Factor xa inhibitors

1. FACTOR Xa INHIBITORS
DR. Govind Singh
PG- JR-1 ( (Respiratory Medicine)

2. FACTOR Xa INHIBITORS
 Rivaroxaban
 Apixaban
 Edoxaban
 OTHERS:-
 Betrixaban
 YM 150
 TAK442.

3. RIVAROXABAN:
Direct factor Xa inhibitor.
Bioavailability:- 80-100%.
Administration- Oral.
Pharmacokinetics:-
 Maximum effect-2hours.
 Half life is 5-9 hours.
 1/3rd Metabolized in Liver and gets excreted in feces.
 1/3rd is cleared as unchanged drug in Urine.

4. Dosage:-
 20mg daily.
 15mg Twice Daily for initial 21 days. (Acute venous thrombosis).
 10mg Daily for post surgical thromboprophylaxis.
Renal dosage:-
30-50ml CCL-15 mg Twice Daily.
15-30ml CCL- 10mg Twice Daily.
<15ml- contraindicated.

5. Precautions:-
 Should be taken with food to achieve maximum absorption.
 Avoid in pregnancy and lactating women.
 Avoid in renal and liver failure patients.
 Bleeding manifestations should be monitored frequently in case of
patients who are already in antiplatelets

6. Indications:-
 Non-Valvular Atrial Fibrillation.
 Deep Vein Thrombosis.
 Pulmonary Embolism.
Contraindications:-
 Renal & liver failure.
 Already in ketoconazole and ritonavir drugs.
 Rifampicin and Phenytoin can reduce plasma concentrations of drug

7. Available Brands:
1. Xarelto 10 mg- BAYER PHARMA (Rs.145 / tablet)
2.Rivaban 10 mg-Lupin(Rs 10/ tablet)
3.Rivaxa 10 mg- Abbott

8. APIXABAN
 Direct factor Xa inhibitor.
 Bioavailability:- 50%.
 Administration- Oral.
Pharmacokinetics:-
 Maximum effect:3-4hours.
 Half life is 9-14 hours.
 Metabolized in Liver and gets excreted in feces, urine and biliary
system

9. DOSAGE:-
 5mg Twice Daily.
 2.5mg Twice Daily, If:
 Age >80 years.
 Weight less than 60 kgs.
 Serum Creatinine >1.5mg/dl.
Precautions:-
 Should be taken with food to achieve maximum absorption.
 Avoid in pregnancy and lactating women.
 No dosage adjustment needed in patients with mild renal and hepatic
failure.
 Avoid in moderate to severe liver failure patients.

10. Indications:-
 Non-Valvular Atrial Fibrillation.
 Deep Vein Thrombosis.
 Pulmonary Embolism.
Adverse effects:-
 Bleeding manifestations.
Antidote- none.

11. AVAILABLE MEDICINE FOR APIXABAN
1. Eliquis (2.5/5 mg)- Pfizer
2. Apigat 2.5/5 mg- Natco Pharma

12. EDOXABAN
 Direct factor Xa inhibitor.
 Bioavailability:- 62%.
 Administration- Oral.
Pharmacokinetics:-
 Maximum effect: 1-2hours.
 Half life is 10 hours.
 Metabolized in Liver and gets excreted in feces, urine and
biliary system.

13. • Indications:-
 Non-Valvular Atrial Fibrillation.
 Deep Vein Thrombosis.
 Pulmonary Embolism.
• Adverse effects:-
 Bleeding manifestations.
 Antidote- None.

14. DOSAGE:-
 60mg Once Daily for Non-Valvular AF.
 30mg Once Daily, If:
 Age >80 years.
 Weight less than 60 kgs.
 Creatinine Clearance <15ml/min.

15. Precautions:-
 Should be taken with food to achieve maximum absorption.
 Avoid in pregnancy and lactating women.
 No dosage adjustment needed in patients with mild renal and hepatic
failure.
 Avoid in moderate to severe liver failure patients

17. TREATMENT OF COMPLICATIONS:
Andexanet alfa:-
 Recombinant modified human factor Xa.
 Developed as a direct factor Xa reversal agent.
 Showed restore of thrombin generation in phase 2 studies.
 Well tolerated.
 Currently in phase 3 clinical trials.

18. PER977(CIREPARANTAG):-
 STILL IN TRIALS.
 Rapidly reversed the effect of multiple anticoagulants

19. ARGATROBAN
 It is a direct thrombin inhibitor.
 Used in the management of heparin-induced thrombocytopenia (HIT),
which is a rare, life-threatening complication of heparin therapy.
 First introduced in Japan in 1990 for the treatment of peripheral
vascular diseases.
Mechanism of Action
 Argatroban is a synthetic compound based on the structure of L-
arginine. It is a direct thrombin inhibitor that binds reversibly to the
active site of thrombin and inhibits its downstream action.

20.  Argatroban is metabolized primarily by hydroxylation and
aromatization via cytochrome P450 enzymes and excreted mainly via
feces.
Administration
 Argatroban is available as an intravenous solution of 1 mg/ml.
 Heparin-induced thrombocytopenia: Discontinue heparin and obtain
baseline PTT. For adult patients, the recommended dose is 2
mcg/kg/min administered as a continuous intravenous infusion.

21. Monitoring
 In patients with HIT, PTT is commonly useful to monitor argatroban
therapy ,and the initial dosing should be adjusted to obtain a steady-
state PTT of 1.5 to 3 times baseline
 There is no Antidote to Reverse its actions.

22. THANK YOU