Generic
Lorlatinib
1 brands available in the market
At a glance
Lorlatinib is a kinase inhibitor used for ALK-positive non-small cell lung cancer (NSCLC) that has progressed on crizotinib and at least one other ALK inhibitor, or alectinib or ceritinib.
Description
Lorlatinib is an ALK/ROS1 tyrosine kinase inhibitor that binds to and inhibits both ALK and ROS1 kinases, disrupting ALK- and ROS1-mediated signaling and inhibiting tumor cell growth in ALK- and ROS1-overexpressing tumor cells.
Indications
- ALK-positive metastatic non-small cell lung cancer (NSCLC) - progressed on crizotinib and at least one other ALK inhibitor, or alectinib or ceritinib
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
ALK/ROS1 Tyrosine Kinase Inhibitor
Pharmacology
Lorlatinib inhibits ALK and ROS1 kinases, disrupting ALK- and ROS1-mediated signaling and inhibiting tumor cell growth in ALK- and ROS1-overexpressing tumor cells.
Mechanism of action
Inhibits ALK and ROS1 signaling to block tumor cell growth.
Dosage
Adult Dose (Oral):
- 100 mg once daily
- With or without food
- Continue until disease progression or unacceptable toxicity
- First dose reduction: 75 mg/day; Second dose reduction: 50 mg/day
Hepatic Impairment: Mild: no dose adjustment; Moderate-severe: recommended dose not established
Administration
- Swallow tablet whole
- Take at the same time each day
- Missed dose: take if remembered, unless less than 4 hours before next dose
Missed dose
Missed dose: take if remembered, unless less than 4 hours before next dose; do not take 2 doses at the same time.
Side effects
Common Side Effects (>10%):
- Hypercholesterolemia (96%)
- Hypertriglyceridemia (90%)
- Edema (57%)
- Hyperglycemia (52%)
- Anemia (52%)
- Peripheral neuropathy (47%)
- Increased AST (37%), ALT (28%)
- Cognitive effects (27%)
- Dyspnea (27%)
- Fatigue (26%)
- Weight gain (24%)
- Mood effects (23%)
Precautions & warnings
- Severe hepatotoxicity occurred with strong CYP3A inducers
- CNS effects (seizures, hallucinations, cognitive changes, mood) may occur
- Increased serum cholesterol and triglycerides; initiate or increase lipid-lowering agents
- PR interval prolongation and AV block reported; monitor ECG
- ILD/pneumonitis may occur
Contraindications
- Coadministration with strong CYP3A inducers
Drug interactions
- Strong CYP3A inducers: decrease lorlatinib plasma concentrations; coadministration contraindicated
- Strong CYP3A inhibitors: increase lorlatinib plasma concentrations
- CYP3A substrates: decrease concentrations of CYP3A substrates; avoid substrates with narrow therapeutic index
Food interactions
Coadministration with strong CYP3A inducers is contraindicated.
Use in pregnancy
Use in Pregnancy: Embryo-fetal harm may occur when administered to a pregnant woman. Females of reproductive potential should use effective non-hormonal contraception during treatment and for 6 months after the final dose.
Use in lactation
Use in Lactation: No data on presence of lorlatinib in human or animal milk. Due to potential for serious adverse reactions, do not breastfeed during treatment and for 7 days after final dose.
Pediatric use
Safety and efficacy not established in pediatric patients below 18 years.
Geriatric use
Limited data in patients 65 years and older; no dose recommendation can be made.
Renal / hepatic impairment
Renal Impairment: Mild-moderate (CrCl 30-89 mL/min): no dose adjustment; Severe (CrCl <30): recommended dose not established.
Hepatic Impairment: Mild: no dose adjustment; Moderate-severe: not recommended.
Overdose effects
Overdose treatment: general supportive measures; ECG monitoring recommended due to dose-dependent PR interval effects; no antidote.
Storage conditions
Store below 30°C, protected from moisture and light; keep out of reach of children.
Chemical structure
Lorlatinib