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Drug overview for HEPARIN SODIUM (heparin sodium,porcine):
Generic name: HEPARIN SODIUM,PORCINE (HEP-a-rin)
Drug class: Heparin
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.
Generic name: HEPARIN SODIUM,PORCINE (HEP-a-rin)
Drug class: Heparin
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 SODIUM (heparin sodium,porcine) have been approved by the FDA:
Indications:
Deep vein thrombosis prevention
Deep venous thrombosis
Disseminated intravascular coagulation
Peripheral arterial embolism
Peripheral arterial thromboembolism prevention
Prevent extracorporeal clotting during hemodialysis
Pulmonary thromboembolism prevention
Pulmonary thromboembolism
Professional Synonyms:
Consumption coagulopathy
Deep vein thrombosis prophylaxis
Deep vein thrombosis
Defibrination syndrome
Disseminated intravascular clotting
DVT prevention
Peripheral artery embolism
Peripheral artery thromboembolism prophylaxis
PTE prophylaxis
Pulmonary embolism
Pulmonary thromboembolism prophylaxis
Indications:
Deep vein thrombosis prevention
Deep venous thrombosis
Disseminated intravascular coagulation
Peripheral arterial embolism
Peripheral arterial thromboembolism prevention
Prevent extracorporeal clotting during hemodialysis
Pulmonary thromboembolism prevention
Pulmonary thromboembolism
Professional Synonyms:
Consumption coagulopathy
Deep vein thrombosis prophylaxis
Deep vein thrombosis
Defibrination syndrome
Disseminated intravascular clotting
DVT prevention
Peripheral artery embolism
Peripheral artery thromboembolism prophylaxis
PTE prophylaxis
Pulmonary embolism
Pulmonary thromboembolism prophylaxis
The following dosing information is available for HEPARIN SODIUM (heparin sodium,porcine):
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.
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.
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.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| HEPARIN SOD 5,000 UNIT/ML VIAL | Maintenance | Adults inject 1.6 milliliters (8,000 unit) by subcutaneous route every 8 hours |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| HEPARIN 50,000 UNIT/10 ML VIAL | Maintenance | Adults inject 1.6 milliliters (8,000 unit) by subcutaneous route every 8 hours |
| HEPARIN SOD 5,000 UNIT/ML VIAL | Maintenance | Adults inject 1.6 milliliters (8,000 unit) by subcutaneous route every 8 hours |
The following drug interaction information is available for HEPARIN SODIUM (heparin sodium,porcine):
There are 6 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Mifepristone/Anticoagulants; Antiplatelets SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Anticoagulants may result in excessive bleeding following the abortion. CLINICAL EFFECTS: The concurrent use of mifepristone with anticoagulants may result in excessive bleeding following the abortion. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The manufacturer of mifepristone states that mifepristone is contraindicated in patients receiving concurrent anticoagulant therapy.(1) If concurrent therapy is deemed medically necessary, 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: The manufacturer of mifepristone states that mifepristone is contraindicated in patients receiving concurrent anticoagulant therapy.(1) |
MIFEPREX, MIFEPRISTONE |
| Heparins/Dabigatran SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Heparin inhibits thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Dabigatran is a direct thrombin inhibitor.(1,2) CLINICAL EFFECTS: Concurrent use of anticoagulants with heparin can enhance the effects of heparin and may increase the risk of bleeding.(1,2) PREDISPOSING FACTORS: Factors associated with an increase risk for bleeding include renal impairment, concomitant use of P-glycoprotein inhibitors, patient age >74 years, coexisting conditions (e.g. recent trauma) or use of drugs (e.g. NSAIDs) associated with bleeding risk, and patient weight <50 kg.(1-3) The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The long-term use of concurrent therapy with Direct Oral Anticoagulants (DOACs) and other anticoagulants is generally considered contraindicated. However, overlap may be necessary when switching therapy from one agent to another in order to prevent thrombotic events. Manufacturer recommendations concerning overlap (if any) and timing of discontinuation versus initiation vary depending upon which agent is being discontinued and initiated. Refer to current prescribing information for both agents for additional details. Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or blood pressure and promptly evaluate patients with any symptoms. Discontinue dabigatran in patients with active pathological bleeding.(2) The UK manufacturer states that the use of unfractionated heparin, heparin derivatives, and low molecular weight heparins with concomitant dabigatran therapy is contraindicated unless switching treatment to or from dabigatran or when unfractionated heparin is given at doses appropriate to maintain open central venous or arterial catheter.(1) When converting from parenteral anticoagulant to dabigatran, administer dabigatran 0-2 hours before the next dose of the parenteral drug is due or at time of discontinuation of a continuously infused anticoagulant.(2) When converting from dabigatran to a parenteral anticoagulant, begin parenteral anticoagulant: -----12 hours after last dose of dabigatran in patients with CrCl greater than or equal to 30ml/min, -----24 hours after last dose of dabigatran in patients with CrCl less than 30 ml/min.(2) 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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: The use of both agents is likely to increase the frequency and occurrence of unwanted bleeding episodes. The use of heparin to maintain catheter patency is acceptable with the use of these agents together.(1,2) |
DABIGATRAN ETEXILATE, PRADAXA |
| Edoxaban/Anticoagulants; Thrombolytics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Additive effects on hemostasis. CLINICAL EFFECTS: Concurrent use of edoxaban with anticoagulants or thrombolytics may increase the risk of bleeding. PREDISPOSING FACTORS: Bleeding risk may be increased in patients with renal impairment and in patients > 75 years of age. Use of multiple agents which affect hemostasis increases the risk for bleeding. PATIENT MANAGEMENT: The long-term use of concurrent therapy with direct oral anticoagulants (DOACs) and other anticoagulants is generally considered contraindicated. However, overlap may be necessary when switching therapy from one agent to another in order to prevent thrombotic events. Manufacturer recommendations concerning overlap (if any) and timing of discontinuation versus initiation vary depending upon which agent is being discontinued and initiated. Refer to current prescribing information for both agents for additional details. Specific recommendations for converting between anticoagulants: - When converting from other (non-vitamin K antagonist) oral anticoagulants to edoxaban, discontinue current oral anticoagulant and start edoxaban at the time of the next scheduled dose of the old oral anticoagulant. - When converting from a low molecular weight heparin (LMWH) to edoxaban, start edoxaban at the time of the next scheduled administration of LMWH. - When converting from unfractionated heparin to edoxaban, discontinue the infusion and start edoxaban 4 hours later. - When converting from edoxaban to another DOAC, discontinue edoxaban and begin the new oral anticoagulant at the time of the next scheduled dose of edoxaban. - When converting from edoxaban to parenteral anticoagulation, start the parenteral anticoagulant at the time of the next dose of edoxaban. - When converting from warfarin to edoxaban, discontinue warfarin and start edoxaban when the INR is < or = to 2.5. - When converting from edoxaban to warfarin, for patients taking 60 mg of edoxaban, reduce the dose to 30 mg and begin warfarin concomitantly. For patients receiving 30 mg of edoxaban, reduce the dose to 15 mg and begin warfarin concomitantly. INR must be measured at least weekly and just prior to the daily dose of edoxaban to minimize the effects of edoxaban on INR measurement. Once a stable INR = or > 2.0 is achieved, edoxaban should be discontinued and the warfarin continued. - A second edoxaban to warfarin conversion option: Discontinue edoxaban and administer a parenteral anticoagulant and warfarin at the time of the next scheduled edoxaban dose. Once a stable INR = or > 2.0 is achieved, the parenteral anticoagulant should be discontinued and the warfarin continued. The use of concurrent therapy with Direct Oral Anticoagulants (DOACs) and thrombolytics is generally considered contraindicated. The manufacturer of alteplase states that the use of alteplase for an indication of acute ischemic stroke is contraindicated in patients receiving anticoagulants. Concurrent use of alteplase and anticoagulants is dependent on the therapeutic indication. In Acute Ischemic Stroke: - Clinical practice guidelines for acute ischemic stroke state the use of thrombolytic therapy for an indication of acute ischemic stroke is contraindicated in patients who have received thrombin inhibitors or factor Xa inhibitors in the previous 48 hours (in normal renal function) and have abnormal laboratory tests such as activated partial thromboplastin time (aPTT), INR, platelet count, ecarin clotting time (ECT), thrombin time, or direct factor Xa assays at presentation. In Acute Myocardial Infarction: - Patients who are receiving thrombolytics for an indication of acute myocardial infarction should be carefully monitored for signs of bleeding, especially at arterial puncture sites, if edoxaban is used concurrently. - The use of thrombolytics in patients with acute myocardial infarction should follow standard management of myocardial infarction, including minimizing arterial and venous puncture; avoid noncompressible arterial puncture; and minimize internal jugular and subclavian venous punctures to decrease bleeding from the noncompressible sites. For all indications: - In the event of serious bleeding, anticoagulants should be discontinued immediately. - 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. - 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: Limited overlap of DOACs with other anticoagulants may be required when initiating or discontinuing DOACs in order to prevent thrombotic events. However, long-term concomitant treatment is not recommended because of increased risk of bleeding. Patients who are receiving thrombolytics should be carefully monitored for signs of bleeding if anticoagulants are being used concurrently or have recently been used. |
SAVAYSA |
