Lovastatin

Lovastatin (Merck's Mevacor) is a member of the drug class of statins, used in combination with diet, weight-loss, and exercise for lowering cholesterol (hypolipidemic agent) in those with hypercholesterolemia to reduce risk of cardiovascular disease. Lovastatin is a naturally occurring drug found in food such as oyster mushrooms^[2] and red yeast rice.

Medical uses[edit]

The primary uses of lovastatin is for the treatment of dyslipidemia and the prevention of cardiovascular disease.^[4] It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels.^[4]

Side effects[edit]

Lovastatin is usually well tolerated, with the most common side effects being, in approximately descending order of frequency:creatine phosphokinase elevation, flatulence, abdominal pain, constipation, diarrhoea, muscle aches or pains, nausea, indigestion, weakness, blurred vision, rash, dizziness and muscle cramps.^[5] As with all statin drugs, it can rarely cause myopathy, hepatotoxicity(liver damage), dermatomyositis or rhabdomyolysis.^[5] This can be life-threatening if not recognised and treated in time, so any unexplained muscle pain or weakness whilst on lovastatin should be promptly mentioned to the prescribing doctor. Other uncommon side effects that should be promptly mentioned to either the prescribing doctor or an emergency medical service include:^[6]

• muscle pain, tenderness, or weakness
• lack of energy
• weakness
• fever
• dark colored urine
• jaundice: yellowing of the skin or eyes
• pain in the upper right part of the stomach
• nausea
• unusual bleeding or bruising
• loss of appetite
• flu-like symptoms
• rash
• hives
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness

These less serious side effects should still be reported if they persist or increase in severity:^[6]

• constipation
• memory loss or forgetfulness
• confusion

Contraindications[edit]

Contraindications, conditions that warrant withholding treatment with lovastatin, include pregnancy, breast feeding, and liver disease. Lovastatin is contraindicated during pregnancy (Pregnancy Category X); it may cause birth defects such as skeletal deformities or learning disabilities. Due to its potential to disrupt infant lipid metabolism, lovastatin should not be taken while breastfeeding.^[7]Patients with liver disease should not take lovastatin.^[8]

Interactions[edit]

As with atorvastatin, simvastatin, and other statin drugs metabolized via CYP3A4, drinking grapefruit juice during lovastatin therapy may increase the risk of side effects. Components of grapefruit juice, the flavonoid naringin, or the furanocoumarin bergamottininhibit CYP3A4 in vitro,^[9] and may account for the in vivo effect of grapefruit juice concentrate decreasing the metabolic clearance of lovastatin, and increasing its plasma concentrations.^[10]

Mechanism of action[edit]

Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme that catalyzes the conversion of HMG-CoA to mevalonate.^[11] Mevalonate is a required building block for cholesterol biosynthesis and lovastatin interferes with its production by acting as a reversible competitive inhibitor for HMG-CoA, which binds to the HMG-CoA reductase. Lovastatin is a prodrug, an inactive lactone in its native form, the beta-lactone closed ring form in which it is administered, is hydrolysed in vivo to the β-hydroxy acid open ring form; which is the active form.

Lovastatin and other statins have recently been studied for their chemopreventive and chemotherapeutic effects in certain cancers. However, based on clinical evidence, such effects could not be demonstrated.^[12] In principle, independent of their hydroxymethyl glutaryl (HMG)-CoA reductase inhibition, lovastatin and other statins reduce proteasomeactivity, leading to an accumulation of cyclin-dependent kinase inhibitors p21 and p27, and G1 phase arrest in breast cancer cell lines. For that purpose, lovastatin is also used experimentally.