CIMETIDINE 

What is cimetidine?

Cimetidine is an H2-antihistamine used for heartburn, stomach ulcers, and acid reflux. It blocks histamine-2 receptors in the stomach, preventing the stomach from secreting as much acid. Famotidine (another H2-antihistamine in the same drug class) may be preferred over cimetidine due to its longer duration of action and higher potency.

How can cimetidine 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 cimetidine. Blocking histamine can lead to anti-inflammatory effects that cimetidine could theoretically be used for to relieve pulmonary and cardiovascular symptoms of long COVID.

What evidence supports cimetidine’s use for long COVID?

Cimetidine has been found to exhibit binding affinity to the SARS-CoV-2 virus that could result in some antiviral activity on a molecular level.¹ However, human studies have not shown cimetidine to have protective properties against an active COVID infection; thus, it should not be used to treat it.²

There is a lack of evidence supporting cimetidine’s use for long COVID symptoms. Several studies have instead looked at the use of famotidine for the relief of cardiovascular and neurologic symptoms of long COVID, such as a fast heart rate, brain fog, and chest pain.³ While these two drugs are very similar, it is believed that famotidine has a unique non-histamine receptor-mediated property that cimetidine does not possess that allows it to relieve certain COVID symptoms.² Therefore, it is likely more efficacious to trial famotidine instead.

What should you be aware of when taking cimetidine?

Although uncommon, cimetidine can cause headaches, dizziness, and drowsiness. It can also have some anti-androgenic effects at high doses, which, in rare cases, may cause enlarged breast tissue in men (also known as gynecomastia). Cimetidine may have more interactions with other drugs you may take compared to famotidine, so you should let your doctor or pharmacist know if you are frequently taking cimetidine. 

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)      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