Lorlatinib (Lorviqua) is an inhibitor targeting anaplastic lymphoma kinase (ALK), primarily indicated for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC). As a highly effective drug that may be accompanied by a variety of adverse reactions, its use must strictly comply with medication standards and undergo comprehensive monitoring.

Precautions for Lorlatinib (Lorviqua) Administration

Dosage and Administration Method

The standard recommended dosage of lorlatinib is 100mg taken orally once daily, which can be administered with food or on an empty stomach.

Tablets should be swallowed whole; do not chew, crush, or split them.

If a tablet is broken, cracked, or incomplete, it should not be taken.

It is recommended to take the medication at a fixed time every day to maintain a stable blood drug concentration.

If a dose is missed, it should be taken immediately unless the time until the next scheduled dose is less than 4 hours. If vomiting occurs after taking the medication, an additional dose should not be taken; instead, the next dose should be administered as originally planned.

Administration in Special Populations

For patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] with AST > ULN, or total bilirubin > 1–1.5 times ULN), no dosage adjustment is required. However, the appropriate dosage for patients with moderate to severe hepatic impairment has not been established.

Patients with mild to moderate renal impairment (creatinine clearance 30–89mL/min) also do not require dosage adjustment, but the dosage for patients with severe renal impairment has not been determined.

There is no significant difference in the efficacy of lorlatinib between elderly patients (≥65 years old) and younger patients, so no special dosage adjustment is needed.

Drug Interactions

Lorlatinib has significant interactions with CYP3A inducers or inhibitors.

Concomitant use of lorlatinib with strong CYP3A inducers (such as rifampicin) is prohibited, as it may cause severe hepatotoxicity.

Before initiating lorlatinib treatment, strong CYP3A inducers should be discontinued for at least 3 half-lives.

Concomitant use with moderate CYP3A inducers should also be avoided. If concurrent use is necessary, close monitoring of liver function is required.

Concomitant use with strong CYP3A inhibitors (such as ketoconazole) should be avoided. If unavoidable, the starting dose of lorlatinib should be reduced to 75mg once daily.

Precautions Related to Fertility and Pregnancy

Based on animal study results, lorlatinib may cause harm to the fetus and is contraindicated in pregnant women.

Women of childbearing potential should use effective non-hormonal contraceptive measures during treatment and for at least 6 months after the last dose (since lorlatinib may render hormonal contraceptives ineffective).

Male patients with female partners of childbearing potential should use effective contraceptive measures during treatment and for 3 months after the last dose.

Lactating women should discontinue breastfeeding and not resume breastfeeding for at least 7 days after the last dose.

Key Monitoring Points for Lorlatinib (Lorviqua) Administration

Monitoring of Central Nervous System (CNS) Effects

Lorlatinib may cause a wide range of CNS adverse reactions, including seizures, hallucinations, changes in cognitive function, mood changes (including suicidal ideation), speech disorders, changes in mental status, and sleep disorders.

Depending on the severity of the adverse reactions, it may be necessary to suspend administration, reduce the dose, or discontinue the drug permanently.

For patients with severe CNS reactions, permanent discontinuation of the drug should be considered.

Monitoring of Blood Lipid Levels

Lorlatinib often causes increases in serum cholesterol and triglycerides.

It is recommended to measure serum cholesterol and triglyceride levels before treatment, at 1 month and 2 months after the start of treatment, and then monitor them regularly thereafter.

For patients with grade 4 hypercholesterolemia or hypertriglyceridemia, administration should be suspended until levels return to ≤ grade 2, then resumed at the same dose. If severe hyperlipidemia occurs again, dose reduction should be considered.

Monitoring of Electrocardiogram (ECG) and Cardiac Function

Lorlatinib may cause PR interval prolongation and atrioventricular (AV) block.

It is recommended to perform ECG examinations regularly before and during treatment.

For patients with second-degree AV block, administration should be suspended until the PR interval is < 200ms, then resumed at a reduced dose.

For patients with the first occurrence of complete AV block, administration should be suspended until a pacemaker is implanted or the PR interval is < 200ms. If a pacemaker is not implanted, administration should be resumed at a reduced dose.

For patients with recurrent complete AV block, consideration should be given to pacemaker implantation or permanent discontinuation of the drug.