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PL Detail-Document #271001 −This PL Detail -Document gives subscribers additional insight related to the

PL Detail-Document #271001

−This PL Detail-Document gives subscribers additional insight related to the Recommendations published in−

PHARMACIST’S LETTER / PRESCRIBER’S LETTER

October 2011

PHARMACIST’S LETTER / PRESCRIBER’S LETTE R October 2011 Comparison of Oral Antithrombotics (Last modified November

Comparison of Oral Antithrombotics

(Last modified November 2011) The recent proliferation of oral anticoagulants and antiplatelet agents has health care professionals questioning how to choose among them. The newest anticoagulants are dabigatran (Pradaxa, Pradax [Canada]) and rivaroxaban (Xarelto). Also look for the direct factor Xa inhibitor apixaban possibly in 2012, and edoxaban and betrixaban in the next few years. The following chart compares the indications, clinical benefit, antidotes, washout, and other therapeutic considerations for these agents.

Abbreviations: ACS = acute coronary syndrome; ADP = adenosine diphosphate; A fib = atrial fibrillation; AV = arteriovenous; AWP = average wholesale price; BID = twice daily; CAD = coronary artery disease; DVT = deep vein thrombosis; LMWH = low molecular weight heparin; LVD = left ventricular dysfunction; MI = myocardial infarction; PE= pulmonary embolism; STEMI = ST segment elevation myocardial infarction; TIA = transient ischemic attack; VTE = venous thromboembolism

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

ANTICOAGULANTS (see information about the investigational drug apixaban at the end of the chart)

 

Dabigatran

U.S.: 5

A

fib: prevents about five more

No specific

Requires BID dosing for

(Pradaxa; Pradax

Thromboembolism (e.g., stroke)

strokes per 1000 patients per year than warfarin. Lower rate of hemorrhagic stroke, higher rate of major GI bleed 7

antidote

A fib. 5,6

[Canada]):

prevention in A fib (150 mg BID) 5

Dispense/store in original container. Once opened, discard after four months (U.S.) or 30 days (Canada). 5,6

direct thrombin

See our PL

inhibitor 5,6

Canada: 6

Detail-

Thromboembolism (e.g., stroke)

 

Document,

(150 mg BID) U.S.: $262.44 (AWP)

prevention in A fib (150 mg BID,

Post-hip/knee replacement (off-label [U.S.]): comparable to enoxaparin for prevention of VTE & mortality (combined endpoint); comparable major bleeding 8-10

Reversing

 

110

mg BID for patients over 80 yrs).

Dabigatran

To switch from warfarin,

VTE prevention post-hip or knee

and

stop warfarin, then start dabigatran when INR <2. 5,6

 

replacement (220 mg once daily x 10

Rivaroxaban

Canada: $103.68

days [knee] or 28 to 35 days [hip]. If started 1-4 hrs post-op, initial dose is

See product labeling for instructions for switching

 

110

mg)

VTE treatment (off-label):

to

warfarin, or to/from

 

comparable to warfarin for prevention

injectable anticoagulants.

of

recurrent VTE or VTE death

Check renal function at baseline, and yearly in

Continued

(combined endpoint); comparable

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #271001: Page 2 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Dabigatran,

 

major bleeding 11

 

patients over 75 years or with CrCl < 50 mL/min. 5

continued

Renal dosing:

A fib (U.S.), use 75 mg

BID if CrCl 15 to

30

mL/min. 5 VTE, use

75

mg x 1, then 150 mg

once daily if CrCl 30 to

50

mL/min. 6 Canada,

contraindicated if CrCl

<

30 mL/min. 6

Causes dyspepsia in over 10% of patients. 7

Caution if 75 years &

over (over 75 years, Canada), poor renal function, or underweight. 5,6,43

Co-administration with

aspirin or clopidogrel about doubles bleeding risk. 6

P-glycoprotein inhibitors

Continued…

(e.g., dronedarone, ketoconazole, verapamil, quinidine, amiodarone) can increase dabigatran levels. Dabigatran dose adjustment may be needed (see labeling). 5,6 Strong p-

may be needed (see labeling). 5 , 6 Strong p- Copyright © 2011 by Therapeutic Research

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #271001: Page 3 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

 

Antidote/

Therapeutic

 

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Dabigatran,

   

glycoprotein inhibitors (e.g., ketoconazole) contraindicated per Canadian labeling. 6 P- glycoprotein inducers (e.g., rifampin, carbamazepine, St. John’s wort, tenofovir) could decrease dabigatran efficacy. 6 Avoid per U.S. labeling.

