lorlatinib: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
lorlatinib: clinical details
Prescribing considerations
- Specialist initiation and supervision are required, with validated confirmation of ALK-positive advanced NSCLC.
- Review psychiatric and neurological history, cardiovascular risk, pulmonary symptoms, glucose control, lipid disorders, pancreatitis risks and visual symptoms.
- Perform a full interaction review, including herbal products, contraception and medicines with narrow therapeutic indices.
- Assess renal and hepatic function; severe impairment requires product-label adjustment and dialysis data are unavailable.
- Discuss reproductive risks and possible effects on male fertility before treatment.
Contraindications and cautions
- Hypersensitivity to lorlatinib or an excipient.
- Concurrent use of a strong CYP3A4/5 inducer.
- The selected formulation should not be used in rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
Monitoring
- Cholesterol and triglycerides at baseline, early after initiation and regularly thereafter.
- ECG before treatment and regularly thereafter, with closer assessment where cardiac risk or conduction disease is present.
- Blood pressure before treatment, shortly after initiation and regularly thereafter.
- Fasting glucose before treatment and periodically thereafter.
- Lipase and amylase before treatment and subsequently as clinically indicated.
- Clinical monitoring for CNS effects, pneumonitis, peripheral neuropathy, visual disturbance, oedema and cardiac symptoms.
- Consider baseline and follow-up left-ventricular function assessment in patients with relevant cardiac risk or symptoms.
Clinical pharmacology
Selective ATP-competitive ALK and ROS1 tyrosine kinase inhibitor. Lorlatinib is primarily metabolised through CYP3A4 and UGT1A4, acts as a moderate CYP3A and P-glycoprotein inducer, and can penetrate the blood-brain barrier.
Formulation and product differences
- The selected product is a dark-pink, oval, immediate-release film-coated tablet containing lactose.
- Tablets must remain intact and should not be chewed, crushed or split.
- No alternative formulation is represented by the selected SmPC.
lorlatinib preparations and strengths
Tablet
Route: Oral
Strengths: 25 mg, 100 mg
lorlatinib interactions
The oncology and pharmacy teams should review prescription medicines, non-prescription products and herbal remedies before treatment and whenever these change.
Strong CYP3A inducers, including rifampicin, carbamazepine, phenytoin and St John's wort
These can markedly reduce lorlatinib exposure and increase liver-injury risk; combined use is contraindicated.
Strong CYP3A inhibitors, including itraconazole, voriconazole, posaconazole, ritonavir and cobicistat
These may increase lorlatinib exposure and toxicity, so alternatives are preferred and specialist management is required.
Grapefruit and grapefruit juice
These may increase lorlatinib concentrations and should be avoided.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.