Clexane (Enoxaparin) is an irreversible inhibitor of factor Xa. It binds to circulating antithrombin III and potentiates its effects. It is used in the treatment and prevention of deep vein thrombosis and pulmonary embolism.

Clexane (Enoxaparin) Uses:

• Acute coronary syndromes:

  • Enoxaparin is used in the management of unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI).

• VTE prophylaxis:

  • It is used after hip or knee replacement surgery, abdominal surgery, or in medical patients with severely restricted mobility during acute illness who are at risk for thromboembolic complications.
  • It is notable that patients at risk of thromboembolic complications who undergo abdominal surgery include those with one or more of the following risk factors:
    • age more than 40 years,
    • obesity,
    • general anesthesia lasting for more than 30 minutes,
    • malignancy,
    • history of DVT or PE.

• DVT treatment (acute):

  • It can also be used as inpatient treatment (patients with or without PE) and outpatient treatment (patients without PE).

However, in patients with VTE (ie, DVT or PE) and without cancer, oral anticoagulants are preferred over low-molecular-weight heparin (LMWH), unless LMWH is used as initial parenteral anticoagulation prior to dabigatran, edoxaban, or while initiating warfarin. In patients with VTE (ie, DVT or PE) and cancer, ACCP recommends LMWH over oral anticoagulants (NOACS) for initial and long-term treatment.

• Off Label Use of Enoxaparin in Adults:

  • Acute symptomatic superficial vein thrombosis of the lower extremity, when it is more than 5 cm in length.
  • As a bridging of anticoagulants in the mechanical heart valve.
  • Acute pulmonary embolism.
  • Bariatric surgeries as prophylaxis for VTE, as such patients are at higher risk.

 

Clexane (Enoxaparin) Dose in Adults:

It is important to note that 1 mg of enoxaparin is equal to 100 units of anti-Xa activity (World Health Organization First International Low Molecular Weight Heparin Reference Standard). Weight-based doses (eg, 1 mg/kg) are commonly rounded to the nearest 10 mg. Local institutional guidelines should also be consulted. Most available prefilled syringes are graduated in 10 mg increments.

Clexane (Enoxaparin) Dose in the treatment of Acute symptomatic superficial vein thrombosis (lower extremity; ≥5 cm in length) (off-label):

• SubQ: 40 mg once daily for 45 days.

The risk of recurrence is high if anticoagulation is discontinued earlier than 45 days. Monitor D-dimer at baseline and again at 45 days, and if d-dimer remains elevated, a longer course might be necessary.

Clexane (Enoxaparin) Dose in the treatment of Ischemic heart disease:

• Acute coronary syndromes:

  • Non-ST elevation acute coronary syndromes:
    • SubQ: 1 mg/kg every 12 hours in conjunction with recommended antiplatelet therapy.
    • Continue for the duration of hospitalization or until percutaneous coronary intervention (PCI) is performed.
    • Some clinicians suggest that enoxaparin, although comparable in efficacy to unfractionated heparin (UFH), does not have a role in patients undergoing an invasive approach due to an increased risk of bleeding, and UFH or bivalirudin is preferred.
  • ST-elevation myocardial infarction (STEMI):
    • It is noteworthy that although the literature includes the use of enoxaparin for patients with STEMI undergoing primary PCI, heparin or bivalirudin is preferred.
    • Initial dosing is the same for patients who undergo reperfusion with fibrinolysis or PCI and for patients who do not undergo reperfusion.
    • Therapy may be continued for up to 8 days with a minimum of 48 hours when undergoing reperfusion with fibrinolysis or until revascularization.
    • Unless it is contraindicated, all patients should receive aspirin and a P2Y inhibitor.
    • In patients with STEMI receiving thrombolytics, initiate enoxaparin between 15 minutes before and 30 minutes after fibrinolytic therapy.
    • Patients <75 years of age:
      • A single IV bolus of 30 mg plus 1 mg/kg with a maximum dose up to 100 mg for the first 2 doses only, then SubQ every 12 hourly.
      • The first SubQ dose should be administered with the IV bolus.
    • Patients ≥75 years of age:
      • Note: No IV bolus is indicated in this population.
      • SubQ: 0.75 mg/kg with a maximum dose of 75 mg for the first 2 doses only, every 12 hourly.

• Clexane (Enoxaparin) dose during PCI, adjunctive therapy (off-label):

  • If the patient undergoing PCI has been treated with multiple doses of enoxaparin and PCI occurs within 8 hours after the last SubQ enoxaparin dose the there is no indication of additional enoxaparin.
  • If PCI occurs 8 to 12 hours after the last SubQ enoxaparin dose in a patient treated with multiple doses of enoxaparin or the patient has received only 1 therapeutic SubQ dose (eg, 1 mg/kg) then administer a single IV dose of 0.3 mg/kg.
  • If PCI occurs 12 hours after the last SubQ dose then one can use an indicated anticoagulation regimen (eg, full-dose UFH or bivalirudin).

It is not generally initiated in patients undergoing elective PCI and not recommended in patients undergoing PCI for acute coronary syndromes.

