Zocor (simvastatin) - New Safety Recommendations on Dosage Associated with the Increased Risk of Muscle Problems - For Health Professionals

Starting date:

November 7, 2012

Posting date:

November 13, 2012

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Issue:

Dosage

Audience:

Healthcare Professionals

Identification number:

RA-15826

This is duplicated text of a letter from Merck Canada Inc. Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on Zocor (simvastatin)

November 7, 2012

Dear Health Care Professional:

Subject: ZOCOR^® (simvastatin) - New Safety Recommendations on Dosage Associated with the Increased Risk of Myopathy/Rhabdomyolysis

Merck Canada Inc., in consultation with Health Canada, would like to inform you of important safety recommendations on dosage related to the increased risk of myopathy/rhabdomyolysis, particularly with the 80 mg dose of ZOCOR^® (simvastatin; also marketed as generics). An increased risk of myopathy/rhabdomyolysis within the recommended dose range for ZOCOR^® (simvastatin) can also be seen with concomitant administration of certain medications.

In patients at high risk of coronary events, ZOCOR^® is indicated to reduce the risk of myocardial infarction, ischemic stroke and total mortality (by reducing coronary heart disease deaths). Please refer to the ZOCOR^® Product Monograph for the complete indication.

• The regular use of the 80 mg dose of simvastatin has been associated with an increased risk of myopathy/rhabdomyolysis, particularly during the first year of treatment.
• The recommended simvastatin dosage is 5 to 40 mg/day. Patients unable to achieve their LDL-C goal with the 40 mg dose of ZOCOR^® should be switched to alternative LDL-C-lowering treatments with lower risks of muscle toxicity.
• Simvastatin 80 mg dose should be restricted to patients who have been taking this dose chronically with no evidence of muscle toxicity or to patients at high risk for cardiovascular complications who do not tolerate other statins and in whom the benefits are expected to outweigh the potential risks.
• Concomitant use of recommended dosage of simvastatin with certain drugs and grapefruit juice increases the risk of myopathy/rhabdomyolysis.

In a clinical trial database in which 41,413 patients were treated with ZOCOR^®, 24,747 (approximately 60%) of whom were enrolled in studies with a median follow-up of at least 4 years, the incidence of myopathy was approximately 0.03%, 0.08% and 0.61% at 20, 40 and 80 mg/day, respectively. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.

In a clinical trial (SEARCH) in which 12,064 patients with a history of myocardial infarction were treated with ZOCOR^® 80 mg/day (mean follow-up 6.7 years), the incidence of myopathy was approximately 1.0% compared with 0.02% for patients on 20 mg/day. Approximately half of these myopathy cases occurred during the first year of treatment.

Patients currently tolerating the 80 mg dose of ZOCOR^® who need an interacting drug that is either contraindicated, such as potent inhibitors of CYP3A4, cyclosporine, danazol, and gemfibrozil, or associated with an increase of plasma level of simvastatin should be switched to an alternative statin with less potential for a drug-drug interaction.

Concomitant use of recommended dosage of simvastatin with certain drugs and food also increases the risk of myopathy/rhabdomyolysis. Therefore, the following dosages and recommendations are indicated:

• Do not exceed 10 mg simvastatin daily with verapamil, diltiazem and fibrates (other than gemfibrozil or fenofibrate);
• Do not exceed 20 mg simvastatin daily with amiodarone and amlodipine;
• Patients should be closely monitored and temporary suspension of simvastatin treatment may be considered while under treatment with fusidic acid;
• Large quantities of grapefruit juice (>1 L daily) should be avoided.

For complete prescribing information and conditions of use, including a list of contraindicated drugs and drugs with dose-related risk myopathy/rhabdomyolysis, please review the revised Product Monograph before prescribing ZOCOR^®. The Product Monograph for ZOCOR^® is available on the Merck Canada product information Web site.

Managing marketed health product-related adverse reactions depends on health care professionals and consumers reporting them. Any case of serious myopathy/rhabdomyolysis or other serious or unexpected adverse reactions in patients receiving ZOCOR^® should be reported to Merck Pharmacovigilance or Health Canada.

Merck Canada Inc., Pharmacovigilance
16750 Trans-Canada Hwy.
Kirkland, Québec H9H 4M7
Fax: 1-800-369-3090

To correct your mailing address or fax number, contact Merck Canada Inc.

To report suspected adverse reactions to these or other health products, please contact Health Canada's Canada Vigilance Program toll-free at 1-866-234-2345, or visit theMedEffect™ Canada Web site for information on how to report.

The Reporting Forms, postage paid labels, and Guidelines can be found on the MedEffect™ Canada Web site in the Adverse Reaction Reporting section. The Reporting Form is also in the Canadian Compendium of Pharmaceuticals and Specialties.

For other health product inquiries related to this communication, please contact Health Canada at:
Marketed Health Products Directorate
E-mail: mhpd_dpsc.public@hc-sc.gc.ca
Telephone: 613-954-6522
Fax: 613-952-7738

If you have any questions regarding this important information or for any medical inquiries, please contact Merck Canada Medical Information at 514-428-8600 or 1-800-567-2594, or Health Canada at the number listed above.

Sincerely,

original signed by

Mauricio Ede, M.D.
Medical Director, Medical Affairs

^® Registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.Used under license.

References:

1. ZOCOR^® (simvastatin) Product Monograph, June 6th, 2012
2. SEARCH Study Collaborative Group Oxford UK. Randomised comparison of more intensive LDL-lowering therapy with 80 mg versus 20 mg simvastatin daily in 12,064 myocardial infarction survivors, 2010. Lancet 2010; 376: 1658-69.