| Apixaban/Anticoagulants; Thrombolytics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Additive effects on hemostasis. CLINICAL EFFECTS: Concurrent use of apixaban with anticoagulants or thrombolytics may increase the risk of bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The long-term use of concurrent therapy with direct oral anticoagulants (DOACs) and other anticoagulants is generally considered contraindicated. However, overlap may be necessary when switching therapy from one agent to another in order to prevent thrombotic events. Manufacturer recommendations concerning overlap (if any) and timing of discontinuation versus initiation vary depending upon which agent is being discontinued and initiated. Refer to current prescribing information for both agents for additional details. Specific recommendations for converting between anticoagulants: - When converting between apixaban and anticoagulants other than warfarin, discontinue the current anticoagulant and begin the new one when next dose is due. - When converting from warfarin to apixaban, discontinue warfarin and begin apixaban when the international normalized ratio (INR) is below 2.0. - Apixaban affects INR. Therefore concurrent administration with warfarin when converting from apixaban to warfarin is not useful in determining target warfarin dose. If continuous anticoagulation is warranted, discontinue apixaban and begin both warfarin and a parenteral anticoagulant when next dose of apixaban is due. Once INR is within range, discontinue the parenteral anticoagulant. The use of concurrent therapy with Direct Oral Anticoagulants (DOACs) and thrombolytics is generally considered contraindicated. The manufacturer of alteplase states that the use of alteplase for an indication of acute ischemic stroke is contraindicated in patients receiving anticoagulants. Concurrent use of alteplase and anticoagulants is dependent on the therapeutic indication. In Acute Ischemic Stroke: - Clinical practice guidelines for acute ischemic stroke state the use of thrombolytic therapy for an indication of acute ischemic stroke is contraindicated in patients who have received thrombin inhibitors or factor Xa inhibitors in the previous 48 hours (in normal renal function) and have abnormal laboratory tests such as activated partial thromboplastin time (aPTT), INR, platelet count, ecarin clotting time (ECT), thrombin time, or direct factor Xa assays at presentation. In Acute Myocardial Infarction: - Patients who are receiving thrombolytics for an indication of acute myocardial infarction should be carefully monitored for signs of bleeding, especially at arterial puncture sites, if apixaban is used concurrently. - The use of thrombolytics in patients with acute myocardial infarction should follow standard management of myocardial infarction, including minimizing arterial and venous puncture; avoid noncompressible arterial puncture; and minimize internal jugular and subclavian venous punctures to decrease bleeding from the noncompressible sites. For all indications: - In the event of serious bleeding, anticoagulants should be discontinued immediately. - 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. - 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: Limited overlap of DOACs with other anticoagulants may be required when initiating or discontinuing DOACs in order to prevent thrombotic events. However, long-term concomitant treatment is not recommended because of increased risk of bleeding. Patients who are receiving thrombolytics should be carefully monitored for signs of bleeding if anticoagulants are being used concurrently or have recently been used. |
ELIQUIS |
| Rivaroxaban/Anticoagulants; Thrombolytics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Additive effects on hemostasis. CLINICAL EFFECTS: Concurrent use of rivaroxaban with anticoagulants or thrombolytics may increase the risk of bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The long-term use of concurrent therapy with direct oral anticoagulants (DOACs) and other anticoagulants is generally considered contraindicated. However, overlap may be necessary when switching therapy from one agent to another in order to prevent thrombotic events. Manufacturer recommendations concerning overlap (if any) and timing of discontinuation versus initiation vary depending upon which agent is being discontinued and initiated. Refer to current prescribing information for both agents for additional details. Specific recommendations for converting between anticoagulants: - When converting from rivaroxaban to anticoagulants other than warfarin and switching to an anticoagulant with rapid onset, discontinue rivaroxaban and begin new anticoagulant when next dose of rivaroxaban is due. - When converting from anticoagulants other than warfarin to rivaroxaban, discontinue current anticoagulant and begin rivaroxaban between 0-2 hours before next evening dose of the drug is due. For patients receiving continuous infusion of unfractionated heparin, simultaneously stop the infusion and administer rivaroxaban. - When converting from warfarin to rivaroxaban, discontinue warfarin and begin rivaroxaban once international normalized ratio (INR) is below 3.0 in adults and below 2.5 in pediatric patients. - When converting from rivaroxaban to warfarin in adults, rivaroxaban affects INR. Therefore concurrent administration with warfarin is not useful in determining target warfarin dose. If continuous anticoagulation is warranted, discontinue rivaroxaban and begin both warfarin and a parenteral anticoagulant when the next dose of rivaroxaban is due. Once INR is within range, discontinue the parenteral anticoagulant. - When converting from rivaroxaban to warfarin in pediatrics, continue rivaroxaban for at least 2 days after the first dose of warfarin. After two days, INR should be measured just prior to the next scheduled dose of rivaroxaban. Once a stable INR = or > 2.0 is achieved, rivaroxaban should be discontinued and warfarin continued. The use of concurrent therapy with Direct Oral Anticoagulants (DOACs) and thrombolytics is generally considered contraindicated. The manufacturer of alteplase states that the use of alteplase for an indication of acute ischemic stroke is contraindicated in patients receiving anticoagulants. Concurrent use of alteplase and anticoagulants is dependent on the therapeutic indication. In Acute Ischemic Stroke: - Clinical practice guidelines for acute ischemic stroke state the use of thrombolytic therapy for an indication of acute ischemic stroke is contraindicated in patients who have received thrombin inhibitors or factor Xa inhibitors in the previous 48 hours (in normal renal function) and have abnormal laboratory tests such as activated partial thromboplastin time (aPTT), INR, platelet count, ecarin clotting time (ECT), thrombin time, or direct factor Xa assays at presentation. In Acute Myocardial Infarction: - Patients who are receiving thrombolytics for an indication of acute myocardial infarction should be carefully monitored for signs of bleeding, especially at arterial puncture sites, if rivaroxaban is used concurrently. - The use of thrombolytics in patients with acute myocardial infarction should follow standard management of myocardial infarction, including minimizing arterial and venous puncture; avoid noncompressible arterial puncture; and minimize internal jugular and subclavian venous punctures to decrease bleeding from the noncompressible sites. For all indications: - In the event of serious bleeding, anticoagulants should be discontinued immediately. - 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. - 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: Patients who are receiving thrombolytics should be carefully monitored for signs of bleeding if anticoagulants are being used concurrently or have recently been used. |
RIVAROXABAN, XARELTO |
| Defibrotide/Selected Anticoagulants; Thrombolytics SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Concurrent use may result in additive effects on hemostasis.(1) CLINICAL EFFECTS: Concurrent use of defibrotide with anticoagulants or thrombolytics may increase the risk of bleeding.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The US manufacturer of defibrotide states that concomitant use with systemic anticoagulant or antithrombotic therapy is contraindicated.(1) In patients who have received prior anticoagulant or thrombolytic therapy, consider delaying the start of defibrotide until the effects of the anticoagulant have abated.(1) If concurrent therapy is deemed medically necessary, closely 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding; gingival bleeding; nosebleeds; unusual bruising; orange/red urine or dark/black stools; new onset of headache, confusion, slurred speech, or vision; acute abdominal pain; or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: In pivotal clinical trials, 176 patients received defibrotide; the use of anticoagulants or thrombolytics was not allowed. Bleeding events not attributed to underlying disease were as follows: epistaxis (14%), pulmonary alveolar hemorrhage (9%), gastrointestinal hemorrhage (9%), pulmonary hemorrhage (9%), intracranial hemorrhage (3%), cerebral hemorrhage (2%). |
DEFITELIO |
There are 9 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 |
|---|---|
| Alteplase/Heparins SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The concurrent use of alteplase and heparins may increase the risk of bleeding. CLINICAL EFFECTS: The concurrent use of alteplase and heparins may result in bleeding episodes. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Use of alteplase and anticoagulants, including heparins, may increase the risk of bleeding if administered prior to, during, or after alteplase therapy. Concurrent use of alteplase and heparins is dependent on the therapeutic indication. In Acute Ischemic Stroke: - Clinical practice guidelines for acute ischemic stroke state the use of thrombolytic therapy for an indication of acute ischemic stroke is contraindicated in patients who have received full treatment doses of heparins within 24 hours preceding the onset of stroke or who have an elevated activated partial thromboplastin time (aPTT) > 40 seconds, prothrombin time (PT) > 15 seconds, INR > 1.7, or platelets <100,000/mm3 at presentation. In Acute Myocardial Infarction: - Patients who are receiving alteplase for an indication of acute myocardial infarction should be carefully monitored for signs of bleeding, especially at arterial puncture sites, if heparin is used concurrently. - The use of alteplase in patients with acute myocardial infarction should follow standard management of myocardial infarction, including minimizing arterial and venous puncture; avoid noncompressible arterial puncture; and minimize internal jugular and subclavian venous punctures to decrease bleeding from the noncompressible sites. For all indications: - In the event of serious bleeding, heparins should be discontinued immediately and consider protamine administration for reversal of heparin. - 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. - 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: The manufacturer of alteplase states that the use of alteplase for an indication of acute ischemic stroke is contraindicated in patients who have received heparin within 24 hours preceding the onset of stroke and who have an elevated activated partial thromboplastin time (aPTT) at presentation. Heparin has been administered concomitantly and following alteplase in the treatment of acute myocardial infarction. Patients who are receiving alteplase with heparin should be carefully monitored for signs of bleeding, especially at arterial puncture sites, if heparin is used concurrently. |
