LESCOL ® Fluvastatin

LESCOL ® is a drug based on fluvastatin (monosodium salt)

THERAPEUTIC GROUP: Hypolipidemic - HMG-CoA reductase inhibitor

IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects

Indications LESCOL ® Fluvastatin

LESCOL ® is used as a pharmacological aid for the treatment of primary hypercholesterolemia and mixed dyslipidemia, to reduce blood levels of total cholesterol, LDL cholesterol, triglycerides and apolipoprotein B. This type of intervention is particularly indicated in subjects with high cardiovascular risk and not responsive to diet therapy or other non-pharmacological measures.

Mechanism of action LESCOL ® Fluvastatin

The fluvastatin, taken orally, is absorbed almost completely at the level of the gastro-intestinal tract, but reaches useful plasma concentrations equal to 24% of the total dose taken.

Linked to plasma proteins, the active ingredient of Lescol ® reaches the liver, where it has its main effect. At the hepatocyte level, in fact, fluvastatin is able to bind and inhibit the HMG-CoA reductase enzyme, necessary for the synthesis of mevalonic acid, a cholesterol precursor. The reduced synthesis of hepatic cholesterol induces an over-expression of LDL receptors, thus guaranteeing a dual cholesterol-lowering action, exerted on the one hand by the reduced synthesis of this sterol and on the other by the increased hepatic uptake.

After its biological action (half-life around 2.5 hours), fluvastatin is metabolized by different isoforms of hepatic cytochromes in inactive metabolites, and more than 90% is eliminated through the faeces, and for the remainder through the urine.

The therapeutic importance of LESCOL ® is due to the well-demonstrated association between elevated levels of LDL cholesterol and blood triglycerides, and cardiovascular events of various nature, even serious ones, and to the preventive effect that the decrease in the aforementioned values exerts on the incidence of numerous cardiovascular diseases.

Studies carried out and clinical efficacy

1 THE EFFECTIVENESS OF THE FLUVASTATINE

The efficacy of fluvastatin has been documented in the literature for over 25 years. This study represents a milestone in the evaluation of the efficacy of fluvastatin in the treatment of primary hypercholesterolemia and heterozygous familial hypercholesterolemia, in patients with LDL cholesterol values above 190 mg / dL. Treatment for at least 12 weeks with fluvastatin at 40 mg / day ensured a reduction in LDL cholesterol levels above 25%.

2. THE EFFECTIVENESS OF FLUVASTATIN IN HYPERTESE PATIENTS

Hypertension is known to be associated with an increased cardiovascular risk, even in the absence of high LDL cholesterol levels. The study in question shows how the administration of fluvastatin can guarantee a significant reduction in systolic pressure, left ventricular mass, insulin resistance and cardiovascular risk indices, even in patients without hypercholesterolemia. These data support the pleiotropic efficacy of LESCOL ® of other Fluvastatin-based drugs.

3. THE FLUVASTATIN IN THE PROTECTION FROM ATEROSCLEROSIS

The metabolic effects of statins, in particular of fluvastatin, are now known, while its pleiotropic functions are not entirely clear. This cellular model of study, in fact, shows how fluvastatin can contribute to safeguarding the integrity of smooth muscle cells in blood vessels, protecting them from oxidative stress thanks to the genesis of factors involved in the antioxidant response.

Method of use and dosage

LESCOL ® 20 / 40mg capsules of fluvastatin or LESCOL ® prolonged-release tablets of fluvstatin 80mg: as mentioned above, the administration of this drug for the treatment of primary hypercholesterolemia should be considered only after having performed a hypolipidic diet for at least 3 months, accompanied by an improvement in lifestyle.

The correct dosage of LESCOL ® should be formulated by the doctor after a careful evaluation of the clinical picture of the patient and the objectives to be achieved, providing, in case of reduced efficacy of the treatment, an increase in the dosage up to 80mg, however not before four weeks after starting therapy. In the same way, once the therapeutic standard is reached, a further adjustment of the dosage could be provided.

Taking LESCOL ® in prolonged-release tablets guarantees a reduction in the absorption rate of fluvastatin by approximately 60%, increasing its persistence in the circulatory stream by about 4 hours.

In both cases the drug should be taken in a single dose, with a glass of water, even in the evening before bedtime.

Warnings LESCOL ® Fluvastatin

Before starting the drug treatment with LESCOL ® it is particularly recommended to undergo a hypolipidic diet and a controlled physical activity for at least 12 weeks. These precautions should also be maintained throughout the pharmacological intervention.

Given the hepatic metabolism of fluvastatin, this active ingredient should be administered with extreme caution in all patients suffering from liver disease or with a previous history of liver disease, constantly monitoring the parameters of liver function (transaminases), and possibly suspending therapy when they reach values 3 times higher than the normal range.

Before treatment with LESCOL ® in patients suffering from alterations in hormone balance or with a previous history of myopathies or skeletal muscle disease, it would be necessary to control the plasma levels of creatinkinase, and monitor them throughout the treatment, given the incidence of myopathies and rhabdomyolysis in patients treated with statins. For the same reason, even in subjects not predisposed to these pathologies, it would be opportune to investigate the presence of muscular pains or chronic fatigue during the whole period of treatment with fluvastatin.

The absence of studies concerning the use of this active ingredient in individuals under the age of 18 or in patients with homozygous familial hypercholesterolemia, does not allow the extension of the therapeutic indication to these groups.

Although dizziness is described as one of the side effects, fluvastatin should not alter normal driving skills or use of machinery.

PREGNANCY AND BREASTFEEDING

Taking LESCOL ® during pregnancy is strongly discouraged, given the importance of cholesterol in proper embryonic and fetal development.

The absence of studies in the literature showing the effects of statins on the health of the newborn, suggest to suspend breastfeeding during drug therapy with LESCOL ®

Interactions

Given the hepatic metabolism of fluvastatin, mediated by numerous enzymatic isoforms of cytochromial enzymes, it is difficult for the concomitant administration of other drugs to significantly affect the pharmacokinetic properties of this active ingredient. The demonstration is given by the absence of clinically relevant changes in blood fluvastatin following the administration of cytochrome 3A4 inhibitors, such as erythromycin or itraconazole.

In contrast, the concomitant administration of rifampicin on healthy volunteers resulted in a 50% reduction in the bioavailability of fluvastatin, thus requiring dosage adjustment.

Other clinically non-relevant changes, for which an adjustment of therapy is generally not necessary, were observed following the administration of antacids and anticoagulants such as warfarin. In the latter case it is necessary to monitor the prothrombin time in order to avoid bleeding episodes, which have rarely been observed.

Contraindications LESCOL ® Fluvastatin

LESCOL ® is contraindicated during pregnancy and lactation, in case of hypersensitivity to one of its components and in case of significant changes in liver function.

Undesirable effects - Side effects

The adverse reactions described following the administration of LESCOL ® were found, in most cases, to be clinically insignificant and transient. The most commonly observed effects were abdominal pain, dyspepsia, headache, insomnia and vertigo.

The hypersensitivity reactions, predominantly dermatological (rash and erythema) or edematous, and the harmful actions on muscle tissue (myalgia, myopathy, rhabdomyolysis) and hepatic have been decidedly more rare.

In any case, all the above mentioned side effects were quickly resolved with the suspension of therapy.