Lorbrena Lorlatinib Tablets

1. Indications and Usage
ALK-Positive Non-Small Cell Lung Cancer (NSCLC):
Indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.
Approval Context:
Treatment-naive patients (first-line therapy).
Patients previously treated with one or more ALK tyrosine kinase inhibitors (TKIs).
2. Dosage and Administration
Recommended Dosage:
100 mg orally once daily.
Administration Instructions:
Administer orally with or without food.
Swallow tablets whole; do not crush, chew, or break.
Dose Modifications:
Dose reductions (to 75 mg or 50 mg once daily) are recommended based on individual safety and tolerability (e.g., for CNS effects, hyperlipidemia, or other severe adverse reactions).
If the 50 mg dose is not tolerated, discontinue LORBRENA.
3. Mechanism of Action
ALK and ROS1 Tyrosine Kinase Inhibitor:
Lorlatinib is a macrocyclic, third-generation TKI that targets ALK and ROS1.
Physiological Effect:
It is designed to inhibit the proliferation of ALK- or ROS1 fusion-positive tumor cells.
It is highly potent against various ALK resistance mutations (e.g., G1202R) and is engineered to effectively cross the blood-brain barrier to target central nervous system (CNS) metastases.
4. Safety and Warnings
CNS Effects:
Lorlatinib can cause CNS effects, including cognitive, psychiatric, and speech disorders. Monitor for symptoms such as memory impairment, mood changes, or difficulty speaking.
Hyperlipidemia:
Elevations in cholesterol and triglycerides occur in the majority of patients. Monitor fasting lipid profile prior to initiation and periodically during treatment.
Pulmonary Toxicity:
Severe and fatal cases of ILD/non-infectious pneumonitis have been reported. Monitor for pulmonary symptoms (cough, dyspnea, hypoxia).
Cardiac Toxicity:
Bradycardia and atrioventricular (AV) block may occur. Monitor heart rate and blood pressure.
Embryo-Fetal Toxicity:
Can cause fetal harm. Advise females of reproductive potential to use effective contraception.
5. Adverse Reactions
Most Common:
Hyperlipidemia, CNS effects (peripheral neuropathy, cognitive effects, mood effects), weight gain, edema, diarrhea, nausea, fatigue, rash, and cough.
6. Drug Interactions
CYP3A Inducers:
Concomitant use with strong CYP3A inducers (e.g., rifampin) is contraindicated as it significantly decreases lorlatinib exposure.
CYP3A Inhibitors:
Concomitant use with strong CYP3A inhibitors increases lorlatinib exposure. Dose reduction should be considered.
CYP3A Substrates:
Lorlatinib is a CYP3A inducer. Caution is advised when co-administering with CYP3A substrates.
7. Pharmaceutical Information
Chemical Name:
N-(4-(2-amino-3,5-dimethylpyridin-4-yl)-2-fluorophenyl)-N-(prop-2-ynyl)cyclopropanecarboxamide.
Storage:
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).