Vorapaxar: Difference between revisions
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|clinicalTrials=Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. | |clinicalTrials=Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. | ||
vorapaxar was evaluated for safety in 13,186 patients, including 2,187 patients treated for more than 3 years, in the Phase 3 study TRA 2°P TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events). The overall study population, patients who had evidence or a history of atherosclerosis involving the coronary (post-MI), cerebral (ischemic stroke), or peripheral vascular (documented history of PAD) systems, was treated once a day with vorapaxar (n=13,186) or placebo (n=13,166). Patients randomized to vorapaxar received treatment for a median of 2.3 years. | |||
The adverse events in the | The adverse events in the vorapaxar-treated (n=10,059) and placebo-treated (n=10,049) post-MI or PAD patients with no history of stroke or TIA are shown below. | ||
====Bleeding==== | ====Bleeding==== | ||
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GUSTO severe bleeding was defined as fatal, intracranial, or bleeding with hemodynamic compromise requiring intervention; GUSTO moderate bleeding was defined as bleeding requiring transfusion of whole blood or packed red blood cells without hemodynamic compromise. (GUSTO: Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries.) | GUSTO severe bleeding was defined as fatal, intracranial, or bleeding with hemodynamic compromise requiring intervention; GUSTO moderate bleeding was defined as bleeding requiring transfusion of whole blood or packed red blood cells without hemodynamic compromise. (GUSTO: Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries.) | ||
The results for the bleeding endpoints in the post-MI or PAD patients without a history of stroke or TIA are shown in Table 1. | The results for the bleeding endpoints in the post-MI or PAD patients without a history of stroke or TIA are shown in Table 1. vorapaxar increased GUSTO moderate or severe bleeding by 55%. | ||
[[Image:Vorapaxar Table 1.png|thumb|left|500px|*Clinically significant bleeding includes any bleeding requiring medical attention including ICH, or clinically significant overt signs of hemorrhage associated with a drop in hemoglobin (Hgb) of ≥3 g/dL (or, when Hgb is not available, an absolute drop in hematocrit (Hct) of ≥15% or a fall in Hct of 9 to <15%).<br> † Hazard ratio is | [[Image:Vorapaxar Table 1.png|thumb|left|500px|*Clinically significant bleeding includes any bleeding requiring medical attention including ICH, or clinically significant overt signs of hemorrhage associated with a drop in hemoglobin (Hgb) of ≥3 g/dL (or, when Hgb is not available, an absolute drop in hematocrit (Hct) of ≥15% or a fall in Hct of 9 to <15%).<br> † Hazard ratio is vorapaxar group vs. placebo group.<br> ‡K-M estimate at 1,080 days.]] | ||
{{clr}} | {{clr}} | ||
The effects of | The effects of vorapaxar on bleeding were examined in a number of subsets based on demographic and other baseline characteristics. Many of these are shown in Figure 1. Such analyses must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses. | ||
[[Image:Vorapaxar Figure 1.png|thumb|left|500px|Figure 1: Subgroup Analyses (GUSTO Moderate or Severe Bleeding) in Post-MI or PAD Patients without a History of Stroke or TIA in the TRA 2°P Study (First Dose to Last Dose + 30 Days)]] | [[Image:Vorapaxar Figure 1.png|thumb|left|500px|Figure 1: Subgroup Analyses (GUSTO Moderate or Severe Bleeding) in Post-MI or PAD Patients without a History of Stroke or TIA in the TRA 2°P Study (First Dose to Last Dose + 30 Days)]] | ||
{{clr}} | {{clr}} | ||
In TRA 2°P, 367 post-MI or PAD patients without a history of stroke or TIA underwent CABG surgery. Study investigators were encouraged not to discontinue treatment with study drug (i.e., | In TRA 2°P, 367 post-MI or PAD patients without a history of stroke or TIA underwent CABG surgery. Study investigators were encouraged not to discontinue treatment with study drug (i.e., vorapaxar or placebo) prior to surgery. Approximately 12.3% of patients discontinued vorapaxar more than 30 days prior to CABG. The relative risk for GUSTO moderate or severe bleeding was approximately 1.2 on vorapaxar vs. placebo. | ||
