Enoxaparin Sodium - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Enoxaparin is a medication that belongs to the blood-thinning group of drugs. It prevents blood clot formation in the veins of the legs in patients who are having surgeries such as hip or knee replacement, abdominal surgery, or those on bed rest. Enoxaparin sodium is often used in combination with other medications, such as Aspirin or Warfarin, to treat many conditions, such as blood clots and heart problems. The FDA approved Enoxaparin sodium in the year 1993 for medical use.

Enoxaparin sodium is approved for prophylaxis and treatment of a condition called deep vein thrombosis (DVT), in which blood clots form in the veins (especially of the legs), leading to leg swelling and pain. In addition, Enoxaparin sodium is used for the prophylaxis and treatment of other conditions such as acute coronary syndrome, venous thromboembolism, periprocedural anticoagulation, percutaneous coronary intervention, unstable angina, and myocardial infarction.

What Is Deep Vein Thrombosis?

The blood can clot when it moves too slowly through the veins. Such blood clots can form in the veins in the body, especially in the legs. This condition is known as DVT or deep vein thrombosis. The most common sites of clots in veins include the lower leg, pelvis, and thigh, but they can occur in other body parts, also. DVT can lead to several health complications and can even be life-threatening. Thus, getting treated for DVT is important. Symptoms such as leg swelling (that comes and goes), pain in the leg on walking or standing, enlarged veins, and red, warm skin in the area are seen in DVT.

Sometimes, the blood clot can detach and enter the bloodstream. The loose blood clot can get lodged in the lungs' blood vessels, leading to a life-threatening condition called pulmonary embolism. This medical emergency presents with shortness of breath, chest pain, coughing up of blood, and increased heart rate. Thus, anticoagulant medications such as Enoxaparin sodium are initiated for DVT patients to prevent blood clot formation.

For Doctors:

FDA-Approved Indications:

The low molecular weight heparin, Enoxaparin sodium, is approved for the following:

• Prophylaxis of deep vein thrombosis (DVT) for patients undergoing surgeries such as hip or knee replacement and abdominal surgery and for patients with acute illness leading to restricted mobility.

• Acute DVT treatment (outpatient treatment).

• Prophylaxis of the ischemia-related complications of non-Q wave MI (myocardial infarction) and unstable angina.

• Treatment of acute STEMI (ST-segment elevation myocardial infarction) that is managed with medical treatment or with percutaneous coronary intervention.

Other Uses of Enoxaparin Sodium:

• Prevention of venous thromboembolism (VTE).

• Inpatient management of acute DVT with or without pulmonary embolism.

• Prevention and management of venous thromboembolism that occurs secondary to malignancy.

• Treatment for prosthetic valve thrombosis and VTE in pregnancy.

• Prophylaxis of arterial thromboembolism and cerebral thromboembolism.

• Management of antiphospholipid antibody syndrome.

• Periprocedural anticoagulation.

What Is the Mechanism of Action?

As Enoxaparin sodium is a low molecular weight derivative of heparin, its mean molecular weight is 4000 to 5000 Daltons. It is usually administered intravenously and has a quick onset of action. Enoxaparin sodium is an anticoagulant (indirect) that binds to and activates antithrombin III to form a complex. This complex inactivates factor Xa (which is required for thrombin formation) irreversibly. Enoxaparin sodium has a lower molecular weight than heparin and a smaller chain length, so it has a better activity to inactivate factor Xa.

Pharmacokinetics:

• Absorption: Thepeak effect is usually four hours after administration. The anti-factor Xa activity is detected for up to 12 hours in plasma.

• Distribution: 4.3 Liters (estimated by anti-factor Xa activity).

• Metabolism: Enoxaparin sodium is metabolized (through desulfation and depolymerization) in the liver.

• Excretion: Enoxaparin sodium is eliminated in urine (renal excretion). The elimination half-life is three to 4.5 hours after a single dose. The half-life increases to seven hours following repeated doses. The drug may accumulate in the kidney and increase the chance of bleeding in patients with renal impairment.