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Clexane (Enoxaparin) Dose in the treatment of Mechanical heart valve (bridging anticoagulation) (off-label):

It is important to know that bridging during periprocedural intervals of subtherapeutic anticoagulation can be considered if there is an additional thromboembolic risk factor, such as atrial fibrillation, left ventricular systolic dysfunction, older-generation mechanical valves, or mechanical mitral or tricuspid valve replacement. Candidates with aortic valve replacement but without additional risk factors for thrombosis, other than the mechanical valve, may not require bridging. It is also reasonable to use enoxaparin for this indication during the gestational period, especially during the first trimester.

• SubQ: It is given as 1 mg/kg every 12 hours.
• Adjust dose based on anti-Xa monitoring. The anti facto X-a levels should be monitored according to local guidelines.

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Clexane (Enoxaparin) Dose in VTE prophylaxis:

For patients who are assessed to be at the highest risk including Caprini score >8, stroke, active cancer, and multiple risk factors, many experts combine pharmacologic methods with mechanical methods or increase the dose frequency to twice daily (eg, 30 or 40 mg twice daily). Titrating up  the dose should always be balanced against the risk of bleeding.

• Clexane (Enoxaparin) Dose for prophylaxis during Bariatric surgery in high risk for VTE patients:

Optimal dose strategies have not yet been established. Dosing regimens based on the best available evidence.

• • BMI ≤50 kg/m²:
    • SubQ: 40 mg every 12 hours initiated at least 2 hours before the procedure.
  • BMI >50 kg/m²:
    • SubQ: 60 mg every 12 hours initiated at least 2 hours prior to the procedure.

The Optimal duration of prophylaxis is yet unstudied, but is usually continued until hospital discharge and may be extended for up to 6 weeks postoperatively depending upon VTE risk. There is no consensus on recommendations for extended prophylaxis following bariatric surgery.

• Clexane (Enoxaparin) dose for prophylaxis in hospitalized medical patients with acute illness at moderate and high risk for VTE (including patients with active cancer):

  • SubQ: It is given as 40 mg once a day.
  • It should be continued for the length of hospital stay or until the patient is fully ambulatory and the risk of VTE has diminished.
  • The extended prophylaxis beyond acute hospital stay is not routinely indicated.

• Clexane (Enoxaparin) dose for prophylaxis in major non-orthopedic surgery (patients with active cancer) (off-label):

Note: Regimens vary and include the following:

• • SubQ: 40 mg started 10 to 12 hours before surgery and 40 mg once a day thereafter OR
  • SubQ: 20 mg started 2 to 4 hours before surgery and 40 mg once a day thereafter OR
  • SubQ: 40 mg once daily started approximately 12 to 24 hours after surgery.

However, the optimal duration of prophylaxis has not yet been studied. It is usually given for a minimum of 7 to 10 days. Extending it up to  4 weeks may be reasonable option in those undergoing major abdominal or pelvic surgery.

• Clexane (Enoxaparin) Dose for prophylaxis in nonorthopedic surgery (patients without cancer):

Note: For patients with a moderate and high risk of VTE and low risk of bleeding:

• • SubQ: 40 mg once a day, with an initial dose given at least 2 hours before abdominal surgery or approximately 12 hours before other non-orthopedic surgery.
  • Alternatively, It can be postponed (pharmacologic prophylaxis) until after surgery (eg, high bleeding risk) when it is safe to initiate.
  • If hemostasis is difficult to achieve postoperatively, withhold prophylaxis until it is safe to reinitiate. Continue until fully ambulatory and risk of VTE has diminished (typically up to 10 days).

• Clexane (Enoxaparin) Dose for prophylaxis in Pregnancy (off-label):

It is notable that for patients at moderate and high VTE risk during antepartum and postpartum periods, the dose intensity is individualized based on risks of thrombosis and bleeding complications.

• • Prophylactic dose:
    • SubQ: 40 mg once every 24 hours.
  • Intermediate dose:
    • SubQ: 40 mg every 12 hours.
    • However, some clinicians use an alternative intermediate regimen of 40 mg SubQ once a day, increasing as pregnancy progresses to 1 mg/kg once a day.
  • Adjusted dose (therapeutic):
    • SubQ: It is given as 1 mg/kg every 12 hours.
    • And it is reserved for patients at the highest risk such as those with a history of recurrent thrombosis or severe thrombophilia.

The Anticoagulation management prior to delivery of the baby is individualized. Options include replacing with UFH at 36 to 37 weeks' gestation or extending to 38 to 39 weeks' gestation, in patients at very low risk of delivery while on enoxaparin. In such patients, discontinue enoxaparin 12 hours before delivery if used as prophylaxis or 24 hours before delivery if used in therapeutic range, particularly if neuraxial anesthesia is planned. It can be restarted after 4 to 6 hours after vaginal delivery or more than 6 to 12 hours after cesarean delivery unless significant bleeding has occurred. Anticoagulation should continue for up to 6 weeks postpartum in high-risk women.

