U.S. BRAND NAMES — CollaCote®; CollaPlug®; CollaTape®
PHARMACOLOGIC CATEGORY
Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Topical: A sufficiently large dressing should be selected so as to completely cover the oral wound
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Wound dressing:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
DOSAGE FORMS: CONCISE
Wound dressing:
Generics:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
Brands:
CollaCote®, CollaPlug®, CollaTape®:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS
Other warnings/precautions: Appropriate use: Should not be used on infected or contaminated wounds.
DRUG INTERACTIONS — There are no known significant interactions.
LACTATION — Compatible
MECHANISM OF ACTION — The highly porous sponge structure absorbs blood and wound exudate. The collagen component causes aggregation of platelets which bind to collagen fibrils. The aggregated platelets degranulate, releasing coagulation factors that promote the formation of fibrin.
Sunday, May 16, 2010
Absorbable collagen (dental)
U.S. BRAND NAMES — CollaCote®; CollaPlug®; CollaTape®
PHARMACOLOGIC CATEGORY
Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Topical: A sufficiently large dressing should be selected so as to completely cover the oral wound
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Wound dressing:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
DOSAGE FORMS: CONCISE
Wound dressing:
Generics:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
Brands:
CollaCote®, CollaPlug®, CollaTape®:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS
Other warnings/precautions: Appropriate use: Should not be used on infected or contaminated wounds.
DRUG INTERACTIONS — There are no known significant interactions.
LACTATION — Compatible
MECHANISM OF ACTION — The highly porous sponge structure absorbs blood and wound exudate. The collagen component causes aggregation of platelets which bind to collagen fibrils. The aggregated platelets degranulate, releasing coagulation factors that promote the formation of fibrin.
PHARMACOLOGIC CATEGORY
Hemostatic Agent
DOSING: ADULTS — Control of bleeding: Topical: A sufficiently large dressing should be selected so as to completely cover the oral wound
DOSING: PEDIATRIC — Refer to adult dosing.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Wound dressing:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
DOSAGE FORMS: CONCISE
Wound dressing:
Generics:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
Brands:
CollaCote®, CollaPlug®, CollaTape®:
3/8" x 3/4"
3/4" x 1 1/2"
1" x 3"
GENERIC EQUIVALENT AVAILABLE — Yes
USE — Hemostatic
ADVERSE REACTIONS SIGNIFICANT — No data reported.
CONTRAINDICATIONS — No data reported
WARNINGS / PRECAUTIONS
Other warnings/precautions: Appropriate use: Should not be used on infected or contaminated wounds.
DRUG INTERACTIONS — There are no known significant interactions.
LACTATION — Compatible
MECHANISM OF ACTION — The highly porous sponge structure absorbs blood and wound exudate. The collagen component causes aggregation of platelets which bind to collagen fibrils. The aggregated platelets degranulate, releasing coagulation factors that promote the formation of fibrin.
Abciximab
U.S. BRAND NAMES — ReoPro®
PHARMACOLOGIC CATEGORY
Antiplatelet Agent, Glycoprotein IIb/IIIa Inhibitor
DOSING: ADULTS
Percutaneous coronary intervention (PCI): I.V.: 0.25 mg/kg bolus administered 10-60 minutes prior to start of PCI followed by an infusion of 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours
Patients with unstable angina not responding to conventional medical therapy with planned PCI within 24 hours: I.V.: 0.25 mg/kg bolus followed by an 18- to 24-hour infusion of 10 mcg/minute, concluding 1 hour after PCI.
ST-elevation MI combination regimen (unlabeled): Half-dose tenecteplase (15-25 mg based on weight), abciximab 0.25 mg/kg bolus then 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours and heparin dosing as follows: Concurrent bolus of 40 units/kg (maximum: 3000 units), then 7 units/kg/hour (maximum: 800 units/hour) as continuous infusion. Adjust to aPTT target of 50-70 seconds.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
DOSAGE FORMS: CONCISE
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Abciximab is intended for coadministration with aspirin postangioplasty and heparin infused and weight adjusted to maintain a therapeutic bleeding time (eg, ACT 300-500 seconds). Solution must be filtered prior to administration. Do not shake the vial.
Bolus dose: Aseptically withdraw the necessary amount of abciximab for the bolus dose into a syringe using a 0.2 or 5 micron low protein-binding syringe filter (or equivalent); the bolus should be administered 10-60 minutes before the procedure.
Continuous infusion: Aseptically withdraw amount required of abciximab for the infusion through a 0.2 or 5 micron low protein-binding syringe filter into a syringe; inject this into 250 mL of NS or D5W to make solution. If a syringe filter was not used when preparing the infusion, administer using an in-line 0.2 or 0.22 micron low protein-binding filter. Note: Alternatively, a standard concentration of 7.2 mg in 250 mL of NS or D5W may also be prepared for all patients and administered at the standard dose (0.125 mcg/kg/minute; maximum: 10 mcg/minute) with a variable rate in mL/hour. Infuse for 12-24 hours via pump after bolus dose; length of therapy dependent on indication.
COMPATIBILITY — Abciximab should be administered in a separate intravenous line. No incompatibilities have been observed with glass bottles or PVC bags.
USE — Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI); prevention of cardiac ischemic complications in patients with unstable angina not responding to conventional therapy when PCI is scheduled within 24 hours
Note: Intended for use with aspirin and heparin, at a minimum.
USE - UNLABELED / INVESTIGATIONAL — ST-elevation MI: Combination regimen of abciximab (full dose), tenecteplase (half dose), and heparin (unlabeled dose)
ADVERSE REACTIONS SIGNIFICANT — As with all drugs which may affect hemostasis, bleeding is associated with abciximab. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.
>10%:
Cardiovascular: Hypotension (14.4%), chest pain (11.4%)
Gastrointestinal: Nausea (13.6%)
Hematologic: Minor bleeding (4.0% to 16.8%)
Neuromuscular & skeletal: Back pain (17.6%)
1% to 10%:
Cardiovascular: Bradycardia (4.5%), peripheral edema (1.6%)
Central nervous system: Headache (6.45)
Gastrointestinal: Vomiting (7.3%), abdominal pain (3.1%)
Hematologic: Major bleeding (1.1% to 14%), thrombocytopenia: <100,000 cells/mm3 (2.5% to 5.6%); <50,000 cells/mm3 (0.4% to 1.7%)
Local: Injection site pain (3.6%)
<1% (Limited to important or life-threatening): Abnormal thinking, allergic reactions/anaphylaxis (possible), AV block, bronchospasm, bullous eruption, coma, confusion, diabetes mellitus, embolism, hyperkalemia, ileus, inflammation, intracranial hemorrhage, myalgia, nodal arrhythmia, pleural effusion, pulmonary embolism, prostatitis, pruritus, stroke, urinary retention, ventricular tachycardia, xerostomia
CONTRAINDICATIONS — Hypersensitivity to abciximab, to murine proteins, or any component of the formulation; active internal hemorrhage or recent (within 6 weeks) clinically-significant GI or GU bleeding; history of cerebrovascular accident within 2 years or cerebrovascular accident with significant neurological deficit; clotting abnormalities or administration of oral anticoagulants within 7 days unless prothrombin time (PT) is ≤ 1.2 times control PT value; thrombocytopenia (<100,000 cells/µL); recent (within 6 weeks) major surgery or trauma; intracranial tumor, arteriovenous malformation, or aneurysm; severe uncontrolled hypertension; history of vasculitis; use of dextran before PTCA or intent to use dextran during PTCA; concomitant use of another parenteral GP IIb/IIIa inhibitor
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Administration may result in human antichimeric antibody formation that can cause hypersensitivity reactions (including anaphylaxis). Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Use with extreme caution in patients with platelet counts <150,000/mm3,>70 minutes duration, or PTCA performed within 12 hours of symptom onset for acute myocardial infarction. Thrombocytopenia: Administration may result in human antichimeric antibody formation that can cause thrombocytopenia; readministration within 30 days or in patients with human antichimeric antibodies (HACA) increases the incidence and severity of thrombocytopenia.
Special populations: Elderly: Use with caution in patients >65 years of age; increased risk of bleeding. Low weight patients: Use with caution in patients weighing <75 kg; increased risk of bleeding. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Diminished efficacy: Administration may result in human antichimeric antibody formation that can cause diminished efficacy. Sheath removal: Prior to pulling the sheath, heparin should be discontinued for 3-4 hours and ACT ≤ 175 seconds or aPTT ≤ 50 seconds. Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.
