Jamonline / 2(2); 2012 / 1416 Review Article

Sapna K et al

Journal of Atoms and Molecules

An International Online Journal
ISSN 2277 1247

A REVIEW ARTICLE TO DEVELOP SUSTAIN RELEASE RIVAROXABAN FORMULATION K.Sapna*, G. Sudhakar, Dr. R. Santosh Kumar Srinivasarao College of Pharmacy, Behind Cricket stadium, P.M Palem, Vishakhapatnam, A.P, India. Received on: 19-03-2012 Introduction: Rivaroxaban is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto.[1] In the United States, it is marketed by Janssen Pharmaceutical.[2] It is the first available orally active direct factor Xa inhibitor. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs four hours after a dose. The effects last 812 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible. Revised on: 10-04-2012 Accepted on: 20042012

Mechanism Rivaroxaban is an oxazolidinone derivative optimized for inhibiting both free Factor Xa and Factor Xa bound in the prothrombinase complex.[5] It is a highly selective direct * Corresponding author Sapna K, Email: sapna.koduri@gmail.com Tel: +91 9177727127 Factor Xa inhibitor with

oral bioavailability and rapid onset of action. Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway cascade, of the blood inhibiting

coagulation

both thrombin formation and development of thrombi. Rivaroxaban does not inhibit

thrombin (activated Factor II), and no effects on platelets have been demonstrated.[1]

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Jamonline / 2(2); 2012 / 141 16 Rivaroxaban has Rivaroxaban dosages ivaroxaban

Sapna K et al

predictable pharmacokinetics across a wide spectrum of patients (age, gender, weight, um race) and has a flat dose response across an eightfold dose range (540 mg).[6] Clinical 40 trial data have shown that it allows

Usual Adult Dose for Deep Vein Thrombosis Prophylaxis after Hip Replacement Surgery Prevention of venous thromboembolism in patients undergoing hip or knee replacement surgery.10 mg orally once a day starting 6 to 10 10 hours after surgery. Duration of therapy is 35 days for hip replacement surgery and 12 days for knee replacement surgery. Usual Adult Dose for Atrial Fibrillation. Nonvalvular Atrial Fibrillation is 20 mg orally, once daily with the evening meal. nce

predictable anticoagulation with no need for dose adjustments and routine coagulation monitoring.[1] However, these trials have

excluded patients with liver disease and end endstage liver disease; therefore, the safety of rivaroxaban in these populations is unknown unknown. Chemistry Rivaroxaban bears a

Renal dose adjustments enal Prophylaxis of Deep Vein Thrombosis: Avoid the use of rivaroxaban in patients with severe renal impairment (creatinine clearance less than 30 mL/min) due to an expected increase in rivaroxaban exposure exposur and

striking structural similarity to the antibiotic linezolid both drugs share the

same oxazolidinone derived core structure. Accordingly, rivaroxaban was studied for any possible antimicrobial effects and for the possibility of mitochondrial toxicity which is toxicity, a known complication of long long-term linezolid use. Studies found that neither rivaroxaban nor its metabolites have any antibiotic effec effect against Gram-positive positive bacteria. bacteria As for

pharmacodynamic effects in this patient population. Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with moderate renal impairment (CrCl 30 to 49 mL/min). Patients who develop acute renal failure while on

mitochondrial toxicity, in vitro studies found the risk to be low, and not likely to be of clinical consequence because rivaroxaban is only meant (and approved) for short short-term use.

rivaroxaban should discontinue the treatment. aban Nonvalvular Atrial Fibrillation Fibrillation: For patients with CrCl 15 to 50 mL/min: 15 mg orally, once daily with the evening meal. Avoid use in patients with CrCl less than 15 mL/min. Periodically assess renal function as clinically indicated (i.e., more frequently in cally

Fig 1 Structure of Rivaroxaban tructure All rights reserved 2011

situations in which renal function may

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Jamonline / 2(2); 2012 / 1416 decline) and adjust therapy accordingly. Discontinue in patients who develop acute renal failure while on rivaroxaban. Liver Dose Adjustments Avoid use in patients with moderate (ChildPugh B) or severe Child-Pugh C) liver dysfunction or any hepatic disease associated with coagulopathy. Dose Adjustments Concomitant use of rivaroxaban with drugs that are combined P-gp and strong CYP450 3A4 inducers (e.g., carbamazepine,

Sapna K et al "FDA Approves XARELTO (rivaroxaban tablets) to Help Prevent Deep Vein

Thrombosis in Patients Undergoing Knee or Hip Replacement Surgery" (Press

release). Janssen Pharmaceutica. "Bayer's Xarelto Approved in Canada" (Press release). Bayer. "Bayers Novel Anticoagulant Xarelto now also Approved in the EU" .Bayer. Roehrig S, Straub A, Pohlmann J, et

al. (September 2005). "Discovery of the novel antithrombotic agent 5-chloro-N-({(5S)-2-

phenytoin, rifampin, St. John's wort) should be avoided. A rivaroxaban dose increase to 20 should be considered if these drugs must be coadministered. The 20 mg dose should be taken with food. Precautions Safety and effectiveness have not been established in pediatric patients. Conclusion From above information Rivaroxaban is low dosage and immediate release drugs are available. In order to our academic research project we are planning a new formulation with natural polymer for sustain release. References "Xarelto: Summary of Product

oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3oxazolidin-5-yl}methyl)thiophene2-

carboxamide (BAY 59-7939): an oral, direct factor Xa inhibitor". Journal of Medicinal Chemistry 48 (19): 59008 Eriksson BI, Borris LC, Dahl OE, et

al. (November 2006). "A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip 237481. European Medicines Agency (2008). "CHP Assessment Report for Xarelto ". replacement". Circulation 114 (22):

Characteristics". Bayer Schering Pharma AG. 2008.

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