• Clexane (Enoxaparin) Dose for prophylaxis during Total hip arthroplasty (THA) or hip fracture surgery:

  • SubQ: 40 mg once a day or 30 mg 12 hourly, with the initial dose administered 12 hours preoperatively or after 12 hours postoperatively once hemostasis is achieved.
  • The optimal duration of prophylaxis is not known, but it is usually given for a minimum of 10 to 14 days.
  • Prophylaxis can be extended beyond the minimum of 10 to 14 days for up to 35 days.
  • It can be discontinued earlier if the patient is fully ambulatory. Some clinicians suggest a duration at the higher end of range (eg, 30 days) for THA..

• Clexane (Enoxaparin) Dose for prophylaxis during total knee arthroplasty (TKA):

  • SubQ: 30 mg every 12 hours, with the initial dose administered 12 hours preoperatively or after 12 hours postoperatively once hemostasis is achieved.
  • The optimal duration of prophylaxis is not studied, but it is usually given for a minimum of 10 to 14 days.
  • Prophylaxis can be extended beyond the minimum of 10 to 14 days for up to 35 days. It can e discontinued earlier if the patient is fully ambulatory.
  • Some clinicians suggest a duration at the lower end of the range (eg, 10 to 14 days) for TKA.

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Clexane (Enoxaparin) Dose in the treatment of VTE:

For timing of initiating oral anticoagulant, see Transitioning between anticoagulants. For patients with active cancer, see VTE treatment in patients with active cancer.

• DVT and/or PE (PE is an off-label use):

  • Inpatient treatment:
    • SubQ: 1 mg/kg every 12 hours is the preffered dose or 1.5 mg/kg once every 24 hours.
    • It is important to note that in select low-risk patients, one might consider outpatient treatment using 1 mg/kg every 12 hours for the remainder of the course after the first dose administered in the hospital or urgent care center.
  • Duration of therapeutic anticoagulation (first episode, general recommendations):
    • The optimal duration of therapy is not studied and depends on many factors, such as whether provoking events were present, patient risk factors for recurrence and bleeding and individual preference.
    • Provoked VTE:
      • 3 months, provided the provoking risk factor is no longer present.
    • Unprovoked PE or DVT (proximal or isolated distal):
      • More than 3 months depending on the risk of VTE recurrence and bleeding.

It is notable that all patients receiving indefinite therapeutic anticoagulation with no specified stop date and should be reassessed at periodic intervals.

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Clexane (Enoxaparin) Dose in the treatment of VTE in patients with active cancer:

• Months 1 to 6:

  • SubQ: Initially it can be given as 1 mg/kg every 12 hours or 1.5 mg/kg once daily for 5 to 10 days followed by long-term anticoagulation for a total duration of 3 to 6 months.
  • The twice-daily dosing may be more efficacious than once-daily dosing based on post hoc data.

• Maintenance beyond 6 months:

  • ACCP and ASCO guidelines for VTE prophylaxis & treatment recommends, considering continuing anticoagulation beyond 6 months in select patients due to the persistent high risk of relapse in those with active cancer.
  • One should consider the risk versus benefit of bleeding and recurrence.

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Clexane (Enoxaparin) Dose in the treatment of VTE in pregnancy:

• SubQ: It is given as 1 mg/kg every 12 hours.
• Some clinicians suggest anti-Xa monitoring for dose adjustment.

The anticoagulation management prior to delivery is individualized. Options include replacing with UFH at approximately 36 to 37 weeks' gestation or extending to 38 to 39 weeks' gestation in patients at very low risk of delivery while on enoxaparin. In such patients, withhold enoxaparin 24 hours before delivery, particularly if neuraxial anesthesia is planned; may restart ≥4 to 6 hours after vaginal delivery or ≥6 to 12 hours after cesarean delivery, unless significant bleeding has occurred. The optimal duration of anticoagulation is not studied. In general, the total duration i.e antepartum plus postpartum should be at least 3 to 6 months with at least 6 weeks postpartum.

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Transitioning between anticoagulants:

This provides general guidance between transitioning one anticoagulant to another.

• Transitioning from another anticoagulant to enoxaparin:

  • The transitioning from therapeutic IV UFH infusion to therapeutic-dose enoxaparin:
    • Withhold UFH and begin enoxaparin within 1 hour.
    • It should be noted that if aPTT is not in the therapeutic range at the time UFH is stopped, then local guidelines should be consulted.

