Fluvastatin

Fluvastatin
Names
Trade namesLescol, others
IUPAC name
  • (3R,5S,6E)-7-[3-(4-Fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid
Clinical data
Drug classStatin[1]
Main usesTreat high cholesterol, high triglycerides, prevent heart disease[2][1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
    Routes of
    use    		By mouth (capsules, tablets)
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa694010
    Legal
    Legal status
    • AU: S4 (Prescription only)
    • CA: ℞-only
    • UK: POM (Prescription only)
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Pharmacokinetics
    Bioavailability24–30%[3][4]
    Protein binding>98%[4]
    MetabolismLiver: CYP2C9 (75%), CYP3A4 (20%), CYP2C8 (5%)[4][5]
    Elimination half-life1–3 hours (capsule), 9 hours (XR formulations)[4][5]
    ExcretionFaeces (95%), urine (5%)[4]
    Chemical and physical data
    FormulaC24H26FNO4
    Molar mass411.473 g·mol−1
    3D model (JSmol)
    SMILES
    • O=C(O)C[C@H](O)C[C@H](O)/C=C/c2c(c1ccccc1n2C(C)C)c3ccc(F)cc3
    InChI
    • InChI=1S/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/m1/s1 checkY
    • Key:FJLGEFLZQAZZCD-MCBHFWOFSA-N checkY

    Fluvastatin, sold under the brand name Lescol among others, is a medication used to treat high cholesterol and high triglycerides and prevent heart disease.[2][1] It is used together with diet and exercise.[1] It is taken by mouth.[2] Up to 4 weeks may be required for maximal effect.[1]

    Common side effects include muscle pain, heart burn, nausea, and headaches.[1] Other side effects may include muscle breakdown, liver problems, high blood sugar, and memory problems.[1] Use during pregnancy may harm the baby.[1] It is a statin and works by blocking HMG-CoA reductase.[1]

    Fluvastatin was patented in 1982 and approved for medical use in 1993.[6][1] It is on the World Health Organization's List of Essential Medicines as an alternative to simvastatin.[7] It is available as a generic medication.[2] In the United Kingdom 4 weeks of medication costs the NHS about £3 to 20 per month as of 2021.[2]

    Medical uses

    Dosage

    It is used at a dose of 20 to 80 mg a day.[2]

    Side effects

    Adverse effects are comparable to other statins. Common are nausea, indigestion, insomnia and headache. Myalgia (muscle pain), and rarely rhabdomyolysis, characteristic side effects for statins, can also occur.[8]

    Interactions

    Contrary to lovastatin, simvastatin and atorvastatin, fluvastatin has no relevant interactions with drugs that inhibit the liver enzyme CYP3A4, and a generally lower potential for interactions than most other statins. Fluconazole, a potent inhibitor of CYP2C9, does increase fluvastatin levels.[8]

    Pharmacology

    Mechanism of action

    Fluvastatin works by blocking the liver enzyme HMG-CoA reductase, which facilitates an important step in cholesterol synthesis.[3]

    Pharmacodynamics

    In a Cochrane systematic review the dose-related magnitudes of fluvastatin on blood lipids was determined. Over the dose range of 10 to 80 mg/day total cholesterol was reduced by 10.7% to 24.9%, LDL cholesterol by 15.2% to 34.9%, and triglycerides by 3% to 17.5%.[9]

    Pharmacokinetics

    The drug is quickly and almost completely (98%) absorbed from the gut. Food intake slows down absorption, but does not decrease it. Due to its first-pass effect, bioavailability is lower: about 24–30%[4][3] according to different sources. Over 98% of the substance is bound to plasma proteins.[3]

    Several cytochrome P450 enzymes (mainly CYP2C9, but also CYP3A4 and CYP2C8)[10] are involved in the metabolism of fluvastatin, which makes is less liable to interactions than most other statins. The main metabolite is inactive and is called "N-desisopropyl propionic acid" in the literature.[3][8]

    93–95% of the drug is excreted via the feces, less than 2% of which in form of the original substance.[3]

    Society and culture

    Names

    Fluvastatin is the INN.[11] Brandnames include Lescol, Canef, Vastin.

    Research

    Data from the Cholesterol Treatment Trialists’ (CTT) publication[12] was used to determine the effects of fluvastatin, atorvastatin and rosuvastatin on LDL cholesterol lowering and reduction of myocardial infarction. In two RCTs an average dose of 72 mg/day fluvastatin reduced LDL cholesterol by 31.9%, and reduced myocardial infarction, relative risk, 0.68 (95% CI 0.55 to 0.85) as compared to placebo. In five RCTs a mean atorvastatin dose of 26 mg/day reduced LDL cholesterol by 44.0% and reduced myocardial infarction, relative risk, 0.67 (95% CI 0.58 to 0.77) as compared to placebo. In four RCTs a mean rosuvastatin dose of 16 mg/day reduced LDL cholesterol by 48.8% and reduced myocardial infarction, relative risk, 0.82 (95% CI 0.73 to 0.93) as compared to placebo. Thus despite reducing LDL cholesterol by a much lesser amount with fluvastatin than atorvastatin and rosuvastatin, fluvastatin reduced myocardial infarction similarly to atorvastatin and to a greater degree than rosuvastatin.[9]

    References

    1. 1 2 3 4 5 6 7 8 9 10 "Fluvastatin Monograph for Professionals". Drugs.com. Archived from the original on 23 January 2021. Retrieved 13 December 2021.
    2. 1 2 3 4 5 6 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 218. ISBN 978-0857114105.
    3. 1 2 3 4 5 6 Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.{{cite book}}: CS1 maint: unrecognized language (link)
    4. 1 2 3 4 5 6 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. S2CID 11716425.
    5. 1 2 "Lescol, Lescol XR (fluvastatin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 18 March 2014. Retrieved 18 March 2014.
    6. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 472. ISBN 9783527607495. Archived from the original on 2020-08-19. Retrieved 2021-10-05.
    7. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
    8. 1 2 3 Dinnendahl, V, Fricke, U, eds. (2012). Arzneistoff-Profile (in German). Vol. 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.{{cite book}}: CS1 maint: unrecognized language (link)
    9. 1 2 Adams SP, Sekhon SS, Tsang M, Wright JM (March 2018). "Fluvastatin for lowering lipids". The Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd. 2018 (3): CD012282. doi:10.1002/14651858.cd012282.pub2. PMC 6494196. PMID 29508377.
    10. ↑ Lescol Monograph on Drugs.com.
    11. ↑ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names (Rec. INN): List 30" (PDF). World Health Organization. 1990. Archived (PDF) from the original on 18 May 2016. Retrieved 29 November 2016.
    12. ↑ Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. (October 2005). "Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins". Lancet. 366 (9493): 1267–78. doi:10.1016/s0140-6736(05)67394-1. PMID 16214597. S2CID 10716362.
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