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Drug overview for TNKASE (tenecteplase):
Generic name: TENECTEPLASE
Drug class: Thrombolytic Agents
Therapeutic class: Hematological Agents
Tenecteplase, a biosynthetic (recombinant DNA origin) form of the enzyme human tissue-type plasminogen activator (t-PA), is a thrombolytic agent.
No enhanced Uses information available for this drug.
Generic name: TENECTEPLASE
Drug class: Thrombolytic Agents
Therapeutic class: Hematological Agents
Tenecteplase, a biosynthetic (recombinant DNA origin) form of the enzyme human tissue-type plasminogen activator (t-PA), is a thrombolytic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
TNKASE 50 MG VIAL
TNKASE 50 MG KIT
The following indications for TNKASE (tenecteplase) have been approved by the FDA:
Indications:
Acute myocardial infarction
Acute thromboembolic stroke
Professional Synonyms:
Acute cerebral infarction due to thromboembolism
Acute MI
Cardiac infarction
Myocardial infarct
Indications:
Acute myocardial infarction
Acute thromboembolic stroke
Professional Synonyms:
Acute cerebral infarction due to thromboembolism
Acute MI
Cardiac infarction
Myocardial infarct
The following dosing information is available for TNKASE (tenecteplase):
The recommended total dose (not to exceed 50 mg) of tenecteplase for adults with acute ST-segment-elevation MI (STEMI) is based on patient weight and should be administered as soon as possible after the onset of STEMI symptoms (see Table 1).
Table 1. Recommended Dosage of Tenecteplase for STEMI.
Patient Weight (kg) Tenecteplase Dose (mg) <60 30 >=60 to <70 35 >=70 to <80 40 >=80 to <90 45 >=90 50
Table 1. Recommended Dosage of Tenecteplase for STEMI.
Patient Weight (kg) Tenecteplase Dose (mg) <60 30 >=60 to <70 35 >=70 to <80 40 >=80 to <90 45 >=90 50
Tenecteplase is administered by IV injection over 5 seconds. Consult the manufacturer's labeling for instructions for using the BD(R) 10-mL syringe with TwinPak(R) Dual Cannula Device for reconstitution and administration of tenecteplase. Tenecteplase is reconstituted by adding 10 mL of sterile water for injection without preservatives to a vial labeled as containing 50 mg of drug and directing the stream of diluent into the powder.
If foaming (usually slight) occurs during reconstitution, the vial should be left undisturbed for several minutes to allow dissipation of any large bubbles. Gently swirl until the contents are completely dissolved. The vial should not be shaken.
The resultant colorless to pale yellow transparent solution contains 5 mg of tenecteplase per mL. Once the appropriate dose is drawn into the syringe, the reconstituted solution of tenecteplase should be inspected visually for particulate matter and discoloration before administration. Because tenecteplase powder for injection and reconstituted solutions of the drug contain no preservatives, the solution preferably should be prepared immediately before use, but may be refrigerated at 2-8oC and used up to 8 hours after reconstitution; any unused solution should be discarded after 8 hours. If tenecteplase is administered via an IV administration set that is infusing a dextrose-containing solution, the line should be flushed with saline prior to and following administration of tenecteplase.
If foaming (usually slight) occurs during reconstitution, the vial should be left undisturbed for several minutes to allow dissipation of any large bubbles. Gently swirl until the contents are completely dissolved. The vial should not be shaken.
