Drug Interaction:
Interaction with CYP3A4 inducers- The conomittant use rivaroxaban and strong CYP3A4 inducers e.g. rifampicin, carbamazepine, phenobarbital or St Johns wort may lead to reduced rivaroxaban plasma concentrations.
Strong CYP3A4 inducers should be co-administered with caution
Enoxaparin- Concomitant use of rivarxoban with enoxaparin results in- - a moderate additive effect on factor Xa activity - no effect on clotting tests compared with rivaroxaban alone - no effect on the pharmacokinetics of rivaroxaban NSAIDs , aspirin, and clopidogtrel- No alteration in pharmacokinetics or pharmcodynamics of rivaroxaban when given with - - Naproxen 500mg - Aspirin 500mg - Clopidogrel 300mg loading dose followed by 75mg maintenance dose Nevertheless, there may be a pronounced pharmacodynamic response in patients receiving naproxen.
A relevant increase in bleeding time was observed in a subset of patients receiving clopidogrel As with all anticoagulants care should be taken with patients on NSAIDs , aspirin, or platelet aggregation inhibitors because the mode of action of these drugs may lead to an increased risk of bleeding
Indication:
XARELTO (rivaroxaban) tablets, for oral use
Initial U.S. Approval: 2011
WARNING:
(A) PREMATURE DISCONTINUATION OF XARELTO
INCREASES THE RISK OF THROMBOTIC EVENTS,
and
(B) SPINAL/EPIDURAL HEMATOMA
See full prescribing information for complete boxed warning
(A) PREMATURE DISCONTINUATION OF XARELTO INCREASES
THE RISK OF THROMBOTIC EVENTS
Premature discontinuation of any oral anticoagulant, including XARELTO,
increases the risk of thrombotic events.
To reduce this risk, consider coverage with another anticoagulant if XARELTO
is discontinued for a reason other than pathological bleeding or completion of a
course of therapy
(B) SPINAL/EPIDURAL HEMATOMA
Epidural or spinal hematomas have occurred in patients treated with XARELTO
who are receiving neuraxial anesthesia or undergoing spinal
puncture. These hematomas may result in long-term or permanent paralysis
Monitor patients frequently for signs and symptoms of neurological impairment and
if observed, treat urgently. Consider the benefits and risks before neuraxial intervention
in patients who are or who need to be anticoagulated
Drug Name- Xarelto
Active Ingredient - Rivaroxaban
To reduce the risk of blood clots, deep vein thrombosis(DVT) and
pulmonary embolism (PE) following knee or hip replacement
surgery
Indication-
Reduce the risk of blood clots, deep vein thrombosis(DVT) and
pulmonary embolism (PE) following knee or hip replacement
surgery
Approved by FDA on 01-7-2011 (Ref- FDA approved List- 2011)
Rivaroxaban tablet 15/20mg ( Additional strength/indication)
Indication-
1.Prevention of deep vein thrombosis and for prevention of
recurrent DVT and pulmonary embolism
2. For the prevention of stroke and systemic embolism in patient
with non-valvular arterial fibrillation
Approved by FDA on 02-09-2014 (Ref- FDA approved List- 2014)
New Drugs Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
1.Rivaroxaban Film coated tablets 30-01-2010
10mg
For the prevention of Venous Thromboembolism in patients (VTE)
in adult patients undergoing Hip or knee replacement Surgery
2.Rivaroboxan Tablet 15/20mg 02-09-2014
Addtl. Strgth/Indcn
i. Treatment of Deep vein Thrombosis and for prevention of recurrent
DVT and Pulmonary Embolism
ii. For the Prevention of stroke and systemic embolism in patient with
Non-valvular arterial Fibrillation
Prevention of venous thromboembolic events
Adverse Reaction:
The most common adverse reaction (>5%) was bleeding.
Contra-Indications:
Rivaroxaban is contraindicated in the following groups- - patients with hypersensitity to the drug or exciepents - those with clinically significant active bleeding - patients with hepatic disease associated with coagulopathy and clinically relevent bleeding risk - pregnant or breast feeding women
Warnings/precautions-
Should be used with caution in patients with increased bleeding risk, including those with- - congenital or acquired bleeding disorders - uncontrolled severe arterial hypertension - active ulcerative gastrointestinal disease - vascular retinopathy - recent intracranial or intracerbral haemorrhage - intraspinal or intracerebral vascular abnormalities - recent brain, spinal, or ophthalmological surgery.
