TOC   |  DRUGS  |   ACP Drug Resource | Medline Drugs Info Site 

Anticoagulation Treatment       See below  Antithrombolytic Agents                   See Cardiac meds  

Heparin | Fondaparinux (Arixtra) | Enoxaparin (Lovenox) | Dalteparin (Fragmin) | Tinzaparin (Innohep) | Coumadin (Warfarin)  | Dabigatran (Pradaxa) |  Rivaroxaban (Xarelto)Apixaban (Eliquis)  | Melagatran (Ximelagaran)  || Antithrombolytic Agents    
Fondaparinux (Arixtra)  
  1. For DVT/PE Treatment:  for at least 5 days until warfarin/Coumadin Rx INR>2 (Coumadine/warfarin may be started within 72 hr of fondaparinux Rx.)
    Weight <50 kg: 5 mg once daily
    Weight 50-100 kg: 7.5 mg once daiy subc  
    Weight >100 kg: 10 mg once daily
  2. For Peri-operative DVT Prophylaxis:
    * 2.5 mg subc daily for 5-9 days, starting 6-8 hr after surfery,
    following abdominal surgery or knee/hip replacement or continuing for 24 days following hip fracture surgery.


Enoxaparin (Lovenox)  Low molecular weight heparin

  1. For DVT/PE Treatment
    Outpatient: 1 mg/kg q12h subc;
    Inpatient:   1 mg/kg q12h or 1.5 mg/kg every 24h  subc for 5-17 days

    or until therapeutic anticoagulation with warfarin/Coumadin is achieved (INR>2 for 2 consecutive days) .
    Warfarin should be started within 72 hr;  
     

  2. For DVT Prophylaxis:
    • For Medical patients with acute illness DVT Prophylaxis: 40 mg subc once daily   
    • For Perioperative DVT Prophylaxis:  (For Renal Impaired CCr<30 ml/min: Enoxaparin/Lovenox 30 mg once daily subc) 
      • Knee replacement surgery: 30 mg q12h subc starting 12-24 hr after surgery.
      • Hip replacement surgery: 40 mg subc 12 hr before surgery, then once daily, may be continued for up to 3 weeks after discharge.
      • Abdominal surgery: 40 mg 2 hr prior to surgery, then daily post op for 7-12 days or until ambulatory (up to 14 days)

  3. For Unstable Angina/Non-Q-wave MI (Acute Coronary Syndrome):  1 mg/kg q12h subc for 2-8 days.
    (For Renal Impaired CCr<30 ml/min: 1 mg/kg once daily subc)

    


Dalteparin (Fragmin) - monitor anti-Xa levels (target 0.5 - 1.5 IU/ml)

  • For Perioperative DVT Prophylaxis:
    • Average-risk Abdominal Surgery: 2500 IU 1-2 hr before surgery, then once daily for 5-10 days.
    • High-risk Abdominal Surgery: 5000 IU evening before surgery, then once daily for 5-10 days OR 2500 IU 1-2 hr before surgery, another 2500 IU 12 hours later, then 5000 IU daily for 5-10 days
    • Hip Replacement Surgery:    5000 IU evening before surgery, then once daily for 5-10 days OR 2500 IU 2 hr before surgery, another 2500 IU same evening of the day of surgery (~ 6 hr after first dose), then 5000 IU once daily for 5-10 days.
  • For Angina/Non-Q-wave MI: 120 IU/kg (not to exceed 10,000 IU) subc q12h with concurrent aspirin.



Tinzaparin (Innohep)  175 anti-Xa IU/kg once daily subc for at least 6 days &
until therapeutic anticoagulation is achieved with warfarin (Coumadin) (INR >2 for 2 consecutive days)   
- (20,000 IU/mL)


Heparin Rx  IV   (PTT 1.5 - 2.3 x control)
- Standard dose: star with 5,000 units  (or 75 u/kg) IV bolus, then IV infusion 800-1,000 u /h (13 u/kg/h) to achieve PTT of 1.5-2x
- Weight-based dose: 80 u/kg IV bolus, then 18 u/kg/h (Ref: Ann IM Nov. 1, 1993:119:875 Raschke RA)
- Check PTT 6 hours after each dose change.
- To reverse heparin effect: Protamine or fresh frozen plasma Rx


    

Heparin | Fondaparinux (Arixtra) | Enoxaparin (Lovenox) | Dalteparin (Fragmin) | Tinzaparin (Innohep) | Coumadin (Warfarin)  | Dabigatran (Pradaxa) |  Rivaroxaban (Xarelto)Apixaban (Eliquis)  | Melagatran (Ximelagaran)  || Antithrombolytic Agents    
 Coumadin (Warfarin)
  • 2-10 mg/day PO
  • Keep Protime INR 2.0 - 3.0 for DVT Rx & prophylaxis. PE Rx, atrial fibrillation, tissue heart valves, cardiomyopathy patients;  
  • Keep Protime INR 2.5 - 3.5 INR for mechanical prosthetic valves, post MI).

