Pravastatin

Pravastatin
Clinical data
Trade names Pravachol
AHFS/Drugs.com Monograph
MedlinePlus a692025
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
    Routes of
    administration    		 oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Bioavailability 18%[1]
    Protein binding 50%[1]
    Metabolism Hepatic (minimal)[1]
    Elimination half-life 1-3 hours[1]
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    ChEBI
    ChEMBL
    ECHA InfoCard 100.216.225 Edit this at Wikidata
    Chemical and physical data
    Formula C23H36O7
    Molar mass 424.528 g/mol
    3D model (JSmol)
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    Pravastatin (marketed as Pravachol or Selektine) is a member of the drug class of statins, used in combination with diet, exercise, and weight loss for lowering cholesterol and preventing cardiovascular disease.

    Medical uses

    Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease.[2] It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels.[2]

    The evidence for the use of pravastatin is generally weaker than for other statins. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT), failed to demonstrate a difference in all-cause mortality or nonfatal myocardial infarction/fatal coronary heart disease rates between patients receiving pravastatin 40 mg daily (a common starting dose) and those receiving usual care.[3]

    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.[4] However, side effects may occur. A doctor should be consulted if symptoms such as heartburn or headache are severe and do not go away.

    These uncommon side effects should be promptly reported to the prescribing doctor or an emergency medical service:[2]

    • muscle pain, tenderness, or weakness
    • lack of energy
    • fever
    • jaundice, yellowing of the skin or eyes
    • pain in the upper right part of the stomach
    • nausea
    • extreme tiredness
    • unusual bleeding or bruising
    • dark-colored urine
    • loss of appetite
    • flu-like symptoms
    • rash
    • hives
    • itching
    • difficulty breathing or swallowing
    • swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
    • hoarseness

    These symptoms should be reported to the prescribing doctor if they persist or increase in severity:

    • heartburn
    • headache
    • memory loss or forgetfulness
    • confusion

    Contraindications, conditions that warrant withholding treatment with pravastatin, include pregnancy and breastfeeding.[5] 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.[6]

    Drug interactions

    Medications that should not be taken with pravastatin include, but are not limited to:[2][5]

    Pravastatin is cleared by the kidneys, giving it a distinct advantage over other statins when a potential for drug interactions using the hepatic pathway exists.

    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.[7] Overall, the result is a reduction in circulating cholesterol and LDL. A minor reduction in triglycerides and an increase in high-density lipoproteins (HDL) are common.

    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.[8] 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.[9]

    The U.S. Food and Drug Administration approved generic pravastatin for sale in the United States for the first time on April 24, 2006. Generic pravastatin sodium tablets are manufactured by Biocon Ltd, India and TEVA Pharmaceuticals in Kfar Sava, Israel.[9]

    References

    1. 1 2 3 4 Neuvonen, PJ; Backman, JT; Niemi, M (2008). "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin". Clinical Pharmacokinetics. 47 (7): 463–74. doi:10.2165/00003088-200847070-00003. PMID 18563955.
    2. 1 2 3 4 "Pravachol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
    3. ↑ No Authors Listed (2002). "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)". JAMA. 288 (23): 2998–3007. doi:10.1001/jama.288.23.2998. PMID 12479764.
    4. ↑ Pfeffer MA, Keech A, Sacks FM, et al. "Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project." Circulation 2002;105:2341-2346
    5. 1 2 Williams, Eni. "Pravachol Side Effects Center". RxList. Retrieved 1 December 2012.
    6. ↑ "Pravastatin". LactMed. U.S. National Library of Medicine. Retrieved 1 December 2012.
    7. ↑ Vaughan, C. J., and A. M. Gotto, Jr. 2004. Update on statins: 2003. Circulation 110: 886–892.
    8. ↑ Jonathan A. Tobert Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors Nature Reviews Drug Discovery 2, 517-526 (July 2003) PMID 12815379
    9. 1 2 "FDA Approves First Generic Pravastatin". Retrieved 2008-01-20.
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