• Transitioning from enoxaparin to another anticoagulant:

  • Transitioning from therapeutic-dose enoxaparin to therapeutic IV UFH infusion:
    • Start IV UFH (rate based on indication) 1 to 2 hours before the next dose of enoxaparin would have been scheduled. The IV UFH loading dose is omitted.
  • Transitioning from prophylactic enoxaparin to therapeutic IV UFH:
    • UFH should be started without any delay.
    • A UFH loading dose may be used if needed.
  • Transitioning from therapeutic-dose enoxaparin to warfarin for VTE treatment:
    • Start warfarin on the first or second treatment day and overlap with enoxaparin until INR is more than 2 for at least 2 measurements, 24 hours apart.
    • The duration of overlap is usually 4 to 5 days.
  • Transitioning from therapeutic-dose enoxaparin to warfarin for nonvalvular atrial fibrillation:
    • In patients who are not at high risk of immediate thromboembolism, warfarin is usually started without parenteral anticoagulant (ie, no bridging is done).
    • In patients who are at high risk of immediate thromboembolism, overlapping with enoxaparin is done until INR is within the therapeutic range.
  • Transitioning from therapeutic-dose enoxaparin to a direct oral anticoagulant (DOAC):
    • Note: In the treatment of VTE, some DOACs (dabigatran, edoxaban) require 5 days of parenteral anticoagulation prior to switching.
  • General transition recommendation:
    • Start DOAC within 2 hours prior to the next scheduled dose of enoxaparin.
  • VTE initial treatment transition (alternative recommendation):
    • For acute VTE, some experts start DOAC within 6 to 12 hours after the last dose of a twice-daily LMWH regimen or within 12 to 24 hours after a once a day LMWH regimen.

 

Clexane (Enoxaparin) Dose in Children:

It is important to note that enoxaparin has approximately 100 anti-factor Xa units/mg enoxaparin (World Health Organization First International Low Molecular Weight Heparin Reference Standard). In order to improve accurate measurement and avoid dilution of enoxaparin pediatric enoxaparin doses, the following methods have reported at some centers:

• Dose rounding to the nearest whole mg (down or up, as appropriate) and administering with 100 unit insulin syringe;
• The dose should be given by taking every precaution.

Clexane (Enoxaparin) Dose for Prophylaxis:

• Infants 1 to <2 months:

  • SubQ: 0.75 mg/kg/dose every 12 hours

• Infants ≥2 months, Children, and Adolescents:

  • SubQ: 0.5 mg/kg/dose every 12 hours

Clexane (Enoxaparin) Dose in the treatment of Thrombosis:

Preliminary data from 213 pediatric patients evaluating 1,061 anti-factor Xa levels suggests that pediatric dose titration in patients of less than 2 years of age may be affected by assay methodology; SubQ:

• Initial:

  • Chest/ AHA guidelines:

    • Infants 1 to <2 months:
      • SubQ: 1.5 mg/kg/dose every 12 hours
    • Infants ≥2 months, Children, and Adolescents:
      • SubQ: 1 mg/kg/dose every 12 hours

  • Alternate dosing:

    • Some studies suggest that initial doses higher than those recommended in the Chest guidelines are required in pediatric patients (especially in young infants or critically ill).
    • Some centers have used the following:
      • 1 to <3 months:
        • 1.8 mg/kg/dose every 12 hours
      • 3 to 12 months:
        • 1.5 mg/kg/dose every 12 hours
      • 1 to 5 years:
        • 1.2 mg/kg/dose every 12 hours
      • 6 to 18 years:
        • 1.1 mg/kg/dose every 12 hours

• Clexane (Enoxaparin) Dosing adjustment, thrombosis treatment:

  • Titrate up the dose to achieve a 4 to 6 hours post-dose target anti-factor Xa level of 0.5 to 1 units/mL.
  • The duration of treatment is based on the thrombosis site, clinical response, and other identified risk factors.
  • The usual duration is between 6 weeks and 3 months.

Previous CHEST guidelines suggested the following dosage adjustments to achieve the target anti-factor Xa range.

Clexane (Enoxaparin) Dosage Titration

Antifactor Xa	Dose Titration	Time to Repeat Antifactor Xa Level
<0.35 units/mL	Increase dose by 25%	4 h after next dose
0.35-0.49 units/mL	Increase dose by 10%	4 h after next the dose
0.5-1 unit/mL	Keep the same dosage	Next day, then 1 wk later, then monthly (4 h after dose)
1.1-1.5 units/mL	Decrease dose by 20%	Before the next dose
1.6 - 2 units/mL	Hold dose for 3 h and decrease dose by 30%	Before the next dose, then 4 h after the next dose
>2 units/mL	Hold all doses until anti-factor Xa is 0.5 units/mL, then decrease dose by 40%	Before next dose and every 12 h until anti-factor Xa <0.5 units/mL
Monitoring anti-factor Xa levels are indicated in very obese patients and those with renal failure.