ACTIVASE, CATHFLO ACTIVASE |
| Ketorolac/Anticoagulants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. Ketorolac impairs platelet function and may prolong bleeding time.(1) Ketorolac also has the potential to produce gastrointestinal ulceration and bleeding.(1-3) CLINICAL EFFECTS: Concurrent use of ketorolac and anticoagulants may increase the risk of bleeding complications.(1-3) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The Australian(1) and UK(2) manufacturers of ketorolac state that the use of ketorolac in patients on anticoagulants, including low-dose heparin,(2) is contraindicated. The US manufacturer of ketorolac states that concurrent therapy with anticoagulants should be undertaken with extreme caution after carefully weighing the benefits of concurrent therapy against the risks and that patients receiving concurrent therapy should be closely monitored.(3) 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Ketorolac has been shown to inhibit platelet aggregation and may prolong bleeding times. Ketorolac-induced inhibition of platelet function disappears within 24 to 48 hours after ketorolac discontinuation. Ketorolac does not affect platelet count, prothrombin time (PT), or partial thromboplastin time (PTT).(1) Ketorolac has been shown in vitro to only slightly reduce warfarin protein binding (from 99.5% to 99.3%.(3) In a study in 12 subjects, ketorolac had no effects on the pharmacokinetics or pharmacodynamics of a single dose of warfarin (25 mg). In another study in 11 subjects, ketorolac increased the mean template bleeding time for 2 doses of heparin from 6.0 to 6.4 minutes.(3) |
BUPIVACAINE-KETOROLAC-KETAMINE, KETOROLAC TROMETHAMINE, ROPIVACAINE-KETOROLAC-KETAMINE, SPRIX, TORONOVA II SUIK, TORONOVA SUIK |
| Bivalirudin; Desirudin/GPIs; Heparin; Thrombolytics; Warfarin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use may result in additive effects on hemostasis.(1,2) CLINICAL EFFECTS: Concurrent use of bivalirudin with GPIs, heparin, or warfarin may increase the risk of bleeding.(1,2) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Concurrent use of bivalirudin and GPIs, heparin, or warfarin should be avoided.(1) Discontinue agents that may increase the risk of hemorrhage prior to initiation of desirudin.(2) 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: In clinical trials, concurrent use of bivalirudin with GPIs, heparin, or warfarin was associated with increased risks of major bleeding events compared to patients not receiving concurrent therapy.(1) Concurrent administration of warfarin did not affect the pharmacokinetics of desirudin; however, greater inhibition of hemostasis was observed as seen by aPPT, PT and INR measurements.(2) |
BIVALIRUDIN |
| 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 |
| Tenecteplase/Heparins SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The concurrent use of tenecteplase and heparins may increase the risk of bleeding. CLINICAL EFFECTS: The concurrent use of tenecteplase and heparins may result in bleeding episodes. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Use of tenecteplase and anticoagulants, including heparins, may increase the risk of bleeding if administered prior to, during, or after tenecteplase therapy. Concurrent use of tenecteplase and heparins is dependent on the therapeutic indication. In Acute Ischemic Stroke: - Clinical practice guidelines for acute ischemic stroke state the use of thrombolytic therapy for an indication of acute ischemic stroke is contraindicated in patients who have received full treatment doses of heparins within 24 hours preceding the onset of stroke or who have an elevated activated partial thromboplastin time (aPTT) > 40 seconds, prothrombin time (PT) > 15 seconds, INR > 1.7, or platelets <100,000/mm3 at presentation. In Acute Myocardial Infarction: - Patients who are receiving tenecteplase for an indication of acute myocardial infarction should be carefully monitored for signs of bleeding, especially at arterial puncture sites, if heparin is used concurrently. - The use of tenecteplase in patients with acute myocardial infarction should follow standard management of myocardial infarction, including minimizing arterial and venous puncture; avoid noncompressible arterial puncture; and minimize internal jugular and subclavian venous punctures to decrease bleeding from the noncompressible sites. For all indications: - In the event of serious bleeding, heparins should be discontinued immediately and consider protamine administration for reversal of heparin. - 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. - 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: The manufacturer of tenecteplase states that formal interaction studies of tenecteplase with other drugs have not been performed. Clinical practice guidelines for acute ischemic stroke state the use of thrombolytic therapy for an indication of acute ischemic stroke is contraindicated in patients who have received heparin within 24 hours preceding the onset of stroke and who have an elevated activated partial thromboplastin time (aPTT) at presentation. Clinical trials of tenecteplase in acute myocardial infarction included concomitant use with heparins. Patients who are receiving tenecteplase with heparin should be carefully monitored for signs of bleeding, especially at arterial puncture sites. |
TNKASE |
| Caplacizumab/Anticoagulants; Antiplatelets SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Bleeding has been reported with the use of caplacizumab.(1) CLINICAL EFFECTS: Concurrent use of caplacizumab with either anticoagulants or antiplatelets may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. hemophilia, coagulation factor deficiencies). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid the use of caplacizumab with anticoagulants and antiplatelets. Interrupt caplacizumab therapy if clinically significant bleeding occurs. Patients may require von Willebrand factor concentrate to rapidly correct hemostasis. If caplacizumab is restarted, closely monitor for signs of bleeding.(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. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Bleeding has been reported with caplacizumab. In clinical studies, severe bleeding adverse reactions of epistaxis, gingival bleeding, upper gastrointestinal hemorrhage, and metrorrhagia were each reported in 1% of patients. Overall, bleeding events occurred in approximately 58% of patients on caplacizumab versus 43% of patients on placebo.(1) In post-marketing reports, cases of life-threatening and fatal bleeding were reported with caplacizumab.(1) |
CABLIVI |
| Lecanemab/Anticoagulants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Microhemorrhage has been reported with the use of lecanemab. Radiographic changes on brain MRI have been noted as amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H) which included microhemorrhage. In addition, intracerebral hemorrhages (ICH) greater than 1 cm in diameter have occurred in patients treated with lecanemab.(1) CLINICAL EFFECTS: Concurrent use of lecanemab with anticoagulants agents may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The US manufacturer of lecanemab advises extreme caution in patients treated with anticoagulants. Evaluate the risks and benefits of concurrent use of lecanemab with anticoagulants.(1) Appropriate use recommendations for lecanemab state patients on anticoagulants should not receive lecanemab.(2) The UK manufacturer of lecanemab contraindicates initiation of lecanemab in patients receiving ongoing anticoagulant therapy. If anticoagulation is necessary, then lecanemab should be paused. Lecanemab can be reinstated if anticoagulation is no longer medically indicated.(3) If concurrent therapy is warranted, patients should be closely monitored for signs and symptoms of microhemorrhage, including headache, nausea/vomiting, confusion, dizziness, visual disturbance, gait difficulties, and loss of coordination, as well as other bleeding and changes in platelet count or International Normalized Ratio (INR).(1) When applicable, perform agent-specific laboratory tests (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as confusion, headache, dizziness, nausea, visual changes, 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 clinical studies, lecanemab was observed to increase ARIA-H, including microhemorrhage and intracerebral hemorrhage. Radiographic changes were classified as mild (<=4 new incidences), moderate (5 to 9 new incidences), or severe (10 or more new incidences. Patients were excluded from clinical trials if taking concurrent anticoagulants or anti-platelets.(1) In Studies 1 and 2, the maximum severity of ARIA-H microhemorrhage was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients. Intracerebral hemorrhage greater than 1 cm in diameter was reported in 0.7% (6/898) of patients in Study 2 after treatment with lecanemab compared to 0.1% (1/897) on placebo. Fatal events of intracerebral hemorrhage in patients taking lecanemab have been observed.(1) In Study 2, baseline use of antithrombotic medications (aspirin, other antiplatelets, or anticoagulants) were allowed if patient was on a stable dose. Aspirin was the most common antithrombotic agent. The incidence of ICH was 0.9% (3/328 patients) in patients taking lecanemab with a concomitant antithrombotic medication at the time of the event compared to 0.6% (3/545 patients) in those who did not receive an antithrombotic. Patients taking lecanemab with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79 patients) compared to none in patients who received placebo. |
LEQEMBI |