Bleeding events that occurred on | Bleeding events that occurred on vorapaxar were treated in the same manner as for other antiplatelet agents. | ||
====Use in Patients with History of Stroke, TIA, or ICH==== | ====Use in Patients with History of Stroke, TIA, or ICH==== | ||
In the TRA 2°P study, patients with a history of ischemic stroke had a higher rate for ICH on | In the TRA 2°P study, patients with a history of ischemic stroke had a higher rate for ICH on vorapaxar than on placebo. vorapaxar is contraindicated in patients with a history of stroke, TIA, or ICH. | ||
====Other Adverse Reactions==== | ====Other Adverse Reactions==== | ||
Adverse reactions other than bleeding were evaluated in 19,632 patients treated with | Adverse reactions other than bleeding were evaluated in 19,632 patients treated with vorapaxar [13,186 patients in the TRA 2°P study and 6,446 patients in the TRA•CER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study]. Adverse events other than bleeding that occurred at a rate that was at least 2% in the vorapaxar group and also 10% greater than the rate in the placebo group are shown in Table 2. | ||
[[Image:Vorapaxar Table 2.png|thumb|left|500px]] | [[Image:Vorapaxar Table 2.png|thumb|left|500px]] | ||
{{clr}} | {{clr}} | ||
The following adverse reactions occurred at a rate less than 2% in the | The following adverse reactions occurred at a rate less than 2% in the vorapaxar group but at least 40% greater than placebo. In descending order of rate in the vorapaxar group: iron deficiency, retinopathy or retinal disorder, and diplopia/oculomotor disturbances. | ||
An increased rate of diplopia and related oculomotor disturbances was observed with | An increased rate of diplopia and related oculomotor disturbances was observed with vorapaxar treatment (30 subjects, 0.2%) vs. placebo (10 subjects, 0.06%). While some cases resolved during continued treatment, information on resolution of symptoms was not available for some cases. | ||
|drugInteractions=Vorapaxar is eliminated primarily by metabolism, with contributions from CYP3A4 and CYP2J2. | |drugInteractions=Vorapaxar is eliminated primarily by metabolism, with contributions from CYP3A4 and CYP2J2. | ||
====Strong CYP3A Inhibitors==== | ====Strong CYP3A Inhibitors==== | ||
Avoid concomitant use of | Avoid concomitant use of vorapaxar with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan). | ||
====Strong CYP3A Inducers==== | ====Strong CYP3A Inducers==== | ||
Avoid concomitant use of | Avoid concomitant use of vorapaxar with strong inducers of CYP3A (e.g., rifampin, carbamazepine, St. John's Wort and phenytoin). | ||
|useInPregnancyFDA=(Description) | |useInPregnancyFDA=(Description) | ||
|useInPregnancyAUS=(Description) | |useInPregnancyAUS=(Description) | ||
Revision as of 19:32, 10 July 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]
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Black Box Warning
|
WARNING: BLEEDING RISK
See full prescribing information for complete Boxed Warning.
Bleeding: Do not use vorapaxar in patients with a history of stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH); or active pathological bleeding.
Antiplatelet agents, including vorapaxar , increase the risk of bleeding, including ICH and fatal bleeding
|
Overview
Vorapaxar is a platelet aggregation inhibitor that is FDA approved for the prophylaxis of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or with peripheral arterial disease (PAD). There is a Black Box Warning for this drug as shown here. Common adverse reactions include bleeding, anemia.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Patients with History of Myocardial Infarction (MI) or with Peripheral Arterial Disease (PAD)
- Dosing Information
- 2.08 mg orally once daily, with or without food.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Vorapaxar in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Vorapaxar in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Vorapaxar FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Vorapaxar in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Vorapaxar in pediatric patients.
Contraindications
History of Stroke, Transient Ischemic Attack (TIA), or Intracranial Hemorrhage (ICH)
- Vorapaxar is contraindicated in patients with a history of stroke, TIA, or ICH because of an increased risk of ICH in this population.