DRUG INTERACTIONS
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Dextran: May enhance the anticoagulant effect of Abciximab. Risk X: Avoid combination
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Monoclonal Antibodies: Abciximab may enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Exceptions: Alefacept. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted. In vitro studies have shown only small amounts of abciximab to cross the placenta. It is not known whether abciximab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Prothrombin time, activated partial thromboplastin time (aPTT), hemoglobin, hematocrit, platelet count, fibrinogen, fibrin split products, transfusion requirements, signs of hypersensitivity reactions, guaiac stools, Hemastix® urine. Platelet count should be monitored at baseline, 2-4 hours following bolus infusion, and at 24 hours (or prior to discharge, if before 24 hours). To minimize risk of bleeding:
Abciximab initiated 18-24 hours prior to PCI: Maintain aPTT between 60-85 seconds during the heparin/abciximab infusion period
During PCI: Maintain ACT between 200-300 seconds
Following PCI (if anticoagulation is maintained): Maintain aPTT between 50-75 seconds
Sheath removal should not occur until aPTT is ≤ 50 seconds or ACT ≤ 175 seconds.
Maintain bleeding precautions, avoid unnecessary arterial and venous punctures, use saline or heparin lock for blood drawing, assess sheath insertion site and distal pulses of affected leg every 15 minutes for the first hour and then every 1 hour for the next 6 hours. Arterial access site care is important to prevent bleeding. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Femoral vein sheath placement should be avoided unless needed. While the vascular sheath is in place, patients should be maintained on complete bedrest with the head of the bed at a 30º angle and the affected limb restrained in a straight position.
Observe patient for mental status changes, hemorrhage; assess nose and mouth mucous membranes, puncture sites for oozing, ecchymosis, and hematoma formation; and examine urine, stool, and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.
CANADIAN BRAND NAMES — ReoPro®
INTERNATIONAL BRAND NAMES — ReoPro (AR, AT, AU, BE, BR, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, IE, IN, IT, KP, LU, MX, MY, NL, NO, PE, PK, PL, PT, SE, SG, TH, TW, ZA)
MECHANISM OF ACTION — Fab antibody fragment of the chimeric human-murine monoclonal antibody 7E3; this agent binds to platelet IIb/IIIa receptors, resulting in steric hindrance, thus inhibiting platelet aggregation
PHARMACODYNAMICS / KINETICS — Half-life elimination: ~30 minutes
PHARMACOLOGIC CATEGORY
Antiplatelet Agent, Glycoprotein IIb/IIIa Inhibitor
DOSING: ADULTS
Percutaneous coronary intervention (PCI): I.V.: 0.25 mg/kg bolus administered 10-60 minutes prior to start of PCI followed by an infusion of 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours
Patients with unstable angina not responding to conventional medical therapy with planned PCI within 24 hours: I.V.: 0.25 mg/kg bolus followed by an 18- to 24-hour infusion of 10 mcg/minute, concluding 1 hour after PCI.
ST-elevation MI combination regimen (unlabeled): Half-dose tenecteplase (15-25 mg based on weight), abciximab 0.25 mg/kg bolus then 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours and heparin dosing as follows: Concurrent bolus of 40 units/kg (maximum: 3000 units), then 7 units/kg/hour (maximum: 800 units/hour) as continuous infusion. Adjust to aPTT target of 50-70 seconds.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
DOSAGE FORMS: CONCISE
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Abciximab is intended for coadministration with aspirin postangioplasty and heparin infused and weight adjusted to maintain a therapeutic bleeding time (eg, ACT 300-500 seconds). Solution must be filtered prior to administration. Do not shake the vial.
Bolus dose: Aseptically withdraw the necessary amount of abciximab for the bolus dose into a syringe using a 0.2 or 5 micron low protein-binding syringe filter (or equivalent); the bolus should be administered 10-60 minutes before the procedure.
Continuous infusion: Aseptically withdraw amount required of abciximab for the infusion through a 0.2 or 5 micron low protein-binding syringe filter into a syringe; inject this into 250 mL of NS or D5W to make solution. If a syringe filter was not used when preparing the infusion, administer using an in-line 0.2 or 0.22 micron low protein-binding filter. Note: Alternatively, a standard concentration of 7.2 mg in 250 mL of NS or D5W may also be prepared for all patients and administered at the standard dose (0.125 mcg/kg/minute; maximum: 10 mcg/minute) with a variable rate in mL/hour. Infuse for 12-24 hours via pump after bolus dose; length of therapy dependent on indication.
COMPATIBILITY — Abciximab should be administered in a separate intravenous line. No incompatibilities have been observed with glass bottles or PVC bags.
USE — Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI); prevention of cardiac ischemic complications in patients with unstable angina not responding to conventional therapy when PCI is scheduled within 24 hours
Note: Intended for use with aspirin and heparin, at a minimum.
USE - UNLABELED / INVESTIGATIONAL — ST-elevation MI: Combination regimen of abciximab (full dose), tenecteplase (half dose), and heparin (unlabeled dose)
ADVERSE REACTIONS SIGNIFICANT — As with all drugs which may affect hemostasis, bleeding is associated with abciximab. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.
>10%:
Cardiovascular: Hypotension (14.4%), chest pain (11.4%)
Gastrointestinal: Nausea (13.6%)
Hematologic: Minor bleeding (4.0% to 16.8%)
Neuromuscular & skeletal: Back pain (17.6%)
1% to 10%:
Cardiovascular: Bradycardia (4.5%), peripheral edema (1.6%)
Central nervous system: Headache (6.45)
Gastrointestinal: Vomiting (7.3%), abdominal pain (3.1%)
Hematologic: Major bleeding (1.1% to 14%), thrombocytopenia: <100,000 cells/mm3 (2.5% to 5.6%); <50,000 cells/mm3 (0.4% to 1.7%)
Local: Injection site pain (3.6%)
<1% (Limited to important or life-threatening): Abnormal thinking, allergic reactions/anaphylaxis (possible), AV block, bronchospasm, bullous eruption, coma, confusion, diabetes mellitus, embolism, hyperkalemia, ileus, inflammation, intracranial hemorrhage, myalgia, nodal arrhythmia, pleural effusion, pulmonary embolism, prostatitis, pruritus, stroke, urinary retention, ventricular tachycardia, xerostomia
CONTRAINDICATIONS — Hypersensitivity to abciximab, to murine proteins, or any component of the formulation; active internal hemorrhage or recent (within 6 weeks) clinically-significant GI or GU bleeding; history of cerebrovascular accident within 2 years or cerebrovascular accident with significant neurological deficit; clotting abnormalities or administration of oral anticoagulants within 7 days unless prothrombin time (PT) is ≤ 1.2 times control PT value; thrombocytopenia (<100,000 cells/µL); recent (within 6 weeks) major surgery or trauma; intracranial tumor, arteriovenous malformation, or aneurysm; severe uncontrolled hypertension; history of vasculitis; use of dextran before PTCA or intent to use dextran during PTCA; concomitant use of another parenteral GP IIb/IIIa inhibitor
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Administration may result in human antichimeric antibody formation that can cause hypersensitivity reactions (including anaphylaxis). Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Use with extreme caution in patients with platelet counts <150,000/mm3,>70 minutes duration, or PTCA performed within 12 hours of symptom onset for acute myocardial infarction. Thrombocytopenia: Administration may result in human antichimeric antibody formation that can cause thrombocytopenia; readministration within 30 days or in patients with human antichimeric antibodies (HACA) increases the incidence and severity of thrombocytopenia.
Special populations: Elderly: Use with caution in patients >65 years of age; increased risk of bleeding. Low weight patients: Use with caution in patients weighing <75 kg; increased risk of bleeding. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Diminished efficacy: Administration may result in human antichimeric antibody formation that can cause diminished efficacy. Sheath removal: Prior to pulling the sheath, heparin should be discontinued for 3-4 hours and ACT ≤ 175 seconds or aPTT ≤ 50 seconds. Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.
DRUG INTERACTIONS
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Dextran: May enhance the anticoagulant effect of Abciximab. Risk X: Avoid combination
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Monoclonal Antibodies: Abciximab may enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Exceptions: Alefacept. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted. In vitro studies have shown only small amounts of abciximab to cross the placenta. It is not known whether abciximab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Prothrombin time, activated partial thromboplastin time (aPTT), hemoglobin, hematocrit, platelet count, fibrinogen, fibrin split products, transfusion requirements, signs of hypersensitivity reactions, guaiac stools, Hemastix® urine. Platelet count should be monitored at baseline, 2-4 hours following bolus infusion, and at 24 hours (or prior to discharge, if before 24 hours). To minimize risk of bleeding:
Abciximab initiated 18-24 hours prior to PCI: Maintain aPTT between 60-85 seconds during the heparin/abciximab infusion period
During PCI: Maintain ACT between 200-300 seconds
Following PCI (if anticoagulation is maintained): Maintain aPTT between 50-75 seconds
Sheath removal should not occur until aPTT is ≤ 50 seconds or ACT ≤ 175 seconds.
