ADDIS ABABA UNIVERSITY

COLLEGE OF HEALTH SCIENCES

SCHOOL OF PHARMACY
DEPARTMENT OF PHARMACOLOGY AND CLINICAL PHARMACY
Drug Information Clerkship
Drug Monograph

Prepared BY Yodahe Mekonnen

PHR/5150/04

Submitted To Ins. Belete Ayalneh (BPharm, MPharm)

Submitted Date 19/11/15

Generic Name: Enoxaparin Sodium

Trade or Brand Name: Clexane, Lovenox
Manufacturer (or source of supply): Sanofi-avenis, France
Therapeutic Category: Anticoagulant drugs or Antithrombotic agent
Classification: Heparins, low molecular weight heparins.
Status: Prescription-only (POM)
Similar Agents: Bemiparin, Dalteparin, Reviparin
Pharmacologic Data
Mechanism of action
Enoxaparin is a low molecular weight heparin with anticoagulant
properties. It acts by enhancing the inhibition rate of activating clotting factors
including thrombin and factor Xa through its action on antithrombin III.

Pharmacokinetics

Heparin

Peak plasma
concentration achieved
24 hours following
subcutaneous
Bioavailability administration

Enoxaparin
Mean absolute
bioavailability of
approximately 100%
(based on anti-Factor Xa
activity) when given
subcutaneous in healthy
individuals.
Maximum anti-factor Xa
and antithrombin (antifactor IIa) activities occur
35 hours after
administration

Absorption

Immediate following
direct IV injection or IV
infusion of full doses.
Onset

Duration

Within 2060 minutes

following deep
subcutaneous injection.
Heparin lock flush
solutions:
Anticoagulation
maintained within the
device for generally up
to 4 hours

Direct IV injection of 30
mg immediately followed
by 1 mg/kg dose
subcutaneous resulted in
postinjection aPTT of 50
seconds.

Substantial anti-factor Xa
activity persists in
plasma for about 12
hours following
administration (40 mg
once daily).
Average aPTT
prolongation on day 1
about 16% higher than
on day 4.

Distribution

Extent

Does not cross the

placenta and is not
distributed into milk

About 4.3 L (based on

anti-factor Xa activity).
Enoxaparin does not
appear to cross the

placenta; not known

whether the drug is
distributed into milk.
Metabolism

May be partially
metabolized in the liver
to uroheparin, which is
partially desulfated
heparin
Small fraction excreted
in urine as unchanged
drug

Metabolized, principally
in the liver via
desulfation and/or
depolymerization, to less
active metabolites
40% of dose is excreted
in urine.

Half-life

12 hours in healthy
adults. Half-life increases
with increasing doses.
Plasma half-life averages
56, 96, and 152 minutes
following IV heparin
sodium doses of 100,
200, or 400 units/kg,
respectively.

4.5 hours after single

subcutaneous dose,
approximately 7 hours
after multiple dosing
(based on anti-factor Xa
activity).

Special
population

AUC increased 65% in

patients with severe
renal impairment (CrCl
less than 30 mL/min).

Clearance reduced in
patients with renal
impairment. In patients
with severe renal
impairment (Clcr <30
mL/minute), anti-factor
Xa exposure (represented
by AUC) was increased
by approximately 65%.

Elimination tool

Possible delayed
elimination and increased
exposure in geriatric
patients.

Table 1. The pharmacokinetics of Enoxaparin

Therapeutic Indications
An anti-coagulant drug used for multiple indications including prevention
of deep vein thrombosis (DVT), a potentially deadly blood clotting condition.
Prevention of deep vein thrombosis (DVT), which may lead to pulmonary embolism
(PE) in patients undergoing hip or knee replacement surgery or abdominal surgery and
in medical patients who are at risk for thromboembolic complications because of
severely restricted mobility during an acute illness; in conjunction with warfarin for
inpatient treatment of acute DVT with or without PE, or outpatient treatment of acute
DVT without PE; prevention of ischemic complications of unstable angina and nonQwave MI when co-administered with aspirin; treatment of acute ST-segment elevation
MI (STEMI) in patients receiving thrombolysis and being managed medically or with
percutaneous coronary intervention (PCI).
Unlabeled Uses
Enoxaparin has some unlabeled use such as prevention of exercise-induced
bronchorestriction; venous thromboembolism; prophylaxis in cancer patients with
central venous catheters; venous thromboembolism prophylaxis in general surgery
and/or gynecologic surgery.
Dosage Forms
Available as enoxaparin sodium Injection; dosage expressed in terms of the salt.
Dosages for enoxaparin sodium or other LMWHs and heparin cannot be used
interchangeably on a unit-for-unit (or mg-for-mg) basis. Enoxaparin sodium has an
approximate anti-factor Xa activity of 100 units/mg using the World Health
Organization (WHO) First International Low Molecular Weight Heparin Reference
Standard. The generic product has been approved in the following strengths: 30 mg/0.3
mL, 40 mg/0.4 mL, 60 mg/0.6 mL, 80 mg/0.8 mL, 100 mg/mL, 120 mg/0.8 mL, and
150 mg/mL.
Enoxaparin must Store at a temperature below 25 oc. It is recommended to not store
multidose vials for more than 28 days after the first use.
Dosage Range
In generally, in clexane (Available Brand Name) 20 mg/0.2ml the treatment does not
last more than 10 days. And in 40 mg/ 0.4 ml at a time of surgery , it will not last more
than 10 days except when prescribed after certain hip operation. In acute medical
condition, treatment duration is 6-14 days.

