Fluvastatin

Fluvastatin belongs to the statin family. It blocks HMG-CoA reductase, the enzyme that controls the rate-limiting step of cholesterol production in the liver: the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A into mevalonate, the very first link in this synthesis pathway. It is what is called a competitive inhibitor, meaning that it takes the place of the substrate on the enzyme and thereby slows the reaction.

Deprived of part of its internal production, the liver responds by making more LDL receptors on its surface. These receptors capture the LDL particles circulating in the blood and remove them from the circulation. This LDL is the one that infiltrates the artery wall and forms atheromatous plaques there, at the origin of heart attack and stroke. By lowering its concentration, fluvastatin acts on the very mechanism of atherosclerosis.

Fluvastatin is indicated for primary hypercholesterolaemia and mixed dyslipidaemia, in addition to diet. It is therefore aimed at people whose cholesterol level remains high despite lifestyle measures, and it reinforces these measures rather than replacing them. It is also prescribed for heterozygous familial hypercholesterolaemia in children aged 10 to 16, a genetically driven form in which cholesterol is high from a very young age.

It is finally used in secondary prevention for patients with coronary artery disease. In this case, the goal is no longer merely to correct a figure: it is to prevent the recurrence of a cardiac event in people whose arteries are already affected. The drop in LDL achieved under treatment slows the progression of the plaques and reduces this risk of a new event.

Fluvastatin has fast pharmacokinetics: its peak blood concentration is reached in less than an hour after taking the capsule, its elimination half-life is about 3 hours, and its absolute bioavailability is on the order of 24 %. The immediate-release capsule is taken in the evening. The extended-release form, for its part, can be taken at any time of day, which leaves more flexibility.

A meal changes absorption: taken with the evening meal, the medicine sees its peak concentration halved, its total exposure fall by about 11 % and its time to action more than double. The regularity of the intake therefore counts as much as the moment chosen. The benefit on cholesterol depends on a treatment continued over time: stopping the statin on one’s own initiative sends the LDL back up, and any change is decided with the doctor who prescribed it.

In clinical trials, the most frequently reported effects are of a digestive and neurological nature. Headaches affect 8.9 % of people on fluvastatin versus 7.8 % on placebo, dyspepsia 7.9 % versus 3.2 %, abdominal pain 4.9 % versus 3.8 % and nausea 3.2 % versus 2.0 %. Myalgia, those muscle pains often feared with statins, concerns 5.0 % of patients versus 4.5 % on placebo.

Muscle damage, myopathy, depends on the dose and manifests as diffuse pain or unexplained muscle tenderness; its most severe form, rhabdomyolysis, remains rare. A rise in liver enzymes may occur, but it is usually transient and resolves with continuation of the treatment. Statins are finally accompanied by an increase of about 9 % in the probability of developing diabetes, which laboratory monitoring watches over.

Diet acts on the same ground as your treatment. Soluble fibre is the best-established example: the EFSA recognises a cause-and-effect relationship between the consumption of barley beta-glucans and the lowering of blood LDL-cholesterol, provided at least 3 grams per day are consumed. These fibres are found in barley and oats, and more broadly in legumes, which provide soluble fibre and plant proteins.

Fluvastatin shares its pathway of action, that of mevalonate, with the production of coenzyme Q10 (ubiquinone). A meta-analysis of placebo-controlled trials shows that statin treatment reduces the blood concentrations of this coenzyme Q10. A link remains debated: coenzyme Q10 supplementation would reduce the muscle symptoms associated with statins, but this result is not a consensus. The plate provides little coenzyme Q10, mainly through oily fish and meats, and the body makes most of it itself. When this production is slowed, a targeted intake makes sense, in addition to your treatment, never in its place.

Fluvastatin is metabolised about 75 % by CYP2C9, 20 % by CYP3A4 and 5 % by CYP2C8. This low dependence on CYP3A4 limits the interactions by this pathway, including that of grapefruit, which poses a problem with other statins. Some combinations nevertheless remain to be monitored: ciclosporin increases exposure to fluvastatin by 90 % and fluconazole by 84 %, which then leads to limiting the dose to 20 mg twice a day. The combination with gemfibrozil should be avoided because of the risk of myopathy.

Laboratory monitoring frames the treatment. A lipid panel is carried out at initiation, then 4 to 12 weeks after the start or adjustment of the dose, in order to check the effect and calibrate the treatment. A liver panel is performed before initiation. Creatine kinase, a marker of muscle damage, is monitored in particular in case of combination with colchicine. This monitoring is precisely what allows the effects described above to be spotted early.