Mobocertinib/Mobocertinib Instructions

1. Common name: Mobocertinib succinate capsules/Mobocertinib/Mobocertinib

Product name:Exkivity/安伟力

2. Indications

Indicated for locally advanced or metastatic non-small cell lung cancer(non-small cell lung cancer) in adults with epidermal growth factor receptor (EGFR) exon20 insertion mutations and whose disease has progressed during or after platinum-based chemotherapy.

Three. Usage and dosage

The recommended dose for adults is 160 mg once daily continued until disease progression or unacceptable toxicity occurs.

Four. Dosage adjustment

Dose reduction levels for adverse reactions:

First dose reduction: 120 mg PO once daily

Second dose reduction: 80 mg PO once daily

QTcInterval prolongation and torsade de pointes:

Level 2(QTcinterval481 to 500ms):

First occurrence: The drug should be discontinued until1grade or lower or baseline; upon recovery, this medication should be resumed at the same dose.

Relapse:This drug should be withheld until Grade 1 or lower or baseline; upon recovery, the drug should be resumed at the next lower dose or should be permanently discontinued.

Grade 3 (QTc interval is at least 501 milliseconds or QTc interval is increased by more than 60 milliseconds):

First occurrence: The drug should be discontinued until grade 1 or lower or baseline; upon recovery, the drug should be resumed at the next lower dose or should be permanently discontinued.

Relapse:This drug should be permanently discontinued.

Grade 4(Torsades de pointes; polymorphic ventricular tachycardia; signs of severe arrhythmia/Symptoms):This drug should be permanently discontinued.

Interstitial lung disease(ILD)/Pneumonia:

Any grade:If ILD/pneumonitis is suspected, the drug should be discontinued; if ILD/pneumonitis is confirmed, the drug should be permanently discontinued.

Reduced ejection fraction or heart failure:

Grade 2reduced ejection fraction:This medication should be withheld until grade 1 or lower or to baseline.

If return to baseline occurs within 2 weeks:The drug should be resumed at the same dose or the next lower dose.

If there is no return to baseline within 2 weeks:The drug should be permanently discontinued.

At least 2 grade heart failure or 3 or 4 grade reduced ejection fraction:The drug should be permanently discontinued.

Diarrhea:

Intolerable or relapsing grade 2 or grade 3:The drug should be discontinued until grade 1 or lower; the drug should be continued at the same dose or the next lower dose.

Level 4:

First occurrence:This medication should be withheld until grade 1 or lower; This medication should be resumed at the next lower dose.

Relapse:This drug should be permanently discontinued.

Five. Contraindications

No

6. adverse reactions

The most common (> 20%)adverse reactions are diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. The most common grade 3 (≥2%) or grade 4 laboratory abnormalities were lymphopenia, increased amylase, increased lipase, decreased potassium, decreased hemoglobin, increased creatinine, and decreased magnesium.

7. Drug interactions

Mainly metabolized by CYP3A4 into active metabolites AP32960 and AP32914. In vitro, mobosetiniband its active metabolitesAP32960 and AP32914 do not inhibit CYP1A2, 2B 6, 2C8, 2C9, 2C19 or 2D6. Mobosetinibis an inhibitor ofP-glycoprotein(P-gp) and breast cancer resistance protein(BCRP). Mobosetinib Does not inhibit bile salt export pump(BSEP), multidrug and toxin extrusion protein(MATE) 1 or 2K, multidrug resistance-associated protein 2 (MRP2) , organic anion transporter (OATP) 1B1 or 1B3, organic anion transporter (OAT) 1or 3, organic cation transporter (OCT) 1or 2. In vitro, mopocitinib is a substrate of P-gp, but not BCRP, OATP1B1, or OATP1B3.

8. Pharmacokinetics

Absorption

Bioavailability

After oral administration, peak plasma concentrations are reached in approximately4 hours.

The average absolute bioavailability is37%.

Systemic exposure increases in a dose-proportional manner over a dose range of 5 to 180 mg per day.

Food

There were no significant differences in systemic exposure or peak plasma concentrations after taking a high-fat meal, a low-fat meal, or an overnight fast. Do not take meals into consideration when dosing.

Plasma protein binding

99.3% (mobosetinib);99.5% (AP 32960);98.6% (AP 32914); independent of drug concentration.

The blood-to-plasma ratio of mobosetinib is 0.76, that of AP32960 is 1.2, and that of AP32914 is 0.71.

Metabolism

Mainly composed ofCYP3AMetabolism; has two active metabolites including AP32960 and AP32914.

AP32960 and AP32914 had similar potency to mobocertinib, accounting for 36% and 4% of pooled plasma drug exposure, respectively.

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