Enoxaparin sodium, sold under the brand name Lovenox among others, is an
anticoagulant medication (blood thinner).
[ It is used to treat and prevent ]deep vein thrombosis
Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enla ...
(DVT) and pulmonary embolism
Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream ( embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathin ...
(PE) including during pregnancy
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
and following certain types of surgery.[ It is also used in those with acute coronary syndrome (ACS) and ]heart attack
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which ma ...
s.[ It is given by injection just under the skin or into a vein.][ It is also used during ]hemodialysis
Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
.
Common side effects include bleeding, fever, and swelling of the legs.[ Bleeding may be serious especially in those who are undergoing a spinal tap.][ Use during ]pregnancy
Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occur ...
appears to be safe for the baby.[ Enoxaparin is in the ]low molecular weight heparin
Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial in ...
family of medications.[
Enoxaparin was first made in 1981 and approved for medical use in 1993.] It is on the World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. Enoxaparin is sold under several brand names and is available as a generic medication.[ Enoxaparin is made from heparin.] In 2020, it was the 350th most commonly prescribed medication in the United States, with more than 500thousand prescriptions.
Medical uses
* Treatment of unstable angina (UA) and non-Q-wave myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
(NQMI), administered concurrently with aspirin
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
* DVT and pulmonary embolism prophylaxis in bed-ridden patients
* DVT prophylaxis in knee replacement surgery
* DVT prophylaxis in hip replacement surgery
* DVT prophylaxis in abdominal surgery
* Treatment of DVT with or without pulmonary embolism
* Treatment of DVT inpatient, with ST-segment elevation myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
(STEMI)
* Bridging treatment for those with INR below therapeutic range
Monitoring
Enoxaparin has predictable absorption, bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
, and distribution therefore monitoring is not typically done. However, there are instances where monitoring may be beneficial for special populations, for example individuals with kidney insufficiency or those that are obese. In this case, anti-Xa units can be measured and dosing adjusted accordingly.
Reversal agent
Protamine sulfate
Protamine sulfate is a medication that is used to reverse the effects of heparin. It is specifically used in heparin overdose, in low molecular weight heparin overdose, and to reverse the effects of heparin during delivery and heart surgery. ...
is less effective at reversing enoxaparin compared to heparin, with a maximum neutralization of approximately 60% of the anti-factor Xa effect.
Pregnancy
* Enoxaparin is a FDA pregnancy category
The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does ''not'' include any risks conferred by pharmaceutical agents or their ...
B drug which means enoxaparin is not expected to cause harm to an unborn baby when used during pregnancy. This statement is based on reproductive studies involving pregnant rats and rabbits. No birth defects
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
or toxic effects to an unborn fetus due to enoxaparin were observed during these animals studies. However a human's response to enoxaparin might be different from that of a small animal, therefore enoxaparin should be used during pregnancy only if there is a definite need.
* Enoxaparin does not cross the placenta therefore it is unlikely an unborn baby would be exposed to it.
* Some fetal deaths have been reported by women who used enoxaparin during pregnancy, but it is unclear if enoxaparin caused these deaths.
* Pregnant woman on enoxaparin should be monitored on a regular basis for bleeding and/or "excessive anticoagulation" especially when the delivery date is approaching. The risk of hemorrhage is higher during delivery if the person is still using enoxaparin and this could endanger the life of the baby and/or the mother.
* The multiple-dose vials of the brand name enoxaparin (Lovenox) contain 15 mg benzyl alcohol
Benzyl alcohol is an aromatic alcohol with the formula C6H5CH2OH. The benzyl group is often abbreviated "Bn" (not to be confused with "Bz" which is used for benzoyl), thus benzyl alcohol is denoted as BnOH. Benzyl alcohol is a colorless liquid w ...
per 1 mL as a preservative. Premature infants who have been given large amounts of benzyl alcohol (99–405 mg/kg/day) have experienced "gasping syndrome".
* Although enoxaparin is used to prevent blood clots, pregnancy alone can raise a woman's risk of clotting.
Side effects
Uncommon (<1%)
* In people with unstable angina or non-Q-wave myocardial infarction:
** Atrial fibrillation, heart failure, lung edema, pneumonia
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severi ...
