Fluvastatin

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Fluvastatin
Fluvastatin.svg
Names
Trade namesLescol, others
  • (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]
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
Routes of
use
By mouth (capsules, tablets)
External links
AHFS/Drugs.comMonograph
US NLMFluvastatin
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)
  • O=C(O)C[C@H](O)C[C@H](O)/C=C/c2c(c1ccccc1n2C(C)C)c3ccc(F)cc3
  • 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. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 "Fluvastatin Monograph for Professionals". Drugs.com. Archived from the original on 23 January 2021. Retrieved 13 December 2021.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 218. ISBN 978-0857114105.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.{{cite book}}: CS1 maint: unrecognized language (link)
  4. 4.0 4.1 4.2 4.3 4.4 4.5 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. 5.0 5.1 "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. 8.0 8.1 8.2 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. 9.0 9.1 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.

External links

Identifiers: