Atorvastatin

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Lipitor (Parke Davis)

10 mg, 20 mg and 40 mg tablets

Indication: hypercholesterolaemia

Patients with persistently high concentrations of cholesterol should receive dietary therapy. If this does not reduce the cholesterol, drug treatment should be considered. The choice of drugs includes the HMG CoA reductase inhibitors. Atorvastatin is a new member of this class.

A daily dose of 10 mg will control hypercholesterolaemia in most patients. A response occurs within two weeks and reaches a maximum in one month. The cholesterol concentration is then measured and the dose adjusted accordingly.

Absorption is reduced by food and antacids, but this may not influence the drug's effects. Atorvastatin is metabolised in the live rand first-pass metabolism reduces its bioavailability to 14%. Most of the metabolites are active so its effects last longer than its half-life of 14 hours. Liver function should be tested before treatment and periodically during treatment. As the metabolism involves cytochrome P450 3A4, there is a potential for interactions with other drugs, such as erythromycin, associated with this enzyme system. Atorvastatin is contraindicated in patients with active liver disease, but, as its metabolites are excreted in bile, it can be used inpatients with renal insufficiency.

Compared with placebo, atorvastatin reduces total cholesterol, LDL cholesterol and plasma triglycerides. Comparative studies found that after 16 weeks' treatment with atorvastatin, the reductions in LDL cholesterol were greater than for lovastatin, pravastatin and simvastatin.

The adverse effects of atorvastatin resemble those of other HMG CoA reductase inhibitors. Less than 2% of the patients in trials had to withdraw because of adverse effects. The most frequent complaints are constipation, flatulence, dyspepsia and abdominal pain. Other adverse events seen in trials include muscle cramps, myopathy, hepatitis and cholestatic jaundice.

In addition to interactions involving cytochrome P450 3A4,atorvastatin interacts with digoxin, oral contraceptives and cholestyramine.

Although atorvastatin appears to be more potent than other drugs in its class, it should not yet supersede them. The other drugs are accumulating data on clinical end-points, while the effect of atorvastatin on morbidity and mortality is unknown, as is its long-term safety.

The manufacturer has studied atorvastatin in hypertriglyceridaemia.1 Although the study only lasted 4 weeks, total triglycerides were reduced; however, there is currently insufficient evidence to support this indication.

References

  1. Bakker-Arkema R, Davidson MH, Goldstein RJ, Davignon J, Issaacsohn JL,Weiss SR, et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA1996;275:128-33.