Durgical
EN
Open the app

Lorlatinib

  • ALK and ROS1 inhibitorsALK and ROS1 inhibitors
  • High alertAn error with this medicine can cause serious harm: double checks and protocols are used.
  • Pregnancy: avoidAvoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting and non-hormonal contraception is used during and after treatment, because the drug makes…

A third-generation ALK and ROS1 inhibitor for ALK-positive lung cancer, first line or after other ALK drugs. Watch mood, thinking, glucose and blood pressure.

Updated

Also called: PF-06463922

Quick facts

Group
ALK and ROS1 inhibitors
Target
ALK and ROS1 receptor tyrosine kinases
Key effects
Weight gain and swelling of the arms · Fatigue
Monitor
ECG before and during treatment · Mood
ATC
L01ED05

No doses: the clinician sets them by the current guideline.

Mechanism of action

The figure shows lorlatinib (PF-06463922), a macrocycle, in the ATP pocket of the human ALK kinase domain.

Target in 3D: ALK and ROS1 receptor tyrosine kinases. PDB structure 4CLI (RCSB PDB, public domain). View the structure at RCSB PDB

Lorlatinib is a compact macrocyclic inhibitor of the ATP site of ALK and ROS1. It was designed to stay active after one or two earlier ALK inhibitors have failed, and it is now also used as first treatment. Blocking the fused kinase stops the tumour's growth signals.

  1. Macrocycle that fills the ATP site of ALK and ROS1
  2. Built to work after earlier ALK inhibitors fail
  3. Fused kinase silenced: tumour growth stops

Indications

  • ALK-positive metastatic non-small cell lung cancer, as first treatment or after other ALK inhibitors. Lung cancer →

Adverse effects

Common

  • Weight gain and swelling of the arms or legs
  • Fatigue
  • Nausea, vomiting, diarrhoea or constipation
  • Rash or itching
  • Numbness or tingling (peripheral neuropathy)

Contraindications

  • Use with strong CYP3A inducers (risk of serious liver injury)

Key interactions

Hormonal contraceptives (pills, patches, rings, injections)
Lorlatinib makes them less effective; a non-hormonal method is used.
St John's wort and other strong CYP3A4 inducers or inhibitors
Change lorlatinib levels.

What is monitored

  • ECG before and during treatment
  • Blood pressure before and during treatment
  • Blood glucose and other laboratory tests
  • Mood, behaviour and cognition

Administration and safety

  • Oral; swallowed whole, never split, crushed, chewed or opened.
  • If the patient vomits after a dose, the dose is not repeated; the next one is taken at the usual time.

Pregnancy and breastfeeding

Avoid in pregnancy. Can harm the fetus: a pregnancy test is done before starting and non-hormonal contraception is used during and after treatment, because the drug makes hormonal contraceptives less effective; breastfeeding is avoided.

Nursing care

  • Ask the patient and family about confusion, mood changes, hallucinations or speech problems at each visit.
  • Check blood pressure; teach signs of high blood sugar (thirst, frequent urination, fruity breath).
  • Report new breathlessness, cough or fever.
  • Confirm a negative pregnancy test and teach non-hormonal contraception (the pill may fail).

Pharmacokinetics

Absorption
Oral tablets, with or without food.
Metabolism
Liver, CYP3A4.
Half-life
About 24 hours.

Test yourself

Think of the answer, then tap the question to see it.

Which family of adverse effects is characteristic of lorlatinib?

Central nervous system effects: confusion, memory and mood changes, hallucinations, speech problems and seizures.

Why is a non-hormonal contraceptive advised with lorlatinib?

Because lorlatinib makes hormonal contraceptives less effective, and the drug can harm the fetus.

Which two measurements are checked before and during lorlatinib besides laboratory tests?

An ECG and the blood pressure.

Add to my cards (3)

More Pharmacology questions →

Connections

← Back to the class: ALK and ROS1 inhibitors

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Lorlatinib: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Lorlatinib - NCI (National Cancer Institute, 2024); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.