 

Clexane (Enoxaparin) Pregnancy Risk Category: B

• Low molecular weight heparin, (LMWH), does not cross the placenta. There have been no reports of increased risks for fetal bleeding and teratogenic effects.
• For the treatment of acute VTE in pregnant ladies, LMWH is preferred to unfractionated heparin. 
• LMWH is preferred over unfractionated heparin in VTE prophylaxis for pregnant women with certain risk factors, such as homozygous Factor V Leiden and antiphospholipid antibodies syndrome with more than three previous pregnancies.
• Women undergoing assisted reproduction therapy are not advised to receive prophylaxis. For women with severe ovarian hyperstimulation syndrome, LMWH therapy may be indicated.
• The prophylactic use LMWH might be an option for women who are having a cesarean section or have other risk factors.
• For pregnant women, consult the current recommendations.
• LMWH can be used by women who have mechanical heart valves.
• If possible, LMWH replacement should be performed prior to conception for women who need long-term anticoagulation with Warfarin and are contemplating pregnancy.
• Consider the following: fetal outcomes (ie. pregnancy loss, malformations), maternal results (ie. VTE, hemorhage), the burden and maternal preference when choosing therapy (Bates 2012). It is preferable to monitor anti-factorXa levels.
• Multiple-dose vials containing benzyl alcohol are not recommended for pregnant women as it can be associated with gasping syndrome in infants. Preservative-free formulations are recommended.

Enoxaparin use during breastfeeding:

• It is unknown whether breast milk contains it.
• Breast milk has been found to contain small amounts of another LMWH. Because they are low in oral bioavailability, LMWHs can cause less adverse reactions in a nursing infant.
• According to the manufacturer the decision to stop or continue breastfeeding during therapy must consider the risks to infants, the benefits to the mother, and the benefits to the mother.
• Breastfeeding women may continue to use LMWH, according to antithrombotic guidelines.

 

Clexane (Enoxaparin) Dose in Kidney Disease:

• CrCl ≥30 mL/minute:

  • There are no specific dosage adjustments provided in the literature. But monitor closely for bleeding.

• CrCl <30 mL/minute:

  • DVT prophylaxis in abdominal surgery, hip replacement, knee replacement, or in medical patients during acute illness:
    • SubQ: 30 mg once a day.
    •  The Canadian labeling recommends 20 to 30 mg once a day dose (based on the risk/ benefit assessment) for prophylaxis in abdominal or colorectal surgery or in medical patients during acute illness.
  • DVT treatment:
    • SubQ: 1 mg/kg once a day.
  • STEMI:
    • <75 years:
      • Initially it is given as IV, 30 mg as a single dose with the first dose of the SubQ maintenance regimen administered at the same time as the IV bolus.
      • The maintenance SubQ dose is 1 mg/kg once daily.
      • The Canadian labeling recommends a maximum dose of 100 mg for the first SubQ dose.
    • ≥75 years of age:
      • IV bolus should be excluded.
      • The maintenance dose is  SubQ: 1 mg/kg once a day The Canadian labeling recommends a maximum dose of 100 mg for the first SubQ dose.
  • Unstable angina, NSTEMI:
    • SubQ: 1 mg/kg once a day.

• Dialysis:

  • Enoxaparin has not been FDA approved for use in dialysis patients. Its excretion is primarily via the renal route.
  • Serious bleeding manifestations have been reported with use in patients who are dialysis-dependent or have severe renal failure.
  • LMWH administration at fixed doses without monitoring has greater unpredictable anticoagulant effects in patients with chronic kidney disease.
  • If used, dosages should be reduced and anti-Xa levels frequently monitored, as accumulation can occur with repeat doses.
  • Many experts would not use enoxaparin in this population especially without timely anti-Xa levels.

• Hemodialysis:

  • It is not dialyzable. The additional doses are not indicated.

• Peritoneal dialysis:

  • Significant drug removal is unlikely based on physiochemical characteristics.

 

Dose in Liver disease:

Caution is advised however no dose adjustments are given in the literature.

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As with all anticoagulants, bleeding is the major adverse effect of enoxaparin. Bleeding may occur at virtually any site. Risk is dependent on multiple variables. At the indicated doses, single injections of enoxaparin can not significantly influence platelet aggregation or affect global clotting time (ie, PT or aPTT).

 

Common Side Effects of Clexane (Enoxaparin):

• Hematologic & oncologic:

  • Anemia
  • Hemorrhage

Less Common Side Effects of Clexane (Enoxaparin):

• Cardiovascular:

  • Peripheral edema

• Central nervous system:

  • Confusion

• Gastrointestinal:

  • Nausea

• Hematologic & oncologic:

  • Major hemorrhage
  • Ecchymoses
  • Thrombocytopenia

• Hepatic:

  • Increased serum ALT
  • Increased serum AST

• Local:

  • Hematoma at injection site
  • Bleeding at injection site
  • Pain at injection site

• Renal:

  • Hematuria

• Miscellaneous:

  • Fever

 

Contraindications to Clexane (Enoxaparin):

• A history of hypersensitivity to enoxaparin (e.g., pruritus and urticaria), heparin or pork products is a contraindication.
• History of immune-mediated, heparin-induced hemothrombocytopenia (HIT), in the last 100 days or in the presence circulating antibodies.
• Active major bleeding

Canadian labeling: Additional contraindications not in US labeling

• Multiple-dose vials for newborns and premature neonates
• Acute and subacute bacterial heart disease.
• Major blood clotting disorders.
• Duodenal or active gastric ulcer.
• Except for systemic emboli, hemorhagic cerebrovascular accident is not considered hemorhagic.
• Hypertension severe and uncontrolled.
• Hemorrhagic or diabetic retinopathy.
• Hemorrhage can also be caused by other conditions and diseases.
• Operation or injury to the brain, spine cord, eyes, ears, and brain.
• Due to the increased risk of bleeding, repeated doses of enoxaparin (1.5 mg/kg daily or 1 mg/kg every 12hrs) are required for epidural or spinal anesthesia.

