Pravastatin

Pravastatin

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.	X
Legal status	℞ Prescription only
Routes	oral
Pharmacokinetic data
Bioavailability	17%
Protein binding	50%
Metabolism	renal and hepatic
Half-life	1.5-2 hours
Identifiers
CAS number	81093-37-0 Y
ATC code	C10AA03
PubChem	CID 54687
DrugBank	DB00175
ChemSpider	49398 Y
UNII	KXO2KT9N0G Y
ChEMBL	CHEMBL1144 Y
Chemical data
Formula	C23H36O7
Mol. mass	424.528 g/mol
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 Y Key:TUZYXOIXSAXUGO-PZAWKZKUSA-N Y
Y (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

Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease.^[1] It is recommended to be used only after other measures such as diet, exercise, and weight reduction have not improved cholesterol levels.^[1]

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.^[2]

Adverse effects and contraindications

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.^[3]

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:^[1]

• 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.^[4] 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.^[5]

Drug Interactions

Medications that should not be taken with pravastatin include, but are not limited to:^[1][4]

• Cimetidine (Tagamet); colchicine (Colcrys);
• cyclosporine (Neoral, Sandimmune);
• ketoconazole (Nizoral);
• Additional cholesterol-lowering medications such as: fenofibrate (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 (Norvir) taken with darunavir (Prezista); and spironolactone (Aldactone).
• Pravastatin is cleared by the kidney giving it a distinct advantage over other statins when there is potential for drug interactions using the hepatic pathway.

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 and, thus, LDL uptake increases, removing it from the bloodstream.^[6] 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, it was originally identified in a bacterium called Nocardia autotrophica by researchers of the Sankyo Pharma Inc..^[7] 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.^[8]

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.^[8]

References

External links

• Pravachol information from the National Institute of Health
• Package insert for Pravachol