LORBRENA® (lorlatinib) may cause serious side effects, including:

• Liver problems due to interactions with other medicines. It is important to know what medicines should not be taken with LORBRENA.
• Central nervous system (CNS) effects. LORBRENA may cause CNS effects, including problems with thinking (such as forgetfulness or confusion), changes in mood (such as depression and thoughts about suicide or dying), psychotic effects such as seeing or hearing things that are not real (hallucinations), seizures, changes in speech and changes in sleep. Tell your healthcare provider if you experience new or worsening symptoms of CNS effects.
• Increases in the cholesterol and triglycerides (lipid) levels in your blood. Most people will have an increase in the lipid levels in their blood during treatment with LORBRENA.
  • If you have increases in the lipid levels in your blood during treatment with LORBRENA, your healthcare provider may need to start you on a medicine to lower the levels. If you are already taking a medicine to lower the lipid levels in your blood, your healthcare provider may need to increase your dose of that medicine.
  • Your healthcare provider should do blood tests to check the lipid levels in your blood before starting treatment, 1 to 2 months after starting treatment, and during treatment with LORBRENA.
• Heart problems. LORBRENA may cause very slow or abnormal heartbeats. Your healthcare provider should check your heart rhythm (electrocardiogram or EKG) before starting and during treatment with LORBRENA. Tell your healthcare provider right away if you feel dizzy or faint or have abnormal heartbeats. In some people, these problems are severe, and your healthcare provider may need to have you stop taking LORBRENA or have a pacemaker placed.
• Lung problems. LORBRENA may cause severe or life-threatening swelling (inflammation) of the lungs during treatment that can lead to death. Symptoms may be similar to those from lung cancer. Tell your healthcare provider right away if you have any new or worsening symptoms of lung problems, including trouble breathing, shortness of breath, cough, or fever.
• High blood pressure (hypertension). Your healthcare provider should check your blood pressure before starting treatment, 2 weeks after starting treatment, and then at least every month during treatment with LORBRENA. Your healthcare provider may need to start or change your blood pressure medicine if you have high blood pressure during treatment with LORBRENA. Tell your healthcare provider right away if you get signs or symptoms of high blood pressure, including headaches, dizziness, blurred vision, chest pain or shortness of breath.
• High blood sugar (hyperglycemia). LORBRENA may increase your blood sugar levels. Your healthcare provider should do blood tests to check your blood sugar levels before starting and during treatment with LORBRENA. Your healthcare provider may need to start or change your blood sugar medicine to control your blood sugar levels. Tell your healthcare provider right away if you get new or worsening signs and symptoms of high blood sugar, including feeling very thirsty, needing to urinate more than usual, or feeling very hungry, sick to your stomach, weak or tired, or confused.

If you have serious side effects during treatment with LORBRENA, your healthcare provider may change your dose, stop your treatment for a period of time, or completely stop treatment with LORBRENA.

Before taking LORBRENA, tell your healthcare provider about all of your medical conditions, including if you:

• have kidney problems
• have had episodes of depression or seizures
• have high levels of cholesterol or triglycerides in your blood
• have problems with your heartbeat
• have lung or breathing problems
• have high blood pressure
• have diabetes or high blood sugar
• are pregnant or plan to become pregnant. LORBRENA can harm your unborn baby.
  • Your healthcare provider will do a pregnancy test before you start treatment with LORBRENA.
  • Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with LORBRENA.
    • — Females who are able to become pregnant should use effective non-hormonal birth control during treatment with LORBRENA and for at least 6 months after the final dose of LORBRENA. Birth control pills (oral contraceptives) and other hormonal forms of birth control may not be effective if used during treatment with LORBRENA. Talk to your healthcare provider about birth control choices that are right for you during this time.
    • — Males who have female partners who are able to become pregnant should use effective birth control during treatment with LORBRENA and for at least 3 months after the final dose of LORBRENA.
• are breastfeeding or plan to breastfeed. It is not known if LORBRENA passes into your breast milk. Do not breastfeed during treatment with LORBRENA and for 7 days after the final dose. Talk to your healthcare provider about the best way to feed your baby during this time.

Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements. LORBRENA may affect the way other medicines work and other medicines may affect the way LORBRENA works, causing side effects.

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when you get a new medicine.

Do not take LORBRENA if you take certain other medicines called strong CYP3A inducers. Ask your healthcare provider for a list of these medicines if you are not sure.

The most common side effects of LORBRENA include:

• swelling in your arms, legs, hands, and feet (edema)
• numbness and tingling feeling in your joints or arms and legs (peripheral neuropathy)
• weight gain
• problems with thinking, such as forgetfulness or confusion
• tiredness (fatigue)
• difficulty breathing
• pain in your joints
• diarrhea
• changes in mood, such as depression and irritability
• high cholesterol and triglyceride levels in the blood
• cough

LORBRENA may cause decreased fertility in males. In males, this could affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.

These are not all of the possible side effects of LORBRENA. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

INDICATION

LORBRENA is a prescription medicine that is used to treat adults with non-small cell lung cancer (NSCLC) that is caused by an abnormal anaplastic lymphoma kinase (ALK) gene and that has spread to other parts of your body.

