Attention should be paid to the administration method, dosage adjustment, and discontinuation criteria when taking lorlatinib. Specific guidelines cover fasting/meal selection, adverse reaction dosage adjustment, and medication recommendations for special populations. The following items are detailed.

1. Administration method

Loratinib is administered orally and should not be cut or chewed when swallowed whole. It can be taken with food or on an empty stomach, and its bioavailability is not affected by food intake. It is recommended to fix the daily medication time to maintain stable blood drug concentration.

(1) Handling of missed services

If missed and at least 4 hours before the next administration, it should be taken immediately; If<4 hours, skip this dose. Prohibit double dose compensation to avoid toxic accumulation.

2 dose adjustment plan

Implement a step-by-step reduction based on the severity of adverse reactions: reduce to 75mg/day for the first time and 50mg/day for the second time. If it is still intolerable, the medication will be permanently discontinued.

(1) Central neurotoxicity

2-3 levels of cognitive impairment require suspension of medication until recovery to 0-1 levels, followed by a reduction in dosage; Grade 4 or recurrent grade 3 requires permanent discontinuation of medication. Avoid driving and precise operation during medication.

(2) Hyperlipidemia

Suspend the elevation of level 4 cholesterol/triglycerides to ≤ level 2 and restore the original dose; Relapse patients need to reduce their dosage. When combined lipid-lowering therapy is ineffective, consider discontinuing the medication.

(3) Abnormal liver function

Mild injury (bilirubin ≤ ULN and AST>ULN) does not require adjustment; Moderate to severe lack of data requires individualized assessment.

3 Discontinuation criteria

The indications for permanent discontinuation of medication include: inability to tolerate a dose of 50mg/day, grade 4 interstitial pneumonia, recurrent grade 3 atrioventricular block without pacemaker installation, etc.

(1) Special populations

Elderly patients do not need to adjust the dosage; Mild to moderate renal impairment (eGFR ≥ 30mL/min) does not require adjustment, while severe cases require careful evaluation.