5

continued

Rivaroxaban

U.S.: 12

Post-hip/knee replacement: at least as

No specific

Once daily dosing. 12,13.18 For A fib, some data suggest once daily dosing insufficient, but BID

(Xarelto): direct

VTE prevention post-hip or knee

effective as enoxaparin for prevention

antidote

factor Xa

replacement (10 mg once daily for 35 days [hip] or 12 days [knee] starting 6-

of

VTE or mortality (combined

inhibitor 12,13

endpoint); comparable major bleeding 14-17

See our PL

10 hrs post-op, assuming hemostasis achieved)

Detail-

dosing untested. 66

(10, 15, or 20 mg

 

Document,

Avoid use with drugs

once daily) U.S.: $262.44 (AWP)

Thromboembolism (e.g., stroke)

A

fib (off-label [Canada]):

Reversing

 

prevention in A fib (20 mg once daily with evening meal to improve absorption)

comparable to warfarin for preventing stroke or systemic embolism in patients with relatively high stroke risk. Comparable major bleeding, but INR in therapeutic range only 55% of time. Lower rate of hemorrhagic stroke, higher rate of major GI bleed. Increase in events after stopping may reflect poor transition to warfarin, not hypercoagulability. 18

DVT treatment (off-label):

Dabigatran

that are BOTH p- glycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posiconazole, ritonavir [all contraindicated, per Canadian labelling], clarithromycin, conivaptan). P- glycoprotein inducers (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort) may decrease efficacy. 12.13 Avoid per U.S. labeling. 12

and

 

Rivaroxaban

(10 mg once daily) Canada: $287.06

 

Canada: 13

VTE prevention post-hip or knee

replacement (10 mg once daily for 35 days [hip] or 14 days [knee], starting 6-10 hrs post-op, assuming hemostasis achieved)

Continued…

comparable to enoxaparin/warfarin for prevention of recurrent VTE;

to enoxaparin/warfarin for prevention of recurrent VTE; Copyright © 2011 by Therapeutic Research Center P.O. Box

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

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(PL Detail-Document #271001: Page 4 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Rivaroxaban,

 

comparable bleeding 19

 

Check renal function periodically (U.S.). 12 Canada, monitor if CrCl close to 30 mL/min. 13

continued

A fib indication requires renal dosing (15 mg with evening meal for CrCl 15 to 50 mL/min). 12 For VTE prevention, avoid if CrCl < 30 mL/min. 12,13

Avoid use with other

anticoagulants; monitor during transition periods. 12 Antiplatelets may increase bleeding risk; co- administer with caution. 12,13

Warfarin (Coumadin, generics): inhibits formation of vitamin-K dependent clotting factors 20,21

U.S.: 20

A fib: prevents stroke (NNT = 32 vs placebo for one year to prevent one stroke) 22

Vitamin K/

Gold standard oral

Prevention/treatment of venous thrombosis/PE

Washout:

anticoagulant; over 50 years’ experience.

five days 20,21,41

Prevention/treatment of

 

INR monitoring required at least every four weeks. 20,21

Many drug and food

thromboembolism due to A fib or prosthetic heart valve

PE/DVT (with initial use of heparin):

reduces risk of recurrence and mortality [Evidence level B; lower quality RCTs] 23 Post-MI: reduces reinfarction, stroke, and mortality (INR 2.8 to 4.8); 25 warfarin (INR 2 to 2.5) plus aspirin (75 mg once daily) superior to aspirin alone or warfarin (INR 2.8 to 4.2)

 

Secondary prevention post-MI Canada: 21

interactions.

