Lorlatinib

Cytostatic · ALK inhibitor

Indications

For the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on: Crizotinib and at least one other ALK inhibitor for metastatic disease; or Alectinib as the first ALK inhibitor therapy for metastatic disease; or Ceritinib as the first ALK inhibitor therapy for metastatic disease.

Dosage

Adults: 100 mg once daily.

Adverse Effects

Edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.

Risk Factor (Pregnancy/Lactation)

Precautions: CNS effects include seizures, hallucinations and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume Lorlatinib at same or reduced dose or permanently discontinue Lorlatinib based on severity. Hyperlipidemia: Initiate or increase the dose of lipid-lowering agents. Withhold and resume Lorlatinib at same or reduced dose based on severity. Atrioventricular Block: Withhold and resume Lorlatinib at same or reduced dose based on severity. Permanently discontinue Lorlatinib for treatment-related ILD/pneumonitis of any severity. Advise males and females of reproductive potential to use an effective non-hormonal method of contraception.

Interactions

CYP3A Inducers, CYP3A Inhibitors, CYP3A Substrates.

Advice to Patient

Advise patients to notify their healthcare provider if they experience new or worsening CNS symptoms, new or worsening cardiac symptoms, new or worsening respiratory symptoms, signs and symptoms of hepatotoxicity. Inform patients that serum cholesterol and triglycerides will be monitored during treatment and accordingly initiation or an increase in the dose of lipid-lowering agents may be required.

Pharmacokinetics

Absorption: Rapid. Metabolism: Primarily via CYP3A4 and UGT1A4, with minor contribution from CYP2CB, CYP2C19, CYP3A5, minor contribution from CYP2C19, CYP3A5, and UGT1A3. Bioavailability: 81%. Half-life elimination: 24 hours. Time to peak: 1.2 hours (range: 0.5 to 4 hours) following a single dose; 2 hours (range: 0.5 to 23 hours) at steady state. Excretion: Urine: 48% (<1% as unchanged drug); feces; 41% (-9% as unchanged drug)

Compiled by Healify Pharmacy from published drug references. How we compile it →

Always consult a pharmacist or doctor.