The resultant colorless to pale yellow transparent solution contains 5 mg of tenecteplase per mL. Once the appropriate dose is drawn into the syringe, the reconstituted solution of tenecteplase should be inspected visually for particulate matter and discoloration before administration. Because tenecteplase powder for injection and reconstituted solutions of the drug contain no preservatives, the solution preferably should be prepared immediately before use, but may be refrigerated at 2-8oC and used up to 8 hours after reconstitution; any unused solution should be discarded after 8 hours. If tenecteplase is administered via an IV administration set that is infusing a dextrose-containing solution, the line should be flushed with saline prior to and following administration of tenecteplase.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for TNKASE (tenecteplase):
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 |
|---|---|
| Tenecteplase/Oral Anticoagulants; Warfarin 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: Tenecteplase catalyzes the cleavage of endogenous plasminogen to generate plasmin which degrades the fibrin matrix of a thrombus.(1-3) CLINICAL EFFECTS: The concurrent use of tenecteplase and warfarin or oral anticoagulants may increase the risk of bleeding.(1-4) 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), Canadian(2) and UK(3) manufacturers of tenecteplase state that use in patients on current oral anticoagulants (INR > 1.3) is contraindicated. The US manufacturer of tenecteplase states that the risks of concurrent therapy with oral anticoagulants must be weighed against the anticipated benefits.(4) Concurrent use of tenecteplase 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 warfarin and 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, 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 receiving warfarin were excluded from participation in thrombolytic clinical trials due to bleeding risk.(1-4) |
ACD-A, ANISINDIONE, CITRATE PHOSPHATE DEXTROSE, DICUMAROL, ELMIRON, HEPARIN SODIUM, JANTOVEN, PENTOSAN POLYSULFATE SODIUM, PHENINDIONE, WARFARIN SODIUM |
| 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 |
| Dabigatran/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: Dabigatran is a direct thrombin inhibitor. When taken with agents that affect clotting factors, increased bleeding episodes can occur. CLINICAL EFFECTS: Concurrent use of dabigatran with anticoagulants or thrombolytics may result in additive or synergistic effects resulting in unwanted bleeding episodes. 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. Specific recommendations for converting between anticoagulants: - When converting from parenteral anticoagulants to dabigatran, administer dabigatran 0-2 hours before the next dose of the parenteral drug is due. - When converting from dabigatran to a parenteral anticoagulant in adults, begin parenteral anticoagulant: --12 hours after last dose of dabigatran in patients with CrCl greater than or equal to 30 ml/min, --24 hours after last dose of dabigatran in patients with CrCl less than 30 ml/min. - When converting from dabigatran to a parenteral anticoagulant in pedatrics, begin the parenteral anticoagulant 12 hours after the last dose of dabigatran. - When converting from warfarin to dabigatran, discontinue warfarin and begin dabigatran when the patient's INR is below 2.0. - When converting from dabigatran to warfarin in adults, start warfarin: --3 days before discontinuing dabigatran in patients with CrCl greater than 50 ml/min, --2 days before discontinuing dabigatran in patients with CrCl of 30 ml/min to 50 ml/min, --1 day before discontinuing dabigatran in patients with CrCl of 15 ml/min to 30 ml/min. --There is no recommendation available for converting dabigatran to warfarin in patients with CrCl less than 15 ml/min. - When converting from dabigatran to warfarin in pediatrics, start warfarin: --3 days before discontinuing dabigatran in patient with eGFR >= 50 ml/min/1.73 m2. --There is no data on using dabigatran in pediatric patients with eGFR < 50 ml/min/1.73 m2. - Dabigatran affects INR. Therefore the INR will better reflect warfarin's effect only after stopping dabigatran for at least 2 days. 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 dabigatran 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. |
DABIGATRAN ETEXILATE, PRADAXA |
| 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 4 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 |
|---|---|
| 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 |
| 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. |
ARIXTRA, ENOXAPARIN SODIUM, ENOXILUV, FONDAPARINUX SODIUM, FRAGMIN, HEPARIN SODIUM, HEPARIN SODIUM IN 0.45% NACL, HEPARIN SODIUM-0.45% NACL, HEPARIN SODIUM-0.9% NACL, HEPARIN SODIUM-D5W, LOVENOX |
| Lecanemab/Thrombolytics 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 thrombolytic agents may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: Patients with ongoing amyloid-related imaging abnormalities (ARIA) may be at increased risk for post-thrombolytic intracranial hemorrhage (ICH). 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: Lecanemab should be used with extreme caution in patients treated with thrombolytics. Evaluate the risks and benefits of concurrent use of lecanemab with thrombolytics.(1) Appropriate use recommendations for lecanemab state patients on lecanemab should not receive thrombolytics.(2) If thrombolytics are warranted, patients receiving concurrent therapy with lecanemab and thrombolytics should be closely monitored for signs and symptoms of bleeding and changes in platelet count or symptoms associated with ARIA-H.(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 computed tomography (CT) scans and magnetic resonance imaging (MRIs) to monitor efficacy and safety of thrombolytic use with lecanemab. Discontinue thrombolytics in patients with active pathologic bleeding.(1) 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 case report, a patient treated with thrombolytics for acute stroke who had received lecanemab experienced severe, multi-focal brain hemorrhages leading to death.(3) 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) |
LEQEMBI |
| Donanemab/Thrombolytics 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 thrombolytic agents may increase the risk of hemorrhage.(1) PREDISPOSING FACTORS: Patients with ongoing amyloid-related imaging abnormalities (ARIA) may be at increased risk for post-thrombolytic intracranial hemorrhage (ICH). 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 thrombolytics. Evaluate the risks and benefits of concurrent use of donanemab with thrombolytics.(1) The manufacturer of donanemab recommends testing for AP0E4 status prior to initiation of treatment.(1) Use of thrombolytics in patients who are homozygous for the APOE4 gene, may have an increased risk of ARIA with donanemab therapy.(1-3) If thrombolytics are warranted, patients receiving concurrent therapy with donanemab and thrombolytics should be closely monitored for signs and symptoms of bleeding and changes in platelet count or symptoms associated with ARIA-H.(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 computed tomography (CT) scans and magnetic resonance imaging (MRIs) to monitor efficacy and safety of thrombolytic use with lecanemab. Discontinue thrombolytics in patients with active pathologic bleeding.(1) 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). 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) 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.(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 |
There are 4 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 |
|---|---|
| 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 |
| 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 |
| 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 |
The following contraindication information is available for TNKASE (tenecteplase):
Drug contraindication overview.
