Lorlatinib

WHY is this medicine prescribed?

Lorlatinib is used to treat a certain type of non-small cell lung cancer (NSCLC) in adults that has spread to other parts of the body. Lorlatinib is in a class of medications called kinase inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps to stop or slow the spread of cancer cells.

Are there OTHER USES for this medicine?

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

HOW should