ZOCOR ® Simvastatin

ZOCOR ® is a drug based on simvastatin

THERAPEUTIC GROUP: Hypolipidemic - HMG-CoA reductase inhibitor

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

Indications ZOCOR ® Simvastatin

ZOCOR ® can be used as a pharmacological aid in case of primary hypercholesterolemia and mixed dyslipidemia, provided that the previous adoption of a hypolipidic diet and a correct lifestyle, lasting for at least 3 months, has not produced the hoped for therapeutic results.

Similarly, this drug can be used in the treatment of more severe forms of primary hypercholesterolemia, such as heterozygous and homozygous familial hypercholesterolemia.

The use of ZOCOR ® can also be extended to patients with normal cholesterol levels but with a high cardiovascular risk, determined by multiple factors (overweight, diabetes mellitus, cardiovascular diseases, atherosclerosis) in order to reduce the incidence of cardiovascular accidents.

Mechanism of action ZOCOR ® Simvastatin

Simvastatin, taken orally by the ZOCOR ® drug, is rapidly absorbed from the gastrointestinal tract and transported by the vein to the liver. The first hepatic step for this active ingredient is essential, in order to guarantee the hydrolysis of simvastatin from the chemical form "lactone" to the respective hydroxy acid, the active metabolite of the drug. This substance, once its therapeutic action is over, will be subsequently excreted mainly through the faeces.

The hydrolysis process described above drastically reduces the bioavailability of the active ingredient, which only reaches its maximum plasma concentrations after two hours, equal to 5% of the oral intake of simvastatin.

Despite this decline, simvastatin is particularly effective in reducing plasma LDL cholesterol levels, exerting its therapeutic action in the liver, where it inhibits the key enzyme in cholesterol synthesis.

In fact, like the other statins, simvastatin can inhibit the enzyme HMG-CoA reductase, preventing the production of mevalonate, an intermediate organic compound in cholesterol metabolism. Consequently, given the reduced synthesis of this lipid, simvastatin up-regulates the expression of hepatocyte receptors for LDL. Ultimately, therefore, the increased hepatic uptake of LDL cholesterol and the reduction of VLDL synthesis guarantees a significant reduction in blood LDL cholesterol levels.

However, the importance of ZOCOR ® in the prevention of cardiovascular diseases seems to be associated also with other mechanisms that do not see the direct and unique involvement of the lipid-lowering effect, given the various studies in the literature that show a significant decrease in morbidity and mortality linked to events cardiovascular in patients at risk but with normal cholesterol levels.

Studies carried out and clinical efficacy

1 THE EFFECTIVENESS OF SIMVASTATIN IN DISLIPIDEMIES

Treatment with simvastatin 40 and 80 mg / day - in patients with dyslipidemia (LDL coleseterol greater than 160 mg / dL and triglycerides greater than 350 mg / dL) - guaranteed a reduction in LDL cholesterol of 6 weeks of treatment respectively 41 and 47%, and triglycerides of 21 and 23%.

2. SIMVASTATINA: DOSE-EFFECTIVENESS REPORT

In this study - conducted on about 12, 000 men suffering from previous myocardial infarction and with cholesterol levels such as to justify the prescription of statins - the relationship between efficacy and occurrence of side effects was assessed at doses of 20 and 80 mg of simvastatin.

The results show that the daily dose of 80mg guaranteed a reduction in cardiovascular events 6% higher than that obtained with the 20mg dose, and a more intense decrease in LDL cholesterol. However, this dose resulted in an increased incidence of myopathies; therefore, the study suggests the use of intermediate doses, in order to obtain a good compromise between therapeutic and collateral effects.

3. STATINE AND CANCER

The question of the real antitumor efficacy of statins is still open. In this study carried out in vitro, on cells and on laboratory animals, the efficacy of simvastatin in reducing the growth capacity of the prostatic tumor mass has been demonstrated, reducing the activation of the cellular pathways involved in this mechanism. Of course, it is absolutely not possible to generalize by extending the effectiveness of these interventions to humans.

Method of use and dosage

ZOCOR ® simvastatin 10/20/40 mg tablets: ZOCOR ® administration in the event of primary hypercholesterolemia should be performed after the initiation of a hypolipid dietary plan and controlled exercise. The starting dose is generally set between 20 and 40 mg per day taken as a single dose, preferably in the evening. In the case of reduced therapeutic efficacy, an adjustment of the dosage should be carried out not earlier than 4 weeks of treatment, a period necessary to achieve maximum therapeutic efficacy.

