Pravastatin

Pravastatin
Names
Trade namesPravachol, Selektine, others
IUPAC name
  • (3R,5R)-3,5-dihydroxy-7-((1R,2S,6S,8R,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)-heptanoic acid
Clinical data
Drug classStatin[1]
Main usesPreventing cardiovascular disease in those at high risk, abnormal lipids[1]
Side effectsJoint pain, diarrhea, nausea, headaches, muscle pains[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
    Routes of
    use    		By mouth
    Defined daily dose30 mg[2]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa692025
    Legal
    License data
    Legal status
    Pharmacokinetics
    Bioavailability18%[3]
    Protein binding50%[3]
    MetabolismLiver (minimal)[3]
    Elimination half-life1-3 hours[3]
    Chemical and physical data
    FormulaC23H36O7
    Molar mass424.534 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C(O)C[C@H](O)C[C@H](O)CC[C@H]2[C@H](/C=C\C1=C\[C@@H](O)C[C@H](OC(=O)[C@@H](C)CC)[C@@H]12)C
    InChI
    • InChI=1S/C23H36O7/c1-4-13(2)23(29)30-20-11-17(25)9-15-6-5-14(3)19(22(15)20)8-7-16(24)10-18(26)12-21(27)28/h5-6,9,13-14,16-20,22,24-26H,4,7-8,10-12H2,1-3H3,(H,27,28)/t13-,14-,16+,17+,18+,19-,20-,22-/m0/s1 checkY
    • Key:TUZYXOIXSAXUGO-PZAWKZKUSA-N checkY

    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.[1] It should be used together with diet changes, exercise, and weight loss.[1] It is taken by mouth.[1]

    Common side effects include joint pain, diarrhea, nausea, headaches, and muscle pains.[1] Serious side effects may include rhabdomyolysis, liver problems, and diabetes.[1] Use during pregnancy may harm the baby.[1] Like all statins, pravastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver that plays a role in producing cholesterol.[1]

    Pravastatin was patented in 1980 and approved for medical use in 1989.[4] It is on the World Health Organization's List of Essential Medicines as an alternative to simvastatin.[5] It is available as a generic medication.[1] In the United States the wholesale cost per dose is less than 0.20 USD as of 2018.[6] In the United Kingdom it costs the NHS about one to two pounds per month as of 2020.[7] In 2017, it was the 24th most commonly prescribed medication in the United States, with more than 24 million prescriptions.[8][9]

    Medical uses

    Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease.[10] It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels.[10]

    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.[11]

    Dosage

    The defined daily dose is 30 mg by mouth.[2]

    Side effects

    Trials indicate pravastatin is well tolerated and displays few noncardiovascular abnormalities in patients.[12] 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:[10]

    • 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.[13] 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.[14]

    Interactions

    Medications that should not be taken with pravastatin include, but are not limited to:[10][13]

    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.

    The combination of fenofibrate with pravastatin is approved for use in the European Union.[15]

    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.[16] 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.[17] 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.[18]

    The Food and Drug Administration (FDA) approved generic pravastatin for use in the United States on April 24, 2006.[18] Generic pravastatin sodium tablets were manufactured by Biocon Ltd, India and TEVA Pharmaceuticals in Kfar Sava, Israel.[18]

    Society and culture

    Cost

    In the United States the wholesale cost per dose is less than 0.20 USD as of 2018.[6] In the United Kingdom it costs the NHS about one to two pounds per month as of 2020.[7] In 2017, it was the 24th most commonly prescribed medication in the United States, with more than 24 million prescriptions.[8][9]

    • Pravastatin costs (US)
      Pravastatin costs (US)
    • Pravastatin prescriptions (US)
      Pravastatin prescriptions (US)

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 "Pravastatin Sodium Monograph for Professionals". Drugs.com. AHFS. Archived from the original on 23 December 2018. Retrieved 23 December 2018.
    2. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 11 October 2020. Retrieved 9 September 2020.
    3. 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.
    4. ↑ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 472. ISBN 9783527607495. Archived from the original on 2018-12-23. Retrieved 2018-12-23.
    5. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
    6. 1 2 "NADAC as of 2018-12-19". Centers for Medicare and Medicaid Services. Archived from the original on 2018-12-19. Retrieved 22 December 2018.
    7. 1 2 BNF (80 ed.). BMJ Group and the Pharmaceutical Press. September 2020 – March 2021. p. 216. ISBN 978-0-85711-369-6.{{cite book}}: CS1 maint: date format (link)
    8. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on 18 March 2020. Retrieved 11 April 2020.
    9. 1 2 "Pravastatin Sodium - Drug Usage Statistics". ClinCalc. 23 December 2019. Archived from the original on 11 April 2020. Retrieved 11 April 2020.
    10. 1 2 3 4 "Pravachol". The American Society of Health-System Pharmacists. Archived from the original on 2 September 2011. Retrieved 3 April 2011.
    11. ↑ 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.
    12. ↑ 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.
    13. 1 2 Williams, Eni. "Pravachol Side Effects Center". RxList. Archived from the original on 29 November 2012. Retrieved 1 December 2012.
    14. ↑ "Pravastatin". LactMed. U.S. National Library of Medicine. Archived from the original on 15 November 2018. Retrieved 1 December 2012.
    15. ↑ "Pravafenix EPAR". European Medicines Agency (EMA). Archived from the original on 24 May 2020. Retrieved 25 April 2020.
    16. ↑ 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.
    17. ↑ 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.
    18. 1 2 3 "FDA Approves First Generic Pravastatin". Food and Drug Administration (FDA) (Press release). Archived from the original on 2010-03-06. Retrieved 2008-01-20.
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