Rivoxan

Rivaroxaban.

Each film coated tablet contains Rivaroxaban 10 mg, 15 mg or 20 mg.

Pharmacodynamics: Rivaroxaban inhibits platelet activation and fibrin clot formation via direct, selective and reversible inhibition of factor Xa (FXa).
Pharmacokinetics: Absorption: Rapid.
Bioavailability: Absolute bioavailability: 10 mg dose: ~80% to 100%;
20 mg dose: ~66% (fasting; increased with food).
Time to peak, plasma: 2 to 4 hours.
Distribution: Vdss: ~50 L.
Protein binding: ~92% to 95% (primarily to albumin).
Metabolism: Hepatic via CYP3A4/5 and CYP2J2.
Excretion: Urine [66% primarily via active tubular secretion (~36% as unchanged drug; 30% as inactive metabolites)]; feces (28% [7% as unchanged drug; 21% as inactive metabolites]).
Half-life elimination: Terminal: 5 to 9 hours; Elderly: 11 to 13 hours.

RIVOXAN 10: Prevention of venous thromboembolism (VTE) in patients undergoing orthopedic surgery of the lower limbs.
RIVOXAN 15 and RIVOXAN 20: Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; Treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism (PE); Treatment of pulmonary embolism (PE) and prevention of recurrent of PE and DVT.

RIVOXAN 10: Usual dose: Prevention of venous thromboembolism (VTE) in patients undergoing orthopedic surgery of the lower limbs: Knee replacement: Oral: 10 mg once daily; 6 to 10 hours postoperatively, recommended total duration of therapy: 14 days.
Hip replacement: Oral: 10 mg once daily; 6 to 10 hours postoperatively, recommended total duration of therapy: 35 days.
Special population: Geriatric: Refer to adult dosing (usual dose).
Renal Impairment: Mild to moderate renal impairment: No dosage adjustment necessary.
Severe renal impairment: Avoid use.
Hepatic Impairment: Mild impairment (Child-Pugh class A): There are no dosage adjustment provided.
Limited data indicates pharmacokinetics and pharmacodynamics response were similar to healthy subjects.
Moderate to severe impairment (Child-Pugh class B or C) and any hepatic disease associated with coagulopathy: Avoid use.
Mode of administration: Dose ≤ 10 mg/day may be administered without regard to meals.
For nasogastric/gastric feeding tube administration, the tablets may be crushed and mixed in 50 mL of water, administer the suspension with 4 hours of preparation. Ten mg tablet may be administered without regards to food.
Patients receiving once-daily dosing who miss a dose should take a dose as soon as possible on the same day; resume therapy the following day as previously taken.
RIVOXAN 15 and RIVOXAN 20: Usual dose: Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation: Oral: 20 mg once daily with the evening meal.
The recommended maximum daily dose of 20 mg.
Treatment of DVT and PE: Oral: Initial: 15 mg twice daily with food for 21 days followed by 20 mg once daily with food.
The recommended maximum daily dose of 30 mg during the first 3 weeks of treatment.
In the following treatment phase the recommended maximum daily dose is 20 mg.
Prevention of recurrent of DVT and PE: Oral: 20 mg once daily with food.
Special population: Geriatric: Refer to adult dosing (usual dose).
Renal Impairment: For Nonvalvular atrial fibrillation: CrCl > 50 mL/minute: No dosage adjustment necessary.
CrCl 15 to 50 mL/minute: 15 mg once daily with the evening meal; discontinue use in patients who develop acute renal failure. Some recommend to avoid use in patients with CrCl < 30 mL/minute.
CrCl < 15 mL/minute: discontinue use in patients who develop acute renal failure. Some recommend to avoid use in patients with CrCl < 30 mL/minute.
For Treatment of DVT and PE and prevention of recurrent DVT and PE: CrCl ≥ 30 mL/minute: No dosage adjustment necessary.
CrCl < 30 mL/minute: Avoid use.
Hepatic Impairment: Mild impairment (Child-Pugh class A): There are no dosage adjustment provided.
Limited data indicates pharmacokinetics and pharmacodynamics response were similar to healthy subjects.
Moderate to severe impairment (Child-Pugh class B or C) and any hepatic disease associated with coagulopathy: Avoid use.
Mode of administration: Administer doses ≥ 15 mg/day with food.
For nasogastric/gastric feeding tube administration, the tablets may be crushed and mixed in 50 mL of water, administer the suspension with 4 hours of preparation and follow administration of 15 mg and 20 mg tablets immediately with enteral feeding.
Patients receiving 15 mg twice daily dosing who miss a dose should take a dose immediately to ensure 30 mg of rivaroxaban is administered per day (two 15 mg tablets may be taken together); resume therapy the following day as previously taken.
Patients receiving once-daily dosing who miss a dose should take a dose as soon as possible on the same day; resume therapy the following day as previously taken.
Conversion: Conversion from warfarin: Discontinue warfarin and initial rivaroxaban as soon as INR falls to < 3.0.
Conversion to warfarin: Discontinue rivaroxaban and initiate both warfarin and a parenteral anticoagulant at the time the next dose of rivaroxaban would have been taken or continue rivaroxaban concomitantly with warfarin until INR ≥ 2 and then discontinue rivaroxaban.
Conversion from continuous infusion unfractionated heparin: Initiate rivaroxaban at the time of the heparin discontinuation.
Conversion to continuous infusion unfractionated heparin: Discontinue rivaroxaban and initiate continuous infusion unfractionated heparin at the time the next dose of rivaroxaban would have been taken.
Conversion from anticoagulants (other than warfarin and continuous infusion unfractionated heparin): Discontinue current anticoagulant and initiate rivaroxaban ≤ 2 hours prior to the next regularly scheduled evening dose of the discontinued anticoagulant.
Conversion to other anticoagulants (other than warfarin): Discontinue rivaroxaban and initiate the anticoagulant at the time the next dose of rivaroxaban would have been taken.