*Active internal bleeding. *History of cerebrovascular accident. *Intracranial or intraspinal surgery or trauma within 2 months.
*Intracranial neoplasm, arteriovenous malformation, or aneurysm. *Known bleeding diathesis. *Severe uncontrolled hypertension.
*Active internal bleeding. *History of cerebrovascular accident. *Intracranial or intraspinal surgery or trauma within 2 months.
*Intracranial neoplasm, arteriovenous malformation, or aneurysm. *Known bleeding diathesis. *Severe uncontrolled hypertension.
There are 11 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Arterial aneurysm |
| Arteriovenous malformation |
| Hemorrhage |
| Increased risk of bleeding |
| Increased risk of bleeding due to coagulation disorder |
| Invasive procedure on brain |
| Invasive procedure on spine |
| Invasive surgical procedure |
| Major traumatic injury |
| Neoplasm of brain |
| Severe uncontrolled hypertension |
There are 8 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute pericarditis |
| Blood dyscrasias |
| Cholesterol embolism |
| Genitourinary tract hemorrhage |
| Retinal hemorrhage |
| Septic thrombophlebitis |
| Severe hepatic disease |
| Subacute infective endocarditis |
There are 0 moderate contraindications.
The following adverse reaction information is available for TNKASE (tenecteplase):
Adverse reaction overview.
Bleeding and hypersensitivity reactions are the most common adverse effects of tenecteplase.
Bleeding and hypersensitivity reactions are the most common adverse effects of tenecteplase.
There are 21 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Gastrointestinal hemorrhage Hemorrhage |
| Rare/Very Rare |
|---|
|
Anaphylaxis Angioedema Atrioventricular block Bradycardia Cerebrovascular accident Cholesterol embolism Genitourinary tract hemorrhage Hypersensitivity drug reaction Hypotension Injection site sequelae Intracranial bleeding Laryngeal edema Mitral valve regurgitation Pericardial effusion Pericardial tamponade Pericarditis Respiratory tract hemorrhage Ventricular premature beats Ventricular tachycardia |
There are 8 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Epistaxis Hematoma Hemoptysis |
| Rare/Very Rare |
|---|
|
Fever Nausea Skin rash Urticaria Vomiting |
The following precautions are available for TNKASE (tenecteplase):
Safety and efficacy have not been established in pediatric patients <18 years of age.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
There are no data on the use of tenecteplase during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published data consisting of a small number of case reports involving the use of related thrombolytic agents in pregnant women have not identified an increased risk of major birth defects. Maternal and direct embryofetal toxicity were not observed in rabbits following a single IV dose of tenecteplase.
In developmental toxicity studies conducted in rabbits, the no observable effect level (NOEL) for maternal or developmental toxicity was a single IV dose of 5 mg/kg, which is approximately 7 times the human exposure (based on AUC) at the dose for STEMI. There are risks to the mother and fetus from acute STEMI, which is a medical emergency in pregnancy and can be fatal if left untreated. The manufacturer states that life-sustaining therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of tenecteplase on the fetus.
In developmental toxicity studies conducted in rabbits, the no observable effect level (NOEL) for maternal or developmental toxicity was a single IV dose of 5 mg/kg, which is approximately 7 times the human exposure (based on AUC) at the dose for STEMI. There are risks to the mother and fetus from acute STEMI, which is a medical emergency in pregnancy and can be fatal if left untreated. The manufacturer states that life-sustaining therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of tenecteplase on the fetus.
