Pitavastatin

Pitavastatin is a synthetic statin that lowers LDL cholesterol by 30% to 45% at 1 to 4 mg daily and raises HDL cholesterol modestly. It is cleared by glucuronidation, with little CYP3A4 or CYP2C9 metabolism, so it has few interactions apart from ciclosporin and rifampicin. It has little effect on blood glucose compared with other statins. It is rarely available in East Africa.

Classification. Statin; HMG CoA reductase inhibitor; moderate to high 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.

Pharmacokinetics. Oral bioavailability about 51%. Half life about 12 hours. Minimal CYP metabolism; taken up by the liver through OATP1B1 and excreted in bile. Protein binding over 99%.

Hypercholesterolaemia and mixed dyslipidaemia, adult. Start 1 to 2 mg once daily; titrate after 4 weeks; maximum 4 mg once daily.

Familial hypercholesterolaemia in children aged 6 years and over (specialist). 1 mg once daily; titrate after 4 weeks; maximum 4 mg once daily in adolescents (lower in younger children).

Kidney impairment. Creatinine clearance 15 to 59 mL/min (including dialysis): start 1 mg once daily; maximum 2 mg once daily.

Interaction limits. Rifampicin: maximum 2 mg daily. Erythromycin: maximum 1 mg daily. Ciclosporin: contraindicated.

Liver impairment. Contraindicated in active disease and in moderate to severe impairment.

Contraindications. Active liver disease or unexplained persistent rise in transaminases; moderate or severe liver impairment; pregnancy; breastfeeding; concurrent ciclosporin; hypersensitivity.

Warnings. Myopathy and rhabdomyolysis; raised liver enzymes; immune mediated necrotising myopathy (rare); new onset diabetes (small, less than with some statins); interstitial lung disease (rare); the 4 mg dose is used with care in kidney impairment.

Adverse effects. Muscle aches, back pain, constipation, diarrhoea, headache, nausea, raised liver enzymes.

Interactions. Ciclosporin: contraindicated. Rifampicin: raised levels (cap at 2 mg). Erythromycin: raised levels (cap at 1 mg). Gemfibrozil, fenofibrate, niacin: myopathy risk; avoid with gemfibrozil. Fusidic acid: stop the statin during the course. Lopinavir and ritonavir: reduced exposure. Warfarin: small effect on INR.

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: creatinine clearance 15 to 59 mL/min: start 1 mg, maximum 2 mg.

• Liver impairment: contraindicated in moderate to severe impairment.

Formulations. Tablets 1, 2, 4 mg.

Administration. Oral once daily at any time of day, with or without food.

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. Creatinine yearly.

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. Giving it with ciclosporin; using 4 mg in kidney impairment; omitting the dose cap with rifampicin or erythromycin; prescribing in moderate liver impairment.