Administration:

About 90 percent of Enoxaparin sodium is available when administered subcutaneously. Thus, it has better bioavailability than heparin. When the drug is administered subcutaneously, it is given alternatively between the right or left posterolateral and anterolateral abdominal wall. Bruising may occur but can be prevented by not rubbing the subcutaneous injection site.

The drug can also be administered intravenously. Healthcare professionals must ensure that they do not mix or co-administer Enoxaparin sodium intravenous formulation (IV) with other medications. IV injection is usually administered during the percutaneous coronary intervention and at the time of ST-elevation myocardial infarction. Normal saline or 5 percent dextrose water must be used to flush the port before administering Enoxaparin sodium. There are no topical forms of Enoxaparin sodium available. Administration of the drug into the muscles is avoided.

Dosage:

The dosage depends on the indications, renal or hepatic impairment, and the adverse events profile. One milligram of Enoxaparin sodium is equal to 100 units of anti-factor Xa activity.

1. DVT Prophylaxis in Abdominal Surgery- 40 mg subcutaneous injection (once daily for up to 12 days).

2. DVT Prophylaxis in Knee Replacement Surgery - 30 mg subcutaneous injection administered every 12 hours (up to 14 days).

3. DVT Prophylaxis in Hip Replacement Surgery - 30 mg subcutaneous injection administered every 12 hours or 40 mg subcutaneous injection once daily (up to 14 days).

4. DVT Prophylaxis in Medical Patients- 40 mg subcutaneous injection once daily for up to 14 days.

5. Acute DVT (With or Without Pulmonary Embolism) Inpatient Treatment - 1 mg/kg subcutaneous injection every 12 hours or 1.5 mg/kg subcutaneous injection once daily for up to 17 days (administered with warfarin).

6. Acute DVT Without Pulmonary Embolism Outpatient Treatment - 1 mg/kg subcutaneous injection administered every 12 hours for up to 17 days (with warfarin).

7. Non-Q-wave MI and Unstable Angina - 1 mg/kg subcutaneous injection administered (with aspirin) once every 12 hours for two to eight days.

8. Acute STEMI (In Patients Younger Than 75) - 30 mg single intravenous bolus and a 1 mg/kg subcutaneous injection followed by 1 mg/kg subcutaneous injection every 12 hours for at least eight days (administered with aspirin).

9. Acute STEMI (In Patients Older Than 75 Years of Age) - No intravenous bolus. 0.75 mg/kg subcutaneous injection administered every 12 hours for at least eight days (with aspirin).

What Is Its Use in Specific Patient Populations?

• Patients With Hepatic Impairment: According to a clinical trial, Enoxaparin sodium decreases hepatic decompensation and the rate of portal vein thrombosis. The drug also increases the probability of survival of the patients (with cirrhosis) by preventing microvascular thrombosis. However, there is an increased chance of bleeding while taking the drug in patients with liver cirrhosis and other comorbidities such as active cancer or hypertension. Thus, Enoxaparin sodium must be initiated with caution in patients with liver cirrhosis.

• Patients With Renal Impairment: Increased bleeding tendency is seen in patients with renal impairment while taking Enoxaparin sodium. Enoxaparin sodium dose adjustment to 1 mg/kg once daily is recommended in patients with a creatinine clearance lesser than 30 mL/min (severe renal impairment). No dose adjustment is required if the creatinine clearance is greater than 30 mL/min.

• Geriatric Patients: Older patients have an increased risk of bleeding, and care must be taken while initiating Enoxaparin sodium.

• Pregnancy: Pregnant women are at a greater risk of venous thromboembolism (VTE), and it can often be life-threatening. Enoxaparin sodium is considered safe in pregnancy as it does not cross the placenta. For VTE prophylaxis, the administration of a 40 mg subcutaneous injection is recommended once daily. Administration of 1 mg/kg every 12 hours is recommended for therapeutic anticoagulation in pregnant women with acute thromboembolism or a recurrent thrombosis history.

