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Name: Mohsin Ali

Class: Phd (1st Semester)

Assignment : Enoxaparin

Submitted to : Sir Ismail Tajik

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DECLARATION
I, Mohsin Ali, hereby declare that this assignment is my own, and not previously submitted to
any other course. I have actually consulted/used all the references (mentioned in the section
“References”) and cited all of them in the text of my assignment.
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TABLE OF CONTENTS

1. Availability of Enoxaparin 4
1.1 Subcutaneous Injection 4
1.2 Marketed Products 4
2. Indications 4
2.1 Venous Thromboembolism (VTE). 4
2.1.1 Deep Vein thrombosis (DVT): 4
2.1.2 Pulmonary Embolism (PE): 4
2.1.3 Treatment: 4
2.1.4 Treatment Protocol: 4
2.2 ST-elevation Myocardial Infarction (STEMI) 5
2.2.1 Treatment 5
2.2.2 Treatment Protocol: 5
2.3 Knee and Hip replacement Surgery 5
2.3.1 Treatment 5
2.3.2 Treatment Protocol 5
2.4 Unstable Angina and Non-Q-wave Myocardial Infarction 5
2.4.1Treatment 6
2.4.2 Treatment protocol 6
3. Adverse Effects
3.1 Hepatotoxicity 6
3.2 Hyperkalemia 6
3.3 Thrombocytopenia 7
3.4 Fever and Skin rashes 8
4. References 8
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1. Availability of Enoxaparin:
1.1. Subcutaneous Injections
available in 20mg, 40mg. 60mg and 80mg strengths
1.2 Marketed products:
i. Inj Clexane 20mg, 40mg. 60mg and 80mg (Sanofi Aventis Pakistan Ltd)
ii. Inj. Clotles-SS 20mg (Himont Chemical Pvt Ltd)
iii. Inj. Enox 20mg, 40mg. 60mg and 80mg (Wilson Pharmaceuticals)
iv. Inj.Oxaprin 20mg, 40mg. 60mg and 80mg (Werrick Pharmaceuticals)

2. Indications:
2.1 Venous Thromboembolism (VTE).
Venous thromboembolism (VTE) is a medical condition in which a blood clot is formed inside a
vein. It is a third leading vascular disease after heart attack and stroke. The most common causes
of VTE are surgery, immobilization, cancer and other cardiovascular diseases. Other risk factors
may include age, obesity and increase blood viscosity. VTE is also associated with different
ethnic groups i.e. the incidence is higher in Caucasians and black Americans than Spanish and
other Asian population.
It is of two types:
2.1.1 Deep Vein thrombosis (DVT): a clinical condition in which clot is formed in deep veins
in body such as arms and legs. The clot is stationary and attached to the vein wall. DVT is two
third of total VTE cases in USA per year.
2.1.2 Pulmonary Embolism (PE): when a clot in deep vein breaks-off and starts movement
with flowing blood to the lungs where it blocks partial or complete blood supply. PE is
approximately one third of total VTE cases in USA per year (1).
2.1.3 Treatment:
Enoxaparin is a low molecular weight heparin (LMWH) which has anti-thrombotic activity in
the body. It primarily acts by binding to anti-thrombin, a protein produced by liver, which leads
to formation of a complex. This complex has greater anti-thrombotic activity than anti-thrombin-
III alone in deactivation of factor Xa and factor IIa (thrombin). Thus, Enoxaparin is an
anticoagulant used for prevention of clot formation before, during or after major surgeries which
are risk factor for venous thrombosis (2).
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2.1.4 Treatment Protocol:

1mg per kg subcutaneous injection twice a day. Administer at same time each day.