Maintain bleeding precautions, avoid unnecessary arterial and venous punctures, use saline or heparin lock for blood drawing, assess sheath insertion site and distal pulses of affected leg every 15 minutes for the first hour and then every 1 hour for the next 6 hours. Arterial access site care is important to prevent bleeding. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Femoral vein sheath placement should be avoided unless needed. While the vascular sheath is in place, patients should be maintained on complete bedrest with the head of the bed at a 30º angle and the affected limb restrained in a straight position.
Observe patient for mental status changes, hemorrhage; assess nose and mouth mucous membranes, puncture sites for oozing, ecchymosis, and hematoma formation; and examine urine, stool, and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.
CANADIAN BRAND NAMES — ReoPro®
INTERNATIONAL BRAND NAMES — ReoPro (AR, AT, AU, BE, BR, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, IE, IN, IT, KP, LU, MX, MY, NL, NO, PE, PK, PL, PT, SE, SG, TH, TW, ZA)
MECHANISM OF ACTION — Fab antibody fragment of the chimeric human-murine monoclonal antibody 7E3; this agent binds to platelet IIb/IIIa receptors, resulting in steric hindrance, thus inhibiting platelet aggregation
PHARMACODYNAMICS / KINETICS — Half-life elimination: ~30 minutes
Abciximab
U.S. BRAND NAMES — ReoPro®
PHARMACOLOGIC CATEGORY
Antiplatelet Agent, Glycoprotein IIb/IIIa Inhibitor
DOSING: ADULTS
Percutaneous coronary intervention (PCI): I.V.: 0.25 mg/kg bolus administered 10-60 minutes prior to start of PCI followed by an infusion of 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours
Patients with unstable angina not responding to conventional medical therapy with planned PCI within 24 hours: I.V.: 0.25 mg/kg bolus followed by an 18- to 24-hour infusion of 10 mcg/minute, concluding 1 hour after PCI.
ST-elevation MI combination regimen (unlabeled): Half-dose tenecteplase (15-25 mg based on weight), abciximab 0.25 mg/kg bolus then 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours and heparin dosing as follows: Concurrent bolus of 40 units/kg (maximum: 3000 units), then 7 units/kg/hour (maximum: 800 units/hour) as continuous infusion. Adjust to aPTT target of 50-70 seconds.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
DOSAGE FORMS: CONCISE
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Abciximab is intended for coadministration with aspirin postangioplasty and heparin infused and weight adjusted to maintain a therapeutic bleeding time (eg, ACT 300-500 seconds). Solution must be filtered prior to administration. Do not shake the vial.
Bolus dose: Aseptically withdraw the necessary amount of abciximab for the bolus dose into a syringe using a 0.2 or 5 micron low protein-binding syringe filter (or equivalent); the bolus should be administered 10-60 minutes before the procedure.
Continuous infusion: Aseptically withdraw amount required of abciximab for the infusion through a 0.2 or 5 micron low protein-binding syringe filter into a syringe; inject this into 250 mL of NS or D5W to make solution. If a syringe filter was not used when preparing the infusion, administer using an in-line 0.2 or 0.22 micron low protein-binding filter. Note: Alternatively, a standard concentration of 7.2 mg in 250 mL of NS or D5W may also be prepared for all patients and administered at the standard dose (0.125 mcg/kg/minute; maximum: 10 mcg/minute) with a variable rate in mL/hour. Infuse for 12-24 hours via pump after bolus dose; length of therapy dependent on indication.
COMPATIBILITY — Abciximab should be administered in a separate intravenous line. No incompatibilities have been observed with glass bottles or PVC bags.
USE — Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI); prevention of cardiac ischemic complications in patients with unstable angina not responding to conventional therapy when PCI is scheduled within 24 hours
Note: Intended for use with aspirin and heparin, at a minimum.
USE - UNLABELED / INVESTIGATIONAL — ST-elevation MI: Combination regimen of abciximab (full dose), tenecteplase (half dose), and heparin (unlabeled dose)
ADVERSE REACTIONS SIGNIFICANT — As with all drugs which may affect hemostasis, bleeding is associated with abciximab. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.
>10%:
Cardiovascular: Hypotension (14.4%), chest pain (11.4%)
Gastrointestinal: Nausea (13.6%)
Hematologic: Minor bleeding (4.0% to 16.8%)
Neuromuscular & skeletal: Back pain (17.6%)
1% to 10%:
Cardiovascular: Bradycardia (4.5%), peripheral edema (1.6%)
Central nervous system: Headache (6.45)
Gastrointestinal: Vomiting (7.3%), abdominal pain (3.1%)
Hematologic: Major bleeding (1.1% to 14%), thrombocytopenia: <100,000 cells/mm3 (2.5% to 5.6%); <50,000 cells/mm3 (0.4% to 1.7%)
Local: Injection site pain (3.6%)
<1% (Limited to important or life-threatening): Abnormal thinking, allergic reactions/anaphylaxis (possible), AV block, bronchospasm, bullous eruption, coma, confusion, diabetes mellitus, embolism, hyperkalemia, ileus, inflammation, intracranial hemorrhage, myalgia, nodal arrhythmia, pleural effusion, pulmonary embolism, prostatitis, pruritus, stroke, urinary retention, ventricular tachycardia, xerostomia
CONTRAINDICATIONS — Hypersensitivity to abciximab, to murine proteins, or any component of the formulation; active internal hemorrhage or recent (within 6 weeks) clinically-significant GI or GU bleeding; history of cerebrovascular accident within 2 years or cerebrovascular accident with significant neurological deficit; clotting abnormalities or administration of oral anticoagulants within 7 days unless prothrombin time (PT) is ≤ 1.2 times control PT value; thrombocytopenia (<100,000 cells/µL); recent (within 6 weeks) major surgery or trauma; intracranial tumor, arteriovenous malformation, or aneurysm; severe uncontrolled hypertension; history of vasculitis; use of dextran before PTCA or intent to use dextran during PTCA; concomitant use of another parenteral GP IIb/IIIa inhibitor
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Administration may result in human antichimeric antibody formation that can cause hypersensitivity reactions (including anaphylaxis). Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Use with extreme caution in patients with platelet counts <150,000/mm3,>70 minutes duration, or PTCA performed within 12 hours of symptom onset for acute myocardial infarction. Thrombocytopenia: Administration may result in human antichimeric antibody formation that can cause thrombocytopenia; readministration within 30 days or in patients with human antichimeric antibodies (HACA) increases the incidence and severity of thrombocytopenia.
Special populations: Elderly: Use with caution in patients >65 years of age; increased risk of bleeding. Low weight patients: Use with caution in patients weighing <75 kg; increased risk of bleeding. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Diminished efficacy: Administration may result in human antichimeric antibody formation that can cause diminished efficacy. Sheath removal: Prior to pulling the sheath, heparin should be discontinued for 3-4 hours and ACT ≤ 175 seconds or aPTT ≤ 50 seconds. Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.
DRUG INTERACTIONS
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Dextran: May enhance the anticoagulant effect of Abciximab. Risk X: Avoid combination
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Monoclonal Antibodies: Abciximab may enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Exceptions: Alefacept. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted. In vitro studies have shown only small amounts of abciximab to cross the placenta. It is not known whether abciximab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Prothrombin time, activated partial thromboplastin time (aPTT), hemoglobin, hematocrit, platelet count, fibrinogen, fibrin split products, transfusion requirements, signs of hypersensitivity reactions, guaiac stools, Hemastix® urine. Platelet count should be monitored at baseline, 2-4 hours following bolus infusion, and at 24 hours (or prior to discharge, if before 24 hours). To minimize risk of bleeding:
Abciximab initiated 18-24 hours prior to PCI: Maintain aPTT between 60-85 seconds during the heparin/abciximab infusion period
During PCI: Maintain ACT between 200-300 seconds
Following PCI (if anticoagulation is maintained): Maintain aPTT between 50-75 seconds
Sheath removal should not occur until aPTT is ≤ 50 seconds or ACT ≤ 175 seconds.
Maintain bleeding precautions, avoid unnecessary arterial and venous punctures, use saline or heparin lock for blood drawing, assess sheath insertion site and distal pulses of affected leg every 15 minutes for the first hour and then every 1 hour for the next 6 hours. Arterial access site care is important to prevent bleeding. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Femoral vein sheath placement should be avoided unless needed. While the vascular sheath is in place, patients should be maintained on complete bedrest with the head of the bed at a 30º angle and the affected limb restrained in a straight position.