Bleeding adverse events will rise from 2/100 patient-years with INR of 2.5-4.9 to
4.8/100 patient-years with an INR of 5.0-5.5, to
75/100 patient-years when INR is 6.5 or over.  (NEJM 1995;333:11 - Cannegieter SC, etc.)

To reverse coumadin effect:  

  • Fresh frozen plasma Rx (quick reversal of the excessive anticoagulation in bleeding pts, but risk of potential infectious complications) 
  • Vit. K (Mephyton) 1-2.5 mg PO if  INR is 5-9 in pts without bleeding; 3-5 mg PO if  INR is > 9.
    (Chest 1998;114 Suppl: 445S - Hirsh J, etc.)
  • Vit. K1 (AquaMephyton/ Phytonadione) 1 mg IV is effective to correct the INR from baseline of 8.0 to 4.6 in 8 hours,  to 3.1 in 24 hours.  While effective, IV route is associated with a small risk of serious anaphylactic reactions. Subcutaneous route 1mg is not as effective as IV route, it changed INR from baseline of 8.5 to 8.0 in 8 hours, and to 5.0 in 24 hours.  (Arch IM Dec. 13, 1999;159:2721 - Guna Raj, etc.)
  • Reversal of Warfarin-Induced Excessive Anticoagulation with Recombinant Human Factor VIIa Concentrate
    Critically prolonged INR and bleeding complications were treated successively and rapidly in all patients, regardless of rFVIIa dose (range, 15 to 90 g/kg of body weight). Indications for use of rFVIIa included an INR greater than 10 in high-risk persons (n = 5), clinical hemorrhage (n = 4), and diagnostic or therapeutic procedures (n = 4)
    Conclusion:  Safe, rapid, and effective administration of rFVIIa corrects critically prolonged INRs and can avert or reverse bleeding associated with warfarin anticoagulation.     Ann Intern Med. Dec. 3, 2002;137:884-888.


*  Dabigatran (Pradaxa), administered at a dose of 150 mg PO twice daily  
For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring.  NEJM December 6, 2009

Dabigatran etexilate is an orally available, potent, direct inhibitor of thrombin. It is rapidly converted by ubiquitous esterases to the active drug, is administered in fixed doses without the need for coagulation monitoring, is excreted by the kidney, and has a half-life of 12 to 17 hours.  Dabigatran has similar efficacy and safety to enoxaparin for the prevention of venous thromboembolism in patients who have had elective hip or knee arthroplasty.  Recently, dabigatran, as compared with warfarin, was shown to have superior safety with equivalent efficacy (when it was administered at a dose of 110 mg twice daily), or superior efficacy with similar safety (when it was administered at a dose of 150 mg twice daily), for the prevention of stroke in patients with atrial fibrillation.

    


Rivaroxaban (Xarelto) 
Rivaroxaban selectively inhibits factor Xa without the need of cofactor (eg, anti-thrombin III) for activity  

Dosing:

  • Arthroplasty of knee - Postoperative deep vein thrombosis;
    Prophylaxis: 10 mg ORALLY once daily beginning at least 6 to 10 hours after surgery and continued for 12 days for knee replacement  
  • Postoperative deep vein thrombosis; Prophylaxis - Repair of hip: 10 mg ORALLY once daily beginning at least 6 to 10 hours after surgery and continued for 35 days for hip replacement

Dosing Adjustment:

  • hepatic impairment, moderate or severe (Child-Pugh B or C): avoid use [1]
  • renal impairment, severe (CrCl less than 30 mL/min): avoid use [1]
  • (with combined p-glycoprotein and strong CYP3A4 inducers): 20 mg ORALLY once daily with food [1]

* The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin.
In patients with non-valvular atrial fibrillation, rivaroxaban (at a daily dose of 20 mg) was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group.  (REF: NEJM August 10, 2011)

    


Apixaban (Eliquis) (at a dose of 5 mg twice daily)

- the direct factor Xa inhibitor  

In this issue of the NEJM Journal, Granger and colleagues report the impressive primary results of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial (ARISTOTLE; ClinicalTrials.gov number, NCT00412984).1 A total of 18,201 subjects with atrial fibrillation and at least one additional risk factor for stroke were enrolled in the trial and were randomly assigned to receive the direct factor Xa inhibitor apixaban (at a dose of 5 mg twice daily) or warfarin (target international normalized ratio [INR], 2.0 to 3.0). The trial was designed to test whether apixaban was noninferior to warfarin with respect to efficacy. The investigators found that apixaban was not only noninferior to warfarin, but actually superior, reducing the risk of stroke or systemic embolism by 21% and the risk of major bleeding by 31%. In predefined hierarchical testing, apixaban, as compared with warfarin, also reduced the risk of death from any cause by 11%.