(5 mg once daily) U.S.: $6.65

Prevention/treatment of venous thrombosis/PE

benefit may not outweigh risk in patients with high bleeding risk. 24

For VTE, long-term,

Canada: $3.43

Prevention/treatment of

thromboembolism due to A fib

Continued…

 
thromboembolism due to A fib Continued…   Copyright © 2011 by Therapeutic Research Center P.O. Box

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

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(PL Detail-Document #271001: Page 5 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Warfarin,

Prevention of reinfarction and

alone (combined endpoint) 26

 

Not more effective than

continued

thromboembolism (e.g., stroke) post- MI (adjunct)

Rheumatic mitral valve disease (off- label): reduces embolic events and mortality in patients with embolic history; reduces embolic events in patients with A fib, promotes resolution of left atrial thrombus [Evidence level B; clinical cohort] 29-31

Mechanical heart valve (off-label, Canada): reduces embolism and valve thrombosis (mostly based on

aspirin for noncardioembolic stroke. 28

TIA (adjunct)

Use with aspirin

(Note: warfarin dosing variable and patient specific.)

increases bleeding risk. But combo may benefit certain high-risk mechanical heart valve patients. Benefit may also outweigh risk in A fib or VTE history plus recent stent, recent CABG, or new stroke despite INR in therapeutic range. 39

nonrandomized, uncontrolled case series) 32

Potential for significant interactions with inducers/inhibitors of CYP2C9, 2C19, 1A2, and

3A4.

ANTIPLATELETS

Aspirin: inhibits

U.S. (vascular indications): 33

Primary CV event prevention (off- label, U.S.): reduces MI in men, ischemic stroke in high-risk women 34

Post-ACS: reduces risk of mortality, re-infarction, and stroke 27

Platelet transfusion 38 / Washout:

five to 10 days 35

In A fib patients

cyclo-oxygenase

Secondary prevention after ischemic

with no stroke risk factors, aspirin 81 to 325 mg daily recommended instead of anticoagulation. 42,65

(81 mg once daily) U.S.: <$1

stroke, TIA, MI, or unstable angina, (81 to 325 mg daily)

Acute MI (81 to 325 mg daily)

Chronic stable angina (81 to 325 mg daily)

 

For primary prevention

Canada: <$1

 

of cardiovascular disease, reserve aspirin for certain high-risk patients (See PL Detail-Document, Aspirin for Primary Prevention). 34

Revascularization procedures

Acute MI: reduces vascular mortality 33 Chronic stable angina (off-label, Canada): reduces risk of MI or

Continued…

(81 to 325 mg daily) Canada (vascular indications): 44

(81 to 325 mg daily) Canada (vascular indications) : 4 4 Copyright © 2011 by Therapeutic

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

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(PL Detail-Document #271001: Page 6 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Aspirin,

Secondary prevention after MI or

sudden death, or serious vascular events (combined endpoints) 47

 

Post-coronary stent, dual antiplatelet therapy is initially indicated. 40

continued

unstable angina (81 to 325 mg once daily)

Primary prevention of MI in high-

TIA or minor noncardioembolic stroke: reduces risk of stroke or death, or vascular death, MI, or stroke (combined endpoints) 64

Use with warfarin

risk patients (81 to 325 mg once daily)

increases bleeding risk. But combo may benefit certain high-risk mechanical heart valve patients. Benefit may also outweigh risk in A fib or VTE history plus recent stent, recent CABG, or new stroke despite INR in therapeutic range. 39

To reduce risk of TIA or recurrent

stroke (81 to 325 mg once daily)

Acute MI (160 mg immediately, then daily for 30 days. Then as for secondary prevention)

Post-coronary stent (off-label):

prevents stent thrombosis 40

Prevention of VTE post-hip

replacement (650 mg BID) (note:

