PLAVIX ® Clopidogrel

PLAVIX® is a medicine based on Clopidogrel.

THERAPEUTIC GROUP: Antithrombotics

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

Indications PLAVIX ® Clopidogrel

PLAVIX ® is used as a pharmacological aid to preventive action against ischemic events on an atherothrombotic basis.

More precisely, PLAVIX® is successfully used in patients suffering from myocardial infarction, ischemic stroke, arteriopathy and acute coronary syndrome, to prevent the onset of cerebral and cardiovascular ischemic events.

Mechanism of action PLAVIX ® Clopidogrel

Clopidogrel, contained in PLAVIX® if taken by mouth, is rapidly absorbed at the gastro-intestinal level, reaching maximum plasma concentration in just 45 minutes.

The active principle undergoes a first pass metabolism through two different routes, supported by completely different liver enzymes responsible for the production of both inactive metabolites and active metabolites, protagonists of the anti-aggregating action.

Linked to plasma proteins, the thiol derivatives (active) of clopidogrel can recognize and irreversibly bind the platelet P2Y receptor, inhibiting its binding to ADP and preventing the consequent activation of the glycoprotein IIb / IIIa complex, involved in the interaction with fibrinogen and in the platelet cap stabilization.

Given the pharmacodynamic properties of this active ingredient, the maximum therapeutic effect will be obtained only after a few days of pharmacological treatment and will tend to persist, even after therapy has been suspended, for the entire period necessary to reform a new platelet pull that is not affected of the action of the drug.

The pharmacokinetic aspect is noteworthy, and in particular that related to hepatic metabolism, for which the synthesis of active metabolites is strongly influenced by the presence of gene variants of the cytochromial enzymes involved and by the possible presence of enzymatic interferents.

This aspect can significantly influence the success of the treatment plan and the possible effects of side effects.

After a half-life of a few hours, the metabolites of clopidogrel are more or less eliminated in equal parts through feces and urine.

Studies carried out and clinical efficacy

CLOPIDOGREL: POSSIBLE REBOUND EFFECT

It is known that discontinuation of clopidogrel therapy is not accompanied by an immediate resumption of platelet function, given the irreversible action of the drug on the platelet receptor structure. However, if this phenomenon has been well understood through the characterization of the molecular mechanisms of action of the active principle, the phenomenon of the increased platelet aggregation observed 1 month after the suspension of therapy remains to be clarified. This effect could be potentially dangerous for the patient's health, exposing him to thrombotic risks.

2. THE USE OF THE CLOPIDOGREL IN THE CORONARY BYPASS

The coronary bypass introduction procedure is routinely followed by the administration of acetyl salicylic acid, in order to avoid rejection. This important study demonstrates how adding clopidogrel to aspirin can further reduce graft occlusion, reducing the risk of bypass failure.

3. THE ADVENT OF THE PHARMACOGENOMIC

Pharmacogenomics is a discipline that is becoming more and more popular in recent years, given the need to customize therapy making it as effective as possible and without side effects.

Very important is the clinical implication of this discipline with regard to treatment with clopidogrel, whose efficacy is strongly influenced by the genetic characteristics of the patient and the polymorphism of the enzyme CYP2C19. Several research groups are directing their efforts towards the genetic characterization of the patient, useful in adjusting the dosage.

Method of use and dosage

PLAVIX® clopidogrel 75 mg tablets as hydrogen sulphate : treatment with clopidogrel generally involves a loading dose of about 300 mg and a continuous treatment at 75 mg daily.

The correct formulation of the dosage, both of loading and maintenance, as well as the period of treatment and the possible association with other active principles, must be carried out by the doctor after a careful evaluation of the clinical picture of the patient and the related therapeutic objectives.

Dosage adjustments should be considered in patients with polymorphisms affecting the enzyme CYP2C19, involved in the synthesis of active metabolites of clopidogrel.

IN ANY CASE, BEFORE TAKING PLAVIX ® Clopidogrel - THE REQUIREMENT AND CHECK OF YOUR DOCTOR IS NECESSARY.

Warnings PLAVIX ® Clopidogrel

Before starting PLAVIX ® therapy it is advisable to carefully check the patient's hematology, and to ascertain the absence of pathologies, traumas or conditions predisposing to the development of bleeding.

A constant monitoring of these parameters should be carried out throughout the therapeutic intervention, and possibly lean towards the suspension of therapy when the data manifest a risky clinical picture.

The therapy should be suspended, at least a seventh before, in the case of surgical or dental procedures at risk of bleeding.

Particular attention should also be paid to patients with liver disease, given the hepatic metabolism of the drug, and to so-called slow metabolisers, for which CYP2C19 gene variants could cause alterations in the synthesis of active metabolites.

The same effect could be achieved in the case of concomitant administration of drugs or molecules of various kinds capable of interfering with the activity of these enzymes.

PLAVIX® contains lactose, therefore it is not recommended in patients with intolerance to glucose / galactose or in patients with lactase enzyme deficiency.

Although clopidogrel does not directly affect vehicle driving skills or the use of machinery, some side effects, such as dizziness and dizziness, could make these activities dangerous.

PREGNANCY AND BREASTFEEDING

At the moment, there are no studies in the literature that attest to the safety or toxicity of clopidogrel on fetal health, when taken during pregnancy.

For this reason, also because of the haemodynamic effects that could increase the risk of fetal bleeding, it is preferable to avoid taking PLAVIX® during the whole pregnancy and breastfeeding.

Interactions

The possible documentable interactions for clopidogrel are multiple and classifiable in pharmacodynamic interactions and pharmacokinetic interactions.

The former, capable of accentuating certain biological actions of the drug, such as the increased bleeding time, include the concomitant administration of anticoagulants: acetyl salicylic acid, heparin, thrombolytics and non-steroidal anti-inflammatory drugs.

Pharmacokinetic interactions are instead supported by active ingredients and various types of molecules that can interfere with the activity of the enzyme CYP2C19 involved in the metabolism of clopidogrel, resulting in a significant variation in the concentrations of the active ingredient in circulation and making it difficult to predict therapeutic efficacy.

Among CYP2C19 inhibitors, therefore able to determine a reduction of the active metabolite of the drug, we recall omeprazole, esomeprazole and proton pump inhibitors, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, ciprofloxacin, cimetidine, carbamazepine, oxicarbazepine and chloramphenicol .

Other interactions have been described, but they are clinically of little relevance.

Contraindications PLAVIX ® Clopidogrel

PLAVIX ® is contraindicated in patients suffering from diseases affecting the coagulation system or at risk of bleeding, and in case of hypersensitivity to one of its components.

The important hepatic metabolism of clopidogrel exposes patients suffering from severe liver failure to serious risks to their health; therefore, PLAVIX ® is also contraindicated in this category of patients.

Undesirable effects - Side effects

The extensive documented clinical trial for clopidogrel described collateral reactions comparable in frequency and severity to those of other antithrombotic drugs of the same category.

The most frequent side effects were those associated with increased bleeding time, with bleeding, epistaxis, bleeding at the injection site, hematomas and gastro-intestinal disorders.

Less frequent but clinically more relevant were episodes of hematuria, gastric ulcer, skin rash, thrombocytopenia, anemia, agranulocytosis and purpura.

Generally, the suspension of therapy is accompanied by a gradual reduction in symptoms, given the time required to recreate a new platelet pull.