| Donanemab/Anticoagulants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Microhemorrhage has been reported with the use of donanemab. Radiographic changes on brain MRI have been noted as amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H) which included microhemorrhage. In addition, intracerebral hemorrhages (ICH) greater than 1 cm in diameter have occurred in patients treated with donanemab.(1) CLINICAL EFFECTS: Concurrent use of donanemab with anticoagulants agents may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Donanemab should be used with extreme caution in patients treated with anticoagulants. Evaluate the risks and benefits of concurrent use of donanemab with anticoagulants.(1) The manufacturer of donanemab recommends testing for AP0E4 status prior to initiation of treatment.(1) Use of anticoagulant agents in patients who are homozygous for the APOE4 gene, may have an increased risk of ARIA with donanemab therapy.(1-3) If concurrent therapy is warranted, patients receiving concurrent therapy with donanemab and anticoagulants should be closely monitored for signs and symptoms of bleeding and changes in platelet count or International Normalized Ratio (INR).(1) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of microhemorrhage, including headache, nausea/vomiting, confusion, dizziness, visual disturbance, gait difficulties, and loss of coordination. General signs of blood loss include 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. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as confusion, headache, dizziness, nausea, visual changes, 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 a double-blind, placebo-controlled clinical study of 1736 participants randomized to receive donanemab (n = 860) or placebo (n = 876), donanemab was observed to increase amyloid related imaging abnormalities-hemosiderin deposition (ARIA-H), including microhemorrhage and intracerebral hemorrhage (ICH). Radiographic changes were classified as mild (<=4 new incidences), moderate (5 to 9 new incidences), or severe (10 or more new incidences). The maximum severity of ARIA-H microhemorrhage was observed as mild in 17% (143/853), moderate in 4% (34/853), and severe in 5% (40/853) of patients taking donanemab.(1) Baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed. The majority of exposures to antithrombotic medications were to aspirin. The incidence of ARIA-H was 30% (106/349) in patients taking donanemab with a concomitant antithrombotic medication within 30 days compared to 29% (148/504) who did not receive an antithrombotic within 30 days of an ARIA-H event.(1) The incidence of ICH greater than 1 cm in diameter was 0.6% (2/349 patients) in patients taking donanemab with a concomitant antithrombotic medication compared to 0.4% (2/504) in those who did not receive an antithrombotic. One fatal ICH occurred in a patient taking donanemab in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.(1) The manufacturer of donanemab states the number of events and the limited exposure to non-aspirin antithrombotic medications limit definitive conclusions about the risk of ARIA or ICH in patients taking antithrombotic medications concurrently with donanemab. If concurrent therapy is warranted, patients should be closely monitored for signs and symptoms of bleeding and changes in platelet count or INR.(1) |
KISUNLA |
| Hemin/Anticoagulants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Mild, transient anticoagulant effects has been reported with the use of hemin.(1) CLINICAL EFFECTS: Concurrent use of hemin with anticoagulants may increase the risk of bleeding.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The manufacturer of hemin states concurrent use with anticoagulant therapy should be avoided.(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. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Mild, transient anticoagulant effects have been reported during clinical studies with hemin.(1) |
PANHEMATIN |
There are 15 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 |
|---|---|
| Heparin/Selected Salicylates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Additive prolongation of bleeding time. CLINICAL EFFECTS: Increased risk of bleeding which may extend for several days beyond discontinuation of salicylates. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If this combination is used, monitor patients for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. A non-acetylated salicylate may be used to avoid antiplatelet activity. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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. Single ingredient aspirin or buffered aspirin products with strengths < or = 325 mg and combination aspirin products which are used to treat cardiovascular disease (e.g. aspirin+statins, aspirin+dipyridamole) are not included in this interaction. DISCUSSION: This interaction is likely to occur. |
ACETYL SALICYLIC ACID, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, ASPIRIN, BALSALAZIDE DISODIUM, BISMUTH SUBSALICYLATE, BUTALBITAL-ASPIRIN-CAFFEINE, CARISOPRODOL-ASPIRIN, CARISOPRODOL-ASPIRIN-CODEINE, CHOLINE MAGNESIUM TRISALICYLAT, COLAZAL, DISALCID, MB CAPS, NORGESIC, NORGESIC FORTE, ORPHENADRINE-ASPIRIN-CAFFEINE, ORPHENGESIC FORTE, PHENYL SALICYLATE, SALSALATE, SODIUM SALICYLATE, URELLE, URETRON D-S, URIBEL TABS, URIMAR-T, URNEVA, URO-MP, URO-SP |
| Platelet Aggregation Inhibitors/Selected Anticoagulants (Vitamin K antagonists); Heparins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Platelet aggregation inhibitors work by irreversibly modifying the platelet ADP receptor and inhibiting the activation of GP IIb/IIIa complex.(1) Concurrent use with anticoagulants may result in additive effects on the clotting cascade. CLINICAL EFFECTS: The concurrent use of platelet aggregation inhibitors and anticoagulants may result in an increased risk of bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Use caution when administering platelet aggregation inhibitors concurrently with anticoagulants.(1) Careful monitoring of appropriate laboratory values for the patient's anticoagulant (e.g. PTT for heparin, anti Xa levels for low-molecular weight heparins, INR for warfarin) as well as signs and symptoms of bleeding is warranted. 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Although a study in patients on long-term warfarin therapy found that the stable anticoagulation status was unaffected by concurrent clopidogrel use,(2) careful monitoring would be prudent. A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of warfarin and dipyridamole resulted in a ratio of rate ratios (95% CI) of 2.07 (1.65-2.6); and warfarin and clopidogrel ratio of rate ratios 1.69 (1.56-1.84). A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 38 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antiplatelets (OR=1.74; 95% CI 1.56-1.94). Increased bleeding risk was also seen in subgroup analyses with aspirin (OR=1.50; 95% CI 1.29-1.74), clopidogrel (OR=3.55; 95% CI 2.78-4.54), and aspirin plus clopidogrel or ticlopidine (OR=2.07, 95% CI 1.33-3.21).(4) |
AGGRASTAT, ASPIRIN-DIPYRIDAMOLE ER, BRILINTA, CILOSTAZOL, CLOPIDOGREL, CLOPIDOGREL BISULFATE, DIPYRIDAMOLE, EFFIENT, EPTIFIBATIDE, KENGREAL, PLAVIX, PRASUGREL HCL, TICAGRELOR, TIROFIBAN HCL, ZONTIVITY |
| Heparins/Selected Anticoagulants (Vitamin K antagonists); Citrates SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Heparin inhibits thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin.(1) CLINICAL EFFECTS: Concurrent use of anticoagulants with heparin can enhance the effects of heparin and may increase the risk of bleeding.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The manufacturer recommends baseline and periodic platelet counts and hematocrits for the entire duration of heparin administration.(1) Monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or blood pressure and promptly evaluate patients with any symptoms. Discontinue heparin in patients with active pathological bleeding unless the benefits outweigh the potential risk.(1) Partial thromboplastin time (aPTT) or whole-blood clotting time (WBC) may be monitored to assess coagulation status.(1) 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: A study of the use of heparin and warfarin in DVT patients concluded that it is safe to use heparin in combination with warfarin(2) with proper monitoring. |
ACD SOLUTION A, ACD-A, ANISINDIONE, ANTICOAGULANT SODIUM CITRATE, CITRATE PHOSPHATE DEXTROSE, CRRT TRISODIUM CITRATE, DICUMAROL, JANTOVEN, PHENINDIONE, SODIUM CITRATE, TRICITRASOL, TRISODIUM CITRATE CRRT, WARFARIN SODIUM |
| Heparins/NSAIDs SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Heparin inhibits thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin.(1) NSAIDs inhibit coagulation by interfering with platelet-aggregation, while inhibition of prostaglandin synthesis increases the risk for gastrointestinal bleeding. CLINICAL EFFECTS: Concurrent use of heparin and an NSAID may increase the risk for bleeding.(1,2) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with multiple disease-associated factors (e.g. thrombocytopenia, advanced liver disease). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g., other anticoagulants, antiplatelets, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Risk of GI bleed may be increased in patients who are of older age, in poor health status, or who use alcohol or smoke. Risk may also be increased with longer duration of NSAID use and prior history of peptic ulcer disease and/or GI bleeding. PATIENT MANAGEMENT: Manufacturers recommend caution and monitoring when using this combination of drugs.(1,2) 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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: Based upon drug mechanisms of action, careful monitoring would be prudent. |
ANAPROX DS, ANJESO, ARTHROTEC 50, ARTHROTEC 75, BROMFENAC SODIUM, CALDOLOR, CAMBIA, CELEBREX, CELECOXIB, COMBOGESIC, COMBOGESIC IV, CONSENSI, COXANTO, DAYPRO, DICLOFENAC, DICLOFENAC POTASSIUM, DICLOFENAC SODIUM, DICLOFENAC SODIUM ER, DICLOFENAC SODIUM MICRONIZED, DICLOFENAC SODIUM-MISOPROSTOL, DIFLUNISAL, DOLOBID, EC-NAPROSYN, ELYXYB, ETODOLAC, ETODOLAC ER, FELDENE, FENOPROFEN CALCIUM, FENOPRON, FLURBIPROFEN, HYDROCODONE-IBUPROFEN, IBU, IBUPAK, IBUPROFEN, IBUPROFEN LYSINE, IBUPROFEN-FAMOTIDINE, INDOCIN, INDOMETHACIN, INDOMETHACIN ER, INFLAMMACIN, INFLATHERM(DICLOFENAC-MENTHOL), KETOPROFEN, KETOPROFEN MICRONIZED, KIPROFEN, LODINE, LOFENA, LURBIPR, MECLOFENAMATE SODIUM, MEFENAMIC ACID, MELOXICAM, NABUMETONE, NABUMETONE MICRONIZED, NALFON, NAPRELAN, NAPROSYN, NAPROTIN, NAPROXEN, NAPROXEN SODIUM, NAPROXEN SODIUM CR, NAPROXEN SODIUM ER, NAPROXEN-ESOMEPRAZOLE MAG, NEOPROFEN, OXAPROZIN, PHENYLBUTAZONE, PIROXICAM, RELAFEN DS, SULINDAC, SUMATRIPTAN SUCC-NAPROXEN SOD, SYMBRAVO, TOLECTIN 600, TOLMETIN SODIUM, TOXICOLOGY SALIVA COLLECTION, TRESNI, TREXIMET, VIMOVO, VIVLODEX, ZIPSOR, ZORVOLEX, ZYNRELEF |
| Drospirenone/Heparin SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Drospirenone has antimineralocorticoid activity and may cause hyperkalemia. Heparin may also increase potassium levels.(1) CLINICAL EFFECTS: Concurrent use of drospirenone and heparin may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal insufficiency, hepatic dysfunction, adrenal insufficiency, and use of potassium supplements, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, and potassium-sparing diuretics may increase potassium levels.(1) PATIENT MANAGEMENT: Patients receiving drospirenone with heparin should have their serum potassium level checked during the first treatment cycle. (1) DISCUSSION: Drospirenone has antimineralocorticoid activity comparable to 25 mg of spironolactone and may result in hyperkalemia. Concurrent use of heparin may also increase potassium levels.(1) |
ANGELIQ, BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, JASMIEL, LO-ZUMANDIMINE, LORYNA, NEXTSTELLIS, NIKKI, OCELLA, SAFYRAL, SLYND, SYEDA, VESTURA, YASMIN 28, YAZ, ZARAH, ZUMANDIMINE |