A fib (off-label): Efficacy inferior to warfarin and not much better than no treatment at all in “real world” use. [Evidence level B; clinical cohort study]. 67

current guidelines recommend against aspirin monotherapy for VTE prophylaxis) 45

Reduction of platelet adhesiveness in hemodialysis patients with silicone rubber AV cannula (dose not specified)

   

Post-carotid endarterectomy (dose not specified)

Cilostazol (Pletal, generics [U.S. only]): inhibits platelet phosphodiesterase

U.S.: 53

Intermittent claudication: increases walking distance 53

No specific

Use with aspirin

Intermittent claudication (100 mg BID)

antidote/

enhances platelet inhibition

vs aspirin alone. No increase in bleeding risk vs aspirin alone noted in patients receiving concomitant cilostazol plus aspirin in clinical trials (n=201). But long-term

Washout:

   

two to three days 41

III

54

(100 mg BID) U.S.: $24.32 Continued…

III 5 4 (100 mg BID) U.S. : $24.32 Continued… Copyright © 2011 by Therapeutic Research

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

(PL Detail-Document #271001: Page 7 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Cilostazol,

     

safety with aspirin unknown. 53

continued

CYP3A4 and CYP2C19 interactions. 53

Clopidogrel (Plavix): blocks platelet ADP P2Y12 receptor 36,37

U.S.: 36

Non-STEMI (with aspirin): reduces cardiovascular death, MI, stroke, or refractory ischemia (combined endpoint) 36,37

Platelet transfusion suggested 36,37 / Washout:

Used with aspirin in

ACS (300 mg load, then 75 mg once

A fib (not first-line), non- STEMI, STEMI, symptomatic CAD, and post-stent. 27,37,46,68

daily, plus aspirin 81 to 325 mg daily; can skip loading dose in STEMI)

 

Recent stroke (75 mg once daily)

 

five to seven days 35

(75 mg once daily) U.S.: $188.66

Recent MI (75 mg once daily)

STEMI (with aspirin): reduces risk of death or death, re-infarction, and/or stroke (combined endpoint) 36,37

Clopidogrel may be

Peripheral artery disease (75 mg once daily)

 

superior to aspirin for secondary prevention of stroke post-stroke/TIA. 52

Canada: $85.22

Canada: 37

Recent MI: reduces risk of stroke,

Efficacy affected by

Secondary prevention in patient

CYP2C19 inhibitors and pharmacogenetics. 54

with atherosclerosis (i.e., patients with a history of stroke or MI, or with peripheral artery disease) (75 mg once daily)

MI, or vascular death (combined endpoint) 36,37

Recent noncardioembolic stroke (off- label, U.S.): reduces risk of stroke,

ACS (300 mg loading dose, then

 

75 mg once daily, plus aspirin 81 to 325 mg once daily; can skip loading dose in STEMI) Thromboembolism (e.g., stroke) prevention in A fib (75 mg once daily plus aspirin 81 mg once daily)

MI, or vascular death (combined endpoint) 36,37

Peripheral artery disease: reduces risk of stroke, MI, or vascular death (combined endpoint) 28,36,37

A fib (with aspirin): reduces vascular events (e.g., stroke). 37,46 But combo not as effective as warfarin, and not safer. 68

But combo not as effective as warfarin, and not safer. 6 8 Copyright © 2011 by

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

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(PL Detail-Document #271001: Page 8 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Dipyridamole (Persantine, generics): inhibits platelet adenosine uptake 48,49

U.S.: 48

Mechanical heart valve (with warfarin or warfarin plus aspirin):

No specific

Four times daily

Prevention of thromboembolism

antidote/

dosing. 48,49

post-heart valve replacement, with warfarin (75 to 100 mg four times

daily)

thromboembolic rates 0.6 to 1.5% per year in case series 32

Washout:

Despite indication, data

two to three days 41

insufficient to recommend for valvular heart disease. 32

(75 mg four times daily) U.S.: $88.79

Canada: 49

 

Prevention of thromboembolism

post-heart valve replacement (100 mg four times daily)

