Jamonline / 2(2); 2012 / 14–16 Sapna K et al

All rights reserved© 2011 www.jamonline.in 14

Review Article

Journal of Atoms and Molecules An International Online JournalAn International Online JournalAn International Online JournalAn International Online Journal ISSN ISSN ISSN ISSN –––– 2277 2277 2277 2277 –––– 1247124712471247

A REVIEW ARTICLE TO DEVELOP SUSTAIN RELEASE RIVAROX ABAN 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 Revised on: 10-04-2012 Accepted on: 20–04–2012

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 8–12 hours, but

factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible.

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

Factor Xa inhibitor with

oral bioavailability and rapid onset of action.

Inhibition of Factor Xa interrupts the intrinsic

and extrinsic pathway of the blood

coagulation cascade, inhibiting

both thrombin formation and development of

thrombi. Rivaroxaban does not inhibit

thrombin (activated Factor II), and no effects

on platelets have been demonstrated.[1]

* Corresponding author

Sapna K,

Email: sapna.koduri@gmail.com

Tel: +91 – 9177727127

Jamonline / 2(2); 2012 / 14–1

All rights reserved© 2011

Rivaroxaban has

predictable pharmacokinetics across a wide

spectrum of patients (age, gender, weight,

race) and has a flat dose response

eightfold dose range (5–40

trial data have shown that it allows

predictable anticoagulation with no need for

dose adjustments and routine coagulation

monitoring.[1] However, these trials have

excluded patients with liver disease and end

stage liver disease; therefore, the safety of

rivaroxaban in these populations is unknown

Chemistry

Rivaroxaban bears a

striking structural similarity to the

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

a known complication of long

use. Studies found that neither rivaroxaban

nor its metabolites have any antibiotic effec

against Gram-positive bacteria

mitochondrial toxicity, in vitro

the risk to be low, and not likely to be of

clinical consequence because rivaroxaban is

only meant (and approved) for short

Fig 1 Structure of Rivaroxaban

16

Rivaroxaban has

across a wide

um of patients (age, gender, weight,

dose response across an

40 mg).[6] Clinical

trial data have shown that it allows

with no need for

dose adjustments and routine coagulation

However, these trials have

excluded patients with liver disease and end-

disease; therefore, the safety of

rivaroxaban in these populations is unknown.

bears a

to the antibiotic

both drugs share the

derived core structure.

rivaroxaban was studied for any

possible antimicrobial effects and for the

mitochondrial toxicity, which is

a known complication of long-term linezolid

use. Studies found that neither rivaroxaban

nor its metabolites have any antibiotic effect

positive bacteria. As for

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-term use.

tructure of Rivaroxaban

Rivaroxaban dosages

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 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

orally, once daily with the evening meal.

Renal dose adjustments

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 exposur

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

rivaroxaban should discontinue the treatment.

Nonvalvular Atrial 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

situations in which renal function may

Sapna K et al

www.jamonline.in 15

ivaroxaban dosages

Usual Adult Dose for Deep Vein Thrombosis

Prophylaxis after Hip Replacement Surgery

Prevention of venous thromboembolism in

patients undergoing hip or knee replacement

10 mg orally once a day starting 6 to

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

nce daily with the evening meal.

enal dose adjustments

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 and

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

aban should discontinue the treatment.

Nonvalvular Atrial 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

cally indicated (i.e., more frequently in

situations in which renal function may

Jamonline / 2(2); 2012 / 14–16 Sapna K et al

All rights reserved© 2011 www.jamonline.in 16

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 (Child-

Pugh 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,

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

Characteristics". Bayer Schering Pharma AG.

2008.

"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.

"Bayer’s 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-

oxo-3- [4-(3-oxomorpholin-4-yl)phenyl]-1,3-

oxazolidin-5-yl}methyl)thiophene- 2-

carboxamide (BAY 59-7939): an oral, direct

factor Xa inhibitor". Journal of Medicinal

Chemistry 48 (19): 5900–8

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 replacement". Circulation 114 (22):

2374–81.

European Medicines Agency (2008). "CHP

Assessment Report for Xarelto ".