Foundations in Pharmacology – Familial Hypercholesterolaemia

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Atorvastatin and its metabolites are excreted in bile, or via the blood into the intestine. The renal route of excretion accounts for around 1% (Lennernäs, 2003). Atorvastatin has an approximate elimination half-life of 14 hours, but the HMG-CoA reductase inhibitory activity persists for up to 30 hours, which is thought to be due to the active metabolites (Lennernäs, 2003).

Efficacy

The reduction in serum cholesterol concentrations varies markedly between the types of statin. Comparative trials have indicated that atorvastatin therapy lead to the greatest reductions in cholesterol concentrations (Smilde et al. 2001).

The British National Formulary (BNF) lists a number of side effects of statin therapy, but the most common are liver dysfunction and myopathy. A 2010 study examined the medical records of over 2 million patients registered with general practitioners in the UK (Hippisley-Cox & Coupland, 2010). The authors found that statin therapy was associated with an increased risk of moderate or serious liver dysfunction, moderate or serious myopathy, cataract and acute renal failure, but also found a beneficial effect on oesophageal cancer. Therefore, the BNF (2013) advises caution when using statins in those with liver disease. NICE (2008b) suggests that patients should have liver function tests on commencement of statin therapy, at 3 months, and again at 12 months. Statins should be avoided in pregnancy due to an increased risk of a deleterious effect on foetal development (BNF, 2013).

There are many drugs that can interact with atorvastatin, major, moderate and minor, such as, clarithromycin and ketoconazole. Combining these medications may significantly increase the blood levels of atorvastatin, leading to increased risk of liver damage as both medications compete for the same metabolism pathway. It is noteworthy that grapefruit juice significantly inhibits cytochrome P450, which is instrumental in the first-pass metabolism, and can therefore lead to an increased risk of statin myopathy (Reddy et al. 2011). This risk is also present in other medications that inhibit cytochrome P450, such as fusidic acid, amiodarone, calcium channel blockers, colchicine and fibrates (BNF, 2013).

In conclusion, atorvastatin has been demonstrated to be the drug of choice in the treatment of FH. Atorvastatin has been prescribed for many years and is considered as one of the most potent agents within the statin drug class, in terms of the LDL cholesterol-lowering effect.

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