Hepamax

Hepamax Cy 216, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant. It has the highest negative charge density of any known biological molecule. Hepamax Cy 216 acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While Hepamax does not break down clots that have already formed, it allows the body's natural clot lysis mechanisms to work normally to break down clots that have already formed. Hepamax Cy 216 binds to and accelerates the activity of antithrombin III. By activating antithrombin III, Hepamax preferentially potentiates the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so Hepamax s inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation.

Hepamax is an anticoagulant used principally in the treatment and prophylaxis of thromboembolic disorders (). It is often described as standard Hepamax or unfractionated Hepamax to distinguish it from low-molecular-weight heparins ().

Hepamax inhibits clotting of blood in vitro and in vivo by enhancing the action of antithrombin III. Antithrombin III, which is present in plasma, inhibits the activity of activated clotting factors including thrombin (factor IIa) and activated factor X (factor Xa). Hepamax increases the rate of this inhibition, but in a manner that is dependent on its dose. With normal therapeutic doses Hepamax has an inhibitory effect on both thrombin and factor Xa. The inhibition of thrombin blocks the conversion of fibrinogen to fibrin, and the inhibition of factor Xa blocks the conversion of prothrombin to thrombin. The low doses that are given subcutaneously for the prophylaxis of thromboembolism have a selective effect on inhibition of factor Xa. Very high doses are reported to reduce the activity of antithrombin III. Hepamax also has some effect on platelet function, inhibits the formation of a stable fibrin clot, and has an antilipidaemic effect

Hepamax injection is an anticoagulant. It is used to decrease the clotting ability of the blood and help prevent harmful clots from forming in blood vessels. Hepamax is sometimes called a blood thinner, although it does not actually thin the blood. Hepamax will not dissolve blood clots that have already formed, but it may prevent the clots from becoming larger and causing more serious problems.

Hepamax is used to prevent or treat certain blood vessel, heart, and lung conditions. Hepamax is also used to prevent blood clotting during open-heart surgery, bypass surgery, kidney dialysis, and blood transfusions. It is used in low doses to prevent the formation of blood clots in certain patients, especially those who must have certain types of surgery or who must remain in bed for a long time. Hepamax may also be used to diagnose and treat a serious blood condition called disseminated intravascular coagulation.

Hepamax is available only with your doctor's prescription.

Usual Adult Dose for Patency Maintenance of Indwelling

Intravenous Devices

Hepamax flush, 10 or 100 units/mL, is injected as a single dose into an intravenous injection device using a volume of solution equivalent to that of the indwelling venipuncture device.

When using daily flushes of Hepamax to maintain patency of single and double lumen central catheters, 10 units/mL is commonly used for younger infants (less than 10 kg) while 100 units/mL is used for older infants, children, and adults.

A single dose should be injected following venipuncture when the indwelling device is not to be used immediately. After each use of the indwelling venipuncture device for injection or infusion of medication, or withdrawal of blood samples, another dose should be injected to restore the effectiveness of the Hepamax lock. The amount of Hepamax solution is sufficient to prevent clotting within the lumen of indwelling venipuncture devices (usually not holding more than 0.2 to 0.3 mL) for up to twenty-four hours.

When the indwelling device is used to administer a drug which is incompatible with Hepamax, the entire Hepamax lock set should be flushed with 0.9% Sodium Chloride Injection, USP before and after the medication is administered. Following the second flush, another dose of Hepamax solution should be injected to restore the effectiveness of the Hepamax lock. When the indwelling device is used for repeated withdrawal of blood samples for laboratory analyses and the presence of Hepamax or saline is likely to interfere with or alter results of the desired blood tests, the in situ Hepamax flush solution should be cleared from the device by aspirating and discarding 1 mL before the desired blood sample is drawn.

Usual Pediatric Dose for Patency Maintenance of Indwelling

Intravenous Devices

Arterial lines: Heparinize with a usual final concentration of 1 unit/mL; range: 0.5 to 2 units/mL; in order to avoid large total doses and systemic effects, use 0.5 unit/mL in low birth weight/premature newborns and in other patients receiving multiple lines containing Hepamax.

Peripheral arterial catheters in situ: Neonates and Children: Continuous IV infusion of Hepamax at a final concentration of 5 units/mL at 1 mL/hour.

Umbilical artery catheter (UAC) prophylaxis: Neonates: Low-dose Hepamax continuous IV infusion via the UAC with a Hepamax concentration of 0.25 to 1 unit/mL.

Prophylaxis for cardiac catheterization via an artery: Neonates and Children: IV: Bolus: 100 to 150 units/kg; for prolonged procedures, further doses may be required.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Precautions

Benzyl alcohol, a preservative in the multiple-dose vial preparations of Hepamax Lock Flush Solution, USP has been associated with toxicity in neonates. Benzyl alcohol has been reported to be associated with a fetal "Gasping Syndrome" in premature infants. Data are unavailable on the toxicity of other preservatives in this age group. Preservative-free Hepamax Lock Flush Solution, USP should be used for maintaining patency of intravenous injection devices in neonates.

Many concentrations of Hepamax are available and range from 1 unit/mL to 20,000 units/mL. Carefully examine each prefilled syringe or vial prior to use to ensure that the correct concentration is chosen. Hepamax lock flush solution is intended only to maintain patency of IV devices and is not to be used for anticoagulant therapy.

Dialysis

Data not available

See also:
What is the most important information I should know about Hepamax?