Warnings and precautions

• Bleeding

  • Pay attention to any signs or symptoms that may indicate bleeding.
  • The risk factors for bacterial endocarditis include congenital and acquired bleeding disorders, active ulcerative and angiodysplastic GI disease, hemorhagic stroke and severe uncontrolled hypertension. Patients who have had recent GI bleeding, ulceration, platelet dysfunction or history of heparin induced thrombocytopenia may also be at increased risk.
  • If bleeding is a problem, it's best to withhold treatment.
  • In overdose situations, protamine can be used as a partial reversal drug. Local guidelines for protamine dosage should be followed.
  • Hemostasis is achieved at the puncture site following PCI to reduce the chance of bleeding. The sheath can be easily removed if a closure device was used.
  • Manual compression should be used if the IV or SubQ doses of enoxaparin have expired.
  • After sheath removal, do not give any more doses. You should monitor the patient for bleeding signs or hematoma formation.

• Hyperkalemia:

  • Check for elevated potassium levels in ECF. Hyperkalemia can result from the suppression of aldosterone.
  • Patients with high risk factors for hyperkalemia are most likely to experience it.

• Thrombocytopenia:

  • It is possible to see low platelet counts. HIT, heparin-induced hemoglobinocytopenia with thrombosis (HITTS) have been reported in cases.
  • Some of these cases are complicated by organ injury, limb ischemia or even death. It is important to monitor platelet counts closely.
  • Patients with a history or HIT should be cautious. Patients with immune-mediated HIT in the past 100 days, or circulating antibodies are not recommended to use it.
  • Patients with a history HIT should not use this medication if it has been more than 100 days since the previous episode.
  • These patients may still experience HIT. Consider the risks and benefits of non-heparin alternatives.
  • If platelets fall below 100,000/mm3 or thrombosis occurs, stop the treatment.
  • Patients with congenital, drug-induced thrombocytopenia and platelet defects should exercise caution.

• Prosthetic heart valves:

  • Because of insufficient data, it is not recommended that patients with prosthetic hearts valves be treated for long-term thromboprophylaxis.

• Renal impairment

  • Renal impairment demands caution.
  • If CrCl is 30mL/minute, dosage adjustment may be necessary.

 

