Fluvastatin

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Structural formula
Structure of the two fluvastatin stereoisomers (out of eight) used as a drug
1: 1 mixture of (3 R , 5 S , 6 E ) form (top) and (3 S , 5 R , 6 E ) form (bottom)
General
Non-proprietary name Fluvastatin
other names
  • (3 R * , 5 S * , 6 E ) -7- [3- (4-fluorophenyl) -1- (1-methylethyl) -1 H -indol-2-yl] -3,5-dihydroxy-6- heptenic acid
  • (3 RS , 5 SR , 6 E ) -7- [3- (4-fluorophenyl) -1- (1-methylethyl) -1 H -indol-2-yl] -3,5-dihydroxy-6-heptenoic acid
Molecular formula
  • C 24 H 26 FNO 4 (fluvastatin)
  • C 24 H 25 FNNaO 4 (fluvastatin sodium salt)
Brief description

pale yellow solid

External identifiers / databases
CAS number
  • 93957-54-1 (fluvastatin)
  • 93957-55-2 (fluvastatin sodium salt)
EC number 695-664-7
ECHA InfoCard 100.224.327
PubChem 446155
DrugBank DB01095
Wikidata Q417942
Drug information
ATC code

C10 AA04

Drug class

Statins

Mechanism of action

HMG-CoA reductase - inhibitor

properties
Molar mass
  • 411.47 g · mol -1 (fluvastatin)
  • 433.45 g · mol -1 (fluvastatin sodium salt)
Physical state

firmly

Melting point

194–197 ° C (fluvastatin sodium salt)

solubility

good in water (30 g l −1 ), DMSO , methanol

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fluvastatin (trade name Locol (D)) is a drug from the group of statins that is used to lower increased total cholesterol and LDL cholesterol levels .

Clinical information

Application areas (indications)

Fluvastatin may be used to lower high total and LDL cholesterol levels when non-pharmacological measures such as diet, exercise and weight loss are ineffective. This applies in particular to patients with primary hypercholesterolemia with the exception of the rare homozygous familial hypercholesterolemia and patients with combined hypercholesterolemia and hypertriglyceridemia , when hypercholesterolemia is the main focus. Fluvastatin is also approved for the prevention of serious cardiac events following cardiac catheter therapy.

Contraindications (contraindications)

Fluvastatin must not be used in patients with active liver disease or with persistent, unexplained elevation of transaminases in the blood serum or with cholestasis . Fluvastatin must also not be used in patients with myopathy or known hypersensitivity to this active ingredient.

There is insufficient clinical experience for its use in children under 9 years of age or in homozygous familial hypercholesterolaemia.

Use during pregnancy and breastfeeding

During pregnancy and in the lactation fluvastatin is contraindicated. There is a reasonable assumption that fluvastatin, like other HMG-CoA reductase inhibitors, can harm the fetus by inhibiting the synthesis of cholesterol and other products of cholesterol metabolism. Pregnancy should therefore be excluded before starting fluvastatin therapy. If pregnancy occurs during therapy, fluvastatin should be discontinued.

unwanted effects

As with other statins, possible side effects include upper abdominal discomfort, increased transaminases and myopathoen.

chemistry

Stereoisomerism

Fluvastatin contains an asymmetrically substituted carbon-carbon double bond in the 6-position and two further stereocenters in positions 3 and 5. There are therefore the following eight stereoisomers : The (3 R , 5 S , 6 E ) form and the corresponding enantiomeric ( 3 S , 5 R , 6 E ) form, as well as the (3 R , 5 S , 6 Z ) form, the (3 S , 5 R , 6 Z ) form, the (3 R , 5 R , 6 E ) shape, the (3 S , 5 S , 6 E ) shape, the (3 R , 5 R , 6 Z ) shape and the (3 S , 5 S , 6 Z ) shape. The drug in the commercial preparations is the racemate [1: 1 mixture] of the (3 R , 5 S , 6 E ) form and the (3 S , 5 R , 6 E ) form. The (3 R , 5 S , 6 E ) enantiomer ( eutomer ) is about 30 times more potent than the (3 S , 5 R , 6 E ) enantiomer ( distomer ).

Trade names

Monopreparations

Cranoc (D), Lescol (A, CH), Locol (D), Nuvastin (A), numerous generics (D, A, CH)

Individual evidence

  1. ↑ a b Fluvastatin data sheet (PDF) from Calbiochem, accessed on December 8, 2015.
  2. ↑ ROTE LISTE 2008, Verlag Rote Liste Service GmbH, Frankfurt am Main, p. 72, ISBN 978-3-939192-20-6 .
  3. ^ The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 722, ISBN 978-0-911910-00-1 .
  4. ↑ a b Fluvastatin data sheet for system suitability, European Pharmacopoeia (EP) Reference Standard from Sigma-Aldrich , accessed on October 31, 2016 ( PDF ).
  5. ↑ a b c Technical information Locol ® 20 / 40mg hard capsules. Novartis Pharma GmbH. July 2007.
  6. ↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 149.
  7. ↑ Boralli VB, Coelho EB, Sampaio SA, Marques MP, Lanchote VL: Enantioselectivity in the pharmacokinetic interaction between fluvastatin and lercanidipine in healthy volunteers . In: J Clin Pharmacol . 49, No. 2, February 2009, pp. 205-211. doi : 10.1177 / 0091270008327536 . PMID 19033449 .
  8. ↑ Red List Online, as of August 2009.
  9. ↑ AM comp. d. Switzerland, as of August 2009.
  10. ↑ AGES-PharmMed, as of August 2009.