Hepamax injection should not be used to flush (clean out) an intravenous (IV) catheter. A separate Hepamax product is available to use as catheter lock flush.

You should not use this medication if you are allergic to Hepamax, or if you have uncontrolled bleeding or a severe lack of platelets in your blood.

Before using Hepamax, tell your doctor if you have high blood pressure, an infection involving your heart, hemophilia or other bleeding disorder, a stomach or intestinal disorder, liver disease, or if you are on your period.

Hepamax can cause you to have bleeding episodes while you are using it and for several weeks after you stop. Call your doctor at once if you have easy bruising or unusual bleeding, such as a nosebleed, black or bloody tarry stools, or any bleeding that will not stop.

Certain medicines can increase your risk of bleeding while you are using Hepamax, such as aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) including ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), ketoprofen (Orudis), ketorolac (Toradol), mefenamic acid (Ponstel), nabumetone (Relafen), piroxicam (Feldene), and others.

Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Women over 60 years of age may be more likely to have bleeding episodes while using Hepamax.

Use Hepamax as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Hepamax is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Hepamax at home, a health care provider will teach you how to use it. Be sure you understand how to use Hepamax. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Hepamax if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Hepamax, contact your doctor.

Ask your health care provider any questions you may have about how to use Hepamax.

Use: Labeled Indications

Anticoagulation: Prophylaxis and treatment of thromboembolic disorders (eg, venous thromboembolism, pulmonary embolism) and thromboembolic complications associated with atrial fibrillation; prevention of clotting in arterial and cardiac surgery; as an anticoagulant for extracorporeal circulation and dialysis procedures.

Note: Hepamax lock flush solution is intended only to maintain patency of IV devices and is not to be used for systemic anticoagulant therapy.

Off Label Uses

Antibiotic lock technique, adjunctive therapy (catheter-salvage strategy)

Based on the 2009 Infectious Diseases Society of America clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection, antibiotic lock therapy may be used as salvage therapy for catheter-related infections in addition to systemic antibiotics when the catheter cannot be removed. Antibiotic lock solutions contain an appropriate antimicrobial and are usually mixed with Hepamax or NS at a sufficient volume to fill the catheter lumen.

Mechanical heart valve, bridging anticoagulation (for interruptions in warfarin therapy)

Based on the 2017 American Heart Association/American College of Cardiology (AHA/ACC) focused update of the 2014 guideline for the management of patients with valvular heart disease, Hepamax may be considered as bridge therapy during intervals of subtherapeutic anticoagulation for patients with mechanical mitral or tricuspid valve replacement. For patients with mechanical aortic valve replacement, bridging is not required unless an additional thromboembolic risk factor is present or the patient has an older-generation mechanical aortic valve.

Mechanical heart valve, postsurgical management (to transition to warfarin)

Data from a limited number of patients in case series and older randomized, controlled trials suggest that IV Hepamax may be beneficial after surgical placement of a mechanical heart valve when transitioning to warfarin.

ST-elevation myocardial infarction

Based on the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction (STEMI), Hepamax is effective and recommended for the treatment of patients presenting with STEMI managed by an invasive strategy with PCI, or by thrombolysis with fibrinolytic therapy.

See also:
What other drugs will affect Hepamax?

Drug Interactions:

Drug/ Laboratory Tests Interactions

Hyperaminotransferasemia: Significant elevations of aminotransferase (SGOT [S-AST] and SGPT [S-ALT]) levels have occurred in a high percentage of patients (and healthy subjects) who have received Hepamax sodium. Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease and pulmonary emboli, rises that might be caused by drugs (Hepamax sodium) should be interpreted with caution.

See also:
What are the possible side effects of Hepamax?

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Hepamax SODIUM INJECTION. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

• Hemorrhage – Hemorrhage is the chief complication that may result from Hepamax therapy. Gastrointestinal or urinary tract bleeding during anticoagulant therapy may indicate the presence of an underlying occult lesion. Bleeding can occur at any site but certain specific hemorrhagic complications may be difficult to detect including:
  • Adrenal hemorrhage, with resultant acute adrenal insufficiency, has occurred with Hepamax therapy, including fatal cases.
  • Ovarian (corpus luteum) hemorrhage developed in a number of women of reproductive age receiving short- or long-term Hepamax therapy.
• Retroperitoneal hemorrhage.
• HIT and HITT, including delayed onset cases.
• Local irritation – Local irritation, erythema, mild pain, hematoma, or ulceration have occurred following deep subcutaneous (intrafat) injection of Hepamax sodium. Because such reactions occur more frequently after intramuscular administration, the IM route is not recommended.
• Histamine-like reactions – Such reactions have been observed at the site of injection. Necrosis of the skin has been reported at the site of subcutaneous injection of Hepamax, occasionally requiring skin grafting.
• Hypersensitivity – Generalized hypersensitivity reactions have been reported with chills, fever, and urticaria as the most usual manifestations; asthma, rhinitis, lacrimation, headache, nausea and vomiting, and anaphylactoid reactions, including shock, occur less frequently. Itching and burning, especially on the plantar site of the feet, may occur.
• Elevations of serum aminotransferases – Significant elevations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels have occurred in patients who have received Hepamax.
• Others – Osteoporosis following long-term administration of high doses of Hepamax, cutaneous necrosis after systemic administration, suppression of aldosterone synthesis, delayed transient alopecia, priapism, and rebound hyperlipemia on discontinuation of Hepamax sodium have been reported.