 Adults:- For preventive treatment in surgery

o In moderate-risk surgery the dosage is one daily injection of 20 mg/0.2ml.
o In high- risk surgery the dosage is one daily injection of 40 mg/0.4 ml
o Hemodialysis- one 1mg/kg dose will be administered.
o Preventive treatment in medicine- dosage is one daily injection of 40
mg/0.4 ml
Children: - not recommended to children.
Elderly Initiate dosing with 0.75 mg/kg subcutaneous every 12 h (max, 75 mg for
the first 2 doses only, followed by 0.75 mg/kg dosing for the remaining doses).
Known Adverse Effects/Toxicities
Cardiovascular: - Atrial fibrillation, heart failure (1%).
Dermatologic: -Cutaneous vasculitis, purpura, skin necrosis occurring at the injection
site or distant from the injection, vesiculobullous rash (postmarketing).
Gastro-Intestinal: -Nausea (3%); diarrhea (2%).
Hematologic-Lymphatic:- Anemia (16%); hemorrhage (13%); major bleeding (4%);
thrombocytopenia (3%); thrombocytopenia with thrombosis, thrombocytosis
(postmarketing).
Hypersensitivity:- Systemic allergic reactions including anaphylactic/anaphylactoid
reactions, pruritus, and urticaria (postmarketing).
Laboratory Tests:- Increased AST and ALT more than 3 times ULN (6%);
hyperkalemia, hyperlipidemia, hypertriglyceridemia (postmarketing).
Local :- Injection-site hemorrhage (5%); ecchymosis (3%); injection-site pain (2%);
erythema, hematoma, mild local irritation, pain; injection-site reactions, including
inflammation, nodules, and oozing (postmarketing).
Respiratory:- Dyspnea (3%); lung edema, pneumonia (1%).
Miscellaneous:- Fever (8%); peripheral edema (6%); confusion, edema, hematuria (2%);
epidural or spinal hematoma (postmarketing).
Prevention of toxicity: - delay dosing of anticoagulant medications for some time
interval after catheter removal to decrease the risk of spinal column bleeding and
subsequent paralysis after spinal injections, including epidural procedures and
lumbar punctures. These new timing recommendations, which can decrease the risk
of epidural or spinal hematoma, will be added to the labels of anticoagulant drugs

known as low molecular weight heparins, including Lovenox and generic enoxaparin
products and similar products.
Special Precautions: Pregnancy: - Category B
Breast- Feeding not contraindicated in breast feeding women.
Contraindications
If the patient has known allergy to the heparin or heparin derivatives, including other
low molecular weight heparins. If the patient has previously had a serious decrease in
plate lets due to heparin, and if there is excess bleeding.
Drug-Drug
Antithrombin:- The risk of severe bleeding may be increased. Close clinical and
laboratory monitoring (aPTT and/or anti-Xa) is indicated during coadministration of
enoxaparin and antithrombin. Adjust the dose of enoxaparin accordingly. Reduced doses
of enoxaparin are recommended when coadministered with antithrombin III.
Drugs that increase the risk of bleeding (eg, oral anticoagulants [eg, warfarin], platelet
inhibitors [eg, dipyridamole], NSAIDs, salicylates, sulfinpyrazone, ticlopidine) Use
enoxaparin with caution because of increased risk of hemorrhagic reactions.
SSRIs (eg, fluoxetine):- The risk of severe bleeding may be increased. Carefully monitor
the coagulation status of the patient and observe the patient for bleeding. Adjust
therapy as needed.
Patient Safety Information

Inform patients who have had neuraxial anesthesia or spinal puncture, especially
if they are taking concomitant NSAIDs, platelet inhibitors, or other
anticoagulants, to watch for signs and symptoms of spinal or epidural hematoma,
such as tingling, numbness (especially in the lower limbs), and muscular
weakness, and to contact their health care provider immediately if they occur.
Advise patients that the use of aspirin and other NSAIDs may enhance the risk of
hemorrhage.
Instruct patient to report any signs of bleeding or bruising; signs of
thrombocytopenia (eg, a rash of dark spots under the skin); or black, bloody, or
tarry stools immediately.
If patient has home therapy, teach patient or family member proper subcutaneous
injection technique.
Caution patient to take safety precautions to prevent cuts and bruising (eg, use
electric razor, soft toothbrush, handrails).

Advise patients to inform their health care providers and dentists that they are
taking enoxaparin or any other product known to affect bleeding before any
surgery is scheduled or before any new drug is taken.

