Pravastatin

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Pravastatin, sold under the brand name Pravachol among others, is a statin medication, used for preventing cardiovascular disease in those at high risk and treating abnormal lipids.<ref name=AHFS2018/> It is suggested to be used together with diet changes, exercise, and weight loss.<ref name=AHFS2018/> It is taken by mouth.<ref name=AHFS2018>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Common side effects include joint pain, diarrhea, nausea, headaches, and muscle pains.<ref name=AHFS2018/> Serious side effects may include rhabdomyolysis, liver problems, and diabetes.<ref name=AHFS2018/> Use during pregnancy may harm the fetus.<ref name=AHFS2018/> Like all statins, pravastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver that plays a role in producing cholesterol.<ref name=AHFS2018/>

Pravastatin was patented in 1980 and approved for medical use in 1989.<ref name=Fis2006>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">Template:Cite book</ref> It is available as a generic medication.<ref name=AHFS2018/> In 2022, it was the 37th most commonly prescribed medication in the United States, with more than 16Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease.<ref name=AHFS>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels.<ref name=AHFS />

Pravastatin has been found to have a similar effectiveness at lowering low-density lipoprotein cholesterol as fluvastatin but evidence indicates that pravastatin may not be as effective as other statin medications.<ref name="Adams_2023">Template:Cite journal</ref> The beneficial effect of pravastatin is dependent on the dose and the potential for side effects or unwanted effects from this medication are not clear from clinical trials.<ref name="Adams_2023" />

Adverse effects and contraindications

Pravastatin has undergone over 112,000 patient-years of double-blind, randomized trials using the 40 mg, once-daily dose and placebos. These trials indicate pravastatin is well tolerated and displays few noncardiovascular abnormalities in patients.<ref name="pmid12021218">Template:Cite journal</ref>

Contraindications, conditions that warrant withholding treatment with pravastatin, include pregnancy and breastfeeding.<ref name=RxList>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Taking pravastatin while pregnant could lead to birth defects. While the amount of pravastatin ingested by an infant from breastfeeding is low, patients breastfeeding should not take pravastatin due to potential effects on the infant's lipid metabolism.<ref name=LactMed>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Drug interactions

Medications that should not be taken with pravastatin include, but are not limited to:<ref name="AHFS"/><ref name=RxList/>

• Cimetidine (Tagamet)
• Colchicine (Colcrys)
• Cyclosporine (Neoral, Sandimmune)
• Ketoconazole (Nizoral)
• Additional cholesterol-lowering medications such as: fenofibrate (Tricor), gemfibrozil (Lopid), cholestyramine (Questran, Questran Light, Cholybar), and niacin (nicotinic acid, Niacor, Niaspan);
• Specific HIV protease inhibitors such as: lopinavir and ritonavir (Kaletra), and ritonavir (Norvir) taken with darunavir (Prezista); and spironolactone (Aldactone).

The combination of fenofibrate with pravastatin is approved for use in the European Union.<ref name="Pravafenix EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Mechanism of action

Pravastatin acts as a lipoprotein-lowering drug through two pathways. In the major pathway, pravastatin inhibits the function of hydroxymethylglutaryl-CoA (HMG-CoA) reductase. As a reversible competitive inhibitor, pravastatin sterically hinders the action of HMG-CoA reductase by occupying the active site of the enzyme. Taking place primarily in the liver, this enzyme is responsible for the conversion of HMG-CoA to mevalonate in the rate-limiting step of the biosynthetic pathway for cholesterol. Pravastatin also inhibits the synthesis of very-low-density lipoproteins, which are the precursor to low-density lipoproteins (LDL). These reductions increase the number of cellular LDL receptors, thus LDL uptake increases, removing it from the bloodstream.<ref name="pmid15313959">Template:Cite journal</ref>

Pharmacokinetics

Oral bioavailability of pravastatin ranges from 17-34% with peak plasma concentration achieved 1-1.5 hours after administration. Absorption of drug is modestly decreased when taken with food however this does not reduce the clinical lipid-lowering effect.<ref name="Pravastatin FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

The 3α-hydroxyisomeric metabolite of pravastatin is also an active HMG-CoA reductase inhibitor with approximately 2.5-10% the potency of the parent compound. Pravastatin has a plasma half-life of 1.8 hours whereas this active metabolite has a half-life up to 77 hours.<ref name="Pravastatin FDA label" />

History

Initially known as CS-514, pravastatin is a derivative of ML236B (compactin), which was identified in a fungus called Penicillium citrinum in the 1970s by researchers of the Sankyo Pharma Inc.<ref name="pmid12815379">Template:Cite journal</ref> It is being marketed outside Japan by the pharmaceutical company Bristol-Myers Squibb. In 2005, Pravachol was the 22nd-highest selling brand-name drug in the United States, with sales totaling $1.3 billion.<ref name="fda announcement">Template:Cite press release</ref>

The Food and Drug Administration (FDA) approved generic pravastatin for use in the United States in April 2006.<ref name="fda announcement" /> Generic pravastatin sodium tablets were manufactured by Biocon Ltd, India and Teva Pharmaceuticals in Kfar Sava, Israel.<ref name="fda announcement" />