Antiviral use linked to lip swelling in man on ACE inhibitor
Precise cause of angioedema attack unknown due to multiple possible triggers
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A 73-year-old man with influenza A, the major cause of seasonal flu, developed sudden upper-lip swelling about one hour after taking the antiviral Tamiflu (oseltamivir), raising suspicion that the medicine may have triggered angioedema, according to a case report.
After Tamiflu was stopped, the swelling gradually improved and resolved within 24 hours. However, the man had also been taking lisinopril, an angiotensin-converting enzyme (ACE) inhibitor often used for high blood pressure, for six years, and influenza itself may have contributed to inflammation. As a result, the precise cause of the angioedema could not be determined.
“The close temporal relationship between oseltamivir administration and the onset of upper-lip swelling supports oseltamivir as a possible trigger; however, this association is heavily confounded by concurrent long-term lisinopril use, and a definitive causal relationship cannot be established,” the author wrote in “Oseltamivir-Associated Angioedema in a Patient Receiving Angiotensin-Converting Enzyme Inhibitor Therapy for Influenza A: A Case Report,” published in the journal Cureus.
Several possible triggers
Angioedema is marked by sudden swelling in the deeper layers of the skin, commonly affecting the lips, tongue, face, or throat.
ACE inhibitors, a class of medications commonly used to treat high blood pressure, can cause angioedema. Importantly, ACE inhibitor-associated angioedema can occur even after years of treatment without previous problems.
Tamiflu is widely used to treat infections caused by influenza A and B viruses. Its most common side effects are gastrointestinal, such as nausea and vomiting, but rare hypersensitivity reactions, including lip and tongue swelling, have also been reported.
In this report, a clinician at the University of Maryland Global Campus described a case illustrating the challenge of identifying the cause of angioedema when several possible triggers — influenza infection, Tamiflu, and chronic ACE inhibitor therapy — are present simultaneously.
Swelling began shortly after taking Tamiflu
The man went to the ER in February 2024 with changes in mental alertness, weakness, sleepiness, cough, and chills. His medical history included a temporary disruption of blood flow to the brain, pulmonary embolism (a blood clot in the lungs), high blood pressure and cholesterol, and noncancerous prostate enlargement.
A molecular test for respiratory viruses was positive for influenza A. His regular medications were continued in the ER, including lisinopril and hydrochlorothiazide, a diuretic that helps the body excrete excess salt and water. He had taken these medications for six years.
After the positive influenza test, he received a 75 mg dose of Tamiflu. About one hour later, he developed sudden swelling of his upper lip.
He remained stable, with no tongue swelling or breathing difficulty. The lip swelling persisted for about an hour, prompting doctors to stop Tamiflu, and then gradually improved over the next two hours.
Because the timing suggested a possible reaction to Tamiflu, clinicians considered the antiviral a potential trigger, although lisinopril-associated angioedema could not be ruled out. He was given an antihistamine and fluids through the vein and monitored for 24 hours, during which the swelling resolved.
This case highlights the challenge of identifying the cause of acute lip swelling in a patient with influenza A who was receiving several medications and had clinical factors associated with angioedema.
He was discharged on his third day in the hospital. At a follow-up visit four days later, no recurrence of lip swelling was reported. Information about whether his blood pressure medication was subsequently changed was unavailable.
Overall, “this case highlights the challenge of identifying the cause of acute lip swelling in a patient with influenza A who was receiving several medications and had clinical factors associated with angioedema,” the researchers wrote.
The short interval between Tamiflu use and swelling supports the antiviral as a possible cause. However, lisinopril remains an important alternative explanation because ACE inhibitor-related angioedema can emerge after years of apparently uneventful treatment.
Influenza-associated inflammation may also have played a role, meaning more than one factor could have contributed.
“Early recognition, discontinuation of suspected offending medications, and close airway monitoring are essential to reduce the risk of life-threatening complications,” the researcher concluded.
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