2.2 ST-elevation Myocardial Infarction (STEMI)

ST-elevation Myocardial Infarction is a type of cardiac arrest in which the blood supply to the
cardiac muscles is reduced due to blockade of coronary arteries by underlying thromboembolic
condition. It is a life-threatening condition which is detected by 12-lead ECG that shows
significant ST segment elevation (3).
2.2.1 Treatment
Enoxaparin binds with antithrombin, a glycoprotein produced by the liver. Enoxaparin enhances
the activity of antithrombin which inactivates several clotting factors such as Xa, IXa, XIa and
IIa. Thus, leads to inhibition of clot formation in STEMI (4).
2.2.2 Treatment Protocol:
Loading dose: 30mg IV bolus with 1mg per kg subcutaneous at once. The cumulative loading
dose should not exceed 100mg.
Maintenance dose: 1mg per kg subcutaneous injection twice a day. Administer at same time each
day.

2.3 Knee and Hip replacement Surgery

Knee and Hip replacement surgeries carries greater risk of thromboembolism even in
prophylactic administration of anticoagulants. The patients undergoing such operations require
thromboprophylaxis with low molecular weight heparins, vitamin K antagonists and other
anticoagulants. Despite this, 15-20% patients develop thromboembolic events immediately after
the surgery (5).
2.3.1 Treatment
Enoxaparin binds with antithrombin, a glycoprotein produced by the liver. Enoxaparin enhances
the activity of antithrombin which inactivates several clotting factors such as Xa, IXa, XIa and
IIa. Thus, leads to inhibition of clot formation in STEMI (4).
2.3.2 Treatment Protocol
The therapy is started in 12-24hrs after the surgery. Initially 30-40mg subcutaneous dose is
administered after every 12hrs i.e. twice a day. The therapy is continued up to 10-35 days, after
which the patient is shifted on oral anticoagulants.

2.4 Unstable Angina and Non-Q-wave Myocardial Infarction

Unstable angina is a medical condition in which the heart does not get enough blood supply due
to coronary arteries blockade and which worsens even after appropriate rest. The blockade may
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be due to thromboembolism and require immediate medical intervention because it may lead to
heart attack (6).
2.4.1Treatment
Enoxaparin binds with antithrombin, a glycoprotein produced by the liver. Enoxaparin enhances
the activity of antithrombin which inactivates several clotting factors such as Xa, IXa, XIa and
IIa. Thus, leads to inhibition of clot formation in STEMI (4).
2.4.2 Treatment protocol
Enoxaparin is currently used concurrently with aspirin for prophylaxis of ischemic complications
of unstable angina and myocardial infarction. Initially 1mg per kg dose of enoxaparin is
administered in two divided doses daily with 100-325 mg aspirin per day.

3. Adverse Effects
3.1 Hepatotoxicity
The continuous administration of enoxaparin for one-week results in elevation of serum
aminotransferases. The reason for this hepatotoxicity is the direct toxic effect of enoxaparin on
hepatocytes (7).
3.1.1 It is a Type A adverse drug reaction with known pharmacology.
3.1.2 Frequency = 6%
3.1.3 Severity = Severe
3.1.4 Diagnosis = Lab test i.e. Liver function test (LFT)
3.1.5 Management = Dose reduction or replacement by oral anticoagulants.
3.1.6 Other hepatotoxicity drugs = Paracetamol, Chlorpromazine, Sulindac, Isoniazid, Halothane.
3.2 Hyperkalemia
Hyperkalemia is another adverse drug event produced after 4-7 days of enoxaparin therapy. The
exact mechanism is unknown but research shows that enoxaparin blocks the angiotensin-II
receptors in adrenal gland which results in decrease production of aldosterone (8).
3.2.1 It is a Type A adverse drug reaction with known pharmacology.
3.2.2 Frequency = rare i.e. 1%
3.2.3 Severity = Severe
3.2.4 Signs and symptoms = Patient with severe hyperkalemia shows signs and symptoms such
as :
 Serum potassium level more than 5.3 mmol/L
 Tiredness and weakness and numbness
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 Nausea and vomiting

