​Lorlatinib (Lorbrena®) Comprehensive Product Guide​MedicineNet+1RxList+1

Active Ingredient and Brand Names

• Generic Name: Lorlatinib

• Brand Name: Lorbrena®

• Chemical Class: Tyrosine Kinase Inhibitor (TKI)​RxList+2Latest news & breaking headlines+2Pfizer Medical Information+2

Mechanism of Action

Lorlatinib is a third-generation TKI that selectively inhibits anaplastic lymphoma kinase (ALK) and ROS1 tyrosine kinases. It is designed to overcome resistance mutations and effectively penetrate the central nervous system (CNS), making it beneficial for patients with brain metastases. ​Oncology News Central+3Pfizer Medical Information+3Pfizer Medical Information+3

Indications and Uses

Lorlatinib is indicated for the treatment of adult patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on:​

• Crizotinib and at least one other ALK inhibitor for metastatic disease, or

• Alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease. ​Pfizer Medical Information+9Oncology News Central+9Pfizer Medical Information+9

Dosage and Administration

• Standard Dosage: 100 mg orally once daily, with or without food.

• Dosage Forms: Tablets available in 25 mg and 100 mg strengths.

• Special Populations:

  • Severe Renal Impairment: 75 mg orally once daily.

  • Hepatic Impairment: No dosage adjustment recommended. ​FDA Access Data+1Pfizer Medical Information+1Labeling

Safety Information and Side Effects

Common Adverse Reactions:

• Hypercholesterolemia and hypertriglyceridemia

• Edema

• Peripheral neuropathy

• Cognitive effects (e.g., mood changes, confusion)

• Weight gain

• Fatigue

• Diarrhea ​MedicineNet+1OUP Academic+1OUP Academic+1MedicineNet+1Latest news & breaking headlines

Serious Adverse Reactions:

• Interstitial lung disease/pneumonitis

• Hepatotoxicity

• Cardiac effects (e.g., atrioventricular block)

• Hyperlipidemia requiring medical management ​FDA Access Data

Warnings and Precautions

• Hepatotoxicity: Severe hepatotoxicity has occurred when lorlatinib is administered with strong CYP3A inducers (e.g., rifampin).

• Central Nervous System Effects: Monitor for cognitive, mood, or speech changes.

• Hyperlipidemia: Initiate or adjust lipid-lowering agents as needed.

• Cardiac Effects: Monitor ECG in patients with a history of cardiac arrhythmias.​Pfizer Medical Information+2Pfizer Medical Information+2Pfizer Medical Information+2

Drug Interactions

CYP3A Inducers:

• Concomitant use with strong CYP3A inducers (e.g., rifampin) is contraindicated due to the risk of severe hepatotoxicity. ​Pfizer Medical Information

CYP3A Inhibitors:

• Avoid concomitant use with strong CYP3A inhibitors (e.g., ketoconazole) as they may increase lorlatinib plasma concentrations.​

Other Considerations:

• Lorlatinib may induce CYP3A and CYP2B6, potentially reducing the effectiveness of hormonal contraceptives. ​SpringerLink

Pharmacokinetics

• Absorption: Peak plasma concentrations occur approximately 1.2 hours after oral administration.

• Distribution: Extensively distributed with a volume of distribution of 3053 L.

• Metabolism: Primarily metabolized by CYP3A4 and UGT1A4.

• Elimination: Eliminated primarily via feces (47.7%) and urine (40.9%). ​Pfizer Medical Information

Clinical Efficacy

In a phase 2 study (Study B7461001), lorlatinib demonstrated an overall response rate of 47% in patients previously treated with one or more ALK inhibitors. ​Oncology News Central+1DrugBank+1

A recent trial presented at the American Society of Clinical Oncology conference showed that 60% of patients treated with lorlatinib experienced no cancer growth for five years, compared to 8% with standard treatment. ​Latest news & breaking headlines

Frequently Asked Questions (FAQ)

Q1: How should lorlatinib be stored?

Store at room temperature between 20°C to 25°C (68°F to 77°F). ​Labeling+1Pfizer Medical Information+1

Q2: Can lorlatinib be taken with food?

Yes, lorlatinib can be taken with or without food.​Drugs.com+10Labeling+10Pfizer Medical Information+10

Q3: Is lorlatinib safe during pregnancy?

Lorlatinib can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after the final dose. ​

Q4: What monitoring is required during lorlatinib therapy?

• Lipid profile monitoring at baseline and periodically thereafter.

• Liver function tests.

• Assessment for CNS effects.

• ECG monitoring in patients with a history of cardiac arrhythmias.​DrugBank+4OUP Academic+4SpringerLink+4

Conclusion

Lorlatinib (Lorbrena®) is a potent third-generation ALK inhibitor offering significant benefits for patients with ALK-positive metastatic NSCLC,