Overdose: The main anticipated effect of rivaroxaban in overdose is hemorrhage; however, in several cases of significant overdose with rivaroxaban, bleeding did not occur.
Mild to moderate toxicity: Treatment is symptomatic and supportive. Monitor for evidence of bleeding.
Severe toxicity: Treatment is symptomatic and supportive. An antidote (ie, coagulation factor Xa) has been developed and may be indicated in patients that require reversal of anticoagulation following a clinically significant rivaroxaban exposure. Transfusion of packed red cell and fresh frozen plasma may be indicated in patients with severe bleeding.
Consider activated charcoal after a recent potentially toxic ingestion and if the patients are able to maintain their airway or if the airway is protected.

Contraindicated in patients with hypersensitivity to rivaroxaban or any component of the formulation.
Contraindicated in patients with clinically significant active bleeding (e.g., intracranial bleeding, gastrointestinal bleeding).
Contraindicated in patients with hepatic disease which is associated with coagulopathy leading to clinically relevant bleeding risk.
Safety and efficacy of rivaroxaban have not been established in pregnant women. Animal data show that rivaroxaban crosses the placental barrier. Therefore use of rivaroxaban is contraindicated throughout pregnancy.
Safety and efficacy of rivaroxaban have not been established in nursing mothers. Animal data indicate that rivaroxaban is secreted into breast milk. Therefore rivaroxaban may only be administered after breastfeeding is discontinued.