| Pentosan/Heparins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Pentosan is a weak anticoagulant with 1/15 the activity of heparin. Concurrent use with heparin may result in additive effects.(1) CLINICAL EFFECTS: Concurrent use of pentosan and heparin may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with pentosan and heparin should be evaluated for hemorrhage.(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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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: Pentosan is a weak anticoagulant with 1/15 the activity of heparin.(1) In a study in 41 patients with interstitial cystitis, the concurrent use of pentosan and heparin (5000 units 3 times daily for 2 days, 5000 units 2 times daily for 12 days, then 5000 units daily as maintenance) resulted in increased response rates at 3 and 9 months, compared with 17 controls receiving pentosan alone.(2) |
ELMIRON, PENTOSAN POLYSULFATE SODIUM |
| SSRIs;SNRIs/Slt Anticoagulants;Antiplatelets;Thrombolytics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Serotonin release by platelets plays a role in hemostasis.(1,2) The increased risk of bleeding may be a result of a decrease in serotonin reuptake by platelets. CLINICAL EFFECTS: Concurrent use of a selective serotonin reuptake inhibitor(1-6) or a serotonin-norepinephrine reuptake inhibitor(7-9) and agents that affect coagulation may result in bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Renal impairment has been associated with an elevated risk of GI bleed in patients on SSRIs.(15) Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Selective serotonin reuptake inhibitors(1-6) or serotonin-norepinephrine reuptake inhibitors(7-9) and agents that affect coagulation should be used concurrently with caution. 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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 a retrospective review of 5 years of data from the Pharmaco-Epidemiologic Prescription Database, hospitalizations for upper gastro-intestinal bleeding in antidepressant users were compared to those in non-antidepressant users. The risk of a bleed in a patient using an NSAID only based on an observed-expected ration was 4.5 and in a patient using low-dose aspirin only was 2.5. Concurrent use of a selective serotonin reuptake inhibitor with NSAIDs or low-dose aspirin increased the risk of bleeding to 12.2 and 5.2, respectively.(10) In another study, there were 16 cases of upper gastrointestinal bleeding in patients receiving concurrent therapy with selective serotonin reuptake inhibitors and NSAIDs. Adjusted relative risk of bleeding with NSAIDs, selective serotonin reuptake inhibitors, or both were 3.7, 2.6, or 15.6, respectively.(11) In a case-control study conducted in users of acenocoumarol or phenprocoumon, 1848 patients who had been hospitalized with abnormal bleeding were each matched to 4 control patients. When patients took both a SSRI and a coumarin, an increased risk of hospitalization due to major non-gastrointestinal bleeding was observed (adjusted OR 1.7), but not due to gastrointestinal bleeding (adjusted OR 0.8).(12) A retrospective review examined patients discharged from a hospital with antiplatelet therapy following a myocardial infarction. When compared to aspirin therapy alone, both aspirin therapy with a SSRI and aspirin, clopidogrel, and SSRI therapy were associated with an increased risk of bleeding (hazard ratios 1.42 and 2.35, respectively.) Compared with dual antiplatelet therapy (aspirin and clopidogrel), use of aspirin and clopidogrel and a SSRI was also associated with increased risk of bleeding (hazard ratio 1.57).(13) In The Rotterdam Study, fluvoxamine increased the risk of over anticoagulation (hazard ratio 2.63). Paroxetine was not associated with an increased risk. There were insufficient numbers of patients taking other SSRIs to assess increased risk.(14) A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of dabigatran and citalopram resulted in a ratio of rate ratios (95% CI) of 1.69 (1.11-2.57).(16) A systematic review and meta-analysis of 22 cohort and case-controlled studies including over 1 million patients found 1.55-fold higher odds of upper gastrointestinal (GI) bleeding in SSRI users compared with non-SSRI users (95% CI, 1.35-1.78). In subgroup analyses, the risk was found to be greatest among participants taking SSRIs concurrently with NSAIDs or antiplatelet medications.(17) |
CELEXA, CITALOPRAM HBR, CYMBALTA, DESVENLAFAXINE ER, DESVENLAFAXINE SUCCINATE ER, DRIZALMA SPRINKLE, DULOXETINE HCL, DULOXICAINE, EFFEXOR XR, ESCITALOPRAM OXALATE, FETZIMA, FLUOXETINE DR, FLUOXETINE HCL, LEXAPRO, OLANZAPINE-FLUOXETINE HCL, PAROXETINE CR, PAROXETINE ER, PAROXETINE HCL, PAROXETINE MESYLATE, PAXIL, PAXIL CR, PRISTIQ, PROZAC, SAVELLA, SERTRALINE HCL, TRINTELLIX, VENLAFAXINE BESYLATE ER, VENLAFAXINE HCL, VENLAFAXINE HCL ER, VIIBRYD, VILAZODONE HCL, ZOLOFT |
| Ibrutinib/Selected Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ibrutinib administration lowers platelet count in the majority of patients.(1,2) In addition, ibrutinib has been shown to inhibit collagen-mediated platelet aggregation.(3-4) Bleeding has been reported with the use of ibrutinib,(1-4) anticoagulants, or antiplatelets alone. CLINICAL EFFECTS: Concurrent use of ibrutinib with either anticoagulants or antiplatelets may increase the risk of hemorrhage. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The Canadian product monograph for ibrutinib recommends concurrent use with anticoagulants or antiplatelets should be approached with caution. If therapeutic anticoagulation is required, consider temporarily withholding ibrutinib therapy until stable anticoagulation in achieved.(2) The US prescribing information for ibrutinib states patients receiving concurrent therapy with ibrutinib and anticoagulants and/or antiplatelets should be closely monitored for changes in platelet count or in International Normalized Ratio (INR). Carefully weigh the risks vs. benefits of concurrent therapy in patients with significant thrombocytopenia. If a bleeding event occurs, follow manufacturer instructions for ibrutinib dose adjustment.(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. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Bleeding has been reported with ibrutinib alone.(1-3) Across 27 clinical trials, grade 3 or higher bleeding events, e.g. subdural hematoma, gastrointestinal bleeding or hematuria, have occurred in up to 4% of patients, with 0.4% fatality. Grade 3 or 4 thrombocytopenia occurred in 5-19% of patients. Bleeding events of any grade occurred in 39% of patients treated with ibrutinib.(1) Concurrent use of anticoagulants or antiplatelets has been reported to increase the risk for major bleeding. In clinical trials, major bleeding occurred in 3.1% of patients taking ibrutinib without concurrent anticoagulants or antiplatelets, 4.4% of patients on concurrent antiplatelets with or without anticoagulants, and 6.1% of patients on concurrent anticoagulants with or without antiplatelets.(1) In an open-label, phase 2 trial of patients with relapsed/refractory mantle cell lymphoma on ibrutinib, 61 patients (55%) on concurrent anticoagulants or antiplatelets had a higher rate of bleeding (69% any grade, 8% grade 3-4) than patients not on anticoagulants or antiplatelets (28% any grade, 4% grade 3-4).(5) A retrospective trial found a hazard ratio of 20 (95% CI, 2.1-200) for patients on ibrutinib with concurrent anticoagulants and antiplatelets. There was a trend towards an increased bleeding risk in patients on either anticoagulants or antiplatelets, but this was not statistically significant on multivariate analysis.(6) A case report of 2 patients with chronic lymphocytic leukemia (CLL) on ibrutinib and dabigatran demonstrated no stroke nor bleeding events during the mean 11.5 month follow-up.(7) A case report of 4 patients with lymphoproliferative disease on concurrent dabigatran and ibrutinib demonstrated no stroke nor major bleeding events. 1 patient experienced grade 2 conjunctival hemorrhage whilst on both ibrutinib and dabigatran. The anticoagulant was withheld and successfully re-initiated at a lower dose with no further bleeding events.(8) |
IMBRUVICA |
| Mifepristone (Cushing)/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Mifepristone is an antagonist at the progesterone receptor which can result in endometrium thickening, cystic dilatation of endometrial glands, or excessive vaginal bleeding. Concurrent use with anticoagulants or antiplatelets may further increase risk. CLINICAL EFFECTS: The concurrent use of mifepristone with anticoagulants or antiplatelets may result in endometrium thickening, cystic dilatation of endometrial glands, or excessive vaginal bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: The manufacturer of mifepristone states that mifepristone should be used with caution in patients receiving concurrent anticoagulant or antiplatelet therapy.(1) If concurrent therapy is deemed medically necessary, 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 test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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. Women experiencing vaginal bleeding during concurrent use should be referred to a gynecologist for further evaluation. DISCUSSION: The manufacturer of mifepristone states that mifepristone should be used with caution in patients receiving concurrent anticoagulant or antiplatelet therapy.(1) |
KORLYM, MIFEPRISTONE |
| Icosapent Ethyl/Anticoagulant;Antiplatelet;Thrombolytic SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: In vitro data suggests that fish oils can competitively inhibit cyclooxygenase which decreases synthesis of thromboxane A1 leading to a decrease in platelet aggregation.(1) CLINICAL EFFECTS: Concurrent use of anticoagulant, antiplatelet, or thrombolytic agents increase bleeding risks. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: If concurrent therapy is deemed medically necessary, 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. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Specific studies with icosapent ethyl and affects on bleeding risk have not been conducted. Concurrent use of anticoagulant, antiplatelet, or thrombolytic agents may increase bleeding risks by impairing platelet function and prolonging bleeding time.(1) Several case reports have shown increased bleeding time and an increased risk of adverse effects from concurrent therapy.(2,3,4) A randomized placebo controlled study of 40 people taking omega-3 fatty acids and oral anticoagulants showed a significant prolongation in bleeding time.(5) |
ICOSAPENT ETHYL, VASCEPA |
