Fexofenadine for long COVID

Fexofenadine (Allegra): 

What is fexofenadine? 

Fexofenadine is an over-the-counter antihistamine medication used to relieve allergy symptoms such as watery eyes, an itchy nose, sneezing, and hives. It is considered to be the least sedating and preferred option for people to take during the day.

How can fexofenadine help with long COVID symptoms?  

Histamine is a chemical our immune system releases that causes our allergy symptoms. Cells in our body called mast cells release histamine, and in some patients after COVID, they may release too much, leading to some of the symptoms of long COVID. Two types of drugs can block histamine in the body, which we call our H1- and H2-antihistamines. Blocking histamine can lead to anti-inflammatory effects that relieve certain long COVID symptoms. Fexofenadine is an H1-antihistamine that, combined with an H2-antihistamine like famotidine (Zantac, Pepcid), may improve some cardiovascular symptoms of long-term COVID-19. These include a high and fast heart rate, a fast heart rate when you stand up, and palpitations. Fexofenadine may also improve post-COVID neurologic symptoms as well although the mechanism is not well understood.  

What evidence supports fexofenadine’s use for long COVID?

Several studies have supported the use of fexofenadine in combination with an H2-antihistamine for long COVID symptoms. In an observational study, the use of histamine blockers demonstrated clinical improvement in 72% of patients with long-COVID.1 In a study of 14 patients taking fexofenadine 180 mg daily with famotidine 40 mg, all patients saw significant improvement in symptoms, including fatigue, brain fog, abdominal disorders, and increased heart rate compared to the control group.2

A study of 49 long COVID patients also found that a combination of an H1- and H2-antihistamine, such as fexofenadine 180 mg twice a day and famotidine 40 mg daily taken for a minimum of 4 weeks, showed an average reduction of about half of their symptoms. Symptoms that were most improved included neurologic symptoms such as brain fog and headaches, chest pain, and fatigue.1

What to look out for with fexofenadine? 

Depending on other medications you take, fexofenadine can worsen some side effects, such as constipation, dry mouth, and dry eyes. It can also cause dizziness or headaches. You should not take it at the same time as antacids that contain aluminum or magnesium because this can make fexofenadine less effective. For those with reduced kidney function, you may need to take a lower dose, such as 60 mg every 12 to 24 hours instead of 180 mg daily.  

References:

1)        Glynne P, Tahmasebi N, Gant V, Gupta R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med. 2022 Jan;70(1):61-67. doi: 10.1136/jim-2021-002051

2)        Salvucci F, Codella R, Coppola A, et al. Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation. Front Cardiovasc Med. 2023 Jul;10. doi: 10.3389/fcvm.2023.1202696