Adagrasib is an oral small molecule drug that covalently binds to the cysteine residue of the mutated protein to inhibit the activity of KRAS protein, immobilizing it in an inactive state, blocking downstream signaling pathways, inhibiting tumor cell proliferation, and promoting apoptosis.

1、 Drug name and main ingredients

1. Common name: Adagrasib

2. Product Name: KRAZATI ™

3. Dosage form: Oral film coated tablets

4. Main ingredients: Each tablet contains 200mg of adagracilib (hydrochloride form)

2、 Indications

KRASG12C mutant non-small cell lung cancer (NSCLC): Used to treat adult patients with locally advanced or metastatic NSCLC confirmed by FDA approved testing, and patients must have received at least one previous systemic treatment. This indication is based on accelerated approval of objective response rate (ORR) and duration of response (DOR), and subsequent confirmatory trials may be required to confirm clinical benefits.

3、 Specifications and characteristics

1. Specification: 200mg/tablet, oval white to off white film coated tablet, with "200" engraved on one side and stylized "M" logo on the other side.

2. Packaging: 120 or 180 tablets per bottle, equipped with a child safety bottle cap and desiccant.

4、 Usage and dosage

1. Recommended dosage: 600mg (3 tablets) orally, twice a day, with an interval of about 12 hours. The whole tablet should be swallowed and can be taken with food or on an empty stomach.

2. Omission treatment: If the missed dose exceeds 4 hours, skip the dose and take it according to the original plan for the next time; No need to take additional medication after vomiting.

3. Dose adjustment:

First dose reduction: 400mg (2 tablets) twice a day;

Secondary reduction: 600mg once daily;

Liver injury: Moderate (Child Pugh B) reduced to 400mg twice daily, severe (Child Pugh C) contraindicated.

5、 Medication precautions

1. Gastrointestinal reactions: 89% of patients experience nausea, diarrhea, or vomiting, with 9% being grade 3-4 and requiring antiemetic and antidiarrheal medication.

2. QT interval prolongation: Avoid using other QT prolonging drugs in combination, monitor electrocardiogram and electrolytes before and during treatment.

3. Hepatotoxicity: 32% of patients showed elevated ALT/AST levels, and liver function was monitored monthly before treatment and for the first 3 months.

4. Interstitial lung disease (ILD): 4.1% of patients develop ILD/pneumonia, and new respiratory symptoms require immediate discontinuation of medication.

6、 Medication for special populations

1. Pregnant women: prohibited, animal experiments show potential embryotoxicity.

2. Breastfeeding period: Breastfeeding is prohibited during the treatment period and within one week of discontinuation of medication.

3. Children: Safety has not been established.

4. Elderly: No need to adjust dosage, but close monitoring is required.

7、 Adverse reactions

1. Common (≥ 25%): Nausea (70%), Diarrhea (69%), Vomiting (57%), Fatigue (55%), Musculoskeletal Pain (38%), Hepatotoxicity (37%), Renal Impairment (33%).

2. Serious reactions: ILD/pneumonia (4.1%, including fatal cases), QT prolongation (6%), liver injury (0.3% drug-induced hepatitis).

8、 Contraindications

There are no absolute contraindications, but it is contraindicated for severe liver injury (Child Pugh C) and the combination of strong CYP3A inducers or sensitive CYP3A substrates.

9、 Drug interactions

1. Strong CYP3A inducers (such as rifampicin): Avoid combination therapy and can reduce exposure to adagrenib by 95%.

2. Sensitive CYP3A substrates (such as midazolam): Combination use leads to a 31 fold increase in substrate AUC, which should be avoided.

3. QT prolongation medication: Combination use is prohibited as it may exacerbate the risk of arrhythmia.

10、 Storage method

Store at room temperature (20-25 ° C), keep the original bottle away from light and moisture, and do not remove or swallow the desiccant.

Adagrasibinformation