- Discontinue vorapaxar in patients who experience a stroke, TIA, or ICH.
Active Pathologic Bleeding
- Vorapaxar is contraindicated in patients with active pathological bleeding such as ICH or peptic ulcer
Warnings
|
WARNING: BLEEDING RISK
See full prescribing information for complete Boxed Warning.
Bleeding: Do not use vorapaxar in patients with a history of stroke, transient ischemic attack (TIA), or intracranial hemorrhage (ICH); or active pathological bleeding.
Antiplatelet agents, including vorapaxar , increase the risk of bleeding, including ICH and fatal bleeding
|
General Risk of Bleeding
- Antiplatelet agents, including vorapaxar, increase the risk of bleeding, including ICH and fatal bleeding.
- vorapaxar increases the risk of bleeding in proportion to the patient's underlying bleeding risk.
- Consider the underlying risk of bleeding before initiating vorapaxar. General risk factors for bleeding include older age, low body weight, reduced renal or hepatic function, history of bleeding disorders, and use of certain concomitant medications (e.g., anticoagulants, fibrinolytic therapy, chronic nonsteroidal anti-inflammatory drugs [NSAIDS], selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors) increases the risk of bleeding
- Avoid concomitant use of warfarin or other anticoagulants.
- Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), coronary artery bypass graft surgery (CABG), or other surgical procedures.
- Withholding vorapaxar for a brief period will not be useful in managing an acute bleeding event because of its long half-life.
- There is no known treatment to reverse the antiplatelet effect of vorapaxar.
- Significant inhibition of platelet aggregation remains 4 weeks after discontinuation.
Strong CYP3A Inhibitors or Inducers
- Strong CYP3A inhibitors increase and inducers decrease vorapaxar exposure.
- Avoid concomitant use of vorapaxar with strong CYP3A inhibitors or inducers
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
vorapaxar was evaluated for safety in 13,186 patients, including 2,187 patients treated for more than 3 years, in the Phase 3 study TRA 2°P TIMI 50 (Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events). The overall study population, patients who had evidence or a history of atherosclerosis involving the coronary (post-MI), cerebral (ischemic stroke), or peripheral vascular (documented history of PAD) systems, was treated once a day with vorapaxar (n=13,186) or placebo (n=13,166). Patients randomized to vorapaxar received treatment for a median of 2.3 years.
The adverse events in the vorapaxar-treated (n=10,059) and placebo-treated (n=10,049) post-MI or PAD patients with no history of stroke or TIA are shown below.
Bleeding
GUSTO severe bleeding was defined as fatal, intracranial, or bleeding with hemodynamic compromise requiring intervention; GUSTO moderate bleeding was defined as bleeding requiring transfusion of whole blood or packed red blood cells without hemodynamic compromise. (GUSTO: Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries.)
The results for the bleeding endpoints in the post-MI or PAD patients without a history of stroke or TIA are shown in Table 1. vorapaxar increased GUSTO moderate or severe bleeding by 55%.
† Hazard ratio is vorapaxar group vs. placebo group.
‡K-M estimate at 1,080 days.
The effects of vorapaxar on bleeding were examined in a number of subsets based on demographic and other baseline characteristics. Many of these are shown in Figure 1. Such analyses must be interpreted cautiously, as differences can reflect the play of chance among a large number of analyses.
In TRA 2°P, 367 post-MI or PAD patients without a history of stroke or TIA underwent CABG surgery. Study investigators were encouraged not to discontinue treatment with study drug (i.e., vorapaxar or placebo) prior to surgery. Approximately 12.3% of patients discontinued vorapaxar more than 30 days prior to CABG. The relative risk for GUSTO moderate or severe bleeding was approximately 1.2 on vorapaxar vs. placebo.
Bleeding events that occurred on vorapaxar were treated in the same manner as for other antiplatelet agents.
Use in Patients with History of Stroke, TIA, or ICH
In the TRA 2°P study, patients with a history of ischemic stroke had a higher rate for ICH on vorapaxar than on placebo. vorapaxar is contraindicated in patients with a history of stroke, TIA, or ICH.
