The contraindications for lorlatinib mainly include patients with severe liver and kidney dysfunction and pregnant women, and special attention should be paid to medication safety. The following items detail specific contraindications and precautions.

1. Severe liver dysfunction patient

The pharmacokinetics of lorlatinib in patients with moderate to severe liver dysfunction have not been studied, and this population is contraindicated. Mild liver dysfunction (total bilirubin ≤ ULN and AST>ULN, or bilirubin 1-1.5 × ULN) can be used normally.

(1) Monitoring requirements

Liver function should be tested before treatment, and ALT/AST should be monitored every 2 weeks during treatment until it stabilizes, and then changed to once a month. Permanent discontinuation of medication is required for grade 3-4 liver toxicity.

Two patients with severe renal insufficiency

Patients with severe renal insufficiency (creatinine clearance rate<30mL/min) are contraindicated as pharmacokinetics have not been studied. Mild to moderate renal insufficiency can be used normally, but it needs to be reduced to 75mg once daily.

(1) Dose adjustment

When there is grade 2 or above renal dysfunction, medication should be suspended and reduced after recovery. Regular monitoring of electrolyte balance and urinary protein is required.

3 Pregnant women

Loratinib has embryotoxicity and is absolutely contraindicated for pregnant women. Before treatment, it is necessary to confirm the pregnancy status, and women of childbearing age should use non hormonal contraceptive measures.

(1) Contraceptive requirements

Female patients require contraception during treatment and 6 months after discontinuation, while male patients require a contraceptive partner during treatment and 3 months after discontinuation.

(2) Accidental pregnancy management

Immediately discontinue medication and refer to obstetrics for evaluation. It is necessary to inform that the risk of fetal malformation is 60% (animal data).

4 Other taboo groups

This includes individuals who are allergic to lorlatinib, those who also use potent CYP3A inducers, and uncontrolled hypertensive/hyperglycemic patients.

(1) Drug interactions

Prohibition of co administration of potent CYP3A inducers such as Levofloxacin may induce liver failure. Moderate acting inducers should be used with caution when combined.