Canada: $56.99

Dipyridamole extended release 200 mg/aspirin 25 mg (Aggrenox):

U.S.: 50

Secondary prevention of stroke:

No specific

BID dosing. 50,51

Secondary prevention of stroke post- stroke/TIA (one capsule BID)

reduces stroke risk; superior to placebo or monotherapy with aspirin or dipyridamole extended-release 50,51

antidote/

Not substitutable with

Washout:

five to 10 days (see aspirin)

dipyridamole plus aspirin separately. 52

inhibits cyclo-

Canada: 51

 

Drug of choice for

oxygenase &

Secondary prevention of stroke in

 

secondary prevention of stroke post-stroke/TIA. 52

platelet adenosine

patients who have had a stroke or TIA (one capsule BID)

uptake 50,51

 

(One capsule BID) U.S.: $215.32

 

Canada: $53.33

(One capsule BID) U.S. : $215.32   Canada : $53.33 Copyright © 2011 by Therapeutic Research

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

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(PL Detail-Document #271001: Page 9 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Prasugrel (Effient):

U.S.: 56

ACS managed with PCI (with aspirin): reduces cardiovascular death, MI, and stroke (combined endpoint) by 2% vs clopidogrel plus aspirin; higher bleeding risk 55

Platelet transfusion suggested 56 / Washout:

Consider dose reduction in patients <60 kg. 56

blocks platelet ADP P2Y12 receptor 57

ACS managed with PCI (including

stenting), with aspirin (60 mg loading dose, then 10 mg once daily with

Not recommended in

patients 75 or older. 56,57

(10 mg once daily) U.S.: $202.68

aspirin 81 to 325 mg once daily)

seven days 35

Contraindicated in

Canada: 57

 

stroke/TIA history. 56,57

 

Efficacy not affected by

Canada: $86.18

ACS managed with PCI (including

pharmacokinetics or CYP450 inhibitors. 56,57

stenting), with aspirin (60 mg loading

Consider for patients

dose, then 10 mg once daily with aspirin 81 to 325 mg once daily)

with low bleeding risk and high cardiovascular event risk, and/or who have had a cardiac event while taking clopidogrel, and for patients with reduced CYP2C19 activity due to a genetic variation or interacting medication.

Use with warfarin

increases bleeding risk. 56,57 Co-administer with caution. 57

Ticagrelor (Brilinta): blocks platelet ADP P2Y12 receptor 58

U.S.: 58

ACS (with aspirin): reduces risk of cardiovascular death, MI, or stroke (combined endpoint) and stent thrombosis vs clopidogrel (with aspirin) 59

Aminocaproic acid or tranexamic acid and/or recombinant factor VIIa suggested 60 /

BID dosing. 58,60

ACS (180 mg loading dose, then

Reversible binding to

90

mg twice daily, with aspirin 81 mg)

platelet receptor. 58

 

Adverse effects

 

Canada: 60

of note include bradycardia, dyspnea, and gynecomastia in men. 58,59

ACS (180 mg loading dose, then

 

Continued…

90

mg twice daily, with aspirin 81 mg)

Continued… 90 mg twice daily, with aspirin 81 mg) Copyright © 2011 by Therapeutic Research Center

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

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(PL Detail-Document #271001: Page 10 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

Ticagrelor,

   

Washout:

Maintenance aspirin dose

continued

(90 mg BID) U.S.: $260.78

five days 58,60

81 mg. Higher doses of aspirin reduce efficacy of ticagrelor. 58

Consider for patients

Canada: $95.90

who have had a cardiac event while taking clopidogrel, and for patients with reduced CYP2C19 activity due to a genetic variation or interacting medication.

CYP3A4 interactions. 58,60

Not studied with oral

anticoagulants. Co- administer with caution. 60

Ticlopidine (generic only):

U.S.: 61

Post-TIA/noncardioembolic stroke:

Platelet transfusion suggested 63 / Washout: ten to 14 days 61,63

Not a first-line agent. 28,52

Secondary prevention of stroke post- stroke/TIA (250 mg BID)

reduces risk of stroke, MI, and vascular death (combined endpoint) 28

BID dosing.