Other Adverse Reactions
Adverse reactions other than bleeding were evaluated in 19,632 patients treated with vorapaxar [13,186 patients in the TRA 2°P study and 6,446 patients in the TRA•CER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study]. Adverse events other than bleeding that occurred at a rate that was at least 2% in the vorapaxar group and also 10% greater than the rate in the placebo group are shown in Table 2.
The following adverse reactions occurred at a rate less than 2% in the vorapaxar group but at least 40% greater than placebo. In descending order of rate in the vorapaxar group: iron deficiency, retinopathy or retinal disorder, and diplopia/oculomotor disturbances.
An increased rate of diplopia and related oculomotor disturbances was observed with vorapaxar treatment (30 subjects, 0.2%) vs. placebo (10 subjects, 0.06%). While some cases resolved during continued treatment, information on resolution of symptoms was not available for some cases.
Postmarketing Experience
There is limited information regarding Vorapaxar Postmarketing Experience in the drug label.
Drug Interactions
Vorapaxar is eliminated primarily by metabolism, with contributions from CYP3A4 and CYP2J2.
Strong CYP3A Inhibitors
Avoid concomitant use of vorapaxar with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan).
Strong CYP3A Inducers
Avoid concomitant use of vorapaxar with strong inducers of CYP3A (e.g., rifampin, carbamazepine, St. John's Wort and phenytoin).
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
(Description)
Pregnancy Category (AUS):
(Description)
Labor and Delivery
(Description)
Nursing Mothers
(Description)
Pediatric Use
(Description)
Geriatic Use
(Description)
Gender
(Description)
Race
(Description)
Renal Impairment
(Description)
Hepatic Impairment
(Description)
Females of Reproductive Potential and Males
(Description)
Immunocompromised Patients
(Description)
Others
(Description)
Administration and Monitoring
Administration
(Oral/Intravenous/etc)
Monitoring
Condition 1
(Description regarding monitoring, from Warnings section)
Condition 2
(Description regarding monitoring, from Warnings section)
Condition 3
(Description regarding monitoring, from Warnings section)
IV Compatibility
Solution
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Y-Site
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Admixture
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Syringe
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
TPN/TNA
Compatible
- Solution 1
- Solution 2
- Solution 3
Not Tested
- Solution 1
- Solution 2
- Solution 3
Variable
- Solution 1
- Solution 2
- Solution 3
Incompatible
- Solution 1
- Solution 2
- Solution 3
Overdosage
Acute Overdose
Signs and Symptoms
(Description)
Management
(Description)
Chronic Overdose
Signs and Symptoms
(Description)
Management
(Description)
Pharmacology
Vorapaxar
| |
| Systematic (IUPAC) name | |
| ? | |
| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | ? |
| Chemical data | |
| Formula | ? |
| Mol. mass | ? |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Mechanism of Action
(Description)
Structure
(Description with picture)
Pharmacodynamics
(Description)
Pharmacokinetics
(Description)
Nonclinical Toxicology
(Description)
Clinical Studies
Condition 1
(Description)
Condition 2
(Description)
Condition 3
(Description)
How Supplied
(Description)
Storage
There is limited information regarding Vorapaxar Storage in the drug label.
Images
Drug Images
{{#ask: Page Name::Vorapaxar |?Pill Name |?Drug Name |?Pill Ingred |?Pill Imprint |?Pill Dosage |?Pill Color |?Pill Shape |?Pill Size (mm) |?Pill Scoring |?NDC |?Drug Author |format=template |template=DrugPageImages |mainlabel=- |sort=Pill Name }}
Package and Label Display Panel
{{#ask: Label Page::Vorapaxar |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
(Patient Counseling Information)
Precautions with Alcohol
Alcohol-Vorapaxar interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Vorapaxar Brand Names in the drug label.
Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
Drug Shortage Status
Drug Shortage
Price
References
The contents of this FDA label are provided by the National Library of Medicine.