Enoxaparin sodium (Inclunox)

1. Health Canada Product Monograph — Enoxaparin sodium

• Used to prevent blood clots (deep vein thrombosis) after hip or knee replacement, and after high-risk abdominal, gynecological, urological, or colorectal surgery.
• Used to prevent deep vein thrombosis in medical patients who are bedridden due to acute illnesses such as moderate to severe heart failure or respiratory conditions.
• Used to prevent clot formation in the extracorporeal circuit (tubing) during hemodialysis.
• Used to treat deep vein thrombosis, with or without pulmonary embolism.
• Used to treat unstable angina or a non-ST-elevation heart attack, together with aspirin.
• Used to treat acute ST-segment elevation myocardial infarction (a major heart attack), including in patients managed with a stent procedure.

• Should not be used in pregnant women unless the treatment benefits clearly outweigh the possible risks, as with other low molecular weight heparins.
• Reports of birth abnormalities, such as anomalies of the brain, limbs, or heart, have occurred in babies born to women who received low molecular weight heparin during pregnancy, though a direct cause has not been established and the rate does not appear higher than in the general population.
• Pregnant women taking enoxaparin are at increased risk of bleeding, which can be serious for both mother and baby, and should be monitored closely.
• Pregnant women with mechanical heart valves are at especially high risk of clot formation on the valve even while on enoxaparin, and this use should only be managed by clinicians experienced in this area.

• Not known whether enoxaparin passes into human breast milk, so caution should be used when it is given to a nursing mother.

• Older adults, especially those 80 and above, are at higher risk of bleeding while taking enoxaparin.
• Close attention to dosing and to other medications, particularly antiplatelet drugs, is advised, along with careful monitoring of elderly patients who have low body weight or reduced kidney function.
• For treatment of a major heart attack, patients 75 and older are given a lower dose without the initial intravenous bolus.

• Safety and effectiveness in children have not been established, and no data are available for this age group.

• Doses vary by indication and are given by subcutaneous injection for most uses, or by a combination of an intravenous bolus followed by subcutaneous injections for an acute major heart attack.
• Typical clot-prevention doses range from 30 to 40 mg once or twice daily depending on the type of surgery, while treatment doses for existing blood clots are weight-based, such as 1 mg/kg every 12 hours or 1.5 mg/kg once daily.
• For hemodialysis, a starting dose of 0.5 to 1 mg/kg is injected into the arterial line of the dialysis circuit at the start of each session.
• Enoxaparin must never be given by intramuscular injection.
• Doses should be individually reduced in patients with severe kidney impairment because drug levels build up more in these patients.
• If a dose is missed by a few hours, take it as soon as remembered; if it is close to the time of the next dose, skip the missed one and resume the regular schedule without doubling up, and contact the doctor or pharmacist if unsure.

• Pain, bruising, or mild irritation at the injection site is common.
• Small hard lumps (nodules) may form at injection sites.
• Injection site hematomas (localized bleeding under the skin) may occur, more often with higher treatment doses.
• Easy bruising may occur.
• Nausea may occur.
• Elevated liver enzymes on blood tests may occur, usually without symptoms.
• Mild allergic skin reactions such as itching, redness, or hives may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Enoxaparin can cause serious bleeding at any site in the body, including the digestive tract, the area behind the abdomen (retroperitoneal), or inside the skull, which has rarely been fatal.
• Heparin-induced thrombocytopenia, a drop in platelet count triggered by an immune reaction to heparin, can occur and may lead to new blood clots forming in arteries or veins.
• Spinal or epidural bleeding (hematoma) can occur in patients receiving spinal or epidural anesthesia or a spinal tap while on enoxaparin, which can cause long-term or permanent paralysis.
• Severe allergic reactions, including anaphylaxis and swelling of the face or throat (angioedema), may occur.
• Skin death (necrosis) at the injection site may occur, usually beginning as painful red or purple patches.
• Blood clots can form on artificial (prosthetic) heart valves despite treatment, particularly in pregnant women.
• Bone thinning (osteoporosis) can develop with long-term use beyond three months.
• Seek immediate medical attention for unusual bruising or bleeding, blood in urine or stool, severe back or leg pain with numbness or weakness, sudden severe headache, or signs of a serious allergic reaction such as facial swelling or difficulty breathing.