It is unknown whether tenecteplase is distributed into human or animal milk; possible effects on the breast-fed infant or on milk production also are not known. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tenecteplase and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
In the ASSENT-2 study, intracranial hemorrhage, strokes, and major bleeding (i.e., bleeding requiring blood transfusions or leading to hemodynamic compromise) occurred more frequently in patients >=65 years of age than in younger adults. Higher mortality rates at 30 days also were observed in patients >=65 years of age. In the Strategic Reperfusion Early After Myocardial Infarction (STREAM) trial evaluating tenecteplase in patients with STEMI who presented within 3 hours of symptom onset and were unable to undergo primary PCI within 1 hour, the initial excess of intracranial hemorrhage observed in patients >=75 years of age was reduced after a protocol amendment to reduce the dose of tenecteplase by 50%. Some clinicians and experts (including the American College of Cardiology (ACC)/American Heart Association (AHA)/Society for Cardiovascular Angiography and Interventions (SCAI) and the European Society of Cardiology (ESC)) recommend a 50% reduction in the dosage of tenecteplase in patients >=75 years of age with STEMI who cannot undergo timely primary PCI.
The following prioritized warning is available for TNKASE (tenecteplase):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for TNKASE (tenecteplase)'s list of indications:
| Acute myocardial infarction | |
| I21 | Acute myocardial infarction |
| I21.0 | ST elevation (STEMi) myocardial infarction of anterior wall |
| I21.01 | ST elevation (STEMi) myocardial infarction involving left main coronary artery |
| I21.02 | ST elevation (STEMi) myocardial infarction involving left anterior descending coronary artery |
| I21.09 | ST elevation (STEMi) myocardial infarction involving other coronary artery of anterior wall |
| I21.1 | ST elevation (STEMi) myocardial infarction of inferior wall |
| I21.11 | ST elevation (STEMi) myocardial infarction involving right coronary artery |
| I21.19 | ST elevation (STEMi) myocardial infarction involving other coronary artery of inferior wall |
| I21.2 | ST elevation (STEMi) myocardial infarction of other sites |
| I21.21 | ST elevation (STEMi) myocardial infarction involving left circumflex coronary artery |
| I21.29 | ST elevation (STEMi) myocardial infarction involving other sites |
| I21.3 | ST elevation (STEMi) myocardial infarction of unspecified site |
| I21.4 | Non-ST elevation (NSTEMi) myocardial infarction |
| I21.9 | Acute myocardial infarction, unspecified |
| I21.A | Other type of myocardial infarction |
| I21.A1 | Myocardial infarction type 2 |
| I21.A9 | Other myocardial infarction type |
| I21.B | Myocardial infarction with coronary microvascular dysfunction |
| I22 | Subsequent ST elevation (STEMi) and non-ST elevation (NSTEMi) myocardial infarction |
| I22.0 | Subsequent ST elevation (STEMi) myocardial infarction of anterior wall |
| I22.1 | Subsequent ST elevation (STEMi) myocardial infarction of inferior wall |
| I22.2 | Subsequent non-ST elevation (NSTEMi) myocardial infarction |
| I22.8 | Subsequent ST elevation (STEMi) myocardial infarction of other sites |
| I22.9 | Subsequent ST elevation (STEMi) myocardial infarction of unspecified site |
| Acute thromboembolic stroke | |
| I63 | Cerebral infarction |
| I63.0 | Cerebral infarction due to thrombosis of precerebral arteries |
| I63.00 | Cerebral infarction due to thrombosis of unspecified precerebral artery |
| I63.01 | Cerebral infarction due to thrombosis of vertebral artery |
| I63.011 | Cerebral infarction due to thrombosis of right vertebral artery |
| I63.012 | Cerebral infarction due to thrombosis of left vertebral artery |
| I63.013 | Cerebral infarction due to thrombosis of bilateral vertebral arteries |
| I63.019 | Cerebral infarction due to thrombosis of unspecified vertebral artery |
| I63.02 | Cerebral infarction due to thrombosis of basilar artery |
| I63.03 | Cerebral infarction due to thrombosis of carotid artery |
| I63.031 | Cerebral infarction due to thrombosis of right carotid artery |
| I63.032 | Cerebral infarction due to thrombosis of left carotid artery |
| I63.033 | Cerebral infarction due to thrombosis of bilateral carotid arteries |
