Pravastatin

Pravastatin is a water soluble statin that lowers LDL cholesterol by 20% to 35%. It lowers heart attacks, strokes and death in people with and without prior cardiovascular disease. It is not metabolised by CYP3A4 and has few interactions, which makes it useful in older adults, people on many drugs, and those on antiretroviral regimens boosted with ritonavir. Its effect is milder than that of atorvastatin or rosuvastatin. It is available in East Africa at modest cost.

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

Mechanism. Blocks the rate limiting step of hepatic cholesterol synthesis; the liver raises LDL receptors and clears more LDL. Hepatic uptake is by an organic anion transporter, which limits muscle exposure.

Pharmacodynamics. LDL cholesterol falls within 1 to 2 weeks, with the full effect at 4 weeks.

Pharmacokinetics. Oral bioavailability about 17%. Half life 1.5 to 2 hours. Not metabolised by CYP3A4; cleared by the liver (about 70%) and kidney (about 20%). Protein binding about 50%.

Primary prevention and hypercholesterolaemia, adult. 10 to 40 mg once daily at night; usual 40 mg; maximum 80 mg once daily.

Established cardiovascular disease, adult. 40 mg once daily at night (80 mg is occasionally used under specialist care).

Elderly or kidney or liver impairment. Start 10 mg once daily.

After organ transplantation with ciclosporin, adult. Start 20 mg once daily; maximum 20 mg daily.

Familial hypercholesterolaemia in children (specialist). Age 8 to 13 years: 20 mg once daily; age 14 to 18 years: 40 mg once daily.

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

Warnings. Myopathy and rhabdomyolysis (lower risk than with other statins); raised liver enzymes; new onset diabetes (small rise); immune mediated necrotising myopathy (rare); kidney impairment (start low); interstitial lung disease (rare).

Adverse effects. Muscle aches, headache, nausea, diarrhoea, abdominal pain, dizziness, raised liver enzymes.

Interactions. Ciclosporin: raised levels, so cap the dose at 20 mg. Gemfibrozil, fenofibrate, niacin: raised myopathy risk. Fusidic acid: stop the statin during the course. Colestyramine and colestipol: give pravastatin 1 hour before or 4 hours after. Warfarin: small effect on INR. Clarithromycin: modest rise.

Special groups.

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

• Breastfeeding: avoid.

• Patients of African ancestry: no dose change.

• Patients with HIV on ritonavir boosted regimens: pravastatin is one of the preferred statins as it is not metabolised by CYP3A4 (darunavir with ritonavir raises levels, so start low).

• Older adults: start 10 mg.

• Kidney impairment: start 10 mg once daily.

• Liver impairment: start 10 mg; contraindicated in active disease.

Formulations. Tablets 10, 20, 40, 80 mg.

Administration. Oral once daily at night, 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. Starting 40 mg in kidney impairment or the elderly; exceeding 20 mg with ciclosporin; taking it with colestyramine at the same time; stopping for mild muscle aches without checking creatine kinase and thyroid function.