 Apnea
 Arrythmias
3.2.5 Management = Administration of IV calcium, Sodium bicarbonate and diuretics.
3.2.6 Other drugs causing hyperkalemia are: ACE inhibitors, Angiotensin receptor blockers,
NSAIDs, Potassium sparing diuretics, Heparin (9).
3.3 Thrombocytopenia
Patients receiving enoxaparin therapy rarely produce thrombocytopenia than heparin. This may
occur due to production of platelet Factor-4 (PF4) antibodies. The platelets count may decrease
below 30,000 cells per microliter within 10 days of therapy (10).
3.3.1 It is a Type B drug allergy reaction with known pharmacology.
3.3.2 Frequency = 3%
3.3.3 Severity = Severe
3.3.4 Signs and symptoms: These include:
 Prolong bleeding from cuts
 Deep vein thrombosis
 Dyspnea
 Epistaxis (11).
3.3.5 Diagnosis = Lab test i.e. Complete blood count (CBC)
3.3.6 Management = Dose reduction or replacement by oral anticoagulants.
3.3.7 Other drugs causing thrombocytopenia are: Thiazide diuretics, ethanol, heparin, NSAIDs,
sulfonamides.
3.4 Fever and Skin rashes
Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) due to enoxaparin
therapy is a rare type of severe reaction occurs after 1-8 weeks of drug utilization. The condition
is characterized by fever, skin rashes, decreased eosinophils and organ damage. This is a delayed
type of hypersensitivity reaction which occurs due to chemical nature of enoxaparin i.e. a
polysaccharide produced from bovine or porcine intestines and lungs (12).
3.4.1 It is a Type B drug allergy reaction with known pharmacology.
3.4.2 Frequency = 5-8%
3.4.3 Severity = Severe
3.4.4 Signs and symptoms: These include:
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 Skin rashes
 Fever
 Organ failure
 Edema of lower limbs
3.4.5 Diagnosis = Physical examination and skin biopsy.
3.4.6 Management = Topical Desonide ointment and Paracetamol.
3.4.7 Other drugs causing DRESS are: Carbamazepine, Amoxicillin, Abacavir, Dapsone,
Allopurinol (13).

4. References

1. White RH. The epidemiology of venous thromboembolism. Circulation. 2003;107(23_suppl_1):I-

4-I-8.
2. Warner GT, Perry CM. Enoxaparin. American Journal of Cardiovascular Drugs. 2001;1(6):477-81.
3. Rubboli A, Capecchi A, Di Pasquale G. Utilizing enoxaparin in the management of STEMI.
Vascular health and risk management. 2007;3(5):691.
4. Carter NJ, McCormack PL, Plosker GL. Enoxaparin. Drugs. 2008;68(5):691-710.
5. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM. Apixaban versus enoxaparin for
thromboprophylaxis after hip replacement. New England Journal of Medicine.
2010;363(26):2487-98.
6. Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012
ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients
with stable ischemic heart disease: a report of the American College of Cardiology
Foundation/American Heart Association task force on practice guidelines, and the American
College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular
Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of
Thoracic Surgeons. Journal of the American College of Cardiology. 2012;60(24):e44-e164.
7. Hahn KJ, Morales SJ, Lewis JH. Enoxaparin-induced liver injury: case report and review of the
literature and FDA Adverse Event Reporting System (FAERS). Drug safety-case reports.
2015;2(1):17.
8. Scalese MJ. Profound hyperkalemia associated with thromboprophylactic enoxaparin.
Therapeutic advances in drug safety. 2016;7(3):120-1.
9. Salem CB, Badreddine A, Fathallah N, Slim R, Hmouda H. Drug-induced hyperkalemia. Drug
safety. 2014;37(9):677-92.
10. Lim SY, Lee SR, Kim YH, Kim JS, Kim SH, Ahn JC, et al. a case of enoxaparin-induced
thrombocytopaenia during treatment of acute myocardial infarction. Cardiovascular journal of
Africa. 2016;27(3):e5.
11. Arepally GM. Heparin-induced thrombocytopenia. Blood. 2017;129(21):2864-72.
12. Ronceray S, Dinulescu M, Le Gall F, Polard E, Dupuy A, Adamski H. Enoxaparin-induced DRESS
syndrome. Case reports in dermatology. 2012;4(3):233.
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13. Walsh S, Creamer D. Drug reaction with eosinophilia and systemic symptoms (DRESS): a clinical
update and review of current thinking. Clinical and Experimental Dermatology: Clinical
dermatology. 2011;36(1):6-11.