A presentation I gave during an Advanced Pharmacy Practice Experience (APPE) in a community pharmacy at a hospital.

1. A REVIEW OF SELECTED ANTICOAGULANTS
Paul Pasco, BA, BS, PharmD Candidate
UTHSC College of Pharmacy
ppasco@uthsc.edu
Monday, April 25, 2022
1
Source: https://bit.ly/3rDVpHp

2. OBJECTIVES
 Provide a detailed comparison of enoxaparin, heparin, and rivaroxaban.
Characteristics that will be compared include:
 Mechanism of action
 Indications
 Routes of administration
 Predictability of response
 Dosing by selected indications
 Renal dose adjustments, if applicable
 Monitoring parameters
 ADRs
 Absolute (estimated) and relative costs
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3. DRUG CLASSES
Anticoagulants
UFH Heparin
Heparin
derivatives
Enoxaparin
Factor Xa
Inhibitors
Rivaroxaban
VKAs
Warfarin
DTIs
Dabigatran
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4. UNFRACTIONATED HEPARIN (UFH)
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Source: https://bit.ly/3LpFnbS

5. UFH
 Indications:
 VTE ppx. in acute medical illness
 VTE ppx. in patients undergoing knee or hip replacement
surgery
 VTE ppx. in pregnant patients
 Does not cross the placenta due to its large size and negative
charge
 Mainly used during the last few weeks of pregnancy, unless
significant renal impairment
 Can use SQ as an outpatient
 Tx. of VTE (including PE)
 ACS
 Medical management (alongside thrombo-/fibrinolytics)
 ECMO
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 MOA:
 Heparin binds to antithrombin III (ATIII),
a natural anticoagulant protein
 Heparin accelerates speed of anticoagulation
effect of AT III 1000x
 Inhibits the activity of Factors IIa and Xa
(equal affinity for each), with some effects on
other clotting factors
 Does not break down existing clots ➔
only prevents clot expansion by preventing
fibrin from forming
 Allows endogenous degradation processes
to break down clot naturally
Whalen K. Lippincott® Illustrated Reviews: Pharmacology. 7th ed. (Feild C, Radhakrishnan R, eds.). Lippincott Wolters Kluwer; 2018: Chapter 21: Anticoagulants and Antiplatelet Agents. Accessed June 2, 2020. https://meded.lwwhealthlibrary.com/book.aspx?bookid=2486

6. UFH: MOA (CONT.)
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Whalen K. Lippincott® Illustrated Reviews: Pharmacology. 7th ed. (Feild C, Radhakrishnan R, eds.). Lippincott Wolters Kluwer; 2018: Chapter 21: Anticoagulants and Antiplatelet Agents. Accessed June 2, 2020. https://meded.lwwhealthlibrary.com/book.aspx?bookid=2486

7. UFH HEPARIN (CONT.)
 Dosing:
 Dosing based on actual body weight
 Can give IV or SQ
 Safe in significant renal dysfunction
 Reversible: 1 mg protamine sulfate to 100 units UFH
 Initial IV tx. dosing forVTE (weight-based):
 Bolus: 80 units/kg
 Infusion: 18 units/kg/hr
 Initial IV tx. dosing forVTE (fixed):
 Bolus: 5000 units
 Infusion: 32,000 units/day
 Lower doses used in ACS
 Bolus of 60-70 units/kg (max 5000 units) + 12-15
units/kg/hr (max 1000 units/hr) for UA and NSTEMI
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 Institutions use formalized protocols to titrate
these IV doses frequently
 Monitor activated partial thromboplastin time
(aPTT)
 Avoids excessive bleeding AND clotting risks by
ensuring the aPTT is in the therapeutic range
 Varies by institution,1.5-2.5x control; ~45-75s
 If aPTT above RR ➔ bleeding risk (and if below RR ➔
clotting risk)
 Usually a nurse-driven protocol
 Predictability
 Can be variable compared to other agents discussed
here (especially when given SQ)
Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral Anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th Ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e24Se43S. doi:10.1378/chest.11-2291

8. UFH:ADRS
 Bleeding
 Osteoporosis (long-term use only)
 ↓ osteoblast formation
 Thrombocytopenia (with HIT/HITT)
 Thrombosis (PLT consumption) + thrombocytopenia
(↓ PLT) ➔ can be fatal
 Hyperkalemia
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Source: https://bit.ly/38lgwaz This Photo by Unknown Author is licensed under CC BY-NC-ND
Signorelli SS, Scuto S, Marino E, Giusti M, Xourafa A, Gaudio A. Anticoagulants and Osteoporosis. International Journal of Molecular Sciences. 2019;20(21). doi:10.3390/ijms20215275

9. UFH: PRICING
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Source: https://bit.ly/3xPFtWl, April 23, 2022

10. UFH: SUMMARY
 Advantages:
 Rapidly and easily reversible over other agents
(has a complete reversal agent and short half-life)
 No renal function limitations
 Can use in pregnancy
 Disadvantages:
 Monitoring requirement (IV)
 Unpredictability (SubQ)
 Higher immunogenicity (HIT/HITT) than other agents
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11. LOW MOLECULAR WEIGHT HEPARIN: ENOXAPARIN (LOVENOX®)
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Source: https://bit.ly/3K9Dmzh

12. ENOXAPARIN (LOVENOX®)
 MOA:
 Extremely similar to UFH
 Inhibits the activity of Factors IIa and Xa, but Xa >>> IIa
 Indications:
 Extremely similar to UFH
 E.g., DVT ppx. in acute medical illness and hip or knee replacement
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13. ENOXAPARIN (LOVENOX®) (MOA CONT.)
13
Whalen K. Lippincott® Illustrated Reviews: Pharmacology. 7th ed. (Feild C, Radhakrishnan R, eds.). Lippincott Wolters Kluwer; 2018: Chapter 21: Anticoagulants and Antiplatelet Agents. Accessed June 2, 2020. https://meded.lwwhealthlibrary.com/book.aspx?bookid=2486

