Rivaroxaban

5 mg twice daily , plus aspirin (75 to 100 mg) once daily. When starting therapy after asuccessful lower extremityrevascularization procedure,initiate once hemostasis has beenestablished. Take with or without food * Calculate CrCl based on actual weight.

6 )] . 4 )] . 5 in pediatric patients to avoid periods of inadequate anticoagulation.

Switching from Rivaroxaban Tablets to Warfarin - Adults:

No clinical trial data are available to guide converting patients from rivaroxaban tablets to warfarin. Rivaroxaban tablets affects INR, so INR measurements made during coadministration with warfarin may not be useful for determining the appropriate dose of warfarin.

One approach is to discontinue rivaroxaban tablets and begin both a parenteral anticoagulant and warfarin at the time the next dose of rivaroxaban tablets would have been taken. Once rivaroxaban tablets are discontinued, INR testing may be done reliably 24 hours after the last dose.

4 )]. , low molecular weight heparin or non-warfarin oral anticoagulant) and omit administration of the other anticoagulant. For unfractionated heparin being administered by continuous infusion, stop the infusion and start rivaroxaban tablets at the same time.

2)]. In deciding whether a procedure should be delayed until 24 hours after the last dose of rivaroxaban tablets, the increased risk of bleeding should be weighed against the urgency of intervention. 1 )]. If oral medication cannot be taken during or after surgical intervention, consider administering a parenteral anticoagulant.

5 mg rivaroxaban tablet dose as recommended at the next scheduled time. On the following day, the patient should continue with their regular regimen. 6 Administration Options For adult patients who are unable to swallow whole tablets, rivaroxaban tablets (all strengths) may be crushed and mixed with applesauce immediately prior to use and administered orally.

3 )]. Administration of rivaroxaban tablets via nasogastric (NG) tube or gastric feeding tube : After confirming gastric placement of the tube, rivaroxaban tablets may be crushed and suspended in 50 mL of water and administered via an NG tube or gastric feeding tube.

Since rivaroxaban absorption is dependent on the site of drug release, avoid administration of rivaroxaban tablets distal to the stomach which can result in reduced absorption and thereby, reduced drug exposure. 3 )]. Crushed rivaroxaban tablets (all strengths) are stable in water and in applesauce for up to 4 hours.

3 )] The most common adverse reaction (>5%) in adult patients wasbleeding. 1 ) The most common adverse reactions (>10%) in pediatric patients were bleeding, cough, vomiting, and gastroenteritis. 1 ) To report SUSPECTED ADVERSE REACTIONS, contact Dr.

Reddy’s Laboratories, Inc. gov/medwatch. 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

During clinical development for the approved indications, 34,947 adult patients were exposed to rivaroxaban. 2 )]. 5 mg twice daily vs. 2% for placebo on background therapy for all patients with aspirin 100 mg once daily. The incidences of important bleeding events in the CAD and PAD populations in COMPASS were similar.

Table 10 shows the number of patients experiencing various types of major bleeding events in the COMPASS trial.

Table 10:

Major Bleeding Events in COMPASS - On Treatment Plus 2 Days* Parameter Rivaroxaban † N=9,134 n (%/year) Placebo † N=9,107 n (%/year) Rivaroxaban vs. 4) * Major bleeding events within each subcategory were counted once per patient, but patients may have contributed events to multiple subcategories.

These events occurred during treatment or within 2 days of stopping treatment in the safety analysis set in COMPASS patients. 5 mg twice daily or placebo. All patients received background therapy with aspirin 100 mg once daily. ‡ Defined as i) fatal bleeding, or ii) symptomatic bleeding in a critical area or organ, such as intraarticular, intramuscular with compartment syndrome, intraspinal, intracranial, intraocular, respiratory, pericardial, liver, pancreas, retroperitoneal, adrenal gland or kidney; or iii) bleeding into the surgical site requiring reoperation, or iv) bleeding leading to hospitalization.

5 WARNINGS AND PRECAUTIONS Risk of bleeding: Rivaroxaban can cause serious and fatal bleeding. 2 ) Pregnancy-related hemorrhage: Use rivaroxaban tablets with caution in pregnant women due to the potential for obstetric hemorrhage and/or emergent delivery.

8) Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome: Rivaroxaban use not recommended. 1 Increased Risk of Thrombotic Events after Premature Discontinuation Premature discontinuation of any oral anticoagulant, including rivaroxaban, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events.

An increased rate of stroke was observed during the transition from rivaroxaban to warfarin in clinical trials in atrial fibrillation patients. 3 , 2. 1 )]. 2 Risk of Bleeding Rivaroxaban increases the risk of bleeding, including in any organ, and can cause serious or fatal bleeding.

In deciding whether to prescribe rivaroxaban tablets to patients at increased risk of bleeding, the risk of thrombotic events should be weighed against the risk of bleeding. Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement.

Discontinue rivaroxaban tablets in patients with active pathological hemorrhage. The terminal elimination half-life of rivaroxaban is 5 to 9 hours in healthy subjects aged 20 to 45 years. Concomitant use of other drugs that impair hemostasis increases the risk of bleeding.

4 )], selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors. 2 )]. Reversal of Anticoagulant Effect A specific agent to reverse the anti-factor Xa activity of rivaroxaban is not available. 3 )]. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban.

Use of procoagulant reversal agents, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa, may be considered but has not been evaluated in clinical efficacy and safety studies.

2 )] Active pathological bleeding ( 4 ) Severe hypersensitivity reaction to rivaroxaban tablets ( 4 )