Lorlatinib / Lorbrena (Everest)

Product Overview

Lorlatinib (also known as Lorlatinib; Brand name: Lorbrena) manufactured by Everest Pharma is a third-generation ALK and ROS1 tyrosine kinase inhibitor (TKI) originally developed by Pfizer.

Lorlatinib was designed with broad coverage against ALK resistance mutations and strong central nervous system (CNS) penetration. It demonstrates potent activity against multiple ALK kinase domain resistance mutations identified during treatment with crizotinib and second-generation ALK inhibitors.

📌 Indications

Lorlatinib is indicated for the treatment of patients with ALK-positive non-small cell lung cancer (NSCLC).

💊 Dosage and Administration

• Recommended dosage: 100 mg orally once daily
• May be taken with or without food
• Continue treatment until disease progression or unacceptable toxicity occurs

Administration Instructions

• Swallow tablets whole
• Do not chew, crush, split, or break tablets
• Do not use damaged or cracked tablets
• Take the medication at approximately the same time each day

Missed Dose Guidance

• If a dose is missed, it may be taken unless the next scheduled dose is within 4 hours
• Do not take two doses at the same time to make up for a missed dose
• If vomiting occurs after administration, do not take an extra dose; continue with the next scheduled dose

📉 Dose Reduction Recommendations

Patients unable to tolerate 50 mg once daily should permanently discontinue treatment.

⚠️ Warnings and Precautions

1. Severe Hepatotoxicity with Strong CYP3A Inducers

Strong CYP3A inducers should be discontinued for at least 3 plasma half-lives before starting Lorlatinib treatment.

2. Central Nervous System (CNS) Effects

Potential CNS effects may include:

• Seizures
• Hallucinations
• Cognitive impairment
• Mood changes, including suicidal thoughts
• Speech disturbances
• Mental status changes
• Sleep disorders

Dose interruption, reduction, or permanent discontinuation may be required depending on severity.

3. Hyperlipidemia

Lipid-lowering therapy may need to be initiated or adjusted during treatment. Dose modification may be necessary depending on severity.

4. Atrioventricular (AV) Block

Treatment interruption or dose reduction may be required if cardiac conduction abnormalities occur.

5. Interstitial Lung Disease (ILD) / Pneumonitis

Lorlatinib should be immediately withheld if ILD or pneumonitis is suspected. Permanent discontinuation may be necessary.

6. Embryo-Fetal Toxicity

Lorlatinib may cause fetal harm. Patients with reproductive potential should use effective non-hormonal contraception during treatment.

⚠️ Common Side Effects

Common adverse reactions may include:

• Swelling of arms, legs, hands, or feet (edema)
• Numbness or tingling sensations in extremities (peripheral neuropathy)
• Difficulty thinking or confusion
• Shortness of breath
• Fatigue
• Weight gain
• Joint pain
• Mood changes
• Depression or anxiety
• Diarrhea