Observe patient for mental status changes, hemorrhage; assess nose and mouth mucous membranes, puncture sites for oozing, ecchymosis, and hematoma formation; and examine urine, stool, and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.
CANADIAN BRAND NAMES — ReoPro®
INTERNATIONAL BRAND NAMES — ReoPro (AR, AT, AU, BE, BR, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, IE, IN, IT, KP, LU, MX, MY, NL, NO, PE, PK, PL, PT, SE, SG, TH, TW, ZA)
MECHANISM OF ACTION — Fab antibody fragment of the chimeric human-murine monoclonal antibody 7E3; this agent binds to platelet IIb/IIIa receptors, resulting in steric hindrance, thus inhibiting platelet aggregation
PHARMACODYNAMICS / KINETICS — Half-life elimination: ~30 minutes
PHARMACOLOGIC CATEGORY
Antiplatelet Agent, Glycoprotein IIb/IIIa Inhibitor
DOSING: ADULTS
Percutaneous coronary intervention (PCI): I.V.: 0.25 mg/kg bolus administered 10-60 minutes prior to start of PCI followed by an infusion of 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours
Patients with unstable angina not responding to conventional medical therapy with planned PCI within 24 hours: I.V.: 0.25 mg/kg bolus followed by an 18- to 24-hour infusion of 10 mcg/minute, concluding 1 hour after PCI.
ST-elevation MI combination regimen (unlabeled): Half-dose tenecteplase (15-25 mg based on weight), abciximab 0.25 mg/kg bolus then 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours and heparin dosing as follows: Concurrent bolus of 40 units/kg (maximum: 3000 units), then 7 units/kg/hour (maximum: 800 units/hour) as continuous infusion. Adjust to aPTT target of 50-70 seconds.
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
DOSAGE FORMS: CONCISE
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Abciximab is intended for coadministration with aspirin postangioplasty and heparin infused and weight adjusted to maintain a therapeutic bleeding time (eg, ACT 300-500 seconds). Solution must be filtered prior to administration. Do not shake the vial.
Bolus dose: Aseptically withdraw the necessary amount of abciximab for the bolus dose into a syringe using a 0.2 or 5 micron low protein-binding syringe filter (or equivalent); the bolus should be administered 10-60 minutes before the procedure.
Continuous infusion: Aseptically withdraw amount required of abciximab for the infusion through a 0.2 or 5 micron low protein-binding syringe filter into a syringe; inject this into 250 mL of NS or D5W to make solution. If a syringe filter was not used when preparing the infusion, administer using an in-line 0.2 or 0.22 micron low protein-binding filter. Note: Alternatively, a standard concentration of 7.2 mg in 250 mL of NS or D5W may also be prepared for all patients and administered at the standard dose (0.125 mcg/kg/minute; maximum: 10 mcg/minute) with a variable rate in mL/hour. Infuse for 12-24 hours via pump after bolus dose; length of therapy dependent on indication.
COMPATIBILITY — Abciximab should be administered in a separate intravenous line. No incompatibilities have been observed with glass bottles or PVC bags.
USE — Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI); prevention of cardiac ischemic complications in patients with unstable angina not responding to conventional therapy when PCI is scheduled within 24 hours
Note: Intended for use with aspirin and heparin, at a minimum.
USE - UNLABELED / INVESTIGATIONAL — ST-elevation MI: Combination regimen of abciximab (full dose), tenecteplase (half dose), and heparin (unlabeled dose)
ADVERSE REACTIONS SIGNIFICANT — As with all drugs which may affect hemostasis, bleeding is associated with abciximab. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.
>10%:
Cardiovascular: Hypotension (14.4%), chest pain (11.4%)
Gastrointestinal: Nausea (13.6%)
Hematologic: Minor bleeding (4.0% to 16.8%)
Neuromuscular & skeletal: Back pain (17.6%)
1% to 10%:
Cardiovascular: Bradycardia (4.5%), peripheral edema (1.6%)
Central nervous system: Headache (6.45)
Gastrointestinal: Vomiting (7.3%), abdominal pain (3.1%)
Hematologic: Major bleeding (1.1% to 14%), thrombocytopenia: <100,000 cells/mm3 (2.5% to 5.6%); <50,000 cells/mm3 (0.4% to 1.7%)
Local: Injection site pain (3.6%)
<1% (Limited to important or life-threatening): Abnormal thinking, allergic reactions/anaphylaxis (possible), AV block, bronchospasm, bullous eruption, coma, confusion, diabetes mellitus, embolism, hyperkalemia, ileus, inflammation, intracranial hemorrhage, myalgia, nodal arrhythmia, pleural effusion, pulmonary embolism, prostatitis, pruritus, stroke, urinary retention, ventricular tachycardia, xerostomia
CONTRAINDICATIONS — Hypersensitivity to abciximab, to murine proteins, or any component of the formulation; active internal hemorrhage or recent (within 6 weeks) clinically-significant GI or GU bleeding; history of cerebrovascular accident within 2 years or cerebrovascular accident with significant neurological deficit; clotting abnormalities or administration of oral anticoagulants within 7 days unless prothrombin time (PT) is ≤ 1.2 times control PT value; thrombocytopenia (<100,000 cells/µL); recent (within 6 weeks) major surgery or trauma; intracranial tumor, arteriovenous malformation, or aneurysm; severe uncontrolled hypertension; history of vasculitis; use of dextran before PTCA or intent to use dextran during PTCA; concomitant use of another parenteral GP IIb/IIIa inhibitor
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Administration may result in human antichimeric antibody formation that can cause hypersensitivity reactions (including anaphylaxis). Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Use with extreme caution in patients with platelet counts <150,000/mm3,>70 minutes duration, or PTCA performed within 12 hours of symptom onset for acute myocardial infarction. Thrombocytopenia: Administration may result in human antichimeric antibody formation that can cause thrombocytopenia; readministration within 30 days or in patients with human antichimeric antibodies (HACA) increases the incidence and severity of thrombocytopenia.
Special populations: Elderly: Use with caution in patients >65 years of age; increased risk of bleeding. Low weight patients: Use with caution in patients weighing <75 kg; increased risk of bleeding. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Diminished efficacy: Administration may result in human antichimeric antibody formation that can cause diminished efficacy. Sheath removal: Prior to pulling the sheath, heparin should be discontinued for 3-4 hours and ACT ≤ 175 seconds or aPTT ≤ 50 seconds. Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.
DRUG INTERACTIONS
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Dextran: May enhance the anticoagulant effect of Abciximab. Risk X: Avoid combination
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Monoclonal Antibodies: Abciximab may enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Exceptions: Alefacept. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Animal reproduction studies have not been conducted. In vitro studies have shown only small amounts of abciximab to cross the placenta. It is not known whether abciximab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
LACTATION — Excretion in breast milk unknown/use caution
MONITORING PARAMETERS — Prothrombin time, activated partial thromboplastin time (aPTT), hemoglobin, hematocrit, platelet count, fibrinogen, fibrin split products, transfusion requirements, signs of hypersensitivity reactions, guaiac stools, Hemastix® urine. Platelet count should be monitored at baseline, 2-4 hours following bolus infusion, and at 24 hours (or prior to discharge, if before 24 hours). To minimize risk of bleeding:
Abciximab initiated 18-24 hours prior to PCI: Maintain aPTT between 60-85 seconds during the heparin/abciximab infusion period
During PCI: Maintain ACT between 200-300 seconds
Following PCI (if anticoagulation is maintained): Maintain aPTT between 50-75 seconds
Sheath removal should not occur until aPTT is ≤ 50 seconds or ACT ≤ 175 seconds.
Maintain bleeding precautions, avoid unnecessary arterial and venous punctures, use saline or heparin lock for blood drawing, assess sheath insertion site and distal pulses of affected leg every 15 minutes for the first hour and then every 1 hour for the next 6 hours. Arterial access site care is important to prevent bleeding. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Femoral vein sheath placement should be avoided unless needed. While the vascular sheath is in place, patients should be maintained on complete bedrest with the head of the bed at a 30º angle and the affected limb restrained in a straight position.
Observe patient for mental status changes, hemorrhage; assess nose and mouth mucous membranes, puncture sites for oozing, ecchymosis, and hematoma formation; and examine urine, stool, and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.