• In Breastfeeding Mothers: Administration of Enoxaparin sodium in doses up to 40 mg daily is considered safe and does not cause any adverse drug reactions in breastfed infants. There are no special precautions required for initiating Enoxaparin sodium in breastfeeding mothers. There is no evidence that Enoxaparin sodium is excreted into breast milk or absorbed by the infant's gastrointestinal tract.

• COVID-19 Considerations: In patients critically ill due to COVID-19 (with or without venous thromboembolism), prophylaxis with Enoxaparin sodium is recommended. Higher-intensity anticoagulation with Enoxaparin sodium may be given to patients with a low risk of bleeding and a high thrombotic risk.

• In Patients With Low Weight: The patients must be monitored and observed for signs of bleeding.

What Are the Drug Interactions?

Medications that increase the risk of hemorrhage must be discontinued before initiating Enoxaparin sodium. Such medications include other anticoagulants, dipyridamole, sulfinpyrazone, NSAIDs, and platelet inhibitors (including acetylsalicylic acid). In case of such co-administration, close laboratory and clinical monitoring must be done.

What Are the Contraindications?

• Major active bleeding (such as gastrointestinal bleeding).

• Anti-platelet antibody test positive (circulating antibodies) along with thrombocytopenia while using Enoxaparin sodium.

• History of heparin-induced thrombocytopenia (within the past three months or 100 days).

• Hypersensitivity to Enoxaparin sodium (anaphylactic reactions, urticaria).

• Hypersensitivity to heparin or pork products.

• Hypersensitivity to benzyl alcohol (for multi-dose formulations especially used in neonates).

What Are the Warnings and Precautions?

• There is an increased risk of hemorrhage when used in patients at risk. Thus, Enoxaparin sodium must be initiated with caution in high-risk patients for hemorrhage.

• In patients (anticoagulated with Enoxaparin) undergoing a spinal puncture or receiving neuraxial anesthesia, epidural or spinal hematomas may occur. These can result in long-term disability or permanent paralysis. Thus, healthcare providers must consider these risks before scheduling patients taking Enoxaparin sodium for spinal procedures.

• While using Enoxaparin sodium for percutaneous coronary revascularization, the healthcare professional must obtain hemostasis at the site of the puncture before sheath removal.

• The drug Enoxaparin sodium must be used with caution in patients with concomitant medical conditions such as uncontrolled hypertension, bleeding diathesis, diabetic retinopathy, recent gastrointestinal ulceration, renal dysfunction, or hemorrhage.

• Enoxaparin sodium must be initiated with caution in those with a history of heparin-induced thrombocytopenia (or circulating antibodies).

• If the patients have thrombocytopenia, the drug must be used cautiously, and the thrombocytopenia must be monitored closely.

• Enoxaparin sodium must not be administered interchangeably with other low molecular-weight heparins or heparin.

• While administering Enoxaparin sodium in pregnant women who have mechanical prosthetic heart valves, frequent monitoring, and drug dose adjustment are essential.

For Patients:

What Is Deep Vein Thrombosis?

In deep vein thrombosis (DVT), a severe medical condition, blood clots are found in veins, usually in the leg. Symptoms of DVT in the leg include throbbing or cramping pain in one leg (usually in the calf or thigh), swelling in the leg, darkened, red and warm skin around the painful area of the leg, and sore, swollen veins in the leg. These symptoms can also occur in a person's arm or other body parts where the blood clot is. Getting medical help for deep vein thrombosis is essential to prevent its complications.

DVT can lead to complications such as pulmonary embolism. The blood clot can detach from the veins and enter circulation (bloodstream). These free clots travel through the bloodstream and may block the blood vessels in the lungs, which can be life-threatening. One must rush to the emergency department or call for emergency care in case of a deep vein thrombosis with pain, swelling in the leg and chest pain, and breathlessness (indicators of pulmonary embolism).

Who Is More Likely to Get Deep Vein Thrombosis?

