Pravastatin

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Pravastatin
Pravastatin.svg
Systematic (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
Trade names Pravachol
AHFS/Drugs.com monograph
MedlinePlus a692025
Pregnancy cat. D (AU) X (US)
Legal status Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routes oral
Pharmacokinetic data
Bioavailability 18%[1]
Protein binding 50%[1]
Metabolism Hepatic (minimal; CYP3A4-mediated)[1]
Half-life 1-3 hours[1]
Identifiers
CAS number 81093-37-0 YesY
ATC code C10AA03
PubChem CID 54687
DrugBank DB00175
ChemSpider 49398 YesY
UNII KXO2KT9N0G YesY
ChEMBL CHEMBL1144 YesY
Chemical data
Formula C23H36O7 
Mol. mass 424.528 g/mol
 YesY (what is this?)  (verify)

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[edit]

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 40mg daily (a common starting dose) and those receiving usual care.[3]

Adverse effects and contraindications[edit]

Pravastatin has undergone over 112,000 patient-years of double-blind randomized trials utilizing the 40mg once daily dose and placebos. These trials indicate that pravastatin is well tolerated and displays few non-cardiovascular 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.

The following is a list of uncommon side effects that 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

The following 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 breast feeding.[5] Taking pravastatin while pregnant could lead to birth defects. While the amount of pravastatin ingested by an infant from breast feeding is low, patients breastfeeding should not take pravastatin due to potential effects on the infant's lipid metabolism.[6]

Drug Interactions[edit]

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

Mechanism of action[edit]

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 and, 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[edit]

Initially known as CS-514, is a derivative of ML236B (compactin), which was originally identified in a fungus called Penicillium citrinum in the 1970s by researchers of the Sankyo Pharma Inc.[8] It is presently 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[edit]

  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 "Prevachol". 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. ^ a b 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. ^ a b "FDA Approves First Generic Pravastatin". Retrieved 2008-01-20. 

External links[edit]