The 40 mg / day dose also appears to be the most tested and effective in reducing cardiovascular risk.

In the treatment of homozygous familial hypercholesterolemia, up to 80 mg of simvastatin daily, taken in doses of 20 mg twice a day and 40 mg before bedtime, can be used concomitantly with other non-pharmacological therapeutic approaches.

The formulation of the correct dosage should be carried out by the doctor after a careful evaluation of the hematoclinic situation, the patient's clinical history and the objectives to be achieved.

IN ANY CASE, BEFORE TAKING ZOCOR ® Simvastatina - THE PRESCRIPTION AND CONTROL OF ITS OWN DOCTOR IS NECESSARY.

Warnings ZOCOR ® Simvastatin

Before and during the drug treatment with statins, it would be advisable to follow a hypolipidic diet with a low percentage of saturated fats and cholesterol, and an adequate lifestyle.

The administration of ZOCOR ® should be carried out with particular caution and possibly accompanied by a monitoring of blood levels of creatine kinase (marker of muscle damage), in the case of patients suffering from myopathies of various kinds, or predisposed to the development of such diseases (elderly, hypothyroid, patients with previous clinical history), given the possible incidence of myopathies and rhabdomyolysis.

Although the frequency of these pathological events tends to decrease drastically in non-predisposed patients, during the therapy with simvastatin it would always be appropriate to investigate the presence of muscular pains, persistent fatigue and asthenia, possibly dosing the plasma levels of the enzyme creatine kinase.

Before starting treatment with ZOCOR ®, liver function, and in particular blood transaminase levels, should also be evaluated in order to choose the correct dose that can avoid side effects. Simvastatin therapy should be suspended or not started in case of severe liver disease or when transaminase concentrations rise to triple levels compared to the normal range.

Treatment should also be suspended in cases of suspected interstitial lung disease, characterized by dyspnea, cough, fever and asthenia.

ZOCOR ® contains lactose; therefore, it could give gastrointestinal problems to patients suffering from glucose / galactose intolerance, or in case of lactase enzyme deficiency.

Simvastatin does not appear to affect the patient's normal reactive capacity, although some side effects, such as vertigo, could theoretically compromise the ability to drive vehicles or use machinery.

PREGNANCY AND BREASTFEEDING

Although a direct teratogenic effect of simvastatin on the fetus is not documented, the reduction of cholesterol levels could determine the absence of constituents necessary for the correct embryonic and fetal development. Therefore, the administration of ZOCOR ® during the whole pregnancy period is strongly contraindicated.

The absence of scientific evidence showing the absence of simvastatin secretion in breast milk suggests suspending breastfeeding in case of ZOCOR ® therapy

Interactions

Given the hepatic metabolism of simvastatin by the cytochrome P450 3A4 enzyme, numerous interactions with drugs of various nature are possible.

In particular :

Concomitant administration of fibrates, niacin, amiodarone, verapramil may increase the incidence of rhabdomyolysis and myopathies;
Intake of cytochrome CYP3A4 inhibitors, an enzyme responsible for the metabolism of simvastatin (grapefruit juice, itraconazole, ketoconazole, inhibitors of HIV protease, erythromycin, clarithromycin, telithromycin and nefazodone), could lead to a significant increase in drug exposure, increasing the incidence of even serious side effects;
The simultaneous administration of ciclosporin, given the inhibitory action on the metabolism of simvastatin, would require an adjustment of the dosage of this maximum active principle within 10mg;

Furthermore, simvastatin, like other statins, could determine an increase in prothrombin time, thus enhancing the therapeutic effects of oral anticoagulants.

Contraindications ZOCOR ® Simvastatin

ZOCOR ® is contraindicated in case of liver diseases, hypersensitivity to one of its components, concomitant administration of inhibitors of the enzyme CYP3A4, and during the period of pregnancy and lactation.

Undesirable effects - Side effects

The incidence of side effects related to ZOCOR ® therapy was quite low, comparable to that found in the control group.

The most common adverse reactions were all relatively minor and generalized, such as diarrhea, nausea, vomiting, dizziness and asthenia.

The incidence and severity of undesirable effects such as myopathies, rhabdomyolysis, liver failure, psychiatric and gastrointestinal disorders, inevitably tends to increase in patients predisposed to certain pathologies, or subjected to therapy with drugs capable of altering the pharmacokinetics of simvastatin.