Pravastatin, sold under the brand name Pravachol among others, is a

statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

medication, used for preventing

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

in those at high risk and treating abnormal lipids. It is suggested to be used together with diet changes, exercise, and weight loss. It is taken by mouth. Common side effects include joint pain, diarrhea, nausea, headaches, and muscle pains. Serious side effects may include rhabdomyolysis, liver problems, and

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

. Use during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

may harm the fetus. Like all statins, pravastatin works by inhibiting

HMG-CoA reductase HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-limiting enzyme (NADH-dependent, ; NADPH-dependent, ) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other ...

, an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

found in

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

that plays a role in producing

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

. Pravastatin was patented in 1980 and approved for medical use in 1989. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2022, it was the 37th most commonly prescribed medication in the United States, with more than 16million prescriptions.

Medical uses

Pravastatin is primarily used for the treatment of

dyslipidemia Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of ...

and the prevention of

. It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels. 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

medications. 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.

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.

Contraindication In medicine, a contraindication is a condition (a situation or factor) that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a rea ...

s, conditions that warrant withholding treatment with pravastatin, include pregnancy and breastfeeding. 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.

Drug interactions

Medications that should not be taken with pravastatin include, but are not limited to: *

Cimetidine Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. With the development of proton pump ...

(Tagamet) *

Colchicine Colchicine is a medication used to prevent and treat gout, to treat familial Mediterranean fever and Behçet's disease, and to reduce the risk of myocardial infarction. The American College of Rheumatology recommends colchicine, nonstero ...

(Colcrys) * Cyclosporine (Neoral, Sandimmune) *

Ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

(Nizoral) * Additional cholesterol-lowering medications such as:

fenofibrate Fenofibrate, sold under the brand name Tricor among others, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared to statins because it treats a different type of cholesterol a ...

(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 Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhi ...

(Norvir) taken with

darunavir Darunavir (DRV), sold under the brand name Prezista among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It is often used with low doses of ritonavir ...

(Prezista); and

spironolactone Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

(Aldactone). The combination of fenofibrate with pravastatin is approved for use in the European Union.

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 Competition is a rivalry where two or more parties strive for a common goal which cannot be shared: where one's gain is the other's loss (an example of which is a zero-sum game). Competition can arise between entities such as organisms, indi ...

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 β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl coenzyme A, is an intermediate in the mevalonate pathway, mevalonate and ketogenesis pathways. It is formed from acetyl CoA and acetoacetyl CoA by HMG-CoA synthase ...

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.

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. 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.

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. It is being marketed outside

Japan Japan is an island country in East Asia. Located in the Pacific Ocean off the northeast coast of the Asia, Asian mainland, it is bordered on the west by the Sea of Japan and extends from the Sea of Okhotsk in the north to the East China Sea ...

by the

pharmaceutical company The pharmaceutical industry is a Medicine, medical industry that discovers, develops, produces, and markets pharmaceutical goods such as medications and medical devices. Medications are then administered to (or Self-medicate, self-administered b ...

Bristol-Myers Squibb The Bristol-Myers Squibb Company, doing business as Bristol Myers Squibb (BMS), is an American multinational pharmaceutical company. Headquartered in Princeton, New Jersey, BMS is one of the world's largest pharmaceutical companies and consist ...

. In 2005, Pravachol was the 22nd-highest selling brand-name drug in the United States, with sales totaling $1.3 billion. The

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) approved generic pravastatin for use in the United States in April 2006. Generic pravastatin sodium tablets were manufactured by Biocon Ltd, India and Teva Pharmaceuticals in Kfar Sava, Israel.

References

{{Portal bar , Medicine Statins Drugs developed by Bristol Myers Squibb Daiichi Sankyo Diols Carboxylic acids Carboxylate esters Bicyclic compounds Beta hydroxy acids Wikipedia medicine articles ready to translate