| I63.039 | Cerebral infarction due to thrombosis of unspecified carotid artery |
| I63.09 | Cerebral infarction due to thrombosis of other precerebral artery |
| I63.1 | Cerebral infarction due to embolism of precerebral arteries |
| I63.10 | Cerebral infarction due to embolism of unspecified precerebral artery |
| I63.11 | Cerebral infarction due to embolism of vertebral artery |
| I63.111 | Cerebral infarction due to embolism of right vertebral artery |
| I63.112 | Cerebral infarction due to embolism of left vertebral artery |
| I63.113 | Cerebral infarction due to embolism of bilateral vertebral arteries |
| I63.119 | Cerebral infarction due to embolism of unspecified vertebral artery |
| I63.12 | Cerebral infarction due to embolism of basilar artery |
| I63.13 | Cerebral infarction due to embolism of carotid artery |
| I63.131 | Cerebral infarction due to embolism of right carotid artery |
| I63.132 | Cerebral infarction due to embolism of left carotid artery |
| I63.133 | Cerebral infarction due to embolism of bilateral carotid arteries |
| I63.139 | Cerebral infarction due to embolism of unspecified carotid artery |
| I63.19 | Cerebral infarction due to embolism of other precerebral artery |
| I63.2 | Cerebral infarction due to unspecified occlusion or stenosis of precerebral arteries |
| I63.20 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified precerebral arteries |
| I63.21 | Cerebral infarction due to unspecified occlusion or stenosis of vertebral arteries |
| I63.211 | Cerebral infarction due to unspecified occlusion or stenosis of right vertebral artery |
| I63.212 | Cerebral infarction due to unspecified occlusion or stenosis of left vertebral artery |
| I63.213 | Cerebral infarction due to unspecified occlusion or stenosis of bilateral vertebral arteries |
| I63.219 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified vertebral artery |
| I63.22 | Cerebral infarction due to unspecified occlusion or stenosis of basilar artery |
| I63.23 | Cerebral infarction due to unspecified occlusion or stenosis of carotid arteries |
| I63.231 | Cerebral infarction due to unspecified occlusion or stenosis of right carotid arteries |
| I63.232 | Cerebral infarction due to unspecified occlusion or stenosis of left carotid arteries |
| I63.233 | Cerebral infarction due to unspecified occlusion or stenosis of bilateral carotid arteries |
| I63.239 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified carotid artery |
| I63.29 | Cerebral infarction due to unspecified occlusion or stenosis of other precerebral arteries |
| I63.3 | Cerebral infarction due to thrombosis of cerebral arteries |
| I63.30 | Cerebral infarction due to thrombosis of unspecified cerebral artery |
| I63.31 | Cerebral infarction due to thrombosis of middle cerebral artery |
| I63.311 | Cerebral infarction due to thrombosis of right middle cerebral artery |
| I63.312 | Cerebral infarction due to thrombosis of left middle cerebral artery |
| I63.313 | Cerebral infarction due to thrombosis of bilateral middle cerebral arteries |
| I63.319 | Cerebral infarction due to thrombosis of unspecified middle cerebral artery |
| I63.32 | Cerebral infarction due to thrombosis of anterior cerebral artery |
| I63.321 | Cerebral infarction due to thrombosis of right anterior cerebral artery |
| I63.322 | Cerebral infarction due to thrombosis of left anterior cerebral artery |
| I63.323 | Cerebral infarction due to thrombosis of bilateral anterior cerebral arteries |
| I63.329 | Cerebral infarction due to thrombosis of unspecified anterior cerebral artery |
| I63.33 | Cerebral infarction due to thrombosis of posterior cerebral artery |
| I63.331 | Cerebral infarction due to thrombosis of right posterior cerebral artery |
| I63.332 | Cerebral infarction due to thrombosis of left posterior cerebral artery |
| I63.333 | Cerebral infarction due to thrombosis of bilateral posterior cerebral arteries |
| I63.339 | Cerebral infarction due to thrombosis of unspecified posterior cerebral artery |
| I63.34 | Cerebral infarction due to thrombosis of cerebellar artery |
| I63.341 | Cerebral infarction due to thrombosis of right cerebellar artery |
| I63.342 | Cerebral infarction due to thrombosis of left cerebellar artery |
| I63.343 | Cerebral infarction due to thrombosis of bilateral cerebellar arteries |
| I63.349 | Cerebral infarction due to thrombosis of unspecified cerebellar artery |
