Lorlatinib Dosage Guide: Recommended Administration for ALK-Positive Lung Cancer

In September 2018, Lorlatinib was first approved for marketing in Japan, followed by approval from the U.S. Food and Drug Administration (FDA) in November of the same year, and then in Europe in March 2019.

Indications for Lorlatinib

Lorlatinib is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are confirmed to be anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

Recommended Dosage for Lorlatinib

The recommended dosage is 100 mg taken orally once daily. Patient selection for the treatment of metastatic NSCLC is based on the presence of ALK positivity in tumor specimens. Treatment should continue until disease progression or unacceptable toxicity occurs.

Administration Recommendations for Lorlatinib

Lorlatinib can be taken with or without food.

Lorlatinib tablets should be swallowed whole and must not be chewed, crushed, or split.

Do not take Lucius Pharmaceuticals Lorlatinib tablets if they are broken, cracked, or not intact.

If a dose is missed, take it as soon as possible unless the next dose is due within 4 hours. Do not take two doses at the same time to make up for a missed dose.

If vomiting occurs, do not take an additional dose; continue with the next scheduled dose as planned.

Monitoring Recommendations for Lorlatinib

Monitor blood pressure two weeks after starting treatment and then at least monthly during treatment.

Monitor serum cholesterol and triglycerides before starting treatment, during the first and second months of treatment, and periodically thereafter.

Obtain an electrocardiogram before starting treatment and periodically thereafter.

Obtain fasting serum glucose before starting treatment and monitor periodically thereafter.

Dose Adjustments for Adverse Reactions to Lorlatinib

First dose reduction: 75 mg taken orally once daily.

Second dose reduction: 50 mg taken orally once daily.

Permanently discontinue Lorlatinib in patients unable to tolerate the 50 mg once daily dosage.

Dose Adjustments for Special Populations on Lorlatinib

Dose Adjustments for Renal Impairment

Mild or moderate renal impairment: Creatinine clearance (CrCl) 30 to 89 mL/min – No dose adjustment recommended.

Severe renal impairment: CrCl 15 to less than 30 mL/min – 75 mg taken orally once daily.

Dose Adjustments for Hepatic Impairment

Mild hepatic impairment: Total bilirubin ≤ ULN with AST > ULN, or total bilirubin >1 to 1.5 times ULN with any AST – No dose adjustment recommended.

Moderate or severe hepatic impairment: No data available.

Dose Adjustments for Specific Adverse Reactions to Lorlatinib

Central Nervous System Adverse Reactions

Grade 1: Continue at the same dose or withhold until recovery to baseline; resume at same or reduced dose.

Grade 2 or 3: Withhold until recovery to Grade 0 or 1; resume at a reduced dose.

Grade 4: Permanently discontinue Lorlatinib.

Hyperlipidemia

Grade 4 hypercholesterolemia or Grade 4 hypertriglyceridemia: Withhold until recovery to Grade 2 or lower; resume at same dose. If severe hypercholesterolemia and/or hypertriglyceridemia recurs, resume at a reduced dose.

Atrioventricular (AV) Block

(1) Second-degree AV block

Withhold until PR interval <200 milliseconds; resume at a reduced dose.

(2) First occurrence of third-degree AV block

Withhold until pacemaker placed or PR interval <200 milliseconds; if pacemaker placed, resume at same dose; if no pacemaker placed, resume at a reduced dose.

(3) Recurrent third-degree AV block

Place pacemaker or permanently discontinue Lorlatinib.

Interstitial Lung Disease (ILD)/Pneumonitis

Any grade treatment-related ILD/pneumonitis: Permanently discontinue Lorlatinib.

Hypertension

Grade 3: Withhold until hypertension recovers to Grade 1 or lower, then resume at same dose. If Grade 3 hypertension recurs, withhold until recovery to Grade 1 or lower and resume at a reduced dose. Permanently discontinue Lorlatinib if adequate hypertension control cannot be achieved with optimal medical management.

Grade 4: Withhold until recovery to Grade 1 or lower and resume at a reduced dose or permanently discontinue. If Grade 4 hypertension recurs, permanently discontinue.

Hyperglycemia

Grade 3 or 4 hyperglycemia despite anti-hyperglycemic treatment.

Withhold until hyperglycemia is adequately controlled, then resume at the next lower dose. Permanently discontinue Lorlatinib if adequate hyperglycemic control cannot be achieved with medical management.