Enoxaparin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
5-Aminosalicylic Acid Derivatives	Heparins (Low Molecular Weight) may have an adverse/toxic effect. In particular, bleeding/bruising risk may be increased.
Antiplatelet Agents (e.g. P2Y12 inhibitors NSAIDs, SSRIs etc.)	May increase the anticoagulant effects of Anticoagulants.
Aliskiren	Aliskiren may increase hyperkalemia by adding Heparins (low mol weight).
Angiotensin II Receptor Blockers	Heparins (Low Molecular Weight) could increase the hyperkalemic effects of Angiotensin II Receptor Bblockers.
Angiotensin-Converting Enzyme Inhibitors	Heparins (Low Molecular Weight) may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors.
Antithrombin	Heparins may have an anticoagulant effect (Low Molecular Weight).
Bromperidol	May increase the toxic/adverse effects of Anticoagulants.
Caplacizumab	May increase the anticoagulant effects of Anticoagulants.
Collagenase (Systemic)	Anticoagulants can increase the toxic/adverse effects of Collagenase Systemic. In particular, there may be an increase in the risk of bleeding and/or bruising at the injection site.
Dasatinib	May increase the anticoagulant effects of Anticoagulants.
Deferasirox	Anticoagulants can increase the toxic/adverse effects of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased.
Deoxycholic Acid	Anticoagulants can increase the toxic/adverse effects of Deoxycholic Acid. The risk of bleeding or bruising may increase in the treatment area.
Eplerenone	Heparins (Low Molecular Weight) can increase the hyperkalemic effects of Eplerenone.
Factor X (Human).	Anticoagulants (Inhibitors Factor Xa) can reduce the therapeutic effects of Factor X (Human).
Fat Emulsion (Fish oil-based)	May increase the anticoagulant effects of Anticoagulants.
Ibritumomab Tiuxetan	Anticoagulants can increase the toxic/adverse effects of Ibritumomab Tiuxetan. Both agents could increase bleeding risk.
Ibrutinib	Anticoagulants may have an adverse/toxic effect that can be increased.
Inotersen	May increase the anticoagulant effects of Anticoagulants.
Limaprost	May increase the toxic/adverse effects of Anticoagulants. There may be an increase in bleeding risk.
Nintedanib	Anticoagulants can increase the toxic/adverse effects of Nintedanib. Particularly, bleeding risks may be increased.
Nonsteroidal Anti-Inflammatory Drugs	May increase the anticoagulant effects of Anticoagulants.
Obinutuzumab	Anticoagulants can increase the toxic/adverse effects of Obinutuzumab. In particular, there may be an increase in the risk of bleeding-related complications.
Omega-3 Fatty Acids	May increase the anticoagulant effects of Anticoagulants.
Palifermin	Heparins (Low Molecular Weight) can increase serum levels of Palifermin.
Pentosan Polysulfate Sodium	May increase the anticoagulant effects of Anticoagulants.
Pentoxifylline	Heparins may have an anticoagulant effect (Low Molecular Weight)
Potassium Salts	Heparins (low mol weight) can increase the hyperkalemic effects of Potassium Salts.
Potassium-Sparing Diuretics	Potassium-Sparing Diuretics may have a hyperkalemic effect if they contain Heparins (Low Molecular Weight). Monitoring serum potassium levels closely is a good management strategy. It is contraindicated to combine spironolactone Canadian with heparins or low molecular weight Heparins, according to the product monograph.
Prostacyclin Analogues	May increase the toxic/adverse effects of Anticoagulants. Combining these anticoagulants may increase the risk of bleeding from the combination.
Salicylates	May increase the anticoagulant effects of Anticoagulants.
Sugammadex	May increase the anticoagulant effects of Anticoagulants.
Sulodexide	May increase the anticoagulant effects of Anticoagulants.
Thrombolytic Agents	May increase the anticoagulant effects of Anticoagulants. Management: Refer to the full drug monograph to learn more about how alteplase can be used for acute ischemic stroke treatment with oral anticoagulants.
Tibolone	May increase the anticoagulant effects of Anticoagulants.
Tipranavir	May increase the anticoagulant effects of Anticoagulants.
Vitamin E (Systemic)	May increase the anticoagulant effects of Anticoagulants.
Vitamin K antagonists (eg warfarin)	Vitamin K Antagonists may have an anticoagulant effect that is enhanced by anticoagulants.
Risk Factor D (Consider therapy modifications)
Desirudin	Desirudin may have an anticoagulant effect that is enhanced by taking anticoagulants.
Estrogen Derivatives	Anticoagulants may have a lower anticoagulant effect. Particularly, some estrogens and progestin/estrogen combination may have prothrombotic side effects that could counteract anticoagulant properties. Management: Consider the potential benefits of estrogens in relation to the increased risk of thromboembolism and procoagulant effects. Some circumstances may make estrogens contraindicated. For more information, refer to the guidelines. Tibolone is an exception.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	Can increase the toxic/adverse effects of Anticoagulants. Possible bleeding.
Progestins	Anticoagulants may have a reduced therapeutic effect. Progestin-estrogen combination and some progestins may have prothrombotic side effects that could counteract anticoagulant properties. Management: Consider the pros and cons of progestins in relation to the possible increased risk of thromboembolism or procoagulant effects. Some circumstances may make progestins contraindicated. For more information, refer to the guidelines.
Risk Factor X (Avoid Combination)
Apixaban	May increase the anticoagulant effects of Anticoagulants. Refer to the separate drug interaction content as well as the full drug monograph content for apixaban and vitamin K antagonists (eg warfarin, Acenocoumarol) during anticoagulant transitions and bridging periods.
Dabigatran Etexilate	May increase the anticoagulant effects of Anticoagulants. Refer to the separate drug interaction content as well as the full drug monograph content for dabigatran, etexilate, and vitamin K antagonists (eg warfarin, Acenocoumarol) during anticoagulant transitions and bridging periods.
Edoxaban	May increase the anticoagulant effects of Anticoagulants. Refer to the separate drug interaction and full drug monograph contents regarding edoxaban and vitamin K antagonists (eg warfarin, Acenocoumarol) during anticoagulant transition or bridging periods. Management: A limited amount of combined use may be recommended during transitions from one anticoagulant treatment to another. For specific information on switching anticoagulant treatment, see the full edoxaban drug monograph.
Hemin	May increase the anticoagulant effects of Anticoagulants.
MiFEPRIStone	Anticoagulants may have an adverse/toxic effect that can be increased. In particular, bleeding risk may increase.
Omacetaxine	Omacetaxine's toxic/adverse effects may be exacerbated by anticoagulants. In particular, bleeding-related events can be more common. Patients with a lower platelet count than 50,000/uL should not use anticoagulants and omacetaxine simultaneously.
Rivaroxaban	Rivaroxaban's anticoagulant effects may be enhanced by anticoagulants. Refer to the separate drug interaction content as well as the full drug monograph content for rivaroxaban use with vitamin K antagonists (eg warfarin, Acenocoumarol) during anticoagulant Transition and Bridging Periods.
Urokinase	May increase the anticoagulant effects of Anticoagulants.
Vorapaxar	May increase the toxic/adverse effects of Anticoagulants. This combination may increase bleeding risk.

 

Monitoring parameters:

• Platelet counts, hemoglobin level, and hematocrit.
• fecal occult blood.
• Signs and symptoms of bleeding.
• Anti-Xa levels as per guidelines.
• Serum creatinine at baseline and during therapy.
• Monitoring of PT and/or aPTT is not recommended.
• Routine monitoring of anti-Xa activity is not required but has been utilized in patients with obesity and renal insufficiency.