: ≥ 0.5%v
Common (>1%)
* Thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...
, i.e. can be associated with heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis (the abnormal formation of blood clots ...
(0.5-5.0% of persons treated for at least five days)
* Elevations in serum aminotransferases: 5.9%-6.1%
* In people undergoing abdominal or colorectal surgery:
** Bleeding, anemia, ecchymosis
A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur close ...
: ≥ 2%
* In persons undergoing hip or knee replacement:
** Fever, nausea, anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
, edema, peripheral edema: ≥ 2%
* In persons with severely restricted mobility during acute illness:
** Dyspnea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing di ...
, thrombocytopenia, confusion, diarrhea, nausea: ≥ 2%
* In people being treated for deep vein thrombosis:
** Injection site hemorrhage, injection site pain, hematuria
Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. “Gross hematuria” occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable w ...
: ≥ 2%
Frequency under investigation
* Local reactions: local irritation, pain, hematoma, ecchymosis, erythema
* Bleeding
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
* Hyperkalemia
Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...
* Transaminitis
In medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), may be an indicator of liver dysfunction. Other terms include transaminasemia, transaminitis, and elevated ...
* Hemorrhage
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...
Boxed warning
The FDA issued a revision to the boxed warning for enoxaparin in October 2013. The revision recommends exercising caution regarding when spinal catheter
In medicine, a catheter (/ˈkæθətər/) is a thin tubing (material), tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgi ...
s are placed and removed in persons taking enoxaparin for spinal puncture or neuroaxial anesthesia. It may be necessary to delay anticoagulant dosing in these persons in order to decrease the risk for spinal or epidural hematomas, which can manifest as permanent or long-term paralysis. Persons at risk for hematomas may present with indwelling epidural catheters, concurrent use of medications that worsen bleeding states such as non-steroidal anti-inflammatory drugs (NSAIDs), or a past medical history of epidural or spinal punctures, spinal injury, or spinal deformations. The FDA recommends that at-risk persons be monitored for bleeding and neurological changes.
Pharmacology
Mechanism of action
Enoxaparin binds to and potentiates antithrombin
Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 432-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-A ...
(a circulating anticoagulant) to form a complex that irreversibly inactivates clotting
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...
factor Xa
Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis.
Fa ...
. It has less activity against factor IIa
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...
(thrombin) compared to unfractionated heparin (UFH) due to its low molecular weight.
Pharmacokinetics
Absorption: Bioavailability (subcutaneous injection) ~ 100%
Distribution: Volume of distribution (anti-Factor Xa activity) = 4.3 liters
Metabolism: Enoxaparin is metabolized in the liver into low molecular weight species by either or both desulfation and depolymerization.
Elimination: A single dose of a subcutaneous injection of enoxaparin has an elimination half-life of 4.5 hours. Approximately 10–40% of the active and inactive fragments from a single dose are excreted by the kidneys. Dose adjustments based on kidney function are necessary in persons with reduced kidney function.
Drug class
Enoxaparin belongs to the class of drugs known as low molecular weight heparins. Other drugs in this class include dalteparin
Dalteparin is a low molecular weight heparin. It is marketed as Fragmin. Like other low molecular weight heparins, dalteparin is used for prophylaxis or treatment of deep vein thrombosis and pulmonary embolism to reduce the risk of a stroke or ...
, fondaparinux
Fondaparinux (trade name Arixtra) is an anticoagulant medication chemically related to low molecular weight heparins. It is marketed by GlaxoSmithKline. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratorie ...
and tinzaparin.
Biosimilars
In September 2016, Inhixa and Thorinane were approved for use in the European Union. Thorinane was withdrawn from the market in October 2019.
In March 2017, Enoxaparin BECAT, Laboratorios ROVI (Spain) obtained marketing authorization in twenty six countries in Europe. The product is now available in Europe.
In October 2020, Noromby and Noromby HP, were approved for medical use in Canada.
In November 2020, and Inclunox HP were approved for medical use in Canada.
In December 2020, Redesca and Redesca HP were approved for medical use in Canada.
References
External links
*
{{DEFAULTSORT:Enoxaparin Sodium
Heparins
Sanofi
World Health Organization essential medicines
Wikipedia medicine articles ready to translate