| Slt Anticoagulants;Antiplatelets;Thrombolytics/Fluvoxamine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Serotonin release by platelets plays a role in hemostasis.(1) Fluvoxamine may cause a decrease in serotonin reuptake by platelets, resulting in an additive risk of bleeding with anticoagulants, antiplatelets, and thrombolytics. CLINICAL EFFECTS: Concurrent use of fluvoxamine and agents that affect coagulation may result in bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Renal impairment has been associated with an elevated risk of GI bleed in patients on SSRIs.(2) Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Concurrent therapy of fluvoxamine and agents that affect coagulation should be undertaken with caution. 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 test (e.g. INR, aPTT, anti Factor Xa inhibition) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. 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 a retrospective review of 5 years of data from the Pharmaco-Epidemiologic Prescription Database, hospitalizations for upper gastro-intestinal bleeding in antidepressant users were compared to those in non-antidepressant users. The risk of a bleed in a patient using an NSAID only based on an observed-expected ration was 4.5 and in a patient using low-dose aspirin only was 2.5. Concurrent use of a selective serotonin reuptake inhibitor with NSAIDs or low-dose aspirin increased the risk of bleeding to 12.2 and 5.2, respectively.(3) In another study, there were 16 cases of upper gastrointestinal bleeding in patients receiving concurrent therapy with selective serotonin reuptake inhibitors and NSAIDs. Adjusted relative risk of bleeding with NSAIDs, selective serotonin reuptake inhibitors, or both were 3.7, 2.6, or 15.6, respectively.(4) In a case-control study conducted in users of acenocoumarol or phenprocoumon, 1,848 patients who had been hospitalized with abnormal bleeding were each matched to 4 control patients. When patients took both a SSRI and a coumarin, an increased risk of hospitalization due to major non-gastrointestinal bleeding was observed (adjusted OR 1.7), but not due to gastrointestinal bleeding (adjusted OR 0.8).(5) A retrospective review examined patients discharged from a hospital with antiplatelet therapy following a myocardial infarction. When compared to aspirin therapy alone, both aspirin therapy with a SSRI and aspirin, clopidogrel, and SSRI therapy were associated with an increased risk of bleeding (hazard ratios 1.42 and 2.35, respectively.) Compared with dual antiplatelet therapy (aspirin and clopidogrel), use of aspirin and clopidogrel and a SSRI was also associated with increased risk of bleeding (hazard ratio 1.57).(6) In The Rotterdam Study, fluvoxamine increased the risk of over anticoagulation (hazard ratio 2.63). Paroxetine was not associated with an increased risk. There were insufficient numbers of patients taking other SSRIs to assess increased risk.(7) A self-controlled case study of 1,622 oral anticoagulant-precipitant drug pairs were reviewed and found 14% of drug pairs were associated with a statistically significant elevated risk of thromboembolism. Concurrent use of dabigatran and citalopram resulted in a ratio of rate ratios (95% CI) of 1.69 (1.11-2.57).(8) |
FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER |
| Fruquintinib; Surufatinib/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bleeding has been reported with the use of fruquintinib and surufatinib.(1,2) CLINICAL EFFECTS: Concurrent use of fruquintinib or surufatinib with either anticoagulants or antiplatelets may increase the risk of hemorrhage.(1,2) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with fruquintinib and anticoagulants and/or antiplatelets should be closely monitored for changes in platelet count or in International Normalized Ratio (INR). If a serious bleeding event occurs, the manufacturer recommends permanent discontinuation of fruquintinib.(1) Patients receiving concurrent therapy with surufatinib and anticoagulants and/or antiplatelets should be closely monitored for changes in platelet count or in INR.If a serious bleeding event occurs, the manufacturer recommends permanent discontinuation of surufatinib.(2) 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. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Bleeding has been reported with fruquintinib in three randomized, double-blinded, placebo-controlled clinical trials. The incidence of grade 1 and grade 2 bleeding events was 28.2%, including gastrointestinal bleeding (10.9%), hematuria (10.6%), and epistaxis (7.5%). The incidence of grade 3 or higher bleeding events was 2.1% and included gastrointestinal bleeding (1.6%) and hemoptysis (0.5%).(1) Bleeding has been reported with surufatinib in clinical trials. Grade 1 and 2 bleeding events included gastrointestinal bleeding, blood in the urine, and gum bleeding. The incidence of grade 3 or greater bleeding events was 4.5%, including gastrointestinal hemorrhage (1.9%), and cerebral hemorrhage (1.1%). Fatalities due to bleeding were reported in 0.3% of patients. The incidence of permanent discontinuation due to bleeding was 2.6% and the incidence of suspension of surufatinib due to bleeding was 3.8%.(2) |
FRUZAQLA |
| Plasminogen/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bleeding has been reported with the use of plasminogen.(1) CLINICAL EFFECTS: Concurrent use of plasminogen with either anticoagulants or antiplatelets may increase the risk of active bleeding during plasminogen therapy, including bleeding from mucosal disease-related lesions that may manifest as gastrointestinal (GI) bleeding, hemoptysis, epistaxis, vaginal bleeding, or hematuria.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with plasminogen and anticoagulants and/or antiplatelets should be closely monitored during plasminogen therapy for active bleeding from mucosal disease-related lesions, including GI bleeding, hemoptysis, epistaxis, vaginal bleeding, or hematuria.(1) Prior to initiation of treatment with plasminogen, confirm healing of lesions or wounds suspected as a source of a recent bleeding event. Monitor patients during and for 4 hours after infusion when administering plasminogen with concurrent anticoagulants, antiplatelet drugs, or other agents which may interfere with normal coagulation.(1) If patient experiences uncontrolled bleeding (defined as any gastrointestinal bleeding or bleeding from any other site that persists longer than 30 minutes), seek emergency care and discontinue plasminogen immediately.(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. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Plasminogen has not been studied in patients at an increased risk of bleeding. Bleeding has been reported with plasminogen in a two single-arm, open-label clinical trials as well as in compassionate use programs. The incidence of hemorrhage in patients with Plasminogen Deficiency Type 1 was 16% (3/19 patients).(1) One of the bleeding events occurred two days after receiving the second dose of plasminogen in a patient with a recent history of GI bleeding due to gastric ulcers. The patient received plasminogen through a compassionate use program and the dose was 6.6 mg/kg body weight every 2 days. Endoscopy showed multiple ulcers with one actively bleeding ulcer near the pylorus.(1) |
RYPLAZIM |
| Tisotumab/Anticoagulants; Antiplatelets SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Bleeding, including hemorrhage, has been reported with the use of tisotumab.(1) CLINICAL EFFECTS: Concurrent use of tisotumab with either anticoagulants, antiplatelets, or NSAIDs may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients receiving concurrent therapy with tisotumab and anticoagulants, antiplatelets, and/or NSAIDs should be closely monitored for signs and symptoms of bleeding and changes in platelet count or International Normalized Ratio (INR). For patients experiencing pulmonary or central nervous system (CNS) hemorrhage, permanently discontinue tisotumab. For grade 2 or greater hemorrhage in any other location, withhold until bleeding has resolved, blood hemoglobin is stable, there is no bleeding diathesis that could increase the risk of continuing therapy, and there is no anatomical or pathologic condition that can increase the risk of hemorrhage. After resolution, either resume treatment or permanently discontinue tisotumab.(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. Discontinue anticoagulation in patients with active pathologic bleeding. 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. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: Hemorrhage occurred in 62% of patients with cervical cancer treated with tisotumab across clinical trials. The most common all grade hemorrhage adverse reactions were epistaxis (44%), hematuria (10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in 5% of patients.(1) |
TIVDAK |
| 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 SODIUM (heparin sodium,porcine):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 7 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Aortic aneurysm with dissection |
| Cerebral amyloid angiopathy |
| Heparin-induced thrombocytopenia |
| Intracerebral hemorrhage |
| Subarachnoid intracranial hemorrhage |
| Subdural intracranial hemorrhage |
| Threatened abortion |
There are 17 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Deep peripheral nerve block |
| Deep plexus block |
| Diverticulitis of gastrointestinal tract |
| Gastrointestinal ulcer |
| Hemophilia |
| Hemorrhage |
| Invasive procedure on brain |
| Invasive procedure on spine |
| Neuraxial anesthesia |
| Placement of indwelling epidural catheter |
| Severe uncontrolled hypertension |
| Subacute infective endocarditis |
| Surgical procedure on eye proper |
| Thrombocytopenic disorder |
| Ulcerative colitis |
There are 6 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Antithrombin III deficiency |
| Hyperkalemia |
| Indwelling vascular catheter |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Osteoporosis |
| Severe hepatic disease |
The following adverse reaction information is available for HEPARIN SODIUM (heparin sodium,porcine):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 24 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Hemorrhage Heparin-induced thrombocytopenia Injection site sequelae Thrombocytopenic disorder |
None. |
| Rare/Very Rare |
|---|
|
Adrenal hemorrhage Anaphylaxis Bronchospastic pulmonary disease Dyschromia Genitourinary tract hemorrhage Hyperkalemia Hypersensitivity drug reaction Increased alanine transaminase Increased aspartate transaminase Injection site necrosis Osteoporosis Ovarian hemorrhage Paresthesia of plantar surface Priapism Renal artery thrombosis Retroperitoneal hemorrhage Skin ulcer Thrombosis in heparin-induced thrombocytopenia Urticaria Vasospasm |
There are 15 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. | None. |
| Rare/Very Rare |
|---|
|
Alopecia Asthma Bruising Chills Erythema Eye tearing Fever Headache disorder Hematoma Nausea and vomiting Pain Peripheral neuropathy Pruritus of skin Rhinitis Skin rash |
The following precautions are available for HEPARIN SODIUM (heparin sodium,porcine):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
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.