The patients at a higher risk of deep vein thrombosis (DVT) are

• Elderly patients over 60 years of age.

• Overweight individuals.

• Those who smoke.

• Patients who have had DVT before.

• Women taking oral contraceptive pills or hormonal replacement therapy.

• Those with cancer or heart failure.

• Patients with varicose veins.

• Patients who are confined to bed or cannot move around much (such as after surgery).

• Individuals who are traveling for a long duration without much movement.

• Women who are pregnant or have just delivered a baby (in the past six weeks).

• Dehydrated individuals.

What Is Enoxaparin Sodium?

Enoxaparin sodium is an injectable medication that is used to prevent blood clots in the legs and other body parts (such as deep venous thrombosis). These blood clots can travel through the blood to the lungs leading to life-threatening complications or death. Enoxaparin sodium is administered to prevent blood clots in a person who undergoes surgery, such as abdominal surgery and knee or hip replacement. This medication also prevents blood clots for patients experiencing heart attacks or chest pain and in patients confined to bed. Enoxaparin sodium is derived from heparin and is a low molecular weight heparin.

What Is the Difference Between Enoxaparin Sodium and Heparin?

Enoxaparin sodium and heparin prevent blood clots inside the body but are indicated for different scenarios. Standard heparin is a liquid medicine administered intravenously (injected directly into the vein) and administered only to hospitalized patients to prevent blood clots during surgery. Patients vary widely in their response to heparin (requiring frequent monitoring), which can cause heparin-induced thrombocytopenia (low platelet count), a life-threatening condition. Thus heparin can be administered only by healthcare providers and cannot be self-injected. Enoxaparin sodium is an injectable medication derived from heparin and also prevents blood clots. Enoxaparin sodium can be injected under the skin (subcutaneous injection). It has predictable efficacy, does not require frequent monitoring, and has lower adverse effects. In addition, the patients can self-administer Enoxaparin sodium at home.

When Is Enoxaparin Sodium Administered?

Enoxaparin sodium is a drug that prevents the formation of blood clots. Thus, Enoxaparin sodium is used to treat deep vein thrombosis in which blood clots are formed, usually in the legs. DVT can lead to pulmonary embolism (blood clots in the lungs that can be fatal). Enoxaparin sodium is used for prophylaxis and treatment of the condition. Enoxaparin sodium also prevents complications in certain types of chest pain (angina) or heart attack. In addition, Enoxaparin sodium is used for other medical conditions that require medications to prevent blood clot formation.

How Is Enoxaparin Sodium Administered?

Enoxaparin sodium is available as injections that can be administered under the skin (subcutaneous injection) and as intravenous injections that can be administered into the patient's veins directly by the healthcare provider.

Warnings:

The injection can cause a serious blood clot (hematoma) around the spinal cord in patients undergoing spinal procedures such as spinal anesthesia or spinal tap. These hematomas can cause long-term disabilities or paralysis. Thus, care must be taken by the healthcare providers while administering Enoxaparin sodium in patients who are undergoing such procedures and in high-risk patients (with a history of spinal procedures and using other medications such as NSAIDs or blood thinners). Patients with symptoms of spinal cord hematoma, such as numbness, back pain or muscle weakness in the legs, and loss of bowel or bladder control, must get emergency medical help.

What Are the Precautions to Take Before Using Enoxaparin Sodium?

• A person must not use Enoxaparin sodium if allergic to heparin, Enoxaparin sodium, and benzyl alcohol.

• One must avoid using Enoxaparin sodium injection if they have decreased platelets in the blood test (with certain antibodies) and have active or uncontrolled bleeding.

• Patients must inform their healthcare provider regarding any underlying conditions that may cause them to bleed, such as bleeding disorder, stroke, bleeding or ulcer in the stomach, recent surgeries, etc.

• Patients must inform their healthcare provider if they have had any spinal cord-related injuries or procedures done.

• Patients must also inform their healthcare provider regarding the medications that they are currently taking to prevent drug interactions or drug-induced complications.