Most common complication is bleeding; major hemorrhages (eg. Intracranial, GI, retinal, epidural hematoma, adrenal bleeding) have been reported. Monitor for signs and symptoms of bleeding.
Spinal or epidural hematomas may occur with neuraxial anesthesia (epidural or spinal anesthesia) or spinal puncture in patients who are anticoagulated; may result in long-term or permanent paralysis.
As with any oral anticoagulant in the absence of adequate alternative anticoagulation, an increased risk of thrombotic events (including stroke) may occur with premature discontinuation of rivaroxaban. Consider the addition of alternative anticoagulant therapy when discontinuing rivaroxaban for reasons other than pathological bleeding or completion of a course of therapy.
Avoid use in patients with moderate to severe hepatic impairment (Child-Pugh classes B and C) or in patients with any hepatic disease associated with coagulopathy.
Use with caution in patients with moderate renal impairment (CrCl 30 to 50 mL/minute) when used for postoperative thromboprophylaxis, including patients receiving concomitant drug therapy that may increase rivaroxaban systemic exposure and those with deteriorating renal function.
Discontinue rivaroxaban at least 24 hours prior to surgery/invasive procedures. Some have recommended to discontinue rivaroxaban 3 days prior to a procedure in patients with a CrCl ≥ 50 mL/minute or 5 days prior in patients with a CrCl < 50 mL/minute.
Use in the Elderly: Use with caution in the elderly.

Pregnancy Risk Factor C.
Adverse events have been observed in animal reproduction studies. Based on ex-vivo data, rivaroxaban crosses the placenta. Information related to the use of rivaroxaban during pregnancy and postpartum is limited. Data are insufficient to evaluate the safety of oral factor Xa inhibitors during pregnancy; use during pregnancy should be avoided. Use may increases the risk of pregnancy related hemorrhage.
Safety and efficacy of rivaroxaban have not been established in nursing mothers. In rats rivaroxaban is secrete into breast milk. Therefore rivaroxaban may only be administered after breastfeeding is discontinued.

Central nervous system: Fatigue, syncope.
Dermatologic: Pruritus, skin blister, wound secretion.
Gastrointestinal: Abdominal pain, dyspepsia, nausea, toothache.
Genitourinary: Urinary tract infection.
Hematologic & oncologic: Hemorrhage, pulmonary hemorrhage.
Hepatic: Increased serum transaminases.
Neuromuscular & skeletal: Back pain, limb pain, muscle spasm, osteoarthritis.
Respiratory: Oropharyngeal pain, sinusitis.
Rare but important or life-threatening: Agranulocytosis, cholestasis, decreased hemoglobin, dysuria, ecchymoses, epidural hematoma, gastrointestinal hemorrhage, hemiparesis, hemophthalmos, hepatitis, hypermenorrhea, hypersensitivity, hypotension, increased amylase, increased blood urea nitrogen, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum creatinine, increased serum lipase, intracranial hemorrhage, jaundice, retroperitoneal hemorrhage, Stevens-Johnson syndrome, subdural hematoma, tachycardia, thrombocytopenia.

Rivaroxaban is a substrate of BCRP, CYP2J2 (minor), CYP3A4 (major), P-glycoprotein.
Concurrent use of rivaroxaban and ketoconazole (systemic), clarithromycin, ritonavir, telaprevir, indinavir, lopinavir, idelalisib, conivaptan, cobicistat, darunavir, itraconazole, atazanavir may result in increased rivaroxaban exposure.
Concurrent use of rivaroxaban and rifampin, nevirapine, primidone, carbamazepine, phenytoin, St. John's wort may result in reduced rivaroxaban plasma concentrations.
Concurrent use of rivaroxaban and warfarin, enoxaparin, fondaparinux, acenocoumarol, dalteparin, phenprocoumon, dabigatran etexilate, argatroban, serotonin norepinephrine reuptake inhibitors and SSRIs, lepirudin, heparin, tinzaparin, bivalirudin, Protein C, desirudin, danaparoid, drotrecogin alfa, phenindione, idelalisib, conivaptan may result in an increased risk of bleeding.
Concurrent use of rivaroxaban and oxcarbazepine may result in decreased rivaroxaban efficacy and possible subtherapeutic anticoagulation which could lead to a thrombotic events.

Store below 30°C.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AF01 - rivaroxaban ; Belongs to the class of direct factor Xa inhibitors. Used in the treatment of thrombosis.

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