LuciRevu Revumenib tablets

I. Drug Name

Generic Name: Revumenib

Chinese Generic Name: Revumenib Tablets; Revumenib

Brand Name: Jinspiro, LuciRevu

Specification:

25 mg/tablet * 30 tablets/box

110 mg/tablet * 30 tablets/box

160 mg/tablet * 30 tablets/box

Manufacturer: Lucius Pharmaceuticals Co., Ltd. (Laos)

Approval Number (Laos National Drug Administration):

25 mg: 11 L 1400/25

110 mg: 11 L 1402/25

160 mg: 11 L 1401/25

Storage Conditions: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.

Pharmacological Classification: Menin-MLL (KMT2A) Interaction Inhibitor

II. Indications

Revumenib is indicated for the treatment of the following conditions:

For the treatment of relapsed or refractory Acute Myeloid Leukemia (AML) in adults and pediatric patients (aged 12 years and older).

Patients must be confirmed by testing to have a *KMT2A* gene rearrangement or an *NPM1* gene mutation.

The recommended dosage of Revumenib varies based on the patient's body weight and whether potent CYP3A4 inhibitors are being co-administered.

Revumenib treatment should be initiated only after the white blood cell count has decreased to below 25 Gi/L. Treatment should be continued until disease progression or unacceptable toxicity occurs. For patients who do not experience disease progression or unacceptable toxicity, treatment should be continued for at least 6 months to allow for the assessment of clinical efficacy.

III. Dosage and Administration

Route of Administration: Oral.

Dosage Form: Tablets.

For patients weighing 40 kg or more who are *not* taking potent CYP3A4 inhibitors:

270 mg orally, twice daily.

For patients weighing 40 kg or more who *are* taking potent CYP3A4 inhibitors:

160 mg orally, twice daily. For patients weighing less than 40 kg who are *not* taking strong CYP3A4 inhibitors:

Administer at a dose of 160 mg/m² per dose, twice daily.

For patients weighing less than 40 kg who *are* taking strong CYP3A4 inhibitors:

Administer at a dose of 95 mg/m² per dose, twice daily.

Examples of strong CYP3A4 inhibitors include: ketoconazole, posaconazole, voriconazole, itraconazole, clarithromycin, ritonavir, cobicistat, nefazodone, aprepitant, verapamil, and diltiazem. Please consult your physician for specific guidance.

Treatment should be continued until disease progression occurs or until unacceptable toxicity develops.

Administration Instructions:

May be taken with or without food.

Tablets should be swallowed whole; do not chew, crush, or break the tablets.

Dosage Adjustments:

In the event of certain adverse reactions (e.g., QT interval prolongation, differentiation syndrome, etc.), your physician will determine—based on the severity of the reaction—whether to temporarily interrupt treatment, reduce the dosage, or permanently discontinue the medication. Do not adjust the dosage on your own.

Missed Doses:

If you miss a dose and more than 4 hours remain before your next scheduled dose, take the missed dose as soon as possible.

If less than 4 hours remain before your next scheduled dose, skip the missed dose and take your next dose at the regularly scheduled time.

Do not take a double dose to make up for a missed dose.

IV. Pharmacology and Classification

Mechanism of Action:

1.  In certain types of leukemia (such as KMT2A-rearranged leukemia or NPM1-mutated leukemia), the menin protein binds to abnormal KMT2A proteins or mutated NPM1 proteins, forming a critical complex that drives the continuous proliferation of cancer cells and prevents their normal differentiation. 

2.  Revumenib is an oral small-molecule inhibitor that binds to the menin protein with high selectivity and potency. 

3.  By inhibiting the interaction between menin and KMT2A or mutated NPM1, Revumenib blocks this abnormal signaling pathway. 

4.  This action induces leukemia cells to undergo differentiation (transforming into normal cells) and ultimately undergo apoptosis (cell death), thereby achieving the therapeutic objective. Target: Precisely targets the key molecular mechanisms underlying the initiation and progression of leukemia; classified as "differentiation therapy."

V. Contraindications

Revumenib is contraindicated in the following patient populations:

1. Patients with a history of severe hypersensitivity to Revumenib or any of its excipients.

VI. Warnings and Precautions

1. Differentiation Syndrome:

This is a common and potentially life-threatening adverse reaction associated with Revumenib treatment. It is caused by the rapid differentiation of leukemia cells and a resultant inflammatory response.