REF: This article (10.1056/NEJMe1109748) was published on August 28, 2011, at NEJM.org.

     


Melagatran (Ximelagaran) 36 mg bid PO - oral direct thrombin inhibitor with a rapid onset of action
JAMA Feb.9, 2005;293:681 Dr. Jean-Noel Fiessinger, etc.

    

Heparin | Fondaparinux (Arixtra) | Enoxaparin (Lovenox) | Dalteparin (Fragmin) | Tinzaparin (Innohep) | Coumadin (Warfarin)  | Dabigatran (Pradaxa) |  Rivaroxaban (Xarelto)Apixaban (Eliquis)  | Melagatran (Ximelagaran)  || Antithrombolytic Agents    
Anti-thrombotic Agents               

Platelet Glycoprotein IIb/IIIa Receptor Antagonists

Integrilin /Eptifibatide  For acute coronary syndrome: 180 ug/kg IV bolus, then infusion of 2 ug/kg/min upto 72 hours, until discharge or CABG;  For percutaneous coronary interventions: 135 ug/kg bolus, then 0.5 ug/kg/min infusion for 24 h.

ReoPro /Abciximab 0.25 ug/kg bolus, then 0.125 ug/kg/min infusion for 12 hours for before & during percutaneous coronary interventions

Aggrastat /Tirofiban 0.4 ug/kg/min bolus for 30 min, then 0.1 ug/kg/min infusion for upto 72h for acute coronary synd.

Refludan (lepirudin) for injection
- The first direct thrombin inhibitor for anticoagulation in patients with HIT (heparin-induced thrombocytopenia).
- Initial Dosage :Anticoagulation in adult patients with HIT and associated thromboembolic disease:
0.4 mg/kg body weight (up to 110 kg) slowly intravenously (eg, over 15 to 20 seconds) as a bolus dose,
followed by 0.15 mg/kg body weight (up to 110 kg)/hour as a continuous intravenous infusion for 2 to 10 days or longer if clinically needed.

Normally the initial dosage depends on the patient's body weight. This is valid up to a body weight of 110 kg. In patients with a body weight exceeding 110 kg, the initial dosage should not be increased beyond the 110 kg body weight dose (maximal initial bolus dose of 44 mg, maximal initial infusion dose of 16.5 mg/h

    

HeHeparin | Fondaparinux (Arixtra) | Enoxaparin (Lovenox) | Dalteparin (Fragmin) | Tinzaparin (Innohep) |
Coumadin (Warfarin)
  | Dabigatran (Pradaxa) |  Rivaroxaban (Xarelto)Apixaban (Eliquis)  | Melagatran (Ximelagaran)     ||  Antithrombolytic Agents   
Antiplatelet Rx   
  • Aspirin 81 - 325 mg/d

  • Plavix/ clopidogrel 75 mg/d
    Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.  (NEJM June 15, 2000 )

    FDA warns against giving clopidogrel with PPIs:
    Clopidogrel (Plavix), an anti-clotting medication, and omeprazole (Prilosec), a proton-pump inhibitor (PPI), should not be used together, because when the drugs are taken together, the effectiveness of clopidogrel is reduced.
  • Ticagrelor 180-mg loading dose, 90 mg twice daily thereafter.
    Ticagrelor versus Clopidogrel/Plavix in Patients with Acute Coronary Syndromes
    At 12 months, the primary end point — a composite of death from vascular causes, myocardial infarction, or stroke — had occurred in 9.8% of patients receiving ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) as compared with 11.7% of those receiving clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types.
      REF: www.nejm.org August 30, 2009

     

  • Ticlid/ ticlopidine 250 mg bid  

    

For Intermittent Claudication:
Pletal/ cilostazol (Inhibitors of phosphodiesterase III) 100 mg tablet bid before meals
Trental/ pentoxifylline 400 mg tab tid with meals

    

Heparin | Fondaparinux (Arixtra) | Enoxaparin (Lovenox) | Dalteparin (Fragmin) | Tinzaparin (Innohep) | Coumadin (Warfarin)  | Dabigatran (Pradaxa) |  Rivaroxaban (Xarelto)Apixaban (Eliquis)  | Melagatran (Ximelagaran)  || Antithrombolytic Agents    

          2011