Heparin Flush

Drug overview for HEPARIN FLUSH (heparin sodium,porcine/pf):

Generic name: HEPARIN SODIUM,PORCINE/PF (HEP-a-rin)
Drug class:
Therapeutic class: Hematological Agents

Heparin, an anionic, sulfated glycosaminoglycan anticoagulant present in mast cells, acts as a catalyst to markedly accelerate the rate at which antithrombin III (heparin cofactor) neutralizes thrombin and activated coagulation factor X (factor Xa). Unless otherwise specified in this monograph, the term ''heparin'' refers to unfractionated heparin, not low molecular weight heparin or both types of heparin.

Heparin is used for prophylaxis and treatment of venous thrombosis and its extension; prophylaxis of postoperative deep-vein thrombosis and pulmonary embolism in patients undergoing major abdominal or thoracic surgery who are at risk for thromboembolism; prophylaxis and treatment of pulmonary embolism; treatment of embolization associated with atrial fibrillation or atrial flutter and/or prosthetic heart valve replacement; treatment of acute and chronic consumptive coagulopathies (disseminated intravascular coagulation (DIC)); and prophylaxis and treatment of peripheral arterial embolism. Heparin is also used to prevent activation of the coagulation mechanism as blood passes through an extracorporeal circuit in dialysis procedures and during arterial and cardiac surgery. In addition, the drug is used as an in vitro anticoagulant in blood transfusions.

Heparin also has been used as adjunctive antithrombotic therapy in patients with unstable angina, non-ST-segment-elevation myocardial infarction (NSTEMI), or ST-segment-elevation myocardial infarction (STEMI). Heparin or a low molecular weight heparin is used when a rapid anticoagulant effect is required. A coumarin anticoagulant (e.g., warfarin) is generally used for follow-up anticoagulant therapy after the effects of therapy with full-dose heparin or a low molecular weight heparin have been established and when long-term anticoagulant therapy is appropriate. When warfarin is administered for follow-up treatment after full-dose heparin, therapy with warfarin and heparin should be overlapped for a short period of time.

DRUG IMAGES

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The following indications for HEPARIN FLUSH (heparin sodium,porcine/pf) have been approved by the FDA:

Indications:
Maintain patency of indwelling intravenous catheter

Professional Synonyms:
Prevent clot occlusion of intravenous catheter

The following dosing information is available for HEPARIN FLUSH (heparin sodium,porcine/pf):

Dosing
Administration
Dosing Information
Generic

Dosage of heparin sodium is expressed in USP units. USP units and international units (IU, units) for heparin sodium are equivalent.

Dosage requirements for full-dose heparin sodium therapy vary greatly among individual patients, and dosage should be carefully individualized based on clinical and laboratory findings in order to obtain optimum therapeutic effects without incurring hemorrhage. (See Laboratory Monitoring of Therapy under Dosage and Administration: Administration.) Because of a lack of adequate and well-controlled studies of heparin in pediatric patients, dosage recommendations in this population generally are based on clinical experience. Geriatric patients (older than 60 years of age) may require a lower dosage of heparin sodium.

(See Cautions: Geriatric Precautions.)

The optimum duration of heparin therapy for thrombotic disorders has not been definitely established and must be determined by the condition being treated and its severity. Full-dose heparin is generally continued for at least 5 days in patients with acute venous thrombosis or pulmonary embolism, and for 2 days in patients with myocardial infarction (MI)+. A coumarin anticoagulant (e.g., warfarin) generally is administered for follow-up treatment after full-dose heparin, and therapy with the 2 drugs is usually overlapped for 4-5 days until an adequate response to the coumarin derivative is obtained (e.g., as indicated by INR values exceeding 2 on two consecutive days).

(See Laboratory Test Interferences: Prothrombin Time.) Several manufacturers recommend abrupt discontinuance of heparin without tapering in patients who have an adequate therapeutic response to a coumarin derivative. However, concern exists that abrupt discontinuance of heparin may result in a high-risk period for rebound thrombosis, although recommendations to reduce this risk remain to be established. In the absence of such recommendations, some clinicians recommend that heparin infusions be reduced in a gradual fashion such as by reducing the rate by 50% over 6 hours and then discontinuing over the next 12 hours.

USP has changed its labeling standard for Heparin Sodium Injection, USP and Heparin Lock Flush Solution, USP to require that carton and container labels for these products clearly state the strength of the entire container (amount of heparin per total volume of container), followed in close proximity by the strength per mL in parentheses. The labeling change eliminates the need to calculate the total amount of heparin in a product containing more than 1 mL and thus reduces the chance of a dosing error. The new labeling standard for heparin was effective as of May 1, 2013.

Clinicians should check the label on all heparin products to confirm the correct formulation and strength prior to dispensing and administering the drug. For full-dose therapy, heparin is administered by IV infusion, intermittent IV injection, or deep subcutaneous (intrafat) injection. For fixed low-dose therapy, heparin usually is administered by deep subcutaneous injection. Heparin should not be administered IM because of the frequency of irritation, pain, and hematoma at the injection site.

