ANTIHYPERLIPIDAEMIC AGENTS - DRUG-INTERACTIONS OF CLINICAL-SIGNIFICANCE

The available antihyperlipidaemic drugs are generally safe and effecti ve, and major systemic adverse effects are uncommon. However, because of their complex mechanisms of action, careful monitoring is required to identify and correct potential drug interactions. Bile acid sequest rants are the most difficult of these agents to administer concomitant ly, because their nonspecific binding results in decreased bioavailabi lity of a number of other drugs, including thiazide diuretics, digital is preparations, beta-blockers, coumarin anticoagulants, thyroid hormo nes, fibric acid derivatives and certain oral antihyperglycaemic agent s. Although the incidence is low, nicotinic acid may cause hepatic nec rosis and so should not be used with drugs that adversely affect hepat ic structure or function. With the HMG-CoA reductase inhibitors, relat ively new agents for which clinical data are still being accumulated, the major problems appear to be rhabdomyolysis, associated with the co ncomitant use of cyclosporin, fibric acid derivatives or erythromycin, and mild, intermittent hepatic abnormalities that may be potentiated by other hepatotoxic drugs. Fibrates also have the potential to cause rhabdomyolysis, although generally only in combination with HMG-CoA re ductase inhibitors, and are subject to binding by concomitantly admini stered bile acid sequestrants. The major interaction involving probuco l is a possible additive effect with drugs or clinical conditions that alter the prolongation of the QTc interval, increasing the potential for polymorphic ventricular tachycardia.