Fluvastatin

Fluvastatin is a synthetic statin that lowers LDL cholesterol by 20% to 35%. It is cleared by CYP2C9, not CYP3A4, so it avoids many of the interactions that affect simvastatin and atorvastatin, but it interacts with fluconazole and other CYP2C9 inhibitors. It is the least potent statin and is used when other statins are not tolerated or interact with other drugs. It is rarely available in East Africa.

Classification. Statin; HMG CoA reductase inhibitor; low intensity.

Mechanism. Blocks the rate limiting step of hepatic cholesterol synthesis; the liver raises LDL receptors and clears more LDL.

Pharmacodynamics. LDL cholesterol falls within 2 weeks, with the full effect at 4 weeks. The extended release form gives a smoother day-long effect.

Pharmacokinetics. Oral bioavailability about 24% (immediate release) and 29% (extended release). Half life about 1 to 3 hours. Metabolised by CYP2C9. Protein binding over 98%. Excreted in faeces.

Hypercholesterolaemia and primary prevention, adult. Start 20 to 40 mg once daily in the evening (immediate release capsules); or 80 mg extended release tablet once daily; usual 40 to 80 mg daily; maximum 80 mg daily (40 mg twice daily or 80 mg extended release).

After coronary intervention, adult. 80 mg daily.

Familial hypercholesterolaemia in children aged 9 years and over (specialist). 20 mg once daily, increased every 6 weeks to a maximum of 80 mg daily (40 mg twice daily or 80 mg extended release).

Ciclosporin. Maximum 20 mg twice daily.

Kidney impairment. Mild to moderate: no adjustment; severe (creatinine clearance under 30 mL/min): use doses above 40 mg with care.

Liver impairment. Contraindicated in active disease.

Contraindications. Active liver disease or unexplained persistent rise in transaminases; pregnancy; breastfeeding; hypersensitivity.

Warnings. Myopathy and rhabdomyolysis (low risk); raised liver enzymes; new onset diabetes (small rise); immune mediated necrotising myopathy (rare); interstitial lung disease (rare).

Adverse effects. Muscle aches, headache, nausea, dyspepsia, abdominal pain, insomnia, raised liver enzymes.

Interactions. Fluconazole, amiodarone and other CYP2C9 inhibitors: raised levels, so use the lowest dose. Ciclosporin: cap at 20 mg twice daily. Gemfibrozil, fenofibrate, niacin: myopathy risk. Fusidic acid: stop the statin during the course. Rifampicin: lowers levels. Warfarin: raised INR. Colestyramine: give fluvastatin 4 hours later. Phenytoin: raised phenytoin levels.

Special groups.

• Pregnancy: stop when pregnancy is planned or confirmed; avoid.

• Breastfeeding: avoid.

• Patients of African ancestry: no dose change.

• Older adults: no dose change; monitor for muscle symptoms.

• Kidney impairment: take care above 40 mg daily in severe disease.

• Liver impairment: contraindicated in active disease.

Formulations. Capsules 20 and 40 mg; extended release tablets 80 mg.

Administration. Oral once daily in the evening for capsules, with or without food; extended release tablets swallowed whole, at any time of day.

Baseline. Lipid profile, alanine aminotransferase, creatinine, creatine kinase if muscle symptoms or risk factors, thyroid function if suspected hypothyroidism, glucose or HbA1c, pregnancy status.

Monitoring. Lipid profile 4 to 12 weeks after starting or changing the dose, then every 6 to 12 months. Alanine aminotransferase at baseline and as needed. Creatine kinase if muscle symptoms occur.

Stopping. Stop for creatine kinase above 10 times the upper limit of normal, rhabdomyolysis, persistent transaminase rise above 3 times the upper limit of normal, or pregnancy.

Common prescribing errors. Using 80 mg as 2 capsules of 40 mg once daily rather than 40 mg twice daily; combining with fluconazole at full dose; ignoring the ciclosporin cap; crushing extended release tablets.