Adverse effects of note include neutropenia, thrombotic thrombocytopenic purpura, diarrhea, and rash. 28

blocks platelet ADP P2Y12 receptor

Prevention of stent thrombosis

 
 

(250 mg BID with low-dose aspirin)

Post-coronary stent (with aspirin):

(250 mg BID) U.S.: $111.68

Canada: 63

Better than aspirin alone or warfarin for preventing death,

 

Prevention of first or recurrent stroke in patients with a history of thromboembolic stroke, minor stroke, reversible ischemic neurological deficit (RIND), TIA, or transient monocular blindness (TMB) (250 mg BID)

Long-term safety with

Canada: $32.57

revascularization, thrombosis, or MI (combined endpoint) 62

anticoagulants not established. 61 Co- administer only with close monitoring. 63

6 1 Co- administer only with close monitoring. 6 3 Copyright © 2011 by Therapeutic Research

Copyright © 2011 by Therapeutic Research Center P.O. Box 8190, Stockton, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249 www.pharmacistsletter.com ~ www.prescribersletter.com ~ www.pharmacytechniciansletter.com

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(PL Detail-Document #271001: Page 11 of 14)

Drug: Mechanism

Approved Indications (Usual Maintenance Dose) b

Clinical Benefit In… c

Antidote/

Therapeutic

pre-op, pre-

Considerations

Cost of 30-day supply a

 

procedure

washout (if

 

indicated)

INVESTIGATIONAL ORAL ANTICOAGULANT

 

Apixaban (Eliquis):

Not yet approved in U.S. or Canada

A fib: at least as effective as warfarin for stroke prevention, systemic embolism, death; less major bleeding 1

No specific

Requires BID dosing for A fib. 1

direct factor Xa inhibitor 1

antidote

For every 1000 A fib

Not yet available

Post-hip/knee replacement: at least as effective as enoxaparin for preventing VTE; comparable bleeding 2,3

patients treated for 1.8 years, apixaban prevents six more strokes, 15 major bleeds, and eight deaths compared to warfarin. 1

Increases risk of

major bleeding when added to antiplatelet agent in patients with acute

coronary syndrome. 4

a. U.S. cost for dose specified (of generic, if available) from drugstore.com at time of writing unless otherwise specified. Canadian prescription drug prices from British Columbia wholesaler Kohl and Frisch Limited. Does not include cost of monitoring.

b. See product labeling for dosing in special populations (e.g., renal impairment, elderly, etc).

c. Based on Level A evidence unless otherwise noted.

Users of this PL Detail-Document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication.

in this article were current as of the date of publication. Copyright © 2011 by Therapeutic

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(PL Detail-Document #271001: Page 12 of 14)

Levels of Evidence

In accordance with the trend towards Evidence-Based Medicine, we are citing the LEVEL OF EVIDENCE for the statements we publish.

Level

Definition

A

High-quality randomized controlled trial (RCT) High-quality meta-analysis (quantitative systematic review)

B

Nonrandomized clinical trial Nonquantitative systematic review Lower quality RCT Clinical cohort study Case-control study Historical control Epidemiologic study

C

Consensus

Expert opinion

D

Anecdotal evidence In vitro or animal study

Adapted from Siwek J, et al. How to write an evidence-based clinical review article. Am Fam Physician 2002;65:251-8.

Project Leader in preparation of this PL Detail- Document: Melanie Cupp, Pharm.D., BCPS

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Cite this document as follows: PL Detail-Document, Comparison of Oral Antithrombotics. Pharmacist’s Letter/Prescriber’s Letter. October 2011.

Evidence and Recommendations You Can Trust … 3120 West March Lane, P.O. Box 8190, Stockton,

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Evidence and Recommendations You Can Trust … 3120 West March Lane, P.O. Box 8190, Stockton, CA

3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249

Copyright 2011 by Therapeutic Research Center

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