XARELTO ® Rivaroxaban

XARELTO ® is a drug based on Rivaroxaban.

THERAPEUTIC GROUP: Antithrombotics

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

Indications XARELTO ® Rivaroxaban

XARELTO ® is indicated as a preventive pharmacological aid - against venous thromboembolism - in adult patients subjected to hip and knee replacement operations.

Mechanism of action XARELTO ® Rivaroxaban

Rivaroxaban, taken orally by XARELTO ® is rapidly absorbed, reaching maximum plasma concentrations after about 2-4 hours after oral administration.

The bioavailability of this active ingredient is very high, constantly exceeding 80% at doses below 15 mg.

Once absorbed, rivaroxaban is conveyed in the circulatory stream largely bound to plasma proteins, in particular to albumin.

XARELTO ® represents an innovative antithrombotic drug, given its mechanism of action that is expressed through the direct inhibition of coagulation factor Xa. By antagonizing the effect of this soluble factor, Rivaroxaban prevents the coagulation pathway from proceeding, either through the extrinsic pathway or through the intrinsic pathway, by blocking a key stage that allows prothrombin to generate thrombin (factor IIa) and initiate thrombus formation, with fibrin production.

The absence of a direct action against platelets or vitamin K guarantees a more controlled action profile, with reduced side effects.

After the biological effect, after about 7-11 hours, rivaroxaban is metabolized in the liver by cytochromial enzymes CYP3A4 and CYP2J2 and subsequently eliminated both via the faeces and urine.

Of the total dose taken, about 1/3 is found unchanged in the urine.

Studies carried out and clinical efficacy

EFFECTIVENESS AND SECURITY OF RIVAROXABAN

Several clinical studies seem to agree on the greater efficacy of rivaroxaban in the prevention of venous thromboembolic diseases following surgery. The data show that XARELTO ® therapy can be not only more effective, but also easier (it is an oral therapy, not parenteral) and safe, significantly reducing bleeding episodes.

2. RIVAROXABAN ALSO IN THE ATRIAL FIBRILLATION

In addition to the greater efficacy in the prevention of venous thromboembolic pathologies due to hip-knee surgery, several clinical trials support the therapeutic efficacy of rivaroxaban as a preventive tool for atrial fibrillation embolism. More precisely, XARELTO ® seems to be at least as effective as warfarin in treating these conditions, but definitely safer and easier to apply for both the doctor and the patient.

3. XARELTO IN THE PREVENTION OF THROMBOEMBOLIC DISEASES

XARELTO ® today represents a valid alternative to warfarin for the treatment of thromboembolic pathologies. In fact, in a study conducted on 4500 patients undergoing surgical hip therapy, post-intervention administration of rivaroxaban ensured a reduction in the incidence of venous embolism thrombus at 0.2%, compared to 2% previously obtained with normal pharmacological prophylaxis .

Method of use and dosage

XARELTO ® rivaroxaban 10 mg tablets : therapy should start a few hours after the operation, however not before the haemostasis has been fully achieved.

At this point the optimal dosage - which appears to be 10 mg, taken once a day - should be continued for about 5 weeks in hip surgery, and for 2 weeks in the knee.

Dosage adjustments should be anticipated in elderly patients or those with hepatic and renal insufficiency.

IN ANY CASE, BEFORE TAKING XARELTO ® Rivaroxaban, THE REQUIREMENT AND CHECK OF YOUR DOCTOR IS NECESSARY.

Warnings XARELTO ® Rivaroxaban

Before starting treatment with XARELTO ® it is advisable to check the patient's coagulation pattern, and then monitor it during the therapeutic intervention.

Even more attention must be paid to patients with a predisposition to the development of hemorrhages, traumatized, subjected to risky medical procedures (such as spinal or epidural puncture), or affected by hematological pathologies with impaired coagulation processes.

For the same reason it would be advisable to advise your doctor, or possibly the rescuers, of taking a drug with anticoagulant effects.

The hepatic metabolism and the renal and hepatic secretion of rivaroxaban make it particularly risky to take the drug in case of reduced functionality of the aforementioned organs, being able to determine a significant increase in blood concentrations of the active ingredient with an increased risk of side effects.

XARELTO ® contains lactose, therefore it could be responsible for gastro-intestinal disorders in patients suffering from glucose-galactose malabsorption and lactase enzyme deficiency.

Some side effects described following the use of XARELTO ® could reduce the patient's normal perceptual abilities and make it dangerous to use machinery or drive vehicles.

PREGNANCY AND BREASTFEEDING

Several experimental evidences, even if only on animal models, have shown a toxic effect on the health of the fetus. Furthermore, the ability to cross the placenta and induced hemodynamic changes could increase the risk of fetal bleeding leading to death or abortion.

For the aforementioned reasons, and due to the absence of further studies concerning the secretion of rivaroxaban in breast milk, intake during pregnancy and the subsequent period of breastfeeding is strongly advised against.

Interactions

The presence of a hepatic metabolism and the involvement of two cytochromial enzymes highly modulable by other active ingredients, expose rivaroxaban to potential pharmacokinetic property disorders.

More precisely, CYP3A4 inhibitors such as ketoconazole, azole antifungals, HIV protease inhibitors and ederithromycin could lead to increased plasma concentrations of this active ingredient, enhancing both therapeutic and toxic effects, while CYP3A4 inducers, such as phenytoin, carbamazepine, phenobarbital or St. John's wort can reduce plasma concentrations by masking the effect.

Anticoagulants, non-steroidal anti-inflammatory drugs and antiplatelet agents, could instead modulate the anticoagulant capacity of the drug.

Contraindications XARELTO ® Rivaroxaban

XARELTO ® is contraindicated in the event of bleeding in progress, pathologies affecting the coagulation system, increased risk of bleeding, true hypersensitivity to the active ingredient or to its excipients, and during the entire period of pregnancy and lactation.

Undesirable effects - Side effects

Clinical studies have observed the incidence of side reactions in about 14% of patients undergoing XARELTO ® therapy. The most commonly observed reactions were in the gastro-intestinal tract, with diarrhea and vomiting and in the liver, with an increase of plasma transaminase concentrations.

The cases of hemorrhages or anemias were more rare, associated with symptoms of varying severity (dizziness, headache, amnesia, paresthesia, pallor, edema, asthenia, widespread pain) depending on the extent of the bleeding.