EFIENT ® Prasugrel

EFIENT® is a drug based on Prasugrel hydrochloride.

THERAPEUTIC GROUP: Antithrombotics

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

Indications EFIENT ® Prasugrel

EFIENT ® is used in the prevention of atherothrombotic-based ischemic events in patients with acute coronary syndrome, myocardial infarction or undergoing primary or delayed percutaneous coronary intervention.

The effectiveness of EFIENT® is highest when administered concomitantly with acetyl salicylic acid.

EFIENT ® Prasugrel mechanism of action

Prasugrel is one of the last active ingredients approved by EMEA for its antithrombotic properties. Belonging to the family of the already known and marketed thienopyridines, it represents a prodrug that, taken by mouth, is immediately hydrolyzed in the intestine and subsequently absorbed.

Following a first-pass metabolism by cytochrome P450 enzymes, susceptible to modulation of their activity, the maximum concentrations of the active ingredient are registered only 30 minutes after intake.

Like the other elements belonging to the thienopyridine family, the active metabolites of prasugrel exert their antithrombotic action by recognizing and irreversibly binding the platelet P2Y receptor, inhibiting its binding to ADP and the consequent activation of the glycoprotein IIb / IIIa complex, involved in the interaction with fibrinogen and stabilization of the platelet plug.

Given the rapid kinetics of action, the therapeutic effect is obtained in narrow time intervals with respect to those described for other similar active ingredients, and tends to disappear, in light of the irreversibility of the bond, only after at least 5 days from the suspension of therapy . After its action, estimated in a half-life of about 7.4 hours, the active metabolite is eliminated for about 70% through the urine, and for the remainder through the faeces.

Studies carried out and clinical efficacy

THE EFFECTIVENESS OF PRASUGREL IN THE ACUTE CORONARY SYNDROME

The TRITON study represents the first clinical trial that demonstrated the therapeutic efficacy of prasugrel. As many as 13, 000 patients with acute coronary syndrome were enrolled in this study and treated with prasugrel or clopidogrel. The results show a better preventive effect of prasugrel compared to clopidogrel in the incidence of ischemic events and myocardial infarction, with a percentage of 10% in patients treated with prasugrel and 12% in those treated with clopidogrel.

2. PRASUGREL: FROM MOLECULAR ADVANTAGES TO CLINICAL RESPONSE

Prasugrel represents the first of the third generation active ingredients belonging to the thienopyridine category. The greatest therapeutic efficacy, observed in various clinical trials, could be ascribed above all to the pharmacokinetic characteristics of this active principle, able to exert inhibitory action on platelet receptors in time intervals decidedly lower than those observed for other active principles. This translates into a faster time frame and a more successful therapy.

3. THE ADVENT OF PRASUGREL

Thienopyridines have been used for more than 15 years in the prevention of atherothrombotic-based ischemic events. For years, ticlopidine was used, later replaced by clopidogrel.

Since 2009, both the EMEA and the FDA have authorized the marketing of a new, active prasugrel, ten times more effective than clopidogrel, and above all less subject to pharmacokinetic changes, and therefore safer.

Method of use and dosage

EFIENT ® 5 mg tablets of prasugrel hydrochloride : the most commonly used dose is a single 60 mg loading dose, followed by a 10 mg maintenance dose, taken as a single daily dose. EFIENT ® is generally given in combination therapy with acetyl salicylic acid.

The duration of the therapeutic intervention, the choice of the correct drug combination, and a possible adjustment of the dosage (required for particular categories of patients at risk), should be established by your doctor after a careful evaluation of the patient's clinical condition.

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

Warnings EFIENT ® Prasugrel

Like other antithrombotic drugs, taking EFIENT ® should be preceded and accompanied by careful monitoring of the haematological and coagulative picture, in order to reduce the potential risk of bleeding. Particular care should be taken in patients subject to these risks, and in particular in patients with recent traumas, peptic ulcers, gastrointestinal bleeding or epistaxis, for which the possibility should also be considered of avoiding drug treatment or suspending it when already in place.

A dosage adjustment may be necessary for patients over 75 years of age, with a body weight less than 60 kg or subjected to concomitant therapy with drugs active on the coagulation system.

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 the so-called slow metabolisers, for which gene variants of the various forms of cytochromial enzymes could determine an alteration of the concentrations of the active metabolite, and therefore of the its therapeutic efficacy.

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

Prasugrel does not directly affect the ability to drive vehicles or use machinery.

PREGNANCY AND BREASTFEEDING

The various experimental evidences, for the moment conducted exclusively on animal guinea pigs, did not show any particular toxic effects on the health of the fetus following the intake of prasugrel during pregnancy. However, the absence of clinical trials and significant data for humans suggest that EFIENT® should be avoided both during pregnancy and lactation.

Interactions

The various studies in the literature on the possible interactions of the various active ingredients with prasugrel show a markedly reduced susceptibility compared to similar active ingredients, such as clopidogrel, which makes EFIENT® safer for the patient's health.

In this regard, the various active ingredients capable of interacting both as inhibitors and as inducers of CYP3A4 (an enzyme responsible for the metabolism of prasugrel), do not appear to produce significant pharmacokinetic variations that alter the functional and biological characteristics of the drug.

More attention should be paid in case of concomitant administration of non-steroidal anti-inflammatory drugs, warfarin, heparin and other drugs acting on the coagulation system, for which it would be possible to increase the anticoagulant effects and an increased risk of bleeding.

Contraindications EFIENT ® Prasugrel

EFIENT® is contraindicated in patients suffering from pathologies, traumas or potentially dangerous diseases due to the onset of bleeding episodes, severe hepatic dysfunction and true hypersensitivity one of its components.

Undesirable effects - Side effects

The most described side effect in the various clinical trials, which led to the discontinuation of drug treatment in about 7% of the population treated with EFIENT® was bleeding, described in the form of gastro-intestinal bleeding, hematuria, hematoma and epistaxis.

More rare were the cases of thrombocytopenia, leukopenia, anemia and purpura.