Rhapsido

• Rhapsido (remibrutinib) is a prescription medicine used to treat 2 types of chronic hives, chronic spontaneous urticaria (CSU) and symptomatic dermographism (SD), in adults who still have symptoms while taking H1 antihistamine treatment.
• Rhapsido tablets are taken twice daily.
• Rhapsido's drug class is Bruton's tyrosine kinase inhibitor (BTKi). Rhapsido works by targeting and blocking the activity of BTK, inhibiting the release of histamine and other proinflammatory mediators.

Rhapsido works by targeting and blocking the activity of a signaling protein called Bruton's tyrosine kinase (BTK). BTK is involved in signaling immune cells (mast cells and basophils) to release histamine and other inflammatory substances that cause hives and itching.

By blocking BTK, Rhapsido reduces the release of histamine and other inflammatory substances from these cells. This helps lessen how often hives occur, how severe they are, and how itchy they are.

Rhapsido is a Bruton's tyrosine kinase inhibitor (BTKi).

Chronic spontaneous urticaria

In the clinical trials REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157), people taking Rhapsido had significantly greater improvement in itching and hives than people taking a placebo. Improvements began as early as week 2. By week 12, 31.1% (REMIX-1) and 27.9% (REMIX-2) of people taking Rhapsido had no itch and no hives, compared with 10.5% and 6.5% of people taking a placebo.

Symptomatic dermographism

Rhapsido was studied in the RemIND trial (NCT05976243). The trial included 115 adults with symptomatic dermographism who still had symptoms despite taking H1 antihistamines. People took Rhapsido 25 mg or a placebo twice daily for 24 weeks.

To measure response, a doctor used a device called a FricTest to lightly rub the skin, then checked for welts. A complete response meant no welts appeared at any of the test sites (a Total Fric Score of 0).

Results came from the 24-week, placebo-controlled part of the trial. After week 24, all patients could take Rhapsido for another 28 weeks.

The usual Rhapsido dose is 1 tablet (25 mg) twice a day with or without food.

Rhapsido tablets should be swallowed whole with water. Do not split, crush, or chew the tablets.

Do not change your dose or stop taking this medicine unless your healthcare provider tells you to. Take this medicine exactly as your healthcare provider tells you to take it.

Risk of bleeding: Rhapsido may increase your risk of bleeding. Your healthcare provider will watch for signs and symptoms of bleeding and may pause your treatment if bleeding happens. Your treatment will also be paused for 3 to 7 days before and after surgery or other invasive procedures. Taking medicines that prevent blood clots (antithrombotic agents) with Rhapsido may further increase your risk of bleeding.

Live attenuated vaccines: You should not receive live or live-attenuated vaccines while taking Rhapsido.

Liver problems: Rhapsido is not recommended if you have mild, moderate, or severe liver problems (hepatic impairment).

Before taking this medicine, tell your healthcare provider about all of your medical conditions, including if you:

• have had a recent surgery or plan to have surgery. Your healthcare provider may tell you to stop taking Rhapsido for at least 3 to 7 days before and after any planned medical or surgical procedures.
• have bleeding problems or are taking a blood thinner medicine.
• have liver problems.
• have recently received or are scheduled to receive an immunization (vaccine). Talk to your healthcare provider about receiving any immunizations before taking this medicine. You should not receive live or live-attenuated vaccines during treatment with Rhapsido.

Pregnancy

Tell your healthcare provider if you are pregnant or plan to become pregnant, as it is not known if this medicine will harm your unborn baby.

Pregnancy exposure registry: If you become pregnant during treatment with this medicine, talk to your healthcare provider about registering in the pregnancy exposure registry for Rhapsido. You or your healthcare provider can enroll in this registry by calling 1-888-669-6682. The purpose of this registry is to collect information about the safety of this medicine during pregnancy.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed, as it is not known if this medicine passes into your breast milk. You and your healthcare provider should decide the best way to feed your baby while taking Rhapsido.

The most common Rhapsido side effects were nasal congestion, sore throat, and runny nose (nasopharyngitis), bleeding, headache, nausea, and abdominal pain. In the symptomatic dermographism trial, Rhapsido side effects over 24 weeks were similar to those seen in people with chronic spontaneous urticaria.

Serious side effects

Rhapsido may cause serious side effects, including an increased risk of bleeding. You will be monitored for signs and symptoms of bleeding and may need to stop your treatment if bleeding happens. Your risk of bleeding may increase if you are also taking a blood-thinning medicine. Tell your healthcare provider right away if you get any signs or symptoms of bleeding, such as:

• bruising, or red or purple skin marks
• pink or brown urine
• headache, dizziness, confusion, or feeling weak
• red or black stools that look like tar.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

You should not receive live or live-attenuated vaccines during treatment with Rhapsido.

If you miss taking your tablet, skip the missed dose, and take the next dose at your regular time. Do not take an extra tablet to make up for a missed dose.

In case of overdose, call the poison control helpline at 1-800-222-1222. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking Rhapsido with certain other medicines may affect how it works, or it may affect how other medicines work and can cause side effects.

• Strong or moderate CYP3A4 inhibitors or inducers: avoid using these with Rhapsido. They can raise or lower the amount of Rhapsido in your blood.
• Medicines that are P-gp substrates, such as digoxin: Rhapsido can increase the levels of these medicines. Your healthcare provider may check you more often for side effects.
• Medicines that prevent blood clots (antithrombotic agents): using these with Rhapsido may increase your risk of bleeding. Your healthcare provider will weigh the risks and benefits of using them together.

Other drugs may interact with this medicine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Chronic spontaneous urticaria (CSU) is a skin disorder characterized by hives (wheals) and angioedema (swelling) that occur without an obvious external trigger and last for 6 weeks or more. Wheals (hives) are itchy, raised, red or skin-colored lesions that can last minutes to hours, and angioedema is deeper swelling, often around the eyes, lips, tongue, or extremities.

In CSU, the immune system mistakenly activates mast cells and basophils, which are immune cells in the skin and blood. This can happen through IgE antibodies (an allergic-type pathway) or IgG antibodies (an autoimmune pathway). When these cells are activated, a signaling protein called BTK helps trigger the release of histamine and other inflammatory substances. This causes itchy hives and swelling.

Symptomatic dermographism, also called dermatographism or "skin writing", is a type of chronic hives, where itchy, raised welts (wheals) appear where the skin has been rubbed, scratched or pressed. Hives can appear due to:

• scratching an itch
• tight clothing, waistbands or bra straps
• towel drying
• carrying a bag on your shoulder

The welts usually follow the line of the rubbing or scratching. They often appear within minutes and then fade, but they can be very itchy and keep coming back.

Store at room temperature between 68°F and 77°F (20°C and 25°C). Brief periods between 59°F and 86°F (15°C and 30°C) are permitted.

Store Rhapsido in the original container to protect from moisture.

Keep out of reach of children.

Active ingredient: remibrutinib

Inactive ingredients: copovidone, croscarmellose sodium, mannitol, microcrystalline cellulose, sodium lauryl sulfate, and sodium stearyl fumarate. The tablet coating is composed of polyethylene glycol 4000, polyvinyl alcohol, red iron oxide (E172), talc, titanium dioxide (E171), and yellow iron oxide (E172).

Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936.