Dosages/ Overdosage Etc:
Indication-
1.Prevention of deep vein thrombosis and for prevention of
recurrent DVT and pulmonary embolism
2. For the prevention of stroke and systemic embolism in patient
with non-valvular arterial fibrillation
Prevention of venous thromboembolic events
INDICATIONS AND USAGE
XARELTOis a factor Xa inhibitor indicated: „h to reduce the risk of stroke and
systemic embolism in patients with nonvalvular atrial fibrillation
- for the treatment of deep vein thrombosis (DVT), pulmonary embolism (PE),
and for the reduction in the risk of recurrence of DVT and of PE
-for the prophylaxis of DVT, which may lead to PE in patients undergoing knee
or hip replacement surgery
DOSAGE AND ADMINISTRATION
Take 15 mg and 20 mg tablets with food; take 10 mg tablets with or without food
Nonvalvular Atrial Fibrillation:
For patients with CrCl >50 mL/min: 20 mg orally, once daily with the evening meal
For patients with CrCl 15 -50 mL/min: 15 mg orally, once daily with the evening meal
Treatment of DVT, PE, and Reduction in the Risk of Recurrence of DVT and of PE:
15 mg orally twice daily with food for the first 21 days for the initial treatment of
acute DVT or PE.
After the initial treatment period, 20 mg orally once daily with food for the remaining
treatment and the long-term reduction in the risk of recurrence of DVT and of PE.
Prophylaxis of DVT Following Hip or Knee Replacement Surgery: 10 mg orally,
once daily with or without food
DOSAGE FORMS AND STRENGTHS
Tablets:10 mg, 15 mg, and 20 mg
Patient Information:
PATIENT COUNSELING INFORMATION
. Instructions for Patient Use
1. Advise patients to take XARELTO only as directed.
2. Remind patients to not discontinue XARELTO without first talking to their healthcare
professional.
3. Advise patients with atrial fibrillation to take XARELTO once daily with the evening meal.
4. Advise patients with DVT and/or PE to take XARELTO 15 mg or 20 mg tablets with food
at approximately the same time every day
5. Advise patients who cannot swallow the tablet whole to crush XARELTO and combine
with a small amount of applesauce followed by food
6. For patients requiring an NG tube or gastric feeding tube, instruct the patient
or caregiver to crush the XARELTO tablet and mix it with a small amount of water
before administering via the tube
7. If a dose is missed, advise the patient to take XARELTO as soon as possible
on the same day and continue on the following day with their recommended
daily dose regimen.
Pharmacology/ Pharmacokinetics:
Pharmacology-
Rivaroxaban is a direct specific and highly selective inhibitor of Factor Xa , an enzyme at the pivotal point of coagulation cascade. Rivaroxaban inhibits both free and fibrin bound Factor Xa as well as Factor Xa in the prothrombinase complex. This is in contrast to the indirect Factor a of fondaparinux which inhibits Factor Xa activity by binding to and potentiating action of antithrombin, and is unable to inhibit prothrombinase -bound Factor Xa
Pharmacokinetics-
Rivaroxaban is rapidly absorbed following oral administration and the maximum plasma concentration Cmax is reached in 2-4 hours. Absolute bioavailability at a dose of 10mg is high, ( 80- 100%) . It exhibits a dose -proprotional plasma time profiles, with a mean terminal elimination half-life of 7-11 hours at steady state
Interaction with Food:
Can be administered with or without food with gastric pH having no efect on absorption
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Pregnancy Category C
There are no adequate or well-controlled studies of XARELTO in pregnant women,
and dosing for pregnant women has not been established.
XARELTO should be used during pregnancy only if the potential benefit justifies
he potential risk to mother and fetus.
2. Nursing Mothers
It is not known if rivaroxaban is excreted in human milk. Rivaroxaban and/or its
metabolites were excreted into the milk of rats. Because many drugs are
excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from rivaroxaban, a decision should be made
whether to discontinue nursing or discontinue XARELTO, taking into account
the importance of the drug to the mother.
3.Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
4. Geriatric Use
In clinical trials the efficacy of XARELTO in the elderly (65 years or older)
was similar to that seen in patients younger than 65 years. Both thrombotic
and bleeding event rates were higher in these older patients, but the
risk-benefit profile was favorable in all age groups
