Dosage of Lorlatinib

1. Recommended Dosage  

The recommended dosage of Lorlatinib is 100 mg orally once daily, with or without food, until disease  progression or unacceptable toxicity.

Swallow tablets whole. Do not chew, crush or split tablets. Do not ingest if tablets are broken, cracked, or  otherwise not intact.  

Take Lorlatinib at the same time each day. If a dose is missed, then take the missed dose unless the next  dose is due within 4 hours. 

Do not take 2 doses at the same time to make up for a missed dose.  Do not take an additional dose if vomiting occurs after Lorlatinib but continue with the next scheduled dose. 

2. Dosage Modifications for Adverse Reactions  

The recommended dose reductions are:

First dose reduction: Lorlatinib 75 mg orally once daily  

Second dose reduction: Lorlatinib 50 mg orally once daily 

Permanently discontinue Lorlatinib in patients who are unable to tolerate 50 mg orally once daily. 

Dosage modifications for adverse reactions of Lorlatinib are provided in Table 1.

3. Concomitant Use of Strong CYP3A Inducers  

Lorlatinib is contraindicated in patients taking strong CYP3A inducers. Discontinue strong CYP3A inducers  for 3 plasma half-lives of the strong CYP3A inducer prior to initiating Lorlatinib.

4.Concomitant Use of Moderate CYP3A Inducers  

Avoid concomitant use of moderate CYP3A inducers with Lorlatinib. If concomitant use with moderate  CYP3A inducers is unavoidable, increase the Lorlatinib dose to 125 mg once daily.

5.Dosage Modification for Strong CYP3A Inhibitors  

Avoid concomitant use of Lorlatinib with strong CYP3A inhibitors. If concomitant use with a strong  CYP3A inhibitor is unavoidable, reduce the starting dose of Lorlatinib from 100 mg orally once daily to  75 mg orally once daily.  

In patients who have had a dose reduction to 75 mg orally once daily due to adverse reactions and who initiate a  strong CYP3A inhibitor, reduce the Lorlatinib dose to 50 mg orally once daily.  

If concomitant use of a strong CYP3A inhibitor is discontinued, increase the Lorlatinib dose (after 3 plasma  half-lives of the strong CYP3A inhibitor) to the dose that was used before starting the strong inhibitor.

6. Dosage Modification for Fluconazole  

Avoid concomitant use of Lorlatinib with fluconazole. If concomitant  use is unavoidable, reduce the starting dose of Lorlatinib from 100 mg orally once daily to 75 mg orally  once daily.

7. Dosage Modification for Severe Renal Impairment  

Reduce the recommended dosage of Lorlatinib for patients with severe renal impairment (creatinine  clearance [CLcr] 15 to < 30 mL/min, estimated by Cockcroft-Gault) from 100 mg to 75 mg orally once daily.

FDA,2021.03