| I63.39 | Cerebral infarction due to thrombosis of other cerebral artery |
| I63.4 | Cerebral infarction due to embolism of cerebral arteries |
| I63.40 | Cerebral infarction due to embolism of unspecified cerebral artery |
| I63.41 | Cerebral infarction due to embolism of middle cerebral artery |
| I63.411 | Cerebral infarction due to embolism of right middle cerebral artery |
| I63.412 | Cerebral infarction due to embolism of left middle cerebral artery |
| I63.413 | Cerebral infarction due to embolism of bilateral middle cerebral arteries |
| I63.419 | Cerebral infarction due to embolism of unspecified middle cerebral artery |
| I63.42 | Cerebral infarction due to embolism of anterior cerebral artery |
| I63.421 | Cerebral infarction due to embolism of right anterior cerebral artery |
| I63.422 | Cerebral infarction due to embolism of left anterior cerebral artery |
| I63.423 | Cerebral infarction due to embolism of bilateral anterior cerebral arteries |
| I63.429 | Cerebral infarction due to embolism of unspecified anterior cerebral artery |
| I63.43 | Cerebral infarction due to embolism of posterior cerebral artery |
| I63.431 | Cerebral infarction due to embolism of right posterior cerebral artery |
| I63.432 | Cerebral infarction due to embolism of left posterior cerebral artery |
| I63.433 | Cerebral infarction due to embolism of bilateral posterior cerebral arteries |
| I63.439 | Cerebral infarction due to embolism of unspecified posterior cerebral artery |
| I63.44 | Cerebral infarction due to embolism of cerebellar artery |
| I63.441 | Cerebral infarction due to embolism of right cerebellar artery |
| I63.442 | Cerebral infarction due to embolism of left cerebellar artery |
| I63.443 | Cerebral infarction due to embolism of bilateral cerebellar arteries |
| I63.449 | Cerebral infarction due to embolism of unspecified cerebellar artery |
| I63.49 | Cerebral infarction due to embolism of other cerebral artery |
| I63.5 | Cerebral infarction due to unspecified occlusion or stenosis of cerebral arteries |
| I63.50 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified cerebral artery |
| I63.51 | Cerebral infarction due to unspecified occlusion or stenosis of middle cerebral artery |
| I63.511 | Cerebral infarction due to unspecified occlusion or stenosis of right middle cerebral artery |
| I63.512 | Cerebral infarction due to unspecified occlusion or stenosis of left middle cerebral artery |
| I63.513 | Cerebral infarction due to unspecified occlusion or stenosis of bilateral middle cerebral arteries |
| I63.519 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified middle cerebral artery |
| I63.52 | Cerebral infarction due to unspecified occlusion or stenosis of anterior cerebral artery |
| I63.521 | Cerebral infarction due to unspecified occlusion or stenosis of right anterior cerebral artery |
| I63.522 | Cerebral infarction due to unspecified occlusion or stenosis of left anterior cerebral artery |
| I63.523 | Cerebral infarction due to unspecified occlusion or stenosis of bilateral anterior cerebral arteries |
| I63.529 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified anterior cerebral artery |
| I63.53 | Cerebral infarction due to unspecified occlusion or stenosis of posterior cerebral artery |
| I63.531 | Cerebral infarction due to unspecified occlusion or stenosis of right posterior cerebral artery |
| I63.532 | Cerebral infarction due to unspecified occlusion or stenosis of left posterior cerebral artery |
| I63.533 | Cerebral infarction due to unspecified occlusion or stenosis of bilateral posterior cerebral arteries |
| I63.539 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified posterior cerebral artery |
| I63.54 | Cerebral infarction due to unspecified occlusion or stenosis of cerebellar artery |
| I63.541 | Cerebral infarction due to unspecified occlusion or stenosis of right cerebellar artery |
| I63.542 | Cerebral infarction due to unspecified occlusion or stenosis of left cerebellar artery |
| I63.543 | Cerebral infarction due to unspecified occlusion or stenosis of bilateral cerebellar arteries |
| I63.549 | Cerebral infarction due to unspecified occlusion or stenosis of unspecified cerebellar artery |
| I63.59 | Cerebral infarction due to unspecified occlusion or stenosis of other cerebral artery |
| I63.8 | Other cerebral infarction |
| I63.9 | Cerebral infarction, unspecified |
Formulary Reference Tool