FAMOTIDINE

What is famotidine?

Famotidine is an H2-antihistamine commonly used for heartburn, indigestion, stomach ulcers, and acid reflux. Blocking histamine-2 receptors in the stomach prevents the stomach from secreting as much acid.

How can famotidine help alleviate certain long COVID symptoms?

Histamine is a chemical our immune system releases that causes 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: H1- and H2-antihistamines, like famotidine. Blocking histamine can lead to anti-inflammatory effects that may make famotidine helpful in relieving certain long COVID symptoms mentioned below.

What evidence supports famotidine’s use for long COVID?

Famotidine has been found to exhibit binding affinity to the SARS-CoV-2 virus that could result in some antiviral activity.¹  It is also believed to have a non-histamine receptor-mediated property that uniquely allows famotidine to relieve certain COVID symptoms that other closely related products in the same drug class do not, such as cimetidine (Tagamet).² A study looking at the combination of cetirizine 10 mg twice a day and famotidine 20 mg twice a day with standard-of-care COVID management found improvement in pulmonary symptoms and reduced intubation rates and duration of hospital stay.³

Several studies have demonstrated a reduction in cardiovascular and neurologic symptoms of long COVID, such as a fast heart rate, brain fog, and chest pain, when a combination of an H1- and H2-antihistamine are used together. These combinations include H1-antihistamines such as fexofenadine, loratadine, and cetirizine with famotidine.^{3, 4, 5}

Another study of 50 patients looked at famotidine alone compared to a placebo and found that patients in the group assigned to famotidine 40 mg twice daily showed improvement in cognitive impairment, depression, and anxiety symptoms from long COVID.⁶

What should you be aware of when using famotidine?

Although uncommon, famotidine can cause headaches, dizziness, constipation, and diarrhea. If taken for long periods, famotidine can also cause some vitamin B12 deficiency. 

References:

1)      Ishola AA, Joshi T, Abdulai SI, Tijjani H, Pundir H, Chandra S. Molecular basis for the repurposing of histamine H2-receptor antagonist to treat COVID-19. J Biomol Struct Dyn. 2022 Aug;40(13):5785-5802. doi: 10.1080/07391102.2021.1873191

2)      Malone RW, Tisdall P, Fremont-Smith P, Liu Y, Huang XP, White KM, Miorin L, Del Olmo EM, Alon A, Delaforge E, Hennecker CD, Wang G, Pottel J, Smith N, Hall JM, Shapiro G, Mittermaier A, Kruse AC, García-Sastre A, Roth BL, Glasspool-Malone J, Ricke DO. COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms. Res Sq [Preprint]. 2020 Aug 31:rs.3.rs-30934. doi: 10.21203/rs.3.rs-30934/v2

3)      Hogan II RB, Hogan III RB, Cannon T, Rappai M, Studdard J, Paul D, Dooley TP. Dual-histamine receptor blockade with cetirizine-famotidine reduces pulmonary symptoms in COVID-19 patients. Pulm Pharmacol Ther. 2020 Aug;63:101942. doi: 10.1016/j.pupt.2020.101942

4)      Salvucci F, Codella R, Coppola A, Zacchei I, Grassi G, Anti ML, Nitisoara N, Luzi L, Gazzaruso C. Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation. Front Cardiovasc Med. 2023 Jul 17;10:1202696. doi: 10.3389/fcvm.2023.1202696

5)      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

6)      Momtazmanesh S, Ansari S, Izadi Z, Shobeiri P, Vatankhah V, Seifi A, Ghiasvand F, Bahrami M, Salehi M, Noorbala AA, Akhondzadeh S. Effect of famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection: A randomized, double-blind, and placebo-controlled study. J Psychosom Res. 2023 Sep;172:111389. doi: 10.1016/j.jpsychores.2023.111389