Patient Information
o Name and description of the medication
This medicinal product is an anticoagulant agent of the so called
low-molecular-weight heparin family. It prevents blood clots from
forming in vein or artery (thrombosis) and also prevents recurrence.
o Dosage form
It is available in injection form
o Route of administration
Subcutaneous administration. For subcutaneous or IV bolus
injection. Do not administer by IM injection.
o Duration of therapy
Elimination half-life is 4.5 h (single dose) to 7 h (repeat dosing)
(based on antifactor Xa activity).
o Special directions and precautions
In order to avoid bleeding, it is essential not to exceed the dose and
duration of treatment. And treatment requires repeated blood tests to
regular check the platelet count.
For patient with acute infection treatment is only warranted if the patient
is above 75 years old, history of venous disease, obesity.
o Side effects
Bleeding of varying seriousness, external or internal
Decreasing in number of platelets in blood
Rare sever skin reaction
Local or general allergic reaction.
o Techniques for self-monitoring
This skin fold should be held throughout the injection. Do not
aspirate into syringe; do not rub site after injection. These activities may
cause tissue damage and subcutaneous bleeding.

Most patients or caregivers can administer enoxaparin injections after learning how to
properly inject it.
Step 1 Wash and dry your hands thoroughly
Step 2 Sit or lie in comfortable position, so that you can see your abdomen.
Step 3 Choose an area on the right or left side of your abdomen, at least 2 inches
from your belly button. Think love handles
Step 4 clean injection sites with an alcohol swab. Let dry
Step 5 Remove the needle cap by pulling it straight off the syringe and discard it
in the sharps collector.
Step 6 Hold the syringe like a pencil in your writing hand.
Step 7 with your other hand; pinch an inch of the cleansed area to make a fold in
the skin. Insert the full length of the needle straight down- at a 900 angle into
the fold of skin.
Step 8 presses the plunger with your thumb until the syringe is empty.
Step 9 pull the needle straight out at the same angle that it was inserted, and
release the skin fold.
Step 10 point the needle down and away from yourself and others and push down
on the plunger to activate the safety shield.
Step 11 places the used syringe in the sharp collector.
o Proper storage :- Store at temperature below 25 0C
o Refill information
The prefilled syringe is ready to use; do not press on the plunger to
expel any air bubbles before administering the injection.the needle should
be introduce perpendicularly, not form the side, into a skin fold held
between the thumb and index finger. For IV injection, use the multidose
vial. Flush IV access with saline or dextrose solution prior to and
following the IV bolus of enoxaparin to clear the port of the drug. Do not
mix or coadminister with other injections or infusions. For IV use,
enoxaparin can be mixed with saline 0.9% solution or dextrose 5% in
water.
o If an injection of enoxaparin missed, take the missed dose as soon as
remember. If it is almost time for the next injection, skip the missed dose
and take next injection.

Cost Comparison:
Heparin
Enoxaparin
Cost
Around 170 birr (the price 358 birr referring
is not present time)( But it Clexane.
is sure that the price is
lower than enoxaparin)
Table 2. Comparison of price of heparin and Enoxaparin

to

Summary

Enoxaparin is a clear, colorless to pale yellow solution and should be inspected

visually for particulate matter and discoloration prior to administration.

Advantage

Disadvantage

Self-Administrate

Not use for pediatric

Pregnancy category raised to B

Delayed elimination and risk of bleeding

possibilities in elderly patient

Bioavailability is approximately 100%.

For Hepatic Function Impairment

Pharmacokinetic studies have not been
conducted so there a risk for use.

Fast onset of time.

Boxed warning that use of the drug in

patients
undergoing
spinal/epidural
anesthesia or spinal puncture increases the
risk of spinal or epidural bleeding and
bruising (hematoma), which may cause
long-term or permanent paralysis.

Table 3. Advantage and Disadvantage of Enoxaparin

Recommendations:
Indicate whether or not the drug should be added to the Drug Formulary of an
institution, assuming they would have patients that would be treated for illnesses where
this drug might be used. Also indicate specific formulary status for the drug (i.e.,
uncontrolled, monitored, restricted, and conditional) and whether the drug will replace
any other product that might already be on the formulary. In addition, present any
information on how the drug is to be placed in any clinical guidelines.
Enoxaparin injection is a prescription only drug which most of the time it has a huge
use for patients with serious need of it. The approval of this medication in formulary
offers the potential for greater affordability for patients in need of this blood thinner. In
comparing with heparin which is available only in hospital it has greater effect in
national level. This medication has greater therapeutic use than the old heparin in sense

of being self-administrate medication , prefilled syringe, having advantage in use of

pregnancy. In addition of having it in hospital formulary, enoxaparin is available in
community pharmacy so it increase patients level of feeling safe regarding fear of out of
stock in hospital pharmacy.

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References
1. Griffiths MC, 1993, USAN and the USP dictionary of drug names. The United
States Pharmacopeial Convention.
2. Enoxaparin sodium, 2013, AHFS DI Essentials, http://www.Drugs.com
3. Spiro TE, Colwell CW, Bona RD et al et al. , 1994.Enoxaparin versus
unfractionated heparin for prevention of venous thromboembolic disease after elective knee
replacement surgery.
4. Clexane package leaflet. Sanofi-avenis,France, Jan 2009
5. Weitz JI. 1998, Low molecular weight heparins.

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