• One must keep their healthcare provider informed about the presence of bleeding disorders, liver disease, kidney disease, blood pressure, diabetes, stomach ulcer, or low platelet count on receiving heparin or other medications.

• Women who are pregnant must inform their doctor regarding their pregnancy before initiating Enoxaparin sodium treatment or prophylaxis.

• Pregnant women with a mechanical heart valve must not take Enoxaparin sodium without informing their healthcare provider.

• One must enquire about the risk associated with their healthcare provider while breastfeeding their baby and initiating the drug.

How Should One Use Enoxaparin Sodium Subcutaneous Injections?

Healthcare professionals should only perform intravenous administration (injection into the vein) of Enoxaparin sodium. Enoxaparin sodium can be self-administered at home subcutaneously (under the skin). It is important to follow all the directions in the medication instruction sheets and use them only as directed by the physician. The person administering the subcutaneous injection must:

• Avoid using Enoxaparin if they do not understand how to inject it.

• Ask their healthcare provider regarding any doubts about the subcutaneous injection of Enoxaparin sodium.

• Avoid using the injection if the medicine has particles in it or has changed colors.

• Prepare the injection only before use.

• Avoid injecting Enoxaparin sodium into muscle.

• Use a different site of injection every time. Avoid injecting into the same site continuously.

• Understand that the patient might require frequent medical tests to determine the duration of Enoxaparin sodium treatment.

• Inform the healthcare provider if undergoing any surgery (including dental).

• Store the medicine at room temperature (away from heat and moisture).

• Understand that each prefilled syringe must be used only once and discarded after a single use (even if some medicine is left in it).

• If using an Enoxaparin sodium bottle (vial), ensure that the medicine is used within 28 days of opening the vial and it is discarded after 28 days.

• Use sterile needles and syringes only once and dispose of them safely.

• Keep Enoxaparin sodium vials and syringes safe and out of reach of pets and children.

What to Do if One Misses a Dose?

The injections can be given as soon as possible. If it is almost time for the next dose, one must not use two doses and skip the missed dose.

What Happens if One Overdose?

Enoxaparin sodium overdose may lead to excessive bleeding, which can be dangerous. It is important to seek emergency medical help and rush to the emergency department for observation and management.

What Should One Avoid While Using Enoxaparin Sodium?

Patients using Enoxaparin sodium must avoid activities that can cause injury or bleeding. They must be vigilant to prevent bleeding during daily activities such as shaving or brushing their teeth.

What Are the Common Drugs That Can Interact With Enoxaparin Sodium?

Many medications that are used to prevent or treat blood clots interact with Enoxaparin sodium. It is important to keep the healthcare provider informed regarding the other medications that a patient is taking before initiating Enoxaparin sodium. The drugs that could affect Enoxaparin sodium include heparin, other anticoagulants, Dipyridamole, Sulfinpyrazone, NSAIDs, and platelet inhibitors (including acetylsalicylic acid).

What Are the Side Effects of Enoxaparin Sodium?

Enoxaparin sodium can cause severe allergic reactions in some patients. One must seek emergency medical care in case of serious allergic reactions such as itching, hives, burning skin, difficulty breathing, or swelling of the face and throat. Suppose the patient experiences signs of spinal hematoma (numbness, back pain, muscle weakness in the legs, loss of bowel or bladder control). In that case, they must call for emergency medical care or rush to the emergency department. If patients notice any side effects from using Enoxaparin sodium, they must visit their healthcare provider for further management. The side effects of Enoxaparin sodium include the following:

• Uncontrolled bleeding.

• Easy bruising.

• Bleeding from the nose and gums.

• Abnormal vaginal bleeding.

• Blood in stool and urine.

• Coughing up blood.

• Blood in vomit.

• Bleeding in the brain (sudden weakness in one side of the body, severe headache, sudden speech or vision problems).

• Anemia (pale skin, tiredness, shortness of breath).

• Injection site reactions.

• Other common side effects include nausea, diarrhea, confusion, and irritation.