No dosing information available.

No generic dosing information available.

The following drug interaction information is available for HEPARIN FLUSH (heparin sodium,porcine/pf):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 1 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Heparin/Coagulation Factor Xa, Inactivated (Andexanet) SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inactivated coagulation factor Xa may bind to the heparin-antithrombin III (ATIII) complex, resulting in heparin unresponsiveness.(1) CLINICAL EFFECTS: Inactivated coagulation factor Xa may inhibit the anticoagulant effect of heparin. The extent and duration of this interaction is unknown.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of inactivated coagulation factor Xa prior to heparinization.(1,2) If anticoagulation is anticipated before the inactivated coagulation factor Xa has been given, consider the use of 4-factor prothrombin complex concentration for factor X inhibitor reversal.(3) If anticoagulation is needed after inactivated coagulation factor Xa has been given, consider an alternative anticoagulant to heparin, like argatroban or bivalirudin.(3) DISCUSSION: A 70-year-old man on rivaroxaban for atrial fibrillation presented with a ruptured abdominal aortic aneurysm (AAA). He was given inactivated coagulation factor Xa to reverse anticoagulation and taken to surgery for AAA repair. During the procedure, he received a total of 14,000 units of unfractionated heparin (UFH) without a change in his activated clotting time (ACT). The patient developed an iliac artery thrombus thought to be a result of the failure to achieve therapeutic anticoagulation during the procedure.(3,4) A 72-year-old man on apixaban for atrial fibrillation underwent an elective radiofrequency ablation procedure complicated by cardiac tamponade. Inactivated coagulation factor Xa was started to reverse anticoagulation. Subsequently, a left ventricular free wall rupture was discovered, and the patient was placed under cardiopulmonary bypass (CPB) for repair. Despite administration of 80,000 units of UFH, the patient's ACT was minimally increased and thrombi formed in the operating field and CPB circuit. Inactivated coagulation factor Xa was stopped and antithrombin III 1,000 units was given, leading to an out of range ACT (>999 seconds). ACT subsequently normalized after administration of protamine sulphate.(5)	ANDEXXA

Drug Interaction

Drug Names

Heparin/Coagulation Factor Xa, Inactivated (Andexanet)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Inactivated coagulation factor Xa may bind to the heparin-antithrombin III (ATIII) complex, resulting in heparin unresponsiveness.(1)

CLINICAL EFFECTS: Inactivated coagulation factor Xa may inhibit the anticoagulant effect of heparin. The extent and duration of this interaction is unknown.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid the use of inactivated coagulation factor Xa prior to heparinization.(1,2) If anticoagulation is anticipated before the inactivated coagulation factor Xa has been given, consider the use of 4-factor prothrombin complex concentration for factor X inhibitor reversal.(3) If anticoagulation is needed after inactivated coagulation factor Xa has been given, consider an alternative anticoagulant to heparin, like argatroban or bivalirudin.(3)

DISCUSSION: A 70-year-old man on rivaroxaban for atrial fibrillation presented with a ruptured abdominal aortic aneurysm (AAA). He was given inactivated coagulation factor Xa to reverse anticoagulation and taken to surgery for AAA repair. During the procedure, he received a total of 14,000 units of unfractionated heparin (UFH) without a change in his activated clotting time (ACT).

The patient developed an iliac artery thrombus thought to be a result of the failure to achieve therapeutic anticoagulation during the procedure.(3,4) A 72-year-old man on apixaban for atrial fibrillation underwent an elective radiofrequency ablation procedure complicated by cardiac tamponade. Inactivated coagulation factor Xa was started to reverse anticoagulation.

Subsequently, a left ventricular free wall rupture was discovered, and the patient was placed under cardiopulmonary bypass (CPB) for repair. Despite administration of 80,000 units of UFH, the patient's ACT was minimally increased and thrombi formed in the operating field and CPB circuit. Inactivated coagulation factor Xa was stopped and antithrombin III 1,000 units was given, leading to an out of range ACT (>999 seconds). ACT subsequently normalized after administration of protamine sulphate.(5)

ANDEXXA

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Lifileucel/Anticoagulants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Internal organ hemorrhage, including intraabdominal and intracranial hemorrhage, has been reported in the presence of persistent or repeated thrombocytopenia following treatment with lifileucel.(1) CLINICAL EFFECTS: Concurrent use or recent therapy with lifileucel and an anticoagulant may increase the risk of life-threatening hemorrhage, including intraabdominal and intracranial hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). PATIENT MANAGEMENT: The US manufacturer states patients with persistent or repeated thrombocytopenia after receiving lifileucel should not use anticoagulants. If anticoagulation therapy is warranted, close monitoring of patients must take place.(1) The US manufacturer recommends withholding or discontinuing lifileucel if internal organ hemorrhage is indicated, or patient is ineligible for IL-2 (aldesleukin) infusion.(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. DISCUSSION: In the open-label single-arm study of 156 adult patients, two cases of internal organ hemorrhage (abdominal hemorrhage and intracranial hemorrhage) leading to death were reported.(1) The incidence of grade 3 or 4 laboratory abnormalities occurring in melanoma patients following treatment with lifileucel included thrombocytopenia (78.2%), neutropenia (69.2%) and anemia (58.3%). Prolonged thrombocytopenia occurred in 30.1% of patients.(1)	AMTAGVI