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.
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.
The following prioritized warning is available for HEPARIN SODIUM (heparin sodium,porcine):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for HEPARIN SODIUM (heparin sodium,porcine)'s list of indications:
| Deep vein thrombosis prevention | |
| Z86.71 | Personal history of venous thrombosis and embolism |
| Z86.711 | Personal history of pulmonary embolism |
| Z86.718 | Personal history of other venous thrombosis and embolism |
| Z86.72 | Personal history of thrombophlebitis |
| Deep venous thrombosis | |
| I80.1 | Phlebitis and thrombophlebitis of femoral vein |
| I80.10 | Phlebitis and thrombophlebitis of unspecified femoral vein |
| I80.11 | Phlebitis and thrombophlebitis of right femoral vein |
| I80.12 | Phlebitis and thrombophlebitis of left femoral vein |
| I80.13 | Phlebitis and thrombophlebitis of femoral vein, bilateral |
| I80.2 | Phlebitis and thrombophlebitis of other and unspecified deep vessels of lower extremities |
| I80.20 | Phlebitis and thrombophlebitis of unspecified deep vessels of lower extremities |
| I80.201 | Phlebitis and thrombophlebitis of unspecified deep vessels of right lower extremity |
| I80.202 | Phlebitis and thrombophlebitis of unspecified deep vessels of left lower extremity |
| I80.203 | Phlebitis and thrombophlebitis of unspecified deep vessels of lower extremities, bilateral |
| I80.209 | Phlebitis and thrombophlebitis of unspecified deep vessels of unspecified lower extremity |
| I80.21 | Phlebitis and thrombophlebitis of iliac vein |
| I80.211 | Phlebitis and thrombophlebitis of right iliac vein |
| I80.212 | Phlebitis and thrombophlebitis of left iliac vein |
| I80.213 | Phlebitis and thrombophlebitis of iliac vein, bilateral |
| I80.219 | Phlebitis and thrombophlebitis of unspecified iliac vein |
| I80.22 | Phlebitis and thrombophlebitis of popliteal vein |
| I80.221 | Phlebitis and thrombophlebitis of right popliteal vein |
| I80.222 | Phlebitis and thrombophlebitis of left popliteal vein |
| I80.223 | Phlebitis and thrombophlebitis of popliteal vein, bilateral |
| I80.229 | Phlebitis and thrombophlebitis of unspecified popliteal vein |
| I80.23 | Phlebitis and thrombophlebitis of tibial vein |
| I80.231 | Phlebitis and thrombophlebitis of right tibial vein |
| I80.232 | Phlebitis and thrombophlebitis of left tibial vein |
| I80.233 | Phlebitis and thrombophlebitis of tibial vein, bilateral |
| I80.239 | Phlebitis and thrombophlebitis of unspecified tibial vein |
| I80.24 | Phlebitis and thrombophlebitis of peroneal vein |
| I80.241 | Phlebitis and thrombophlebitis of right peroneal vein |
| I80.242 | Phlebitis and thrombophlebitis of left peroneal vein |
| I80.243 | Phlebitis and thrombophlebitis of peroneal vein, bilateral |
| I80.249 | Phlebitis and thrombophlebitis of unspecified peroneal vein |
| I80.25 | Phlebitis and thrombophlebitis of calf muscular vein |
| I80.251 | Phlebitis and thrombophlebitis of right calf muscular vein |
| I80.252 | Phlebitis and thrombophlebitis of left calf muscular vein |
| I80.253 | Phlebitis and thrombophlebitis of calf muscular vein, bilateral |
| I80.259 | Phlebitis and thrombophlebitis of unspecified calf muscular vein |
| I80.29 | Phlebitis and thrombophlebitis of other deep vessels of lower extremities |
| I80.291 | Phlebitis and thrombophlebitis of other deep vessels of right lower extremity |
| I80.292 | Phlebitis and thrombophlebitis of other deep vessels of left lower extremity |
| I80.293 | Phlebitis and thrombophlebitis of other deep vessels of lower extremity, bilateral |
| I80.299 | Phlebitis and thrombophlebitis of other deep vessels of unspecified lower extremity |
| I82.4 | Acute embolism and thrombosis of deep veins of lower extremity |
| I82.40 | Acute embolism and thrombosis of unspecified deep veins of lower extremity |
| I82.401 | Acute embolism and thrombosis of unspecified deep veins of right lower extremity |
| I82.402 | Acute embolism and thrombosis of unspecified deep veins of left lower extremity |
| I82.403 | Acute embolism and thrombosis of unspecified deep veins of lower extremity, bilateral |
| I82.409 | Acute embolism and thrombosis of unspecified deep veins of unspecified lower extremity |
| I82.41 | Acute embolism and thrombosis of femoral vein |
| I82.411 | Acute embolism and thrombosis of right femoral vein |
| I82.412 | Acute embolism and thrombosis of left femoral vein |
| I82.413 | Acute embolism and thrombosis of femoral vein, bilateral |
| I82.419 | Acute embolism and thrombosis of unspecified femoral vein |
| I82.42 | Acute embolism and thrombosis of iliac vein |
| I82.421 | Acute embolism and thrombosis of right iliac vein |
| I82.422 | Acute embolism and thrombosis of left iliac vein |
| I82.423 | Acute embolism and thrombosis of iliac vein, bilateral |
| I82.429 | Acute embolism and thrombosis of unspecified iliac vein |
| I82.43 | Acute embolism and thrombosis of popliteal vein |
| I82.431 | Acute embolism and thrombosis of right popliteal vein |
| I82.432 | Acute embolism and thrombosis of left popliteal vein |
| I82.433 | Acute embolism and thrombosis of popliteal vein, bilateral |
| I82.439 | Acute embolism and thrombosis of unspecified popliteal vein |
| I82.44 | Acute embolism and thrombosis of tibial vein |
| I82.441 | Acute embolism and thrombosis of right tibial vein |
| I82.442 | Acute embolism and thrombosis of left tibial vein |
| I82.443 | Acute embolism and thrombosis of tibial vein, bilateral |
| I82.449 | Acute embolism and thrombosis of unspecified tibial vein |
| I82.45 | Acute embolism and thrombosis of peroneal vein |
| I82.451 | Acute embolism and thrombosis of right peroneal vein |
| I82.452 | Acute embolism and thrombosis of left peroneal vein |
| I82.453 | Acute embolism and thrombosis of peroneal vein, bilateral |
| I82.459 | Acute embolism and thrombosis of unspecified peroneal vein |
| I82.46 | Acute embolism and thrombosis of calf muscular vein |
| I82.461 | Acute embolism and thrombosis of right calf muscular vein |
| I82.462 | Acute embolism and thrombosis of left calf muscular vein |
| I82.463 | Acute embolism and thrombosis of calf muscular vein, bilateral |
| I82.469 | Acute embolism and thrombosis of unspecified calf muscular vein |
| I82.49 | Acute embolism and thrombosis of other specified deep vein of lower extremity |
| I82.491 | Acute embolism and thrombosis of other specified deep vein of right lower extremity |
| I82.492 | Acute embolism and thrombosis of other specified deep vein of left lower extremity |
| I82.493 | Acute embolism and thrombosis of other specified deep vein of lower extremity, bilateral |
| I82.499 | Acute embolism and thrombosis of other specified deep vein of unspecified lower extremity |
| I82.4Y | Acute embolism and thrombosis of unspecified deep veins of proximal lower extremity |
| I82.4Y1 | Acute embolism and thrombosis of unspecified deep veins of right proximal lower extremity |
| I82.4Y2 | Acute embolism and thrombosis of unspecified deep veins of left proximal lower extremity |
| I82.4Y3 | Acute embolism and thrombosis of unspecified deep veins of proximal lower extremity, bilateral |
| I82.4Y9 | Acute embolism and thrombosis of unspecified deep veins of unspecified proximal lower extremity |
| I82.4Z | Acute embolism and thrombosis of unspecified deep veins of distal lower extremity |
| I82.4Z1 | Acute embolism and thrombosis of unspecified deep veins of right distal lower extremity |
| I82.4Z2 | Acute embolism and thrombosis of unspecified deep veins of left distal lower extremity |
| I82.4Z3 | Acute embolism and thrombosis of unspecified deep veins of distal lower extremity, bilateral |
| I82.4Z9 | Acute embolism and thrombosis of unspecified deep veins of unspecified distal lower extremity |
| I82.5 | Chronic embolism and thrombosis of deep veins of lower extremity |
| I82.50 | Chronic embolism and thrombosis of unspecified deep veins of lower extremity |
| I82.501 | Chronic embolism and thrombosis of unspecified deep veins of right lower extremity |
| I82.502 | Chronic embolism and thrombosis of unspecified deep veins of left lower extremity |
| I82.503 | Chronic embolism and thrombosis of unspecified deep veins of lower extremity, bilateral |
| I82.509 | Chronic embolism and thrombosis of unspecified deep veins of unspecified lower extremity |
| I82.51 | Chronic embolism and thrombosis of femoral vein |
| I82.511 | Chronic embolism and thrombosis of right femoral vein |
| I82.512 | Chronic embolism and thrombosis of left femoral vein |
| I82.513 | Chronic embolism and thrombosis of femoral vein, bilateral |
| I82.519 | Chronic embolism and thrombosis of unspecified femoral vein |
