Header Ads Widget

Responsive Advertisement

Side effects of lipid lowering therapy and how should they be monitored?

Statins

These are generally well tolerated. In the major end point trials, adverse events were little different from placebo.

• Myositis, defined as painful, tender muscles with a high CPK, is rare, occurring with a frequency of lower than 1 in 10,000 patient years. Routine CPK measurement is not recommended as modest elevations (generally secondary to physical activity) are quite common even in patients on placebo treatment. It is important to remember that black patients have higher CPKs than whites, and that hypothyroidism is an important cause of raised CPK. Patients should be warned to stop the drugs if severe muscle pain is experienced.

• Liver function should be checked prior to statin therapy as abnormal hepatic function and high alcohol intake are relative contraindications for these drugs which are metabolised principally through the liver. Approximately one in 400 patients will develop greater than 3-fold transaminase increases which revert to normal with dose reduction or stopping of the drug. They can be used in moderate renal impairment. It is good practice to check liver function tests periodically during statin therapy.

Fibrates

These are also generally well tolerated but can also cause myositis and hepatic dysfunction. Clofibrate (in the WHO trial) was associated with increased gallstone formation through increased biliary cholesterol content. This drug is now redundant and the newer fibrates have less impact on biliary composition. Doubt remains concerning long term safety with the fibrate class in terms of non-cardiac mortality. However the WHO clofibrate trial was the major contributor to this concern. The recent VA HIT study (reported at the AHA meeting in Dallas, November 1998) showed that gemfibrozil reduced risk by approximately a quarter in post-MI men with average LDL but low HDL cholesterol concentrations with no increase in non-CHD adverse events.

Drug interactions

Care should be exercised when statins are combined with fibrates or used in patients taking cyclosporin (e.g. transplant patients) as the risk of side effects (particularly myositis) is increased. Dosage should be limited in transplant patients taking cyclosporin as drug levels are increased. Care should also be exercised when used in combination with drugs metabolised through the cytochrome P450 pathway (e.g. antifungals, erythromycin) as there is a potential for interactions. There is a theoretical potential for interaction with warfarin but the author has not found this a problem in practice.

Resins

The resins are associated with a high frequency of gastrointestinalside effects which limit their use. They may interfere with the absorption of other drugs so should be taken either one hour before or four hours after other therapeutic agents. The resins theoretically may interfere with the absorption of fat soluble vitamins and folic acid but this is not a major problem in practice. However, perhaps with increasing indication of the role of homocysteine as a risk factor, folic acid supplements might be recommended in patients on resins.

Post a Comment

0 Comments