14. ENOXAPARIN (LOVENOX®) (CONT.)
 Dosing:
 DVT tx:
 1 mg/kg, SubQ, q12 hours (outpatient, w/o PE) OR
 1.5 mg/kg, SubQ, daily (only if inpatient, +/- PE) for at least 5
days (~5-7 days total) concurrently withVKA
 Reversal:
 1 mg enoxaparin = 100 units anti-Xa activity (anticoagulant)
 1 mg protamine sulfate = 100 units Xa activity (coagulant)
 Reduced efficacy of antidote in cases where reversal
may be needed
 Renal dose adjustments:
 Yes
 If CrCl < 30 mL/min, avoid use or reduce dose by 50%
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 Monitoring
 CrCl
 Factor Xa levels ➔ only in SELECT populations or
during treatment, NOT ppx.
 Pregnancy
 CrCl < 30 mL/min
 Weight < 50 kg or > 190 kg
 Routes of administration
 SubQ (F = 90%)
 IV (rarely done, F = 100%)
Sanofi-Aventis. Lovenox (Enoxaparin Sodium Injection): Highlights of Prescribing Information.; 2017:1-41. Accessed April 24, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020164s110lbl.pdf

15. ENOXAPARIN (LOVENOX®): PRICING
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Source: https://bit.ly/3rKJOWX, April 19, 2022

16. ENOXAPARIN (LOVENOX®): SUMMARY
 Advantages:
 Can use in pregnancy
 Lower immunogenicity (HIT/HITT) than
other agents
 No routine monitoring requirement
 Greater predictability vs. SubQ UFH
 Disadvantages:
 Not as rapidly or easily reversible over other agents
(only partially neutralized by reversal agent and has a longer
half-life than UFH)
 Renal function limitations (CrCl < 30 mL/min)
 More expensive than the other two options covered in this
presentation,
but does not require hospitalization like UFH
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Source: https://bit.ly/38j0PRc

17. RIVAROXABAN (XARELTO®)
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18. RIVAROXABAN (XARELTO®)
 MOA:
 Only affects Xa
 No factor IIa activity
 Indications (FDA-Approved):
 NVAF
 DVT/PE tx. and ppx for recurrence
 DVT/PE ppx in knee or hip replacement surgery
 VTE ppx. in acutely ill medical patients
 Thromboprophylaxis in pediatric patients ≥ 2 years with congenital
heart disease after the Fontan Procedure
 ADRs
 Bleeding
 Dizziness, vomiting
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Janssen Pharmaceuticals. Xarelto® (Rivaroxaban): Highlights of Prescribing Information.; 2022:1-34. Accessed April 24, 2022. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/XARELTO-pi.pdf

19. RIVAROXABAN (XARELTO®) (CONT.)
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 Dosing:
 NVAF
 Dosing is different with starter pack than below
 CrCl > 50 mL/min: 20 mg, PO, daily with dinner.
 CrCl 15-50 mL/min: 15 mg, PO, daily with dinner.
 DVT ppx: 10 mg, PO, daily with or without food.
 Renal dose adjustments:
 As in example above. Contraindicated with CrCl <15
mL/min.
 Monitoring
 Anti-Xa in select patients
 Routes of administration
 PO only
Janssen Pharmaceuticals. Xarelto® (Rivaroxaban): Highlights of Prescribing Information.; 2022:1-34. Accessed April 24, 2022. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/XARELTO-pi.pdf

20. RIVAROXABAN (XARELTO®): SUMMARY
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 Advantages:
 Oral agent
 No routine monitoring required
 Disadvantages:
 More expensive than UFH
 Costly in general
 Requires food (vs. IV/SubQ agents)
 Not indicated in pregnancy
Janssen Pharmaceuticals. Xarelto® (Rivaroxaban): Highlights of Prescribing Information.; 2022:1-34. Accessed April 24, 2022. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/XARELTO-pi.pdf
Source: https://bit.ly/3xPVk7m

21. RIVAROXABAN (XARELTO®): PRICING
21
Source: https://bit.ly/3rNRyYz, April 19, 2022

22. PUTTING IT ALL TOGETHER: SIDE-BY-SIDE COMPARISON
CHARACTERISTICS UFH ENOXAPARIN RIVAROXABAN
MOA Inhibits IIa, Xa Inhibits IIa, Xa Inhibits Xa ONLY
Indications Many, such asVTE tx, ppx
Many, similar to UFH (VTE tx,
ppx after orth. surgery, others)
OnlyTE ppx. w/NVAF, VTE
ppx. after orth. surgery
Routes of
Administration
IV/SQ SQ PO
Predictability
Variable compared to
other agents (esp. SubQ)
Predictable Predictable
Renal Dose Adjustments No Yes, CrCl < 30 mL/min Yes, CrCl < 50 mL/min
Monitoring aPTT None or anti-Xa testing None or anti-Xa testing
ADRs
Bleeding, osteoporosis,
HIT/HITT
Bleeding, osteoporosis,
HIT/HITT
Bleeding,
dizziness, vomiting
Risk of HIT Highest Much lower than UFH None
Relative Cost
$ (but more w/ hosp.
costs if IV therapy)
$$$ $$ 22

23. QUESTIONS?
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24. A REVIEW OF SELECTED ANTICOAGULANTS
Paul Pasco, BA, BS, PharmD Candidate
UTHSC College of Pharmacy
ppasco@uthsc.edu
Monday, April 25, 2022
24
Source: https://bit.ly/3rDVpHp