Drug Interaction

Drug Names

Lifileucel/Anticoagulants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Internal organ hemorrhage, including intraabdominal and intracranial hemorrhage, has been reported in the presence of persistent or repeated thrombocytopenia following treatment with lifileucel.(1)

CLINICAL EFFECTS: Concurrent use or recent therapy with lifileucel and an anticoagulant may increase the risk of life-threatening hemorrhage, including intraabdominal and intracranial hemorrhage.(1)

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia).

PATIENT MANAGEMENT: The US manufacturer states patients with persistent or repeated thrombocytopenia after receiving lifileucel should not use anticoagulants. If anticoagulation therapy is warranted, close monitoring of patients must take place.(1) The US manufacturer recommends withholding or discontinuing lifileucel if internal organ hemorrhage is indicated, or patient is ineligible for IL-2 (aldesleukin) infusion.(1)

If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: In the open-label single-arm study of 156 adult patients, two cases of internal organ hemorrhage (abdominal hemorrhage and intracranial hemorrhage) leading to death were reported.(1) The incidence of grade 3 or 4 laboratory abnormalities occurring in melanoma patients following treatment with lifileucel included thrombocytopenia (78.2%), neutropenia (69.2%) and anemia (58.3%). Prolonged thrombocytopenia occurred in 30.1% of patients.(1)

AMTAGVI

The following contraindication information is available for HEPARIN FLUSH (heparin sodium,porcine/pf):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 1 contraindications. Absolute contraindication.

Contraindication List
Heparin-induced thrombocytopenia

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Thrombocytopenic disorder

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hemorrhage
Hyperkalemia

The following adverse reaction information is available for HEPARIN FLUSH (heparin sodium,porcine/pf):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 8 severe adverse reactions.

More Frequent	Less Frequent
Hemorrhage Heparin-induced thrombocytopenia Thrombocytopenic disorder	None.

Rare/Very Rare
Anaphylaxis Hypersensitivity drug reaction Paresthesia of plantar surface Thrombosis in heparin-induced thrombocytopenia Urticaria

There are 9 less severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Asthma Chills Eye tearing Fever Headache disorder Nausea and vomiting Peripheral neuropathy Pruritus of skin Rhinitis

The following precautions are available for HEPARIN FLUSH (heparin sodium,porcine/pf):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Increased fetal resorptions have been observed in animals when heparin was administered during the period of organogenesis in dosages higher than the maximum human dosage; there are no adequate and well-controlled studies to date using heparin in pregnant women. Published reports have not shown any evidence of a teratogenic potential or other adverse fetal effects when the drug is used during pregnancy; because heparin does not cross the human placenta, any fetal complications that may occur are likely to be related to other indirect factors (e.g., severe maternal disease). Long-term (e.g., longer than 1 month) heparin therapy during pregnancy can result in maternal osteopenia and osteoporosis, and prophylactic calcium and vitamin D supplementation has been suggested to reduce this risk.

At least one case of fatal cerebral hemorrhage has occurred in a woman receiving heparin and aspirin to prevent pregnancy loss following in vitro fertilization. (See Uses: Complications of Pregnancy.) Heparin should be used during pregnancy only if the potential benefits justify the potential risks to the fetus; if needed, use of a preservative (benzyl alcohol)-free formulation is recommended. When anticoagulant therapy is required in pregnant women, ACCP generally recommends the use of a low molecular weight heparin because of a more favorable adverse effect profile.

For information on the prophylactic use of heparin to improve pregnancy outcomes in certain women at risk (e.g., those with antiphospholipid syndrome), see Uses: Complications of Pregnancy.

Because of its high molecular weight, heparin is not likely to be distributed into human milk; any heparin that is ingested during breastfeeding would not be absorbed by a nursing infant. However, if benzyl alcohol is present in maternal serum, it is likely to distribute into human milk and be absorbed by a nursing infant. The manufacturer recommends caution if heparin is used in nursing women.

ACCP recommends that heparin be continued in nursing women who are already receiving such therapy. If heparin therapy is required in nursing women, use of a preservative (benzyl alcohol)-free formulation is recommended.

No enhanced Geriatric Use information available for this drug.

Maintain patency of indwelling intravenous catheter
Z45.2	Encounter for adjustment and management of vascular access device