CopiXa Tablet

CopiXa is a factor Xa inhibitor indicated:

• To reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
• For the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE), in patients who have undergone hip or knee replacement surgery
• For the treatment of DVT and PE, and for the reduction in the risk of recurrent DVT and PE following initial therapy

Apixaban acts by inhibiting coagulation, and thus prevents development of blood clots. As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT), INR, and activated partial thromboplastin time (aPTT). Changes observed in these clotting tests at the expected therapeutic dose, however, are small, subject to a high degree of variability, and not useful in monitoring the anticoagulation effect of apixaban.

Recommended Dose: The recommended dose of Apixaban for most patients is 5 mg taken orally twice daily.

Dosage Adjustments: The recommended dose of Apixaban is 2.5 mg twice daily in patients with any 2 of the following characteristics: age ≥80 years, body weight ≤60 kg, serum creatinine ≥1.5mg/dl.

CYP3A4 and P-gp inhibitors: When Apixaban is coadministered with drugs that are strong dual inhibitors of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin) the recommended dose is 2.5 mg twice daily.

Missed Dose: If a dose of Apixaban is not taken at the scheduled time, the dose should be taken as soon as possible on the same day and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose.

Discontinuation for Surgery and Other Interventions: Apixaban should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. Apixaban should be discontinued at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding or where the bleeding would be non-critical in location and easily controlled.

Switching from or to Apixaban: Switching from warfarin to Apixaban: Warfarin should be discontinued and Apixaban started when the international normalized ratio (INR) is below 2.0.

Switching from Apixaban to warfarin: Apixaban affects INR, so that INR measurements during co-administration with warfarin may not be useful for determining the appropriate dose of warfarin. If continuous anticoagulation is necessary, discontinue Apixaban and begin both a parenteral anticoagulant and warfarin at the time the next dose of Apixaban would have been taken, discontinuing the parenteral anticoagulant when INR reaches an acceptable range.

Switching between Apixaban and anticoagulants other than warfarin: Discontinue one being taken and begin the other at the next scheduled dose.

CopiXa is a substrate of both CYP3A4 and P-gp. Inhibitors of CYP3A4 and P-gp increase exposure to CopiXa and increase the risk of bleeding. Inducers of CYP3A4 and P-gp decrease exposure to CopiXa and increase the risk of stroke.

Apixaban is contraindicated in patients with the following conditions: Active pathological bleeding. Severe hypersensitivity reaction to Apixaban (i.e. anaphylactic reactions).

CopiXa can cause a skin rash or severe allergic reaction.

Pregnancy: There are no adequate and well-controlled studies of Apixaban in pregnant women. Treatment is likely to increase the risk of hemorrhage during pregnancy and delivery. Apixaban should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus.

Labor and Delivery: Safety and effectiveness of Apixaban during labor and delivery have not been studied in clinical trials. Consider the risks of bleeding and of stroke in using Apixaban in this condition.

Nursing Mothers: It is unknown whether Apixaban or its metabolites are excreted in human milk. Women should be instructed either to discontinue breastfeeding or to discontinue Apixaban therapy, taking into account the importance of the drug to the mother.

Increased Risk of Stroke with Discontinuation of CopiXa Discontinuing CopiXa in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from CopiXa to warfarin in clinical trials in patients with nonvalvular atrial fibrillation. If CopiXa must be discontinued for a reason other than pathological bleeding, consider coverage with another anticoagulant.

Hepatic Impairment: No dose adjustment is required in patients with mild hepatic impairment. Because patients with moderate hepatic impairment may have intrinsic coagulation abnormalities and there is limited clinical experience with CopiXa in these patients, dosing recommendations cannot be provided CopiXa is not recommended in patients with severe hepatic impairment

Renal Impairment: The dosing adjustment for moderate renal impairment is described above. No data inform use in patients with creatinine clearance <15 ml/min or on dialysis.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Of the total subjects in clinical studies of CopiXa, >69% were 65 and older, and >31% were 75 and older. The effects of CopiXa on the risk of stroke and major bleeding compared to warfarin were maintained in geriatric subjects.

There is no antidote to CopiXa. Overdose of CopiXa increases the risk of bleeding. Activated charcoal may be useful in the management of CopiXa overdose.

Anti-coagulants, Anti-platelet drugs, Fibrinolytics (Thrombolytics), Oral Anti-coagulants

Keep in a dry place and store below 30°C. Protect from light and keep out of the reach of children.