| I82.52 | Chronic embolism and thrombosis of iliac vein |
| I82.521 | Chronic embolism and thrombosis of right iliac vein |
| I82.522 | Chronic embolism and thrombosis of left iliac vein |
| I82.523 | Chronic embolism and thrombosis of iliac vein, bilateral |
| I82.529 | Chronic embolism and thrombosis of unspecified iliac vein |
| I82.53 | Chronic embolism and thrombosis of popliteal vein |
| I82.531 | Chronic embolism and thrombosis of right popliteal vein |
| I82.532 | Chronic embolism and thrombosis of left popliteal vein |
| I82.533 | Chronic embolism and thrombosis of popliteal vein, bilateral |
| I82.539 | Chronic embolism and thrombosis of unspecified popliteal vein |
| I82.54 | Chronic embolism and thrombosis of tibial vein |
| I82.541 | Chronic embolism and thrombosis of right tibial vein |
| I82.542 | Chronic embolism and thrombosis of left tibial vein |
| I82.543 | Chronic embolism and thrombosis of tibial vein, bilateral |
| I82.549 | Chronic embolism and thrombosis of unspecified tibial vein |
| I82.55 | Chronic embolism and thrombosis of peroneal vein |
| I82.551 | Chronic embolism and thrombosis of right peroneal vein |
| I82.552 | Chronic embolism and thrombosis of left peroneal vein |
| I82.553 | Chronic embolism and thrombosis of peroneal vein, bilateral |
| I82.559 | Chronic embolism and thrombosis of unspecified peroneal vein |
| I82.56 | Chronic embolism and thrombosis of calf muscular vein |
| I82.561 | Chronic embolism and thrombosis of right calf muscular vein |
| I82.562 | Chronic embolism and thrombosis of left calf muscular vein |
| I82.563 | Chronic embolism and thrombosis of calf muscular vein, bilateral |
| I82.569 | Chronic embolism and thrombosis of unspecified calf muscular vein |
| I82.59 | Chronic embolism and thrombosis of other specified deep vein of lower extremity |
| I82.591 | Chronic embolism and thrombosis of other specified deep vein of right lower extremity |
| I82.592 | Chronic embolism and thrombosis of other specified deep vein of left lower extremity |
| I82.593 | Chronic embolism and thrombosis of other specified deep vein of lower extremity, bilateral |
| I82.599 | Chronic embolism and thrombosis of other specified deep vein of unspecified lower extremity |
| I82.5Y | Chronic embolism and thrombosis of unspecified deep veins of proximal lower extremity |
| I82.5Y1 | Chronic embolism and thrombosis of unspecified deep veins of right proximal lower extremity |
| I82.5Y2 | Chronic embolism and thrombosis of unspecified deep veins of left proximal lower extremity |
| I82.5Y3 | Chronic embolism and thrombosis of unspecified deep veins of proximal lower extremity, bilateral |
| I82.5Y9 | Chronic embolism and thrombosis of unspecified deep veins of unspecified proximal lower extremity |
| I82.5Z | Chronic embolism and thrombosis of unspecified deep veins of distal lower extremity |
| I82.5Z1 | Chronic embolism and thrombosis of unspecified deep veins of right distal lower extremity |
| I82.5Z2 | Chronic embolism and thrombosis of unspecified deep veins of left distal lower extremity |
| I82.5Z3 | Chronic embolism and thrombosis of unspecified deep veins of distal lower extremity, bilateral |
| I82.5Z9 | Chronic embolism and thrombosis of unspecified deep veins of unspecified distal lower extremity |
| I82.62 | Acute embolism and thrombosis of deep veins of upper extremity |
| I82.621 | Acute embolism and thrombosis of deep veins of right upper extremity |
| I82.622 | Acute embolism and thrombosis of deep veins of left upper extremity |
| I82.623 | Acute embolism and thrombosis of deep veins of upper extremity, bilateral |
| I82.629 | Acute embolism and thrombosis of deep veins of unspecified upper extremity |
| I82.72 | Chronic embolism and thrombosis of deep veins of upper extremity |
| I82.721 | Chronic embolism and thrombosis of deep veins of right upper extremity |
| I82.722 | Chronic embolism and thrombosis of deep veins of left upper extremity |
| I82.723 | Chronic embolism and thrombosis of deep veins of upper extremity, bilateral |
| I82.729 | Chronic embolism and thrombosis of deep veins of unspecified upper extremity |
| I82.A | Embolism and thrombosis of axillary vein |
| I82.A1 | Acute embolism and thrombosis of axillary vein |
| I82.A11 | Acute embolism and thrombosis of right axillary vein |
| I82.A12 | Acute embolism and thrombosis of left axillary vein |
| I82.A13 | Acute embolism and thrombosis of axillary vein, bilateral |
| I82.A19 | Acute embolism and thrombosis of unspecified axillary vein |
| I82.A2 | Chronic embolism and thrombosis of axillary vein |
| I82.A21 | Chronic embolism and thrombosis of right axillary vein |
| I82.A22 | Chronic embolism and thrombosis of left axillary vein |
| I82.A23 | Chronic embolism and thrombosis of axillary vein, bilateral |
| I82.A29 | Chronic embolism and thrombosis of unspecified axillary vein |
| I82.B | Embolism and thrombosis of subclavian vein |
| I82.B1 | Acute embolism and thrombosis of subclavian vein |
| I82.B11 | Acute embolism and thrombosis of right subclavian vein |
| I82.B12 | Acute embolism and thrombosis of left subclavian vein |
| I82.B13 | Acute embolism and thrombosis of subclavian vein, bilateral |
| I82.B19 | Acute embolism and thrombosis of unspecified subclavian vein |
| I82.B2 | Chronic embolism and thrombosis of subclavian vein |
| I82.B21 | Chronic embolism and thrombosis of right subclavian vein |
| I82.B22 | Chronic embolism and thrombosis of left subclavian vein |
| I82.B23 | Chronic embolism and thrombosis of subclavian vein, bilateral |
| I82.B29 | Chronic embolism and thrombosis of unspecified subclavian vein |
| I82.C | Embolism and thrombosis of internal jugular vein |
| I82.C1 | Acute embolism and thrombosis of internal jugular vein |
| I82.C11 | Acute embolism and thrombosis of right internal jugular vein |
| I82.C12 | Acute embolism and thrombosis of left internal jugular vein |
| I82.C13 | Acute embolism and thrombosis of internal jugular vein, bilateral |
| I82.C19 | Acute embolism and thrombosis of unspecified internal jugular vein |
| I82.C2 | Chronic embolism and thrombosis of internal jugular vein |
| I82.C21 | Chronic embolism and thrombosis of right internal jugular vein |
| I82.C22 | Chronic embolism and thrombosis of left internal jugular vein |
| I82.C23 | Chronic embolism and thrombosis of internal jugular vein, bilateral |
| I82.C29 | Chronic embolism and thrombosis of unspecified internal jugular vein |
| T82.897 | Other specified complication of cardiac prosthetic devices, implants and grafts |
| Disseminated intravascular coagulation | |
| D65 | Disseminated intravascular coagulation [defibrination syndrome] |
| O45.02 | Premature separation of placenta with disseminated intravascular coagulation |
| O45.021 | Premature separation of placenta with disseminated intravascular coagulation, first trimester |
| O45.022 | Premature separation of placenta with disseminated intravascular coagulation, second trimester |
| O45.023 | Premature separation of placenta with disseminated intravascular coagulation, third trimester |
| O45.029 | Premature separation of placenta with disseminated intravascular coagulation, unspecified trimester |
| O46.02 | Antepartum hemorrhage with disseminated intravascular coagulation |
| O46.021 | Antepartum hemorrhage with disseminated intravascular coagulation, first trimester |
| O46.022 | Antepartum hemorrhage with disseminated intravascular coagulation, second trimester |
| O46.023 | Antepartum hemorrhage with disseminated intravascular coagulation, third trimester |
| O46.029 | Antepartum hemorrhage with disseminated intravascular coagulation, unspecified trimester |
| P60 | Disseminated intravascular coagulation of newborn |
| Peripheral arterial embolism | |
| I74.2 | Embolism and thrombosis of arteries of the upper extremities |
| I74.3 | Embolism and thrombosis of arteries of the lower extremities |
| I74.4 | Embolism and thrombosis of arteries of extremities, unspecified |
| Pulmonary thromboembolism | |
| I26 | Pulmonary embolism |
| I26.0 | Pulmonary embolism with acute cor pulmonale |
| I26.02 | Saddle embolus of pulmonary artery with acute cor pulmonale |
| I26.09 | Other pulmonary embolism with acute cor pulmonale |
| I26.9 | Pulmonary embolism without acute cor pulmonale |
| I26.92 | Saddle embolus of pulmonary artery without acute cor pulmonale |
| I26.93 | Single subsegmental thrombotic pulmonary embolism without acute cor pulmonale |
| I26.94 | Multiple subsegmental thrombotic pulmonary emboli without acute cor pulmonale |
| I26.99 | Other pulmonary embolism without acute cor pulmonale |
| I27.82 | Chronic pulmonary embolism |
Formulary Reference Tool