Symptoms include: fever, dyspnea, hypotension, rapid weight gain, pleural or pericardial effusions, renal insufficiency, etc.

Management: Immediate medical attention is required upon the onset of symptoms. Treatment involves the administration of corticosteroids (e.g., dexamethasone) and hemodynamic support. Temporary interruption of Revumenib administration may be necessary.

2. QT Interval Prolongation:

Revumenib can cause prolongation of the QT interval in cardiac electrical activity, thereby increasing the risk of life-threatening ventricular arrhythmias (e.g., Torsades de Pointes).

Monitoring: Electrocardiogram (ECG) and electrolyte (potassium, calcium, magnesium) monitoring should be performed prior to treatment and periodically throughout the course of therapy.

Management: Depending on the severity of the QT interval prolongation, temporary interruption of the drug, dose adjustment, or permanent discontinuation of the drug may be required.

3. Embryo-Fetal Toxicity:

Based on its mechanism of action, Revumenib may cause fetal harm when administered to pregnant women.

Recommendations:

Women of reproductive potential should use effective contraception during treatment and for at least 1 week after the last dose.

Male patients with female partners of reproductive potential should use effective contraception during treatment and for at least 1 week after the last dose.

VII. Drug Interactions

QT-Prolonging Drugs: Concomitant use with other medications known to prolong the QT interval (e.g., certain antibiotics, antipsychotics, antiarrhythmics) may result in additive risk; such combinations should be avoided or used with extreme caution.

Strong CYP3A Inhibitors and Inducers:

Revumenib is metabolized via the hepatic CYP3A enzyme system. Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) significantly increase Revumenib plasma concentrations, thereby increasing the risk of adverse reactions. Concomitant use should be avoided; if co-administration is necessary, the Revumenib dosage must be reduced. 

Strong CYP3A inducers (e.g., rifampin, carbamazepine) significantly decrease Revumenib plasma concentrations, potentially compromising therapeutic efficacy. Concomitant use should be avoided.

VIII. Adverse Reactions

Key adverse reactions reported in clinical trials include:

Very Common (≥20%):

Differentiation syndrome

Nausea, vomiting, diarrhea, constipation

Fatigue

Decreased appetite

Peripheral edema

Pyrexia (Fever)

Rash

Common (≥10% to <20%):

QT interval prolongation

Hypotension

Dyspnea (Shortness of breath)

Headache

Laboratory Abnormalities:

Anemia, thrombocytopenia, neutropenia

Electrolyte abnormalities (hypokalemia, hypocalcemia, hypophosphatemia)

Liver function test abnormalities (elevated transaminases)

IX. Use in Specific Populations

Pregnant Women: Contraindicated. Based on its mechanism of action, the drug may cause harm to the fetus.

Lactating Women: It is recommended to discontinue breastfeeding during treatment and for at least one week following the final dose.

Pediatric Patients: The safety and efficacy of Revumenib have been established in children aged 12 years and older. Data regarding children under 12 years of age are currently insufficient.

Hepatic/Renal Impairment: Data on the use of Revumenib in patients with moderate-to-severe hepatic impairment or severe renal impairment are limited; therefore, the drug should be used with caution and under close medical supervision.

X. Storage

Store at room temperature between 20°C and 25°C.

Keep in the original packaging to protect from moisture.

Keep out of the sight and reach of children.

Summary and Patient Information:

Revumenib represents a significant breakthrough in the field of precision therapy for leukemia. Patients must:

1.  Undergo genetic testing (specifically for *KMT2A* rearrangements or *NPM1* mutations) prior to initiating treatment to confirm eligibility.

2.  Strictly adhere to their physician's instructions regarding the timing and dosage of the medication. 3. Thoroughly understand and remain vigilant for symptoms of differentiation syndrome and QT interval prolongation; contact your doctor immediately if any related signs appear.

4. Inform your doctor of all other medications you are currently taking (including prescription drugs, over-the-counter medications, and herbal remedies).

5. Strictly adhere to your doctor's follow-up schedule, and undergo regular monitoring such as blood tests and electrocardiograms (ECGs).