CANADIAN BRAND NAMES — ReoPro®
INTERNATIONAL BRAND NAMES — ReoPro (AR, AT, AU, BE, BR, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, IE, IN, IT, KP, LU, MX, MY, NL, NO, PE, PK, PL, PT, SE, SG, TH, TW, ZA)
MECHANISM OF ACTION — Fab antibody fragment of the chimeric human-murine monoclonal antibody 7E3; this agent binds to platelet IIb/IIIa receptors, resulting in steric hindrance, thus inhibiting platelet aggregation
PHARMACODYNAMICS / KINETICS — Half-life elimination: ~30 minutes
Abatacept
U.S. BRAND NAMES — Orencia®
PHARMACOLOGIC CATEGORY
Antirheumatic, Disease Modifying
DOSING: ADULTS — Rheumatoid arthritis: I.V.: Dosing is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter:
<60 kg: 500 mg
60-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: PEDIATRIC — JIA: I.V.:
(For additional information see "Abatacept: Pediatric drug information")
Children ≥ 6 years and <75 kg: 10 mg/kg, repeat dose at 2 and 4 weeks after initial infusion, and every 4 weeks thereafter
Children ≥ 6 years and >75 kg: Note: Dosage is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose and every 4 weeks thereafter:
75-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: ELDERLY — Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.
DOSING: ADJUSTMENT FOR TOXICITY — Withhold therapy for patients with serious infections.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg [contains maltose]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 30 minutes. Administer through a 0.2-1.2 micron low protein-binding filter
COMPATIBILITY — Stable in NS.
USE
Treatment of moderately- to severely-active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs
Treatment of moderately- to severely-active juvenile idiopathic arthritis (JIA); may be used as monotherapy or in combination with methotrexate
Note: Abatacept should not be used in combination with anakinra or TNF-blocking agents
ADVERSE REACTIONS SIGNIFICANT — Note: Percentages not always reported; COPD patients experienced a higher frequency of COPD-related adverse reactions (COPD exacerbation, cough, dyspnea, pneumonia, rhonchi)
>10%:
Central nervous system: Headache (≤ 18%)
Gastrointestinal: Nausea
Respiratory: Nasopharyngitis (12%), upper respiratory tract infection
Miscellaneous: Infection (adults 54%; children 36%), antibody formation (2% to 41%)
1% to 10%:
Cardiovascular: Hypertension (7%)
Central nervous system: Dizziness (9%), fever
Dermatologic: Rash (4%)
Gastrointestinal: Dyspepsia (6%), abdominal pain, diarrhea
Genitourinary: Urinary tract infection (6%)
Neuromuscular & skeletal: Back pain (7%), limb pain (3%)
Respiratory: Cough (8%), bronchitis, pneumonia, rhinitis, sinusitis
Miscellaneous: Infusion-related reactions (2% to 9%), herpes simplex, influenza
<1% (Limited to important or life-threatening): Acute lymphocytic leukemia, anaphylaxis, anaphylactoid reactions, cellulitis, COPD exacerbation, disease flare, diverticulitis, dyspnea, flushing, hypersensitivity, hypotension, joint wear, lung cancer, lymphoma; malignancies (including bile duct, bladder, breast, cervical, melanoma, myelodysplastic syndrome, prostate, renal, skin, thyroid and uterine); ovarian cyst, pruritus, pyelonephritis, rhonchi, urticaria, varicella infection, wheezing
CONTRAINDICATIONS — There are no contraindications listed within the FDA-approved labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Rare cases of hypersensitivity, anaphylaxis, or anaphylactoid reactions have been reported; medication for the treatment of hypersensitivity reactions should be available for immediate use. Infections: Caution should be exercised when considering the use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Malignancy: Use may affect defenses against malignancies (via T cell inhibition); impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma and lung cancer has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma.
Disease-related concerns: COPD: Use caution with chronic obstructive pulmonary disease (COPD), higher incidences of adverse effects (COPD exacerbation, cough, rhonchi, dyspnea) have been observed; monitor closely.
Concurrent drug therapy issues: Anakinra: The manufacturer does not recommend concurrent use with anakinra. TNF-blocking agents: Adult patients receiving therapy in combination with TNF-blocking agents had higher rates of infections (including serious infections) than patients on TNF-blocking agents alone. Concurrent use with TNF-blocking agents is not recommended. Monitor for signs and symptoms of infection when transitioning from TNF-blocking agents to abatacept.
Special populations: Elderly: Use with caution, higher incidences of infection and malignancy were observed in the elderly. Pediatrics: Not FDA approved for use in children <6 years of age. Tuberculosis-positive patients: Safety has not been established in tuberculosis-positive patients; screen patients for latent tuberculosis infection prior to initiating therapy. Treat patients testing positive according to standard therapy prior to initiating abatacept.
Dosage form specific issues: Maltose: May contain maltose, which may result in falsely-elevated serum glucose readings on the day of infusion.
Other warnings/precautions: Hepatitis screening: Patients should be screened for viral hepatitis prior to use; antirheumatic therapy may cause reactivation of hepatitis B. Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently or within 3 months of discontinuation of therapy; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS
Anti-TNF Agents: May enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Avoid echinacea (has immunostimulant properties; consider therapy modifications).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Due to the potential risk for development of autoimmune disease in the fetus, use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to abatacept during pregnancy (1-877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions and possible effects on the developing immune system, breast-feeding is not recommended.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Orencia)
250 mg (1): $528.09
MONITORING PARAMETERS — Signs and symptoms of infection, signs and symptoms of infusion reaction; hepatitis and TB screening prior to therapy initiation
CANADIAN BRAND NAMES — Orencia®
INTERNATIONAL BRAND NAMES — Orencia (AR, CH, CN, CO, CZ, DE, DK, EE, FR, GB, IE, NO, PE, SE)
MECHANISM OF ACTION — Selective costimulation modulator; inhibits T-cell (T-lymphocyte) activation by binding to CD80 and CD86 on antigen presenting cells (APC), thus blocking the required CD28 interaction between APCs and T cells. Activated T lymphocytes are found in the synovium of rheumatoid arthritis patients.
PHARMACODYNAMICS / KINETICS
Distribution: Vss: 0.02-0.13 L/kg
Half-life elimination: 8-25 days
PATIENT INFORMATION — This drug can only be administered by infusion. Do not have any vaccinations while using this medication without consulting prescriber first. You will be more prone to infection. Avoid crowds and wash your hands frequently. Report infections (local or in your whole body) to prescriber immediately. You will need an overall health assessment prior to each treatment to ensure that you do not have an active infection. You may experience headache or dizziness (use caution when driving) or nausea (small frequent meals or sucking lozenges may help).
PHARMACOLOGIC CATEGORY
Antirheumatic, Disease Modifying
DOSING: ADULTS — Rheumatoid arthritis: I.V.: Dosing is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter:
<60 kg: 500 mg
60-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: PEDIATRIC — JIA: I.V.:
(For additional information see "Abatacept: Pediatric drug information")
Children ≥ 6 years and <75 kg: 10 mg/kg, repeat dose at 2 and 4 weeks after initial infusion, and every 4 weeks thereafter
Children ≥ 6 years and >75 kg: Note: Dosage is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose and every 4 weeks thereafter:
75-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: ELDERLY — Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.
DOSING: ADJUSTMENT FOR TOXICITY — Withhold therapy for patients with serious infections.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg [contains maltose]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 30 minutes. Administer through a 0.2-1.2 micron low protein-binding filter
COMPATIBILITY — Stable in NS.
USE
Treatment of moderately- to severely-active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs
Treatment of moderately- to severely-active juvenile idiopathic arthritis (JIA); may be used as monotherapy or in combination with methotrexate
Note: Abatacept should not be used in combination with anakinra or TNF-blocking agents
ADVERSE REACTIONS SIGNIFICANT — Note: Percentages not always reported; COPD patients experienced a higher frequency of COPD-related adverse reactions (COPD exacerbation, cough, dyspnea, pneumonia, rhonchi)
>10%:
Central nervous system: Headache (≤ 18%)
Gastrointestinal: Nausea
Respiratory: Nasopharyngitis (12%), upper respiratory tract infection
Miscellaneous: Infection (adults 54%; children 36%), antibody formation (2% to 41%)
1% to 10%:
Cardiovascular: Hypertension (7%)
Central nervous system: Dizziness (9%), fever
Dermatologic: Rash (4%)
Gastrointestinal: Dyspepsia (6%), abdominal pain, diarrhea
Genitourinary: Urinary tract infection (6%)
Neuromuscular & skeletal: Back pain (7%), limb pain (3%)
Respiratory: Cough (8%), bronchitis, pneumonia, rhinitis, sinusitis
Miscellaneous: Infusion-related reactions (2% to 9%), herpes simplex, influenza
<1% (Limited to important or life-threatening): Acute lymphocytic leukemia, anaphylaxis, anaphylactoid reactions, cellulitis, COPD exacerbation, disease flare, diverticulitis, dyspnea, flushing, hypersensitivity, hypotension, joint wear, lung cancer, lymphoma; malignancies (including bile duct, bladder, breast, cervical, melanoma, myelodysplastic syndrome, prostate, renal, skin, thyroid and uterine); ovarian cyst, pruritus, pyelonephritis, rhonchi, urticaria, varicella infection, wheezing
CONTRAINDICATIONS — There are no contraindications listed within the FDA-approved labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Rare cases of hypersensitivity, anaphylaxis, or anaphylactoid reactions have been reported; medication for the treatment of hypersensitivity reactions should be available for immediate use. Infections: Caution should be exercised when considering the use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Malignancy: Use may affect defenses against malignancies (via T cell inhibition); impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma and lung cancer has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma.
