Lorlatinib

What it is and how it works

Mechanism of Action Lorlatinib is a kinase inhibitor with in vitro activity against ALK 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 mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. In mice subcutaneously implanted with tumors harboring EML4 fusions with either ALK variant 1 or ALK mutations, including the G1202R and I1171T mutations detected in tumors at the time of disease progression on ALK inhibitors, administration of lorlatinib resulted in antitumor activity.

Mechanism class: Kinase Inhibitors · Cytochrome P450 3A Inducers · P-Glycoprotein Inducers

Indications

® is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. LORBRENA is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. ( 1 , 2.1 )

Dosage and administration (summary)

Recommended dosage : 100 mg orally once daily. Severe Hepatic Impairment : 50 mg orally once daily. ( 2.5 , 8.6 , 12.3 ) Renal Impairment : 75 mg orally once daily. ( 2.6 , 8.7 , 12.3 ) Patient Selection Select patients for the treatment of metastatic NSCLC with LORBRENA based on the presence of ALK positivity in tumor specimens . Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics . Recommended Dosage The recommended dosage of LORBRENA is 100 mg orally once daily, with or without food, until disease progression or unacceptable toxicity . Swallow tablets whole. Do not chew, crush or split tablets.

Contraindications

is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity . Concomitant use with strong CYP3A inducers.

Warnings and precautions

• Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers : Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. ( 2.4 , 5.1 ) • Central Nervous System (CNS) Effects : CNS effects include seizures, psychotic effects and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume LORBRENA at same or reduced dose or permanently discontinue LORBRENA based on severity.

Pregnancy

Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action , LORBRENA can cause embryo-fetal harm when administered to a pregnant woman. There are no available data on LORBRENA use in pregnant women.

Storage and supply

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) .

Source: Lorlatinib (Lorbrena) — US FDA prescribing information, 2026-02-13, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.