• Use with extreme caution in patients at increased risk of bleeding, including those with a history of stomach or intestinal ulcers.
• Use with caution in patients with impaired kidney function, and reduce the dose in those with severe kidney impairment because of higher drug exposure.
• Use with caution in patients with impaired liver function.
• Use with caution in patients at the extremes of body weight, either very low or very high, since dosing has not been fully established in these groups.
• Use with caution around the time of spinal or epidural anesthesia or spinal puncture, allowing appropriate time between the injection and the procedure.
• Use with caution in elderly patients, particularly those with low body weight or reduced kidney function.
• Platelet counts should be checked before starting treatment and periodically afterward to monitor for thrombocytopenia.

• Contraindicated in patients with known hypersensitivity to enoxaparin, other low molecular weight heparins, or heparin.
• Contraindicated in patients with a history of immune-mediated heparin-induced thrombocytopenia within the past 100 days, or with circulating antibodies to platelet factor.
• Contraindicated in active bacterial infection of the heart lining (endocarditis).
• Contraindicated in patients with active bleeding.
• Contraindicated in major blood clotting disorders.
• Contraindicated in active stomach or duodenal ulcers.
• Contraindicated in bleeding (hemorrhagic) stroke, except when caused by a blood clot elsewhere in the body.
• Contraindicated in severe, uncontrolled high blood pressure.
• Contraindicated in diabetic or hemorrhagic disease of the retina.
• Contraindicated in other conditions or diseases involving a heightened risk of bleeding.
• Contraindicated after recent injury to, or surgery on, the brain, spinal cord, eyes, or ears.
• Spinal or epidural anesthesia is contraindicated when repeated treatment doses of enoxaparin are required, due to increased bleeding risk.

• Combining enoxaparin with oral anticoagulants, antiplatelet drugs such as aspirin or clopidogrel, other NSAIDs, or thrombolytic (clot-busting) drugs increases the risk of bleeding, and these combinations should generally be avoided unless specifically indicated.
• When aspirin is used together with enoxaparin for unstable angina or a heart attack, it is given intentionally as part of standard treatment but still requires monitoring for bleeding.
• Agents that affect normal clotting should ideally be stopped before starting enoxaparin unless there is a specific reason to continue them.
• Enoxaparin does not appear to interact with common liver drug-metabolizing pathways, but its use can raise liver enzyme results on blood tests, which should be kept in mind when interpreting labs.

• No specific food interactions have been identified with enoxaparin, as it is given by injection rather than taken orally.

• Subcutaneous doses are typically given once or twice daily at evenly spaced times, and should be injected into the fatty tissue of the abdomen, alternating between the left and right sides.
• For intravenous use in an acute major heart attack, an initial bolus is given followed by subcutaneous dosing every 12 hours.

• Store at room temperature between 15 and 25 degrees C, and do not freeze; pre-filled syringes are for single use, and any unused portion should be discarded.

• This is an injectable blood thinner used to prevent or treat dangerous blood clots, including after surgery or during treatment for a heart attack.
• It is given as a subcutaneous injection into the abdomen, usually once or twice a day, at the dose and schedule set by the prescriber.
• Common effects include pain, bruising, or a small lump at the injection site.
• Contact the doctor's office immediately for unusual bleeding or bruising, blood in urine or stool, black or tarry stools, sudden severe back pain, or numbness or weakness in the legs, since these can signal serious bleeding.
• Rotate and alternate injection sites between the left and right sides of the abdomen, and do not rub the area after injecting.
• Store the syringes at room temperature protected from freezing, and tell every prescriber and dentist that this medication is being used before any procedure.