Disease-related concerns: COPD: Use caution with chronic obstructive pulmonary disease (COPD), higher incidences of adverse effects (COPD exacerbation, cough, rhonchi, dyspnea) have been observed; monitor closely.
Concurrent drug therapy issues: Anakinra: The manufacturer does not recommend concurrent use with anakinra. TNF-blocking agents: Adult patients receiving therapy in combination with TNF-blocking agents had higher rates of infections (including serious infections) than patients on TNF-blocking agents alone. Concurrent use with TNF-blocking agents is not recommended. Monitor for signs and symptoms of infection when transitioning from TNF-blocking agents to abatacept.
Special populations: Elderly: Use with caution, higher incidences of infection and malignancy were observed in the elderly. Pediatrics: Not FDA approved for use in children <6 years of age. Tuberculosis-positive patients: Safety has not been established in tuberculosis-positive patients; screen patients for latent tuberculosis infection prior to initiating therapy. Treat patients testing positive according to standard therapy prior to initiating abatacept.
Dosage form specific issues: Maltose: May contain maltose, which may result in falsely-elevated serum glucose readings on the day of infusion.
Other warnings/precautions: Hepatitis screening: Patients should be screened for viral hepatitis prior to use; antirheumatic therapy may cause reactivation of hepatitis B. Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently or within 3 months of discontinuation of therapy; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS
Anti-TNF Agents: May enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Avoid echinacea (has immunostimulant properties; consider therapy modifications).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Due to the potential risk for development of autoimmune disease in the fetus, use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to abatacept during pregnancy (1-877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions and possible effects on the developing immune system, breast-feeding is not recommended.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Orencia)
250 mg (1): $528.09
MONITORING PARAMETERS — Signs and symptoms of infection, signs and symptoms of infusion reaction; hepatitis and TB screening prior to therapy initiation
CANADIAN BRAND NAMES — Orencia®
INTERNATIONAL BRAND NAMES — Orencia (AR, CH, CN, CO, CZ, DE, DK, EE, FR, GB, IE, NO, PE, SE)
MECHANISM OF ACTION — Selective costimulation modulator; inhibits T-cell (T-lymphocyte) activation by binding to CD80 and CD86 on antigen presenting cells (APC), thus blocking the required CD28 interaction between APCs and T cells. Activated T lymphocytes are found in the synovium of rheumatoid arthritis patients.
PHARMACODYNAMICS / KINETICS
Distribution: Vss: 0.02-0.13 L/kg
Half-life elimination: 8-25 days
PATIENT INFORMATION — This drug can only be administered by infusion. Do not have any vaccinations while using this medication without consulting prescriber first. You will be more prone to infection. Avoid crowds and wash your hands frequently. Report infections (local or in your whole body) to prescriber immediately. You will need an overall health assessment prior to each treatment to ensure that you do not have an active infection. You may experience headache or dizziness (use caution when driving) or nausea (small frequent meals or sucking lozenges may help).
Abatacept
U.S. BRAND NAMES — Orencia®
PHARMACOLOGIC CATEGORY
Antirheumatic, Disease Modifying
DOSING: ADULTS — Rheumatoid arthritis: I.V.: Dosing is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter:
<60 kg: 500 mg
60-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: PEDIATRIC — JIA: I.V.:
(For additional information see "Abatacept: Pediatric drug information")
Children ≥ 6 years and <75 kg: 10 mg/kg, repeat dose at 2 and 4 weeks after initial infusion, and every 4 weeks thereafter
Children ≥ 6 years and >75 kg: Note: Dosage is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose and every 4 weeks thereafter:
75-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: ELDERLY — Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.
DOSING: ADJUSTMENT FOR TOXICITY — Withhold therapy for patients with serious infections.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg [contains maltose]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 30 minutes. Administer through a 0.2-1.2 micron low protein-binding filter
COMPATIBILITY — Stable in NS.
USE
Treatment of moderately- to severely-active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs
Treatment of moderately- to severely-active juvenile idiopathic arthritis (JIA); may be used as monotherapy or in combination with methotrexate
Note: Abatacept should not be used in combination with anakinra or TNF-blocking agents
ADVERSE REACTIONS SIGNIFICANT — Note: Percentages not always reported; COPD patients experienced a higher frequency of COPD-related adverse reactions (COPD exacerbation, cough, dyspnea, pneumonia, rhonchi)
>10%:
Central nervous system: Headache (≤ 18%)
Gastrointestinal: Nausea
Respiratory: Nasopharyngitis (12%), upper respiratory tract infection
Miscellaneous: Infection (adults 54%; children 36%), antibody formation (2% to 41%)
1% to 10%:
Cardiovascular: Hypertension (7%)
Central nervous system: Dizziness (9%), fever
Dermatologic: Rash (4%)
Gastrointestinal: Dyspepsia (6%), abdominal pain, diarrhea
Genitourinary: Urinary tract infection (6%)
Neuromuscular & skeletal: Back pain (7%), limb pain (3%)
Respiratory: Cough (8%), bronchitis, pneumonia, rhinitis, sinusitis
Miscellaneous: Infusion-related reactions (2% to 9%), herpes simplex, influenza
<1% (Limited to important or life-threatening): Acute lymphocytic leukemia, anaphylaxis, anaphylactoid reactions, cellulitis, COPD exacerbation, disease flare, diverticulitis, dyspnea, flushing, hypersensitivity, hypotension, joint wear, lung cancer, lymphoma; malignancies (including bile duct, bladder, breast, cervical, melanoma, myelodysplastic syndrome, prostate, renal, skin, thyroid and uterine); ovarian cyst, pruritus, pyelonephritis, rhonchi, urticaria, varicella infection, wheezing
CONTRAINDICATIONS — There are no contraindications listed within the FDA-approved labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Rare cases of hypersensitivity, anaphylaxis, or anaphylactoid reactions have been reported; medication for the treatment of hypersensitivity reactions should be available for immediate use. Infections: Caution should be exercised when considering the use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Malignancy: Use may affect defenses against malignancies (via T cell inhibition); impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma and lung cancer has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma.
Disease-related concerns: COPD: Use caution with chronic obstructive pulmonary disease (COPD), higher incidences of adverse effects (COPD exacerbation, cough, rhonchi, dyspnea) have been observed; monitor closely.
Concurrent drug therapy issues: Anakinra: The manufacturer does not recommend concurrent use with anakinra. TNF-blocking agents: Adult patients receiving therapy in combination with TNF-blocking agents had higher rates of infections (including serious infections) than patients on TNF-blocking agents alone. Concurrent use with TNF-blocking agents is not recommended. Monitor for signs and symptoms of infection when transitioning from TNF-blocking agents to abatacept.
Special populations: Elderly: Use with caution, higher incidences of infection and malignancy were observed in the elderly. Pediatrics: Not FDA approved for use in children <6 years of age. Tuberculosis-positive patients: Safety has not been established in tuberculosis-positive patients; screen patients for latent tuberculosis infection prior to initiating therapy. Treat patients testing positive according to standard therapy prior to initiating abatacept.
Dosage form specific issues: Maltose: May contain maltose, which may result in falsely-elevated serum glucose readings on the day of infusion.
Other warnings/precautions: Hepatitis screening: Patients should be screened for viral hepatitis prior to use; antirheumatic therapy may cause reactivation of hepatitis B. Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently or within 3 months of discontinuation of therapy; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS
Anti-TNF Agents: May enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Avoid echinacea (has immunostimulant properties; consider therapy modifications).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Due to the potential risk for development of autoimmune disease in the fetus, use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to abatacept during pregnancy (1-877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions and possible effects on the developing immune system, breast-feeding is not recommended.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Orencia)
250 mg (1): $528.09
MONITORING PARAMETERS — Signs and symptoms of infection, signs and symptoms of infusion reaction; hepatitis and TB screening prior to therapy initiation
CANADIAN BRAND NAMES — Orencia®
INTERNATIONAL BRAND NAMES — Orencia (AR, CH, CN, CO, CZ, DE, DK, EE, FR, GB, IE, NO, PE, SE)
MECHANISM OF ACTION — Selective costimulation modulator; inhibits T-cell (T-lymphocyte) activation by binding to CD80 and CD86 on antigen presenting cells (APC), thus blocking the required CD28 interaction between APCs and T cells. Activated T lymphocytes are found in the synovium of rheumatoid arthritis patients.
