Apixaban 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 ≥1.5 mg/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: Warfarin should be discontinued, and Apixaban should be initiated once the international normalized ratio (INR) falls below 2.0.

Switching from Apixaban to warfarin: Apixaban can influence INR values, making INR measurements during combined use with warfarin unreliable for dose adjustment. If ongoing anticoagulation is required, stop Apixaban and initiate both a parenteral anticoagulant and warfarin at the time the next Apixaban dose would have been due. The parenteral anticoagulant should be discontinued once INR reaches the target range.

Switching between Apixaban and anticoagulants other than warfarin: Discontinue the current anticoagulant and start the alternative at the time of the next scheduled dose.

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

Apixaban is contraindicated in patients with the following conditions: active pathological bleeding and severe hypersensitivity reactions to Apixaban (e.g., anaphylaxis).

Apixaban may cause skin rash or severe allergic reactions in some patients.

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: The safety and effectiveness of apixaban during labor and delivery have not been studied in clinical trials. Consider the risks of bleeding and stroke when 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 Apixaban Discontinuing apixaban in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from apixaban to warfarin in clinical trials in patients with nonvalvular atrial fibrillation. If apixaban 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 apixaban in these patients, dosing recommendations cannot be provided. Apixaban 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 apixaban, >69% were 65 and older, and >31% were 75 and older. The effects of apixaban on the risk of stroke and major bleeding compared to warfarin were maintained in geriatric subjects.

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