Benazepril with Alteplase, Recombinant Interaction Details
Brand Names Associated with Benazepril
- Benazepril
- Lotensin®
- Lotrel® (as a combination product containing Benazepril, Amlodipine)
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Mar 04, 2024
Interaction Effect
An increased risk of orolingual angioedema
Interaction Summary
Use caution when administering alteplase to patients who take ACE inhibitors. An increased risk of orolingual angioedema has been observed in patients with acute ischemic stroke being treated with alteplase and receiving concomitant ACE inhibitors[1][2][3]. In case reports, angioedema occurred up to 2 hours after alteplase infusion. Patients receiving alteplase infusion should be monitored closely during and for several hours after infusion for signs of orolingual angioedema. Appropriate therapy should be initiated (ie, antihistamines, steroids or epinephrine) if orolingual angioedema occurs and discontinuation of alteplase infusion should be considered [4].
Severity
Major
Onset
Rapid
Evidence
Established
How To Manage Interaction
Use caution when administering alteplase to patients who take ACE inhibitors. An increased risk of orolingual angioedema has been observed in patients with acute ischemic stroke being treated with alteplase and receiving concomitant ACE inhibitors. In case reports, angioedema occurred up to 2 hours after alteplase infusion. Patients receiving alteplase infusion should be monitored closely during and for several hours after infusion for signs of orolingual angioedema. Appropriate therapy should be initiated (ie, antihistamines, steroids or epinephrine) if orolingual angioedema occurs and discontinuation of alteplase infusion should be considered[4].
Mechanism Of Interaction
Increase in bradykinin production by alteplase; decrease in bradykinin breakdown by ACE inhibitors
Literature Reports
A) A 58-year-old male receiving combination benazepril/amlodipine developed orolingual angioedema within 5 minutes of completing intravenous alteplase treatment for acute stroke. Head CT, erythrocyte sedimentation rate, immunoglobulin E, and CBC with differential were unremarkable. Anaphylactic reaction was not likely as the airway was not compromised and hemodynamic parameters were stable. The patient was treated with dexamethasone and a histamine antagonist and symptoms resolved completely over the next 48 hours [1].
B) In a prospective study of patients who received alteplase for stroke (n=120), the overall incidence of orolingual angioedema was 1.7% (n=2/120; 95% confidence interval (CI), 0.2% to 5.9%) with a 5% (n=1/19) incidence in patients receiving concurrent ACE inhibitors compared with a 1% (n=1/101) incidence in patients not receiving ACE inhibitors (p=0.1). In both patients who developed orolingual angioedema, it occurred bilaterally and within 30 minutes after alteplase infusion. In the patient receiving a concurrent ACE inhibitor, the orolingual angioedema was severe. CT findings excluded the possibility of lingual hematoma, and both patients had infarction involving the insular region. Both patients were treated with steroids and antihistamines and symptoms resolved gradually. Another study of stroke patients with alteplase-associated angioedema and concurrent ACE inhibitor use was evaluated. Among both studies, an increased risk was revealed for alteplase-induced angioedema in patients receiving ACE inhibitors (odds ratio, 37; 95% CI, 8 to 171; p less than 0.001) [2].
C) In a prospective study of patients who received alteplase for acute ischemic stroke (n=176), the overall incidence of orolingual angioedema was 5.1% (n=9/176; 95% confidence interval (CI), 2.3% to 9.5%). Among the patients who developed orolingual angioedema, 7 patients were receiving an ACE inhibitor (lisinopril, n=4; cilazapril, n=1; enalapril, n=1; ramipril, n=1), resulting in a relative risk (RR) of 13.6 (95% CI, 3 to 62.7) for the development of angioedema in patients receiving ACE inhibitors. In most cases, the angioedema was mild, unilateral, and developed contralaterally to the ischemic hemisphere. Patients were treated with histamine antagonists and steroids and symptoms resolved over 1 to 24 hours. Alberta Stroke Program Early CT Scale (ASPECTS) score analysis also revealed a higher risk (RR 6.4 (95% CI, 1.4 to 30) of orolingual angioedema for patients with infarction involving the insula and anterior frontal cortex regions [3].
References
1 ) Rafii MS, Koenig M, & Ziai WC: Orolingual angioedema associated with ACE inhibitor use after rtPA treatment of acute stroke. Neurology 2005; 65(12):1906-.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
2 ) Engelter ST, Fluri F, Buitrago-Tellez C, et al: Life-threatening orolingual angioedema during thrombolysis in acute ischemic stroke. J Neurol 2005; 252(10):1167-1170.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
3 ) Hill MD, Lye T, Moss H, et al: Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke. Neurology 2003; 60(9):1525-1527.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
4 ) Product Information: ACTIVASE(R) IV injection, alteplase IV injection. Genentech,Inc, South San Fransisco, CA, 2005.
Benazepril Overview
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Benazepril is used alone or in combination with other medications to treat high blood pressure. Benazepril is in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten the blood vessels, so blood flows more smoothly.
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High blood pressure is a common condition, and when not treated it can cause damage to the brain, heart, blood vessels, kidneys, and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
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The prescribing information for each drug, as published on DailyMED, is also used.
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