Lorlatinib

DAE Class; Rx

Common Brand Names; Lorbrena

• Antineoplastics, Anaplastic Lymphoma Kinase Inhibitors

Kinase inhibitor
Used for certain types of metastatic NSCLC
Risk of serious hepatotoxicity when administered with CYP3A inducers; contraindicated with strong CYP3A inducers

Indicated for metastatic non-small cell lung cancer (NSCLC) in patients whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test

Coadministration with strong CYP3A inducers due to potential for serious hepatotoxicity

7%)

Dyspnea (27%)

Fatigue (26%)

Weight gain (24%)

Increased lipase (24%)

Increased alkaline phosphatase (24%)

Thrombocytopenia (23%)

Arthralgia (23%)

Mood effects (23%)

Diarrhea (22%)

Increased amylase (22%)

Lymphopenia (22%)

Hyperkalemia (21%)

Hypomagnesemia (21%)

Headache (18%)

Cough (18%)

Nausea (18%)

Myalgia (17%)

Dizziness (16%)

Vision disorder (15%)

Constipation (15%)

Rash (14%)

Back pain (13%)

Pain in extremity (13%)

Vomiting (12%)

Speech effects (12%)

Pyrexia (12%)

Upper respiratory tract infection (12%)

Grades 3 or 4

• Hypercholesterolemia (18%)
• Hypertriglyceridemia (18%)

1-10% (All Grades)

Sleep effects (10%)

Hallucinations (7%)

Pneumonia (3.4%)

Dyspnea (2.7%)

Pyrexia (2%)

Mental status changes (1.4%)

Respiratory failure (1.4%)

1-10% (Grades 3 or 4)

Dyspnea (5.4%)

Hyperglycemia (5%)

Hypophosphatemia (4.8%)

Anemia (4.8%)

Increased amylase (3.9%)

Lymphopenia (3.4%)

Peripheral neuropathy (2.7%)

Increased AST/ALT (2.1%)

Cognitive effects (2%)

Mood effects (1.7%)

Vomiting (1%)

Increased alkaline phosphatase (1%)

Hypokalemia (1%)

Hypoalbuminemia (1%)

<1% (Grades 3 or 4)

Vision disorder

Nausea

Diarrhea

Headache

Dizziness

Speech effects

Arthralgia

Myalgia

Back pain

Pain in extremity

Fatigue

Pyrexia

Rash

Thrombocytopenia

Increased serum cholesterol and triglycerides may occur; initiate or increase dose of lipid-lowering agents in patients with hyperlipidemia; monitor serum cholesterol and triglycerides; withhold and resume at same dose for first occurrence; resume at same or a reduced dose for recurrence based on severity

PR interval prolongation and AV block reported; monitor ECG before initiating treatment and periodically thereafter; withhold and resume at reduced dose or at same dose in patients who undergo pacemaker placement; permanently discontinue for recurrence in patients without a pacemaker

Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur; promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, and fever); immediately withhold drug in patients with suspected ILD/pneumonitis; permanently discontinue therapy for treatment-related ILD/pneumonitis of any severity

Hypertension reported; median time to onset was 6.4 months (1 day to 2.8 years), and 2.3% of patients temporarily discontinued for hypertension; control blood pressure before initiating; monitor blood pressure after 2 weeks and at least monthly thereafter during treatment; withhold and resume at reduced dose or permanently discontinue drug based on severity

Hyperglycemia can occur; median time to onset of hyperglycemia was 4.8 months (1 day to 2.9 years), and 0.8% of patients temporarily discontinued for hyperglycemia; assess fasting serum glucose prior to initiating and monitor periodically thereafter; withhold and resume at reduced dose or permanently discontinue based on severity

Fetal harm may occur

Pregnancy

Based on findings from animal studies and its mechanism of action, embryo-fetal harm may occur when administered to a pregnant woman

No available data on use in pregnant women

Advise pregnant women of the potential risk to fetus

Verify pregnancy status in females of reproductive potential before initiating treatment

Lactation

No data on presence of lorlatinib or its metabolites in either human or animal milk or its effects on the breastfed infant or on milk production

Because of potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment and for 7 days after final dose

Adults

100 mg PO once daily.

Geriatric

100 mg PO once daily.

Adolescents

Safety and efficacy not established.

Children

Safety and efficacy not established.

Infants

Safety and efficacy not established.

Neonates

Safety and efficacy not established.

Lorlatinib