Lorviqua is a third-generation ALK inhibitor used for the treatment of ALK positive non-small cell lung cancer, with the advantage of penetrating the blood-brain barrier and overcoming drug-resistant mutations. The standard dosage is 100mg orally once a day, and the dosage needs to be adjusted according to adverse reactions and special population conditions, while paying attention to multiple medication precautions such as central nervous system effects and hyperlipidemia.

1. Usage and dosage

The standard dose is 100mg orally once daily, and treatment is continued until disease progression or intolerable toxicity occurs. If the missed dose is less than 4 hours before the next administration, it should be skipped and double the dose should not be taken.

(1) Principle of dose adjustment

Reduce to 75mg/day for the first dose and 50mg/day for the second dose. If the patient still cannot tolerate 50mg/day, the medication should be permanently discontinued. For patients with severe renal insufficiency, the dosage should be reduced to 75mg/day.

(2) Adjustment for special populations

Mild to moderate liver and kidney dysfunction does not require adjustment. Severe renal insufficiency (creatinine clearance rate 15-30mL/min) requires a reduction to 75mg/day. Elderly patients do not require special adjustments.

2 Resistance mechanisms

Loratinib inhibits various ALK resistant mutations, including G1202R. Its resistance mechanism may involve ALK secondary mutations (such as L1198F), pathway activation (such as EGFR pathway), or histological transformation.

3 Precautions

(1) Central nervous system impact

May cause epilepsy, cognitive impairment, etc., with a median onset time of 1.4 months. If there is a reaction of level 2 or above, it should be paused and reduced, and if it is level 4, the medication should be permanently discontinued.

(2) Cardiovascular risk

Electrocardiogram monitoring is required. If atrioventricular block occurs, medication should be suspended. Recurrent third degree block requires implantation of a pacemaker or permanent discontinuation of medication.

(3) Metabolic abnormalities

Regular monitoring of blood lipids, glucose, and blood pressure is required before and during treatment. Grade 3 or above hyperglycemia or hypertension should be temporarily suspended and the dosage adjusted.

(4) Interstitial lung disease

Suspected symptoms should be evaluated immediately, and any grade of ILD/pneumonia diagnosed requires permanent discontinuation of medication.

(5) Drug interactions

Do not use potent CYP3A inducers in combination and avoid using moderate inducers. Attention should be paid to the potential impact on drug metabolism of other CYP3A substrates.