Your healthcare provider will perform a test to make sure that LORBRENA is right for you.

It is not known if LORBRENA is safe and effective in children.

Please see Full Prescribing Information and Patient Information.

--Brand Name--
US Brand Name: Lorbrena

--Description--
Lorlatinib is used to treat metastatic (cancer that has already spread) non-small cell lung cancer in patients who have a certain type of abnormal anaplastic lymphoma kinase (ALK) gene. Your doctor will perform a test to check for the ALK gene before you use this medicine.

Lorlatinib is an antineoplastic (cancer) agent. It interferes with the growth of cancer cells, which are eventually destroyed by the body.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms: Tablet

--Before Using--
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric
Appropriate studies have not been performed on the relationship of age to the effects of lorlatinib in the pediatric population. Safety and efficacy have not been established.

Geriatric
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of lorlatinib in the elderly.

Breastfeeding
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Drug Interactions
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Apalutamide
• Bacillus of Calmette and Guerin Vaccine, Live
• Carbamazepine
• Dengue Tetravalent Vaccine, Live
• Enzalutamide
• Fosphenytoin
• Ivosidenib
• Lonafarnib
• Lumacaftor
• Mavacamten
• Measles Virus Vaccine, Live
• Mitotane
• Mumps Virus Vaccine, Live
• Phenytoin
• Ranolazine
• Rifampin
• Rifapentine
• Rubella Virus Vaccine, Live
• Smallpox Monkeypox Vaccine
• St John's Wort
• Typhoid Vaccine
• Varicella Virus Vaccine, Live
• Yellow Fever Vaccine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abametapir
• Acalabrutinib
• Adenovirus Vaccine Type 4, Live
• Adenovirus Vaccine Type 7, Live
• Alfentanil
• Amiodarone
• Amlodipine
• Aprepitant
• Atogepant
• Atrasentan
• Avacopan
• Avanafil
• Avapritinib
• Bedaquiline
• Benzhydrocodone
• Berotralstat
• Boceprevir
• Bosentan
• Bosutinib
• Brigatinib
• Budesonide
• Buprenorphine
• Bupropion
• Buspirone
• Cabozantinib
• Capivasertib
• Capmatinib
• Cariprazine
• Cenobamate
• Cholera Vaccine
• Clarithromycin
• Cobicistat
• Cobimetinib
• Codeine
• Conivaptan
• Crinecerfont
• Cyclosporine
• Dabigatran Etexilate
• Daridorexant
• Darifenacin
• Darunavir
• Dasatinib
• Defactinib
• Desogestrel
• Deutivacaftor
• Dienogest
• Digoxin
• Dihydrocodeine
• Dihydroergotamine
• Diltiazem
• Dofetilide
• Dronedarone
• Drospirenone
• Duvelisib
• Ebola Zaire Vaccine, Live
• Efavirenz
• Elacestrant
• Eletriptan
• Encorafenib
• Ensartinib
• Entrectinib
• Eplerenone
• Erdafitinib
• Ergotamine
• Estetrol
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Etravirine
• Everolimus
• Fedratinib
• Felodipine
• Fentanyl
• Fexinidazole
• Finerenone
• Flibanserin
• Fluconazole
• Fluticasone
• Fosaprepitant
• Fruquintinib
• Gestodene
• Glasdegib
• Hydrocodone
• Ibrexafungerp
• Ibrutinib
• Idelalisib
• Ifosfamide
• Indinavir
• Infigratinib
• Influenza Virus Vaccine, Live
• Itraconazole
• Ivabradine
• Ivacaftor
• Ketoconazole
• Larotrectinib
• Lazertinib
• Lefamulin
• Lemborexant
• Lenacapavir
• Leniolisib
• Letermovir
• Levonorgestrel
• Lomitapide
• Lopinavir
• Lovastatin
• Lumateperone
• Lurasidone
• Maraviroc
• Medroxyprogesterone
• Meperidine
• Mestranol
• Methadone
• Midazolam
• Mitapivat
• Mobocertinib
• Modafinil
• Nafcillin
• Naloxegol
• Nefazodone
• Nelfinavir
• Neratinib
• Nifedipine
• Nirogacestat
• Nomegestrol
• Norelgestromin
• Norethindrone
• Norgestimate
• Norgestrel
• Oliceridine
• Olutasidenib
• Omaveloxolone
• Oxycodone
• Paclitaxel
• Paclitaxel Protein-Bound
• Pacritinib
• Paliperidone
• Palovarotene
• Pemigatinib
• Perampanel
• Phenobarbital
• Pimavanserin
• Pimozide
• Pirtobrutinib
• Posaconazole
• Pralsetinib
• Praziquantel
• Pretomanid
• Primidone
• Quetiapine
• Quinidine
• Quizartinib
• Repotrectinib
• Revumenib
• Rifabutin
• Rimegepant
• Ripretinib
• Ritonavir
• Rotavirus Vaccine, Live
• Saquinavir
• Segesterone
• Selpercatinib
• Selumetinib
• Sildenafil
• Simvastatin
• Sirolimus
• Sufentanil
• Suzetrigine
• Tacrolimus
• Taletrectinib
• Tazemetostat
• Telaprevir
• Telithromycin
• Temsirolimus
• Tenofovir Alafenamide
• Tezacaftor
• Ticagrelor
• Tipranavir
• Tolvaptan
• Tramadol
• Triazolam
• Ubrogepant
• Ulipristal
• Vanzacaftor
• Vardenafil
• Venetoclax
• Voclosporin
• Vonoprazan
• Voriconazole
• Voxelotor
• Warfarin
• Zanubrutinib
• Zolpidem
• Zuranolone

