Simvastatin: new contraindications, precautions and dosage recommendations

The TGA is advising health professionals to limit the prescribing of high dose (80 mg/day) simvastatin and to be aware of new contraindications and precautions for the use of simvastatin with other medicines.

Patients on high dose simvastatin and those taking certain other medicines have an increased risk of developing myopathy (muscle weakness) and, more rarely, rhabdomyolysis¹.

Simvastatin is used to control elevated cholesterol, or hypercholesterolemia. It is recommended to be used only after other measures such as diet, exercise, and weight reduction have not improved cholesterol levels.

1. The breakdown of muscle fibres resulting in the release of muscle fibre contents (myoglobin) into the bloodstream. Some of these are harmful to the kidney and frequently result in kidney damage.

Information for health professionals

Dosage

The TGA recommends that 80 mg/day simvastatin should only be used in patients at high risk of cardiovascular complications who have not achieved their treatment goals on lower doses.

Interactions with other medicines

Concomitant administration of simvastatin with the following medicines is now contraindicated:

• gemfibrozil
• cyclosporine
• danazol
• potent CYP3A4 inhibitors, for example:
  • itraconazole
  • ketoconazole
  • posaconazole
  • HIV protease inhibitors
  • erythromycin
  • clarithromycin
  • telithromycin
  • nefazodone.

Specific precautions (such as lower recommended simvastatin doses) now exist for patients taking the following medicines:

• moderate inhibitors of CYP3A4
• amiodarone
• the calcium channel blockers verapamil, diltiazem and amlodipine
• fibrates other than gemfibrozil (which is now contraindicated)
• niacin (≥1 g/day)
• colchicine.

For detailed precautions on interactions with other medicines, and the recommended course of action, please refer to the article in the December edition of Medicines Safety Update.

The TGA is working with the sponsors of simvastatin and simvastatin-containing products to update the Product Information. The Product Information for Zocor has already been amended and is available on the TGA website.

Information for patients

You should talk to your doctor if you are taking simvastatin, and you have:

• muscle pain, tenderness or weakness
• dark or red coloured urine
• unexplained tiredness.

Reporting an adverse event

Patients and health professionals are encouraged to report adverse reactions associated with simvastatin to the TGA. Your report will contribute to our monitoring of this medicine.

The TGA cannot give personal advice about an individual's medical condition. Consumers are strongly encouraged to talk with a health professional if they are concerned about a possible adverse reaction to any medicine.