Belumosudil is a kinase inhibitor that regulates immune response and fibrosis signaling pathways by inhibiting the activity of ROCK2 and ROCK1, and is used to treat chronic graft-versus-host disease (chronic graft-versus-host disease).

1、 Drug name

1. Common name: Besudil

2. Product Name: REZUROCK

3. English name: Belumosudil

2、 Indications

This product is suitable for the treatment of chronic graft-versus-host disease (chronic GVHD) in adult and pediatric patients aged 12 years and above who have previously received at least two systemic treatments but have failed.

3、 Specifications and characteristics

This product is a 200mg tablet. It is a film coated irregular piece.

4、 Main components

1. Active ingredient: Besudil Methanesulfonate (each tablet contains 200 milligrams of Besudil, equivalent to 242.5 milligrams of Besudil Methanesulfonate).

2. Accessories: The core of the tablet contains microcrystalline cellulose, hydroxypropyl methylcellulose, cross-linked sodium carboxymethyl cellulose, colloidal silica, and magnesium stearate. The film coating contains polyvinyl alcohol, polyethylene glycol, talc powder, titanium dioxide, and iron oxide yellow.

5、 Usage and dosage

1. Recommended dosage: 200mg, once daily, taken orally with meals.

2. Usage: The whole tablet should be swallowed, and should not be cut, crushed, or chewed. Take it approximately at the same time every day.

3. Duration of treatment: Medication should be continued until the progression of chronic GVHD requires new systemic treatment.

6、 Dose adjustment

1. Dose adjustment for adverse reactions: For grade 3 hepatotoxicity (AST or ALT elevation to 5-20 times the upper limit of normal) or grade 2 bilirubin elevation (1.5-3 times the upper limit of normal), administration should be suspended until it returns to grade 0-1 and the original dose restored. For grade 4 hepatotoxicity (AST or ALT exceeding 20 times the upper limit of normal) or grade 3 or above bilirubin elevation (exceeding 3 times the upper limit of normal), the medication should be permanently discontinued. For other grade 3 non hematological adverse reactions, the medication should be suspended until it returns to grade 0-1 before resuming treatment; Level 4 will result in permanent discontinuation of medication.

2. Drug interaction dose adjustment: When used in combination with potent CYP3A inducers or proton pump inhibitors, the dose of this product should be increased to 200 milligrams twice daily.

7、 Medication precautions

1. Medication time: It must be taken with meals to increase drug absorption.

2. Missed dose: If a dose is missed, it should be taken as soon as possible on the same day and taken at the normal time the next day. Extra doses should not be taken to compensate for missed doses.

3. Vomiting: The instructions do not explicitly mention the treatment after vomiting. It is recommended to consult a doctor.

8、 Medication for special populations

1. Pregnant women: Based on animal data and mechanism of action, this product may cause fetal harm and is contraindicated for pregnant women. Women of childbearing age should take effective contraceptive measures during treatment and at least one week after the last dose. Before starting treatment, the pregnancy status should be verified.

2. Breastfeeding women: It is recommended that women stop breastfeeding during the treatment period and at least one week after the last dose.

3. Male and female reproductive age: may impair male and female fertility, but the effects are considered reversible. Men and their female partners with fertility potential should take effective contraceptive measures during treatment and at least one week after the last dose.

4. Children: The safety and efficacy of pediatric patients aged 12 and above have been established. The safety and efficacy of pediatric patients under the age of 12 have not been determined.

5. Elderly patients: No clinically significant differences in safety or efficacy were observed compared to younger patients.

6. Liver/kidney dysfunction: No studies have been conducted on patients with severe liver or kidney dysfunction, and the risk and benefit should be balanced when initiating treatment for such patients.

9、 Adverse reactions

1. The most common adverse reactions (≥ 20%) include: infection, fatigue, nausea, diarrhea, difficulty breathing, cough, edema, bleeding, abdominal pain, musculoskeletal pain, headache, decreased blood phosphate, increased gamma glutamyltransferase, decreased lymphocytes, and hypertension.

2. Adverse reactions that may lead to permanent discontinuation of medication: nausea (>3% of patients).

3. Adverse reactions that may cause dose interruption: infection (11%), diarrhea (4%).

10、 Contraindications

There are currently no clear contraindications.

11、 Drug interactions

1. Strong CYP3A inducer: Combined use can reduce the exposure of besudil, which may decrease the efficacy, and the dosage of this product needs to be increased.

2. Proton pump inhibitors: Combined use can significantly reduce the exposure of besudil, which may decrease the efficacy. Therefore, the dosage of this product needs to be increased.

3. This product is an inhibitor of CYP3A, CYP2C8, CYP2D6, and UGT1A9, and may inhibit certain transporters (such as BCRP, P-gp, OATP1B1). Caution should be exercised when combined with drugs with narrow therapeutic windows metabolized by these enzymes.

12、 Storage method

Store at 20 ℃ to 25 ℃ (68 ℉ to 77 ℉); Allow short distance transportation between 15 ℃ and 30 ℃ (59 ℉ and 86 ℉). It should be stored in the original packaging bottle to prevent moisture, and the desiccant inside the bottle should be retained. The bottle cap must be tightly closed after each opening.

Belumosudilinformation