Remibrutinib

Remibrutinib is a selective, oral Bruton’s tyrosine kinase (BTK) inhibitor. The active ingredient binds covalently (this type of binding irreversibly inhibits the enzyme) to the active site of Bruton’s tyrosine kinase, thereby leading to sustained inactivation of the enzyme.

In chronic spontaneous urticaria, the mechanism of action of remibrutinib is based on the inhibition of IgE-mediated degranulation in mast cells and basophils. This reduces the release of histamine and other proinflammatory mediators, which is mediated, among other things, by pathogenic IgE or by IgG directed against FcεRI or IgE. The effect of remibrutinib is not related to the response to omalizumab (Gimeno R et al. 2023).

Absorption: Remibrutinib is rapidly absorbed following oral administration. Maximum plasma concentration is reached in approximately one hour across the studied dose range of 0.5 mg to 600 mg. The degree of absorption is nearly complete, at approximately 87%; however, due to presystemic metabolism, the absolute oral bioavailability is significantly lower at 34%. A high-fat meal increased the AUC (“area under the curve” = the area under the plasma concentration-time curve of a drug) by 33%, while Cmax (Cmax = the maximum plasma concentration of a drug reached in the blood plasma after administration) decreased by 5%.

Distribution: Remibrutinib distributes readily to blood cells with a blood-plasma ratio of 0.813. Plasma protein binding is 95.4% and is concentration-independent.

Metabolism: Remibrutinib is primarily metabolized via CYP3A4. This process produces 18 inactive metabolites, each of which is detectable in the blood only in small amounts. Remibrutinib itself is the most abundant substance in the blood, accounting for 16.7%.

Elimination: The mean steady-state elimination half-life is one to two hours. The mean apparent oral clearance is approximately 160 L/h.

Remibrutinib is excreted 72.9% in the feces and 27.1% in the urine. Renal excretion of unchanged remibrutinib is low and amounts to less than 1% of the dose following oral administration.

Remibrutinib is used in adults to treat chronic spontaneous urticaria when symptoms cannot be adequately controlled with H1 antihistamines (Metz M et al. 2025).

Pregnancy: To date, there is only very limited experience with the use of remibrutinib during pregnancy. Based on experimental evidence of reproductive toxicity, the use of remibrutinib during pregnancy is not recommended.

Breastfeeding: Breastfeeding should be avoided during treatment with remibrutinib and for one week after the last dose, as a risk to the infant cannot be ruled out.

The recommended dosage is 25 mg of remibrutinib twice daily. It should be taken once in the morning and once in the evening.

Remibrutinib is taken by mouth. It can be taken with or without food. The tablets should be swallowed whole with water and must not be broken, crushed, or chewed to ensure that the full dose is taken correctly.

Upper respiratory tract infections, herpesvirus infections, headache, petechial hemorrhages, hematuria, nausea, abdominal pain, back pain, pyrexia.

Risk of bleeding: Mild to moderate mucocutaneous bleeding, such as bruising, petechiae, or contusions, may occur with remibrutinib. The risk of bleeding must be weighed when remibrutinib is used concomitantly with antithrombotic agents. Treatment should be interrupted in the event of significant bleeding.

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For patients who do not respond to treatment for chronic spontaneous urticaria after 24 weeks, discontinuation of therapy should be considered.

Interruption of Therapy During Surgery: A temporary interruption may be necessary before and after surgical procedures. Depending on the type of procedure and the individual’s risk of bleeding, remibrutinib should be paused three to seven days before and three to seven days after surgery.

1. Gimeno R et al. (2023) Remibrutinib inhibits hives-inducing effector cells stimulated by serum from patients with chronic urticaria, regardless of FcεR1 expression levels and clinical response to omalizumab. Clin Transl Allergy 13:e12227.
2. Jilma B et al. (2025) Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med 392:2075–2076.
3. Metz M et al. (2025) REMIX-1 and REMIX-2 Investigators; REMIX-1 Investigators; REMIX-2 Investigators. Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med 392(10):984–994.