PHARMACODYNAMICS / KINETICS
Distribution: Vss: 0.02-0.13 L/kg
Half-life elimination: 8-25 days
PATIENT INFORMATION — This drug can only be administered by infusion. Do not have any vaccinations while using this medication without consulting prescriber first. You will be more prone to infection. Avoid crowds and wash your hands frequently. Report infections (local or in your whole body) to prescriber immediately. You will need an overall health assessment prior to each treatment to ensure that you do not have an active infection. You may experience headache or dizziness (use caution when driving) or nausea (small frequent meals or sucking lozenges may help).
PHARMACOLOGIC CATEGORY
Antirheumatic, Disease Modifying
DOSING: ADULTS — Rheumatoid arthritis: I.V.: Dosing is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter:
<60 kg: 500 mg
60-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: PEDIATRIC — JIA: I.V.:
(For additional information see "Abatacept: Pediatric drug information")
Children ≥ 6 years and <75 kg: 10 mg/kg, repeat dose at 2 and 4 weeks after initial infusion, and every 4 weeks thereafter
Children ≥ 6 years and >75 kg: Note: Dosage is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose and every 4 weeks thereafter:
75-100 kg: 750 mg
>100 kg: 1000 mg
DOSING: ELDERLY — Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.
DOSING: ADJUSTMENT FOR TOXICITY — Withhold therapy for patients with serious infections.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg [contains maltose]
DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Infuse over 30 minutes. Administer through a 0.2-1.2 micron low protein-binding filter
COMPATIBILITY — Stable in NS.
USE
Treatment of moderately- to severely-active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs
Treatment of moderately- to severely-active juvenile idiopathic arthritis (JIA); may be used as monotherapy or in combination with methotrexate
Note: Abatacept should not be used in combination with anakinra or TNF-blocking agents
ADVERSE REACTIONS SIGNIFICANT — Note: Percentages not always reported; COPD patients experienced a higher frequency of COPD-related adverse reactions (COPD exacerbation, cough, dyspnea, pneumonia, rhonchi)
>10%:
Central nervous system: Headache (≤ 18%)
Gastrointestinal: Nausea
Respiratory: Nasopharyngitis (12%), upper respiratory tract infection
Miscellaneous: Infection (adults 54%; children 36%), antibody formation (2% to 41%)
1% to 10%:
Cardiovascular: Hypertension (7%)
Central nervous system: Dizziness (9%), fever
Dermatologic: Rash (4%)
Gastrointestinal: Dyspepsia (6%), abdominal pain, diarrhea
Genitourinary: Urinary tract infection (6%)
Neuromuscular & skeletal: Back pain (7%), limb pain (3%)
Respiratory: Cough (8%), bronchitis, pneumonia, rhinitis, sinusitis
Miscellaneous: Infusion-related reactions (2% to 9%), herpes simplex, influenza
<1% (Limited to important or life-threatening): Acute lymphocytic leukemia, anaphylaxis, anaphylactoid reactions, cellulitis, COPD exacerbation, disease flare, diverticulitis, dyspnea, flushing, hypersensitivity, hypotension, joint wear, lung cancer, lymphoma; malignancies (including bile duct, bladder, breast, cervical, melanoma, myelodysplastic syndrome, prostate, renal, skin, thyroid and uterine); ovarian cyst, pruritus, pyelonephritis, rhonchi, urticaria, varicella infection, wheezing
CONTRAINDICATIONS — There are no contraindications listed within the FDA-approved labeling.
WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Rare cases of hypersensitivity, anaphylaxis, or anaphylactoid reactions have been reported; medication for the treatment of hypersensitivity reactions should be available for immediate use. Infections: Caution should be exercised when considering the use in patients with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued. Malignancy: Use may affect defenses against malignancies (via T cell inhibition); impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma and lung cancer has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma.
Disease-related concerns: COPD: Use caution with chronic obstructive pulmonary disease (COPD), higher incidences of adverse effects (COPD exacerbation, cough, rhonchi, dyspnea) have been observed; monitor closely.
Concurrent drug therapy issues: Anakinra: The manufacturer does not recommend concurrent use with anakinra. TNF-blocking agents: Adult patients receiving therapy in combination with TNF-blocking agents had higher rates of infections (including serious infections) than patients on TNF-blocking agents alone. Concurrent use with TNF-blocking agents is not recommended. Monitor for signs and symptoms of infection when transitioning from TNF-blocking agents to abatacept.
Special populations: Elderly: Use with caution, higher incidences of infection and malignancy were observed in the elderly. Pediatrics: Not FDA approved for use in children <6 years of age. Tuberculosis-positive patients: Safety has not been established in tuberculosis-positive patients; screen patients for latent tuberculosis infection prior to initiating therapy. Treat patients testing positive according to standard therapy prior to initiating abatacept.
Dosage form specific issues: Maltose: May contain maltose, which may result in falsely-elevated serum glucose readings on the day of infusion.
Other warnings/precautions: Hepatitis screening: Patients should be screened for viral hepatitis prior to use; antirheumatic therapy may cause reactivation of hepatitis B. Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently or within 3 months of discontinuation of therapy; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
DRUG INTERACTIONS
Anti-TNF Agents: May enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
ETHANOL / NUTRITION / HERB INTERACTIONS — Herb/Nutraceutical: Avoid echinacea (has immunostimulant properties; consider therapy modifications).
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Due to the potential risk for development of autoimmune disease in the fetus, use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to abatacept during pregnancy (1-877-311-8972).
LACTATION — Excretion in breast milk unknown/not recommended
BREAST-FEEDING CONSIDERATIONS — Due to the potential for adverse reactions and possible effects on the developing immune system, breast-feeding is not recommended.
PRICING — (data from drugstore.com)
Solution (reconstituted) (Orencia)
250 mg (1): $528.09
MONITORING PARAMETERS — Signs and symptoms of infection, signs and symptoms of infusion reaction; hepatitis and TB screening prior to therapy initiation
CANADIAN BRAND NAMES — Orencia®
INTERNATIONAL BRAND NAMES — Orencia (AR, CH, CN, CO, CZ, DE, DK, EE, FR, GB, IE, NO, PE, SE)
MECHANISM OF ACTION — Selective costimulation modulator; inhibits T-cell (T-lymphocyte) activation by binding to CD80 and CD86 on antigen presenting cells (APC), thus blocking the required CD28 interaction between APCs and T cells. Activated T lymphocytes are found in the synovium of rheumatoid arthritis patients.
PHARMACODYNAMICS / KINETICS
Distribution: Vss: 0.02-0.13 L/kg
Half-life elimination: 8-25 days
PATIENT INFORMATION — This drug can only be administered by infusion. Do not have any vaccinations while using this medication without consulting prescriber first. You will be more prone to infection. Avoid crowds and wash your hands frequently. Report infections (local or in your whole body) to prescriber immediately. You will need an overall health assessment prior to each treatment to ensure that you do not have an active infection. You may experience headache or dizziness (use caution when driving) or nausea (small frequent meals or sucking lozenges may help).
Abacavir, lamivudine, and zidovudine
U.S. BRAND NAMES — Trizivir®
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.
DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).
(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
DOSING: ELDERLY — Use with caution.
DOSING: RENAL IMPAIRMENT — Clcr ≤ 50 mL/minute: Avoid use.
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
DOSAGE FORMS: CONCISE
Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to food or water.
USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®
ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.
The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.
>10%:
Central nervous system: Headache (13%), malaise (12%), fatigue (12%)
Gastrointestinal: Nausea (19%)
1% to 10%:
Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%)
Dermatologic: Rash (5%)
Endocrine & metabolic: Triglycerides increased (2% grade 3-4)
Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%)
Hematologic: Neutropenia (5%)
Hepatic: ALT increased (6%)
Neuromuscular & skeletal: CPK increased (7%)
Otic: Ear infection (5%)
Respiratory: Nose/throat infection (5%)
Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)
Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status.
WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients testing positive for the presence of the HLA-B*5701 allele are at an increased risk for hypersensitivity reactions. Screening for HLA-B*5701 allele status is recommended prior to initiating abacavir-containing therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated abacavir therapy. Trizivir® is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Trizivir® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. To report these events on Trizivir® hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. Coronary heart disease: Use may increase risk of myocardial infarction; use caution in patients with risks for coronary heart disease; modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking) should be minimized prior to use. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr ≤ 50 mL/minute.
Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
Special populations: Adolescents and Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.
DRUG INTERACTIONS
Acyclovir-Valacyclovir: May enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy
Clarithromycin: May enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification
DOXOrubicin: May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification
DOXOrubicin (Liposomal): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification
Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination
Fluconazole: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
Interferons: May enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Methadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Probenecid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Abacavir. Risk C: Monitor therapy
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Rifamycin Derivatives: May increase the metabolism of Zidovudine. Exceptions: Rifabutin. Risk D: Consider therapy modification
Stavudine: Zidovudine may diminish the therapeutic effect of Stavudine. Risk X: Avoid combination
Trimethoprim: May decrease the excretion of LamiVUDine. Risk C: Monitor therapy
Valproic Acid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Zalcitabine: LamiVUDine may diminish the therapeutic effect of Zalcitabine. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — May be taken without regard to food or water.
PRICING — (data from drugstore.com)
Tablets (Trizivir)
300-150-300 mg (60): $1431.91
MONITORING PARAMETERS — Blood glucose, CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, bilirubin, serum transaminases, triglycerides, serum amylase; HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status; signs and symptoms of hypersensitivity, particularly in patients untested for the HLA-B*5701 allele; signs and symptoms of pancreatitis; observe for appearance of opportunistic infections
CANADIAN BRAND NAMES — Trizivir®
INTERNATIONAL BRAND NAMES — Tricivir (AR, CN); Trivudin (AR); Trizivir (AT, AU, BE, BG, CH, CL, CO, CR, CZ, DE, DK, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PE, PT, RU, SE, TR, TW, UY, VE)
MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.
PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.
PHARMACOLOGIC CATEGORY
Antiretroviral Agent, Reverse Transcriptase Inhibitor (Nucleoside)
DOSING: ADULTS — HIV treatment: Oral: 1 tablet twice daily. Note: Not recommended for patients <40 kg.
DOSING: PEDIATRIC — HIV treatment: Adolescents: Refer to adult dosing (not recommended for patients <40 kg).
(For additional information see "Abacavir, lamivudine, and zidovudine: Pediatric drug information")
DOSING: ELDERLY — Use with caution.
DOSING: RENAL IMPAIRMENT — Clcr ≤ 50 mL/minute: Avoid use.
DOSING: HEPATIC IMPAIRMENT — Use contraindicated.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
DOSAGE FORMS: CONCISE
Tablet:
Trizivir®: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg
GENERIC EQUIVALENT AVAILABLE — No
ADMINISTRATION — Administer without regard to food or water.
USE — Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir®
ADVERSE REACTIONS SIGNIFICANT — Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.
The following information is based on CNA3005 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agents for additional information.
>10%:
Central nervous system: Headache (13%), malaise (12%), fatigue (12%)
Gastrointestinal: Nausea (19%)
1% to 10%:
Central nervous system: Fever/chills (6%), depression (6%), anxiety (5%)
Dermatologic: Rash (5%)
Endocrine & metabolic: Triglycerides increased (2% grade 3-4)
Gastrointestinal: Nausea and vomiting (10%), diarrhea (7%), amylase increased (2%)
Hematologic: Neutropenia (5%)
Hepatic: ALT increased (6%)
Neuromuscular & skeletal: CPK increased (7%)
Otic: Ear infection (5%)
Respiratory: Nose/throat infection (5%)
Miscellaneous: Hypersensitivity (2% to 9% based on abacavir component), viral infection (5%)
Other (frequency unknown): Pancreatitis, GGT increased, fat redistribution, immune reconstitution syndrome
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity to abacavir regardless of HLA-B*5701 status.
WARNINGS / PRECAUTIONS
Boxed warnings: Chronic hepatitis B: See "Disease-related concerns" below. Hematologic toxicity: See "Concerns related to adverse effects" below. HIV: Appropriate use: See "Disease-related concerns" below. Hypersensitivity reactions: See "Concerns related to adverse effects" below. Lactic acidosis/hepatomegaly: See "Concerns related to adverse effects" below. Myopathy: See "Concerns related to adverse effects" below.
Concerns related to adverse effects: Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance). Hematologic toxicity: [U.S. Boxed Warning]: Zidovudine has been associated with hematologic toxicities (eg, neutropenia, anemia); use with caution in patients with bone marrow compromise. Hypersensitivity reactions: [U.S. Boxed Warning]: Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir®). Patients testing positive for the presence of the HLA-B*5701 allele are at an increased risk for hypersensitivity reactions. Screening for HLA-B*5701 allele status is recommended prior to initiating abacavir-containing therapy or reinitiating therapy in patients of unknown status, including patients who previously tolerated abacavir therapy. Trizivir® is not recommended in patients testing positive for the HLA-B*5701 allele. Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir® should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status. Trizivir® SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (eg, interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (eg, acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir® is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or cannot be ruled out regardless of HLA-B*5701 status. To report these events on Trizivir® hypersensitivity, a registry has been established (1-800-270-0425). Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection; further evaluation and treatment may be required. Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy or prolonged exposure) and suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis). Myopathy: [U.S. Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy and myositis.
Disease-related concerns: Chronic hepatitis B: [U.S. Boxed Warning]: Exacerbation of hepatitis B has been reported with discontinuation of lamivudine in coinfected HIV/HBV patients; monitor hepatic function closely for several months after discontinuing Trizivir® in coinfected patients. Coronary heart disease: Use may increase risk of myocardial infarction; use caution in patients with risks for coronary heart disease; modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, and smoking) should be minimized prior to use. HIV: Appropriate use: [U.S. Boxed Warning]: This combination should only be used as part of a multidrug regimen for which the individual components are indicated. Renal impairment: Trizivir®, as a fixed-dose combination tablet, should not be used in patients with Clcr ≤ 50 mL/minute.
Concurrent drug therapy issues: Interferon alfa: Use with caution in combination with interferon alfa with or without ribavirin in HIV/HBV coinfected patients; monitor closely for hepatic decompensation, anemia, or neutropenia; dose reduction or discontinuation of interferon and/or ribavirin may be required if toxicity evident.
Special populations: Adolescents and Adults <40 kg: Trizivir®, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment. Pediatrics: Trizivir®, as a fixed-dose combination tablet, should not be used in children.
DRUG INTERACTIONS
Acyclovir-Valacyclovir: May enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy
Clarithromycin: May enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification
DOXOrubicin: May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification
DOXOrubicin (Liposomal): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine. Risk D: Consider therapy modification
Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Risk X: Avoid combination
Fluconazole: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Hematologic toxicity is of specific concern. Risk D: Consider therapy modification
Interferons: May enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Methadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Probenecid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Protease Inhibitors: May decrease the serum concentration of Abacavir. Risk C: Monitor therapy
Ribavirin: May enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Rifamycin Derivatives: May increase the metabolism of Zidovudine. Exceptions: Rifabutin. Risk D: Consider therapy modification
Stavudine: Zidovudine may diminish the therapeutic effect of Stavudine. Risk X: Avoid combination
Trimethoprim: May decrease the excretion of LamiVUDine. Risk C: Monitor therapy
Valproic Acid: May decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Zalcitabine: LamiVUDine may diminish the therapeutic effect of Zalcitabine. Risk D: Consider therapy modification
ETHANOL / NUTRITION / HERB INTERACTIONS — Ethanol: Ethanol may increase the risk of toxicity.
PREGNANCY RISK FACTOR — C
PREGNANCY IMPLICATIONS — See individual agents.
LACTATION — See individual agents.
BREAST-FEEDING CONSIDERATIONS — See individual agents.
DIETARY CONSIDERATIONS — May be taken without regard to food or water.
PRICING — (data from drugstore.com)
Tablets (Trizivir)
300-150-300 mg (60): $1431.91
MONITORING PARAMETERS — Blood glucose, CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, bilirubin, serum transaminases, triglycerides, serum amylase; HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status; signs and symptoms of hypersensitivity, particularly in patients untested for the HLA-B*5701 allele; signs and symptoms of pancreatitis; observe for appearance of opportunistic infections
CANADIAN BRAND NAMES — Trizivir®
INTERNATIONAL BRAND NAMES — Tricivir (AR, CN); Trivudin (AR); Trizivir (AT, AU, BE, BG, CH, CL, CO, CR, CZ, DE, DK, FI, FR, GB, GR, HK, HN, IE, IL, IT, MX, NL, NO, PE, PT, RU, SE, TR, TW, UY, VE)
MECHANISM OF ACTION — The combination of abacavir, lamivudine, and zidovudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance.
PHARMACODYNAMICS / KINETICS — Bioavailability studies of Trizivir® show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.
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