Lorlatinib/Lorlatinib Instructions

1. Generic name: Lorlatinib,Lorlatinib

Product name:LORBRENA, Borena

Other names: Lorlatinib, Tuolike, Lorviqua, Decoder

2. Indications:

Lorlatinib/lorlatinib (Lorlatinib) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive on an FDA-approved test.

3. Usage and dosage:

1. Before treatment: Based on the presence of ALK positivity in tumor specimens, doctors will choose to use lorlatinib to treat patients with metastatic non-small cell lung cancer.

2. Recommended dose: The recommended dose of lorlatinib is 100 mg orally once daily, which can be taken with or without food until disease progression or unacceptable toxicity occurs. Lorlatinib comes as a tablet that patients should swallow whole and take at the same time every day. Do not chew, crush, or split tablets. Do not ingest if tablets are broken, cracked, or incomplete. If a dose is missed, take the missed dose unless the next dose is due within 4 hours. Do not take 2 doses at the same time to make up for a missed dose. If vomiting occurs after taking this medicine, do not take additional doses but continue with the next scheduled dose.

3. Dose adjustment: If a patient experiences adverse reactions during treatment with lorlatinib, the doctor will adjust the drug dose according to the severity of the condition. The first dose can be adjusted to 75 mg orally once a day; the second dose can be adjusted to 50 mg orally once a day; patients who cannot tolerate 50 mg orally once a day should permanently discontinue use.

(1) If coadministration with a moderate CYP3A inducer is unavoidable, thelorlatinibdose may be increased to 125 mg orally once daily; if this is not possible To avoid concomitant use with strong CYP3A inhibitors, reduce the starting dose to 75 mg orally once daily; for patients who have adverse reactions that require a dose reduction to 75 mg/day and for patients starting strong CYP3A inhibitors, reduce the dose to 50 mg/day. Lorlatinib is contraindicated in patients taking strong CYP3A inducers.

(2) Avoid coadministration of lorlatinib with fluconazole. If unavoidable, reduce starting dose of lorlatinib to 75 mg PO once daily;

(3) Severe Renal Impairment: Reduce the oral dose of lorlatinib to 75 mg once daily in patients with severe renal impairment (creatinine clearance [CLcr] 15-<30 mL/min).

4. Adverse reactions:

In clinical studies of lorlatinib, the most common adverse reactions were edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, joint pain, diarrhea, and mood effects; the most common grade 3-4 laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia.

5. Supply and storage:

Lorlatinib is available as tablets containing25 mg or 100 mg lorlatinib and can be stored at 20°C to 25°C (68°F to 77°F); tolerances are between 15°C and 30°C (59°F to 86°F).

6. Taboo:

Due to the potential for severe hepatotoxicity, lorlatinib is contraindicated in patients taking strong CYP3A inducers.

7. Mechanism of action:

Lorlatinib is a kinase inhibitor with in vitro activity againstALK and ROS1, as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2 and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some detected in tumors during disease progression against crizotinib and other ALK inhibitors.

In mice implanted subcutaneously with tumors containing EML4 fusions harboring ALK variant 1 or ALK mutations, including the G1202R and I1171T mutations detected in tumors upon disease progression on ALK inhibitor treatment, administration of lorlatinib resulted in antitumor activity. Lorlatinib also showed antitumor activity and prolonged survival in mice intracranially implanted with an EML4-ALK driven tumor cell line. The overall antitumor activity of lorlatinib in in vivo models was dose-dependent and associated with inhibition of ALK phosphorylation.

8. Special groups:

1. Women: According to the results of animal studies and its mechanism of action, lorlatinib taken by pregnant women may cause embryo-fetal damage. Advise female patients of childbearing potential to use an effective non-hormonal method of contraception during treatment and for at least 6 months after the last dose as hormonal contraceptives may be ineffective. Do not breastfeed during treatment and for 7 days after the last dose.

2. According to animal studies, lorlatinib may temporarily damage male fertility. Based on the results of the genotoxicity studies, it is recommended that men with female partners use effective contraception during treatment and for at least 3 months after the final dose.