Other Interactions
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Depression, history of or
• Diabetes or
• Heart rhythm problems or
• Hyperglycemia (high blood sugar) or
• Hyperlipidemia (high fat in the blood) or
• Hypertension (high blood pressure) or
• Lung or breathing problems or
• Seizures, history of—Use with caution. May make these conditions worse.
• Kidney disease, severe or
• Liver disease, moderate or severe—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

--Proper Use--
Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine comes with a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.

You may take this medicine with or without food.

Swallow the tablet whole. Do not chew, crush, or split it.

Dosing
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets):
For non-small cell lung cancer:

• Adults—100 milligrams (mg) once a day. Your doctor may adjust your dose as needed and tolerated.
• Children—Use and dose must be determined by your doctor.

Missed Dose
If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose this medicine and it is within 4 hours of your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take extra medicine to make up for a missed dose. Do not take extra medicine if you vomit.

Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

--Precautions--
It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. It may also cause birth defects if the father is using it when his sexual partner becomes pregnant. If you are a woman who can get pregnant, your doctor may do tests before you start using this medicine to make sure you are not pregnant. Birth control pills may not work as well to prevent pregnancy when used with this medicine. Use another form of birth control (eg, condoms, spermicide) along with your pills. Female patients should use effective birth control during treatment and for at least 6 months after the last dose. Male patients who have female partners should use effective birth control during treatment and for at least 3 months after the last dose. If you think you have become pregnant while using this medicine, tell your doctor right away.

Talk with your doctor before using this medicine if you plan to have children. Some men who use this medicine have become infertile (unable to have children).

Do not use this medicine together with rifampin (Rifadin®). Using these medicines together may increase risk for serious liver problems.

Cancer medicines can cause diarrhea, nausea, vomiting, or stomach pain in most people, sometimes even after receiving medicines to prevent it. Ask your doctor or nurse about other ways to control these unwanted effects.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause brain or nerve problems. Check with your doctor right away if you have changes in your behavior, discouragement, feeling sad or empty, irritability, lack of appetite, loss of interest or pleasure, seizures, thoughts of killing oneself, tiredness, trouble concentrating, or trouble sleeping.

Contact your doctor right away if you have any changes to your heart rhythm. You might feel dizzy or faint, or you might have a slow, fast, pounding, or uneven heartbeat.

This medicine may cause swelling of the lungs (pneumonitis) or interstitial lung disease. These are life-threatening conditions and require immediate medical attention. The symptoms may be similar to the symptoms of lung cancer. Check with your doctor right away if you have new or worsening cough, fever, or trouble breathing.

You will need to have your blood pressure measured before starting this medicine and while you are using it. If you notice any change to your recommended blood pressure, call your doctor right away. Symptoms of high blood pressure are blurred vision, severe headache, a slow or fast heartbeat, lightheadedness, or dizziness.

This medicine may affect your blood sugar levels. Check with your doctor right away if you have increased thirst or increased urination. If you notice a change in the results of your urine or blood sugar tests, or if you have any questions, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

--Side Effects--
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Actions that are out of control
• aggression
• agitation
• anxiety
• black, tarry stools
• bleeding gums
• blood in the urine or stools
• blurred vision or other changes in vision
• body aches or pain
• burning, crawling, itching, numbness, prickling, "pins and needles", tingling, or painful sensations
• changes in behavior
• chills
• cough
• defects in intelligence, short-term memory, learning ability, and attention
• difficult or labored breathing
• difficulty in breathing
• discouragement
• dizziness
• dry mouth
• ear congestion
• false or unusual sense of well-being
• feeling sad or empty
• fever
• flushed, dry skin
• fruit-like breath odor
• headache
• hoarseness
• increased hunger
• increased thirst
• increased urination
• irritability
• lack of appetite
• loss of interest or pleasure
• loss of voice
• lower back or side pain
• nausea
• nervousness
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• pounding in the ears
• runny or stuffy nose
• seeing, hearing, or feeling things that are not there
• skin rash
• slow or fast heartbeat
• sneezing
• sore throat
• stomach pain
• sweating
• swelling
• talking, feeling, and acting with excitement
• thoughts of killing oneself
• tightness in the chest
• trouble concentrating
• trouble sleeping
• trouble breathing
• unexplained weight loss
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• weakness in the arms, hands, legs, or feet

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Abnormal dreams
• back pain
• constipation
• difficulty in moving
• difficulty in speaking
• drowsiness
• joint pain
• muscle aches, cramps, pains, or stiffness
• pain in the arms or legs
• sleep talking
• swollen joints

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.