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From Wikipedia, the free encyclopedia

Pravastatin
Pravastatin.svg
Clinical data
Trade namesPravachol, Selektine, other
AHFS/Drugs.comMonograph
MedlinePlusa692025
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability18%[1]
Protein binding50%[1]
MetabolismLiver (minimal)[1]
Elimination half-life1-3 hours[1]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.216.225 Edit this at Wikidata
Chemical and physical data
FormulaC23H36O7
Molar mass424.528 g/mol g·mol−1
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

Pravastatin, sold under the brand name Pravachol among others, is a statin medication, used preventing cardiovascular disease in those at high risk and treating abnormal lipids.[2] It should be used together with diet changes, exercise, and weight loss.[2] It is taken by mouth.[2]

Common side effects include joint pain, diarrhea, nausea, headaches, and muscle pains.[2] Serious side effects may include rhabdomyolysis, liver problems, and diabetes.[2] Use during pregnancy may harm the baby.[2] Like all statins, pravastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver that plays a role in producing cholesterol.[2]

Pravastatin was patented in 1980 and approved for medical use in 1989.[3] It is available as a generic medication.[2] In the United States the wholesale cost per dose is less than 0.20 USD as of 2018.[4] In the United Kingdom it costs the NHS about a pound per dose.[5] In 2016 it was the 27th most prescribed medication in the United States with more than 24 million prescriptions.[6]

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Transcription

Contents

Medical uses

Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease.[7] It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels.[7]

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.[8]

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.[9] 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:[7]

  • 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.[10] 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.[11]

Drug interactions

Medications that should not be taken with pravastatin include, but are not limited to:[7][10]

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.[12] 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.[13] 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.[14]

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.[14]

References

  1. ^ a b c d 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. ^ a b c d e f g h "Pravastatin Sodium Monograph for Professionals". Drugs.com. AHFS. Retrieved 23 December 2018.
  3. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 472. ISBN 9783527607495.
  4. ^ "NADAC as of 2018-12-19". Centers for Medicare and Medicaid Services. Retrieved 22 December 2018.
  5. ^ British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 202. ISBN 9780857113382.
  6. ^ "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
  7. ^ a b c d "Pravachol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  8. ^ ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (December 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.
  9. ^ Pfeffer MA, Keech A, Sacks FM, Cobbe SM, Tonkin A, Byington RP, Davis BR, Friedman CP, Braunwald E (May 2002). "Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project". Circulation. 105 (20): 2341–6. doi:10.1161/01.cir.0000017634.00171.24. PMID 12021218.
  10. ^ a b Williams E. "Pravachol Side Effects Center". RxList. Retrieved 1 December 2012.
  11. ^ "Pravastatin". LactMed. U.S. National Library of Medicine. Retrieved 1 December 2012.
  12. ^ Vaughan CJ, Gotto AM (August 2004). "Update on statins: 2003". Circulation. 110 (7): 886–92. doi:10.1161/01.CIR.0000139312.10076.BA. PMID 15313959.
  13. ^ Tobert JA (July 2003). "Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors". Nature Reviews. Drug Discovery. 2 (7): 517–26. doi:10.1038/nrd1112. PMID 12815379.
  14. ^ a b "FDA Approves First Generic Pravastatin". Retrieved 2008-01-20.

External links

This page was last edited on 29 September 2019, at 17:22
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