Pravastatin is an HMG-CoA reductase inhibitor (statin) indicated as adjunct therapy to diet for:

• Reducing the risk of myocardial infarction (MI), revascularization procedures, and cardiovascular mortality in hypercholesterolemic patients without clinically evident coronary heart disease (CHD)
• Reducing total mortality by lowering coronary death, MI, revascularization, stroke/TIA, and slowing progression of coronary atherosclerosis in patients with clinically evident CHD
• Reducing elevated Total cholesterol (Total-C), LDL-C, ApoB, and triglycerides (TG), and increasing HDL-C in primary hypercholesterolemia and mixed dyslipidemia
• Reducing elevated serum triglycerides in hypertriglyceridemia
• Treating primary dysbetalipoproteinemia in patients not responding to diet therapy
• Treating children and adolescents aged 8 years and older with heterozygous familial hypercholesterolemia after inadequate response to diet therapy

Pravastatin is a selective inhibitor of hepatic HMG-CoA reductase in humans. Inhibition of this enzyme reduces cholesterol biosynthesis, as HMG-CoA reductase represents an early rate-limiting step in the cholesterol synthesis pathway. This reduction in cholesterol synthesis leads to an increase in LDL receptor expression on cell surfaces and enhances receptor-mediated uptake and clearance of LDL cholesterol. Additionally, by reducing LDL production, pravastatin also decreases hepatic synthesis of VLDL, since LDL serves as a precursor for VLDL formation.

General Dosing Information: The patient should be placed on a standard cholesterol-lowering diet before receiving pravastatin and should continue on this diet during treatment with pravastatin.

Adult Patients: The recommended starting dose is 40 mg once daily. If a daily dose of 40 mg does not achieve desired cholesterol levels, 80 mg once daily is recommended. In patients with significant renal impairment, a starting dose of 10 mg daily is recommended. pravastatin can be administered orally as a single dose at any time of the day, with or without food. Since the maximal effect of a given dose is seen within 4 weeks, periodic lipid determinations should be performed at this time and dosage adjusted according to the patient’s response to therapy and established treatment guidelines.

Children (Ages 8 to 13 Years): The recommended dose is 20 mg once daily in children 8 to 13 years of age. Doses greater than 20 mg have not been studied in this patient population.

Adolescents (Ages 14 to 18 Years): The recommended starting dose is 40 mg once daily in adolescents 14 to 18 years of age. Doses greater than 40 mg have not been studied in this patient population. Children and adolescents treated with pravastatin should be reevaluated in adulthood and appropriate changes made to their cholesterol-lowering regimen to achieve adult goals for LDL-C.

Concomitant use with other lipid-lowering agents such as fibrates or niacin (≥1 g/day) increases the risk of skeletal muscle toxicity. Caution is advised when co-prescribing with pravastatin.

Cyclosporine: increases pravastatin exposure; limit dose to 20 mg once daily.

Clarithromycin: increases pravastatin exposure; limit dose to 40 mg once daily.

• Hypersensitivity to pravastatin or any component of the formulation.
• Active liver disease or unexplained persistent elevation of serum transaminases.
• Pregnancy or women who may become pregnant.
• Nursing mothers.

In short-term clinical studies, the most commonly reported adverse effects (≥2% and higher than placebo), regardless of causality, include musculoskeletal pain, nausea/vomiting, upper respiratory tract infection, diarrhea, and headache.

Pregnancy Category X. Safety in pregnancy has not been established. Available data from inadvertent exposure do not show clear adverse outcomes, but there are no adequate and well-controlled studies in pregnant women. Pravastatin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, and patients should be informed of possible risks. A small amount is excreted in breast milk. Due to the risk of serious adverse effects in nursing infants, breastfeeding is contraindicated during pravastatin therapy.

Skeletal muscle effects such as myopathy and rhabdomyolysis may occur. Risk factors include age over 65 years, uncontrolled hypothyroidism, and renal impairment. Patients should report any muscle pain, tenderness, or weakness promptly. Discontinue therapy if myopathy is suspected or confirmed.

Liver enzyme elevations may occur. Liver function tests should be performed before starting treatment and periodically thereafter as clinically indicated.

Statins

Store below 30°C, protect from light and moisture. Keep out of reach of children.