy and after that in accordance with the label for that statin.  Due to the unknown effects of the increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, ezetimibe is not recommended in these patients.  In clinical trials, there was no increased incidence of myopathy or rhabdomyolysis associated with ezetimibe.  However, myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs.  There are no adequate and well-controlled studies of ezetimibe in pregnant women.  Ezetimibe should not be used in pregnant or nursing women unless the benefit outweighs the potential risks.  The safety and effectiveness of ezetimibe with fibrates have not been established; therefore, co-administration with fibrates is not recommended.

Important information about simvastatin
Simvastatin should not be used by anyone allergic to any of its components, with liver disease, or by women who are pregnant, breast-feeding or likely to become pregnant.  Muscle pain or weakness in people taking simvastatin should be reported to a doctor because these could be signs of a serious side effect.  Doctors may perform blood tests before and periodically during treatment with simvastatin to check for liver problems.  People taking 80 mg of simvastatin should receive an additional liver function test at three months.  To help avoid serious side effects, discuss with your doctor medicine or food you should avoid while taking simvastatin.  In clinical trials, adverse reactions usually have been mild and transient.  Most common side effects included headache (3.5 percent), abdominal pain (3.2 percent) and constipation (2.3 percent).