[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [ALK and ROS1 inhibitors](https://durgical.com/en/pharmacology/classes/alk-and-ros1-inhibitors/) › Lorlatinib # Lorlatinib ## ALK and ROS1 inhibitors? ALK and ROS1 inhibitors ## High alert? An error with this medicine can cause serious harm: double checks and protocols are used. ## Pregnancy: avoid? 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… 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 Nov 1, 2026 Also called: PF-06463922 ## Quick facts **Group** [ALK and ROS1 inhibitors](https://durgical.com/en/pharmacology/classes/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. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Clinical What the labels mean - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ✂**ALK and ROS1 receptor tyrosine kinases**Lorlatinib ⓘ 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](https://www.rcsb.org/structure/4CLI) · Drag to rotate · pinch to zoom 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. - Macrocycle that fills the ATP site of ALK and ROS1 - Built to work after earlier ALK inhibitors fail - 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 →](https://durgical.com/en/conditions/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) ### Serious (rare, important) - Central nervous system effects: confusion, memory problems, mood changes, hallucinations, speech or sleep disturbances, seizures - Hypertension - Hyperglycaemia - Hepatotoxicity - Breathlessness or cough from lung inflammation ## 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. ## Memory aid «LORLatinib gets into the head»: the ALK inhibitor whose warnings are about the mind (mood, memory, hallucinations) and the pill (it weakens hormonal contraception). ## 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)](https://durgical.app/estudiar/?add=/en/pharmacology/lorlatinib/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## What the labels mean **High alert** An error with this medicine can cause serious harm: double checks and protocols are used. **Pregnancy: avoid** 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… ## Connections ## Related drugs 2 - [Alectinib](https://durgical.com/en/pharmacology/alectinib/) - [Crizotinib](https://durgical.com/en/pharmacology/crizotinib/) ## Related conditions 1 - [Lung cancer](https://durgical.com/en/conditions/lung-cancer/) [← Back to the class: ALK and ROS1 inhibitors](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a619005.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Lorlatinib - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/lorlatinib) (National Cancer Institute, 2024); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01ED05) (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. --- Source: https://durgical.com/en/pharmacology/lorlatinib/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/lorlatinib/