SELECTIN® Pravastatin

SELECTIN ® is a drug based on pravastatin sodium salt

THERAPEUTIC GROUP: Hypolipidemic - HMG-CoA reductase inhibitor

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

Indications SELECTIN ® Pravastatin

SELECTIN ® is used as a pharmacological treatment of mixed dyslipidemia and heterozygous primary or familial hypercholesterolemia, when an appropriate diet and a healthy lifestyle have not produced satisfactory therapeutic results.

SELECTIN ® can also be used in the prevention of cardiovascular diseases in patients with previous clinical history of coronary events, myocardial infarction, cerebrovascular events and various types of diseases of the cardiovascular system.

SELECTIN ® is also used in the treatment of post-transplant hyperlipidaemia in patients receiving immunosuppressive therapy.

Mechanism of action SELECTIN ® Pravastatin

Pravastatin, taken orally, is rapidly absorbed from the gastro-enteric tract, reaching its maximum plasma concentration after about 1.5 hours from its intake. Most of the drug undergoes a hepatic first pass metabolism, with formation of inactive metabolites, which causes the absolute bioavailability of pravastatin to drop to about 17% of the total dose taken.

The active proportion selectively penetrates into the liver cells, exerting a direct inhibition on the enzyme HMG-CoA reductase, necessary for the hepatic synthesis of cholesterol. The reduction of cholesterol levels inside the hepatocyte, through a positive feedback mechanism, increases the expression of LDL receptors on the cell surface, thus improving the uptake of low-density lipoproteins (called LDL). This double action, also accompanied by an inevitable reduction in the synthesis of VLDL (precursors of LDL), determines an appreciable drop in blood LDL cholesterol concentrations already after a week of treatment. The therapeutic effect, however, tends to be maximized only in the fourth week from the start of treatment.

This biological effect, probably also supported by a pleiotropic action of statins, results in a significant reduction in cardiovascular risk and in the incidence of related diseases.

After about an hour and a half from the intake, pravastatin is largely eliminated through the faeces, while the remaining portion is excreted in the urine.

Studies carried out and clinical efficacy

1 THE EFFECTIVENESS OF PRAVASTATINA

This study, conducted on patients with hypercholesterolemia (total cholesterol greater than 250mg / dL) and hypertension, showed how the administration of pravastatin at doses of 20 and 40 mg daily could guarantee a reduction of over 27% in total cholesterol and about 35% of LDL cholesterol, regardless of the type of antihypertensive treatment performed.

2. THE PLEIOTROPIC EFFECTIVENESS OF PRAVASTATINA

Several studies around the world are trying to clarify and identify the non-lipid-lowering effects of provastatin, probably involved in the prevention of cardiovascular diseases. This study, conducted in vitro on cell cultures, has shown how provastatin can exert a powerful antioxidant and vasoprotective action, through mechanisms that are independent of the inhibition of mevalonic acid production.

3. ANTICANCER STATINE?

Several studies, still in an experimental phase, support the antitumor action of statins, exercised through the inhibition of cholesterol synthesis (a necessary element for the formation of cell membranes). This clinical trial used pravastatin as an adjuvant for chemotherapy in the treatment of advanced gastric cancer, without however obtaining any kind of improvement. The discrepancy between the biological hypothesis - supported by in vitro experiments - and clinical practice, does not allow us to express a unambiguous opinion on this utility.

Method of use and dosage

SELECTIN ® 20/40 mg pravastatin tablets: the most commonly used dosage in the treatment of primary hypercholesterolemia is between 10 and 40 mg per day, taken as a single dose, possibly before going to sleep. The formulation of the specific dosage must be carried out by the doctor after a careful evaluation of the patient's physio-pathological state, and after excluding possible causes of secondary hypercholesterolemia. Based on the therapeutic objective and the results found it is possible to provide for an adjustment of the dosage, after about 4 weeks, a period necessary to obtain the maximum therapeutic effect.

In any case, before undertaking any drug treatment, it would be appropriate to adopt a healthy lifestyle and a hypolipidic diet, to be continued even during the therapeutic process.

In the prevention of cardiovascular diseases, the dose of SELECTIN ® generally used was 40 mg / day, while in post transplantation hyperlipidemia the dose of 10 mg / day was generally used, to eventually adapt it later in case of reduced therapeutic response.

IN EVERY CASE, BEFORE TAKING SELECTIN ® Pravastatin - THE PRESCRIPTION AND CONTROL OF YOUR OWN DOCTOR IS NECESSARY.

Warnings SELECTIN ® Pravastatin

Like other statins, pravastatin therapy requires monitoring of liver function and transaminases. It is indeed necessary to administer this drug with caution in patients with a history of liver disease, in order to avoid - albeit rare - unpleasant side effects.

The same caution should be maintained towards patients with a previous history of myopathies, or predisposed to the development of skeletal muscle diseases; in these cases, periodic monitoring of creatine kinase levels would be necessary to avoid episodes of rhabdomyolysis. The same follow-up, on the other hand, is not required for patients without such clinical histories, provided that the absence of muscle pain and persistent weakness is always ascertained.

Given the presence of lactose among the excipients, SELECTIN ® could create gastro-intestinal problems in patients with reduced glucose / galactose tolerance, or with lactase enzyme deficiency syndrome.

In light of the current studies and the mechanism of action of the drug, pravastatin should not affect the patient's normal attention span; therefore, it does not seem to alter the ability to drive or use machinery.

PREGNANCY AND BREASTFEEDING

Several studies have shown the absence of teratogenic effects of pravastatin on the fetus; however the use of SELECTIN ® is strongly contraindicated in pregnancy, given the importance of cholesterol during the phases of embryogenesis and fetal development.

Breastfeeding should also be suspended in case of treatment with pravastatin, although the shares of the active substance found in breast milk are negligible.

Interactions

Unlike many other statins and inhibitors of the HMG-CoA reductase enzyme, the hepatic metabolism of pravastatin is not solely supported by the cytochrome P450 3A4. This characteristic therefore reduces the potential interactions with its inhibitors or inducers (acetylsalicylic acid, warfarin, cyclosporine ...) and keeps its pharmacokinetic profile quite stable.

An adjustment of the dose, on the other hand, is required in case of concomitant intake of other drugs with lipid-lowering action.

Contraindications SELECTIN ® Pravastatin

SELECTIN ® is contraindicated in case of hypersensitivity to one of its components, of various types of liver disease and during the period of pregnancy and lactation.

Undesirable effects - Side effects

The various studies carried out on the tolerability and safety of pravastatin have shown that the incidence of side effects is comparable to that observed in the control sample. The most common adverse reactions were all relatively minor and generalized, such as diarrhea, nausea, vomiting, flatulence, dizziness and asthenia.

More serious reactions involving the skeletal, cardiovascular and hepatic muscles, were decidedly more rare and transient, so much so that they disappeared rapidly following the suspension of therapy.