For patients weighing more than 144 kg, if anti-Xa monitoring is available, adjusting the dose is based on anti-Xa activity is required. If anti-Xa monitoring is unavailable, reduce dose if bleeding occurs. Observe obese patients closely for signs of thromboembolism. Monitoring anti-Xa activity is indicated in pregnant women receiving therapeutic doses of enoxaparin or when receiving enoxaparin for the prevention of thromboembolism with mechanical heart valves.

 

How to administer Clexane (Enoxaparin)?

Note: Enoxaparin is available in 100 mg/mL and 150 mg/mL concentrations. SubQ:

• Administer by deep SubQ injection alternating between the left or right anterolateral and left or right posterolateral abdominal wall.
• Do not mix with other infusions or injections. In order to minimize bruising, do not rub the injection site.
• To avoid loss of drug from the 30 mg and 40 mg prefilled syringes, do not expel the air bubble from the syringe prior to injection.

IV:

• STEMI and PCI only:
  • The US labeling recommends using the multiple-dose vial to prepare IV doses.
  • The Canadian labeling recommends either the multiple-dose vial or a prefilled syringe.
  • Do not mix or co-administer with other medications; may be administered with NS or D W.
  • Flush IV access site with a sufficient amount of NS or D5-W prior to and following IV bolus administration.
  • When used prior to percutaneous coronary intervention or as part of treatment for ST-elevation myocardial infarction (STEMI), a single dose may be administered IV except when the patient is ≥75 years of age and is experiencing STEMI then only administer by SubQ injection.

 

Mechanism of action of Clexane (Enoxaparin):

• Standard heparin is composed of components having molecular weights between 4000 and 30,000 daltons, with a median of 16,000 daltons.
• Heparin is an anticoagulant. It increases the inhibition rate for clotting proteases through antithrombin III, impairing normal hemostasis, and inhibiting factor Xa.
• Heparins of low molecular weight have a limited effect on activated partial thromboplastin times and strongly inhibit factorXa.
• Enoxaparin is made from porcine hemoparin. It undergoes benzylation and then alkaline polymerization.
• The average molecular weight for enoxaparin (=20%) is 4500 daltons. It is distributed as (>=68%) 2000 to 8800 daltons and (=18%) >8000 Daltons.
• Enoxaparin has a higher ratio of anti-factor Xa to anti-factor IIa activity than unfractionated heparin.

The onset of action:

• Peak effect: SubQ: Antifactor Xa and antithrombin (anti-factor IIa): 3 to 5 hours

Duration:

• 40 mg dose: Antifactor Xa activity: ~12 hours.

Protein binding:

• Does not bind to heparin-binding proteins.

Metabolism:

• Hepatic, via desulfation and depolymerization to lower molecular weight molecules with very low biological activity

Bioavailability:

• Adults: SubQ: ~100%

Half-life elimination, plasma:

• 2 to 4 times longer than standard heparin, independent of dose; based on anti-Xa activity: 4.5 to 7 hours

Excretion:

• Urine (40% of the dose as active and inactive fragments; 10% as active fragments; 8% to 20% of anti-factor Xa activity is recovered within 24 hours)

Clearance:

• Decreased by 30% in patients with CrCl <30 mL/minute.

 

International Brand Names of Enoxaparin Injection:

• Lovenox
• Lovenox HP
• Bnoxaparin
• Clenox
• Clexane
• Clexane Forte
• Cutenox
• Dilutol
• Enoclex
• Flenox
• Klexane
• Lomoh-40
• Lomoh60
• Lovenox
• Microparin
• Olxarin

 

Enoxaparin Brand Names in Pakistan:

Enoxaparin Injection 20 Mg in Pakistan
Clexane	Sanofi Aventis (Pakistan) Ltd.
Clotles-Ss	Himont Chemical (Pvt) Ltd.
Enox	Wilsons Pharmaceuticals
Oxaprin	Werrick Pharmaceuticals
Prolongin	Kurative Pak (Pvt) Ltd

 

Enoxaparin Injection 40 Mg in Pakistan
Clexane	Sanofi Aventis (Pakistan) Ltd.
Enox	Wilsons Pharmaceuticals
Oxaprin	Werrick Pharmaceuticals
Prolongin	Kurative Pak (Pvt) Ltd

 

Enoxaparin Injection 60 Mg in Pakistan
Clexane	Sanofi Aventis (Pakistan) Ltd.
Enox	Wilsons Pharmaceuticals
Oxaprin	Werrick Pharmaceuticals
Prolongin	Kurative Pak (Pvt) Ltd

 

Enoxaparin Injection 80 Mg in Pakistan
Clexane	Sanofi Aventis (Pakistan) Ltd.
Enox	Wilsons Pharmaceuticals
Oxaprin	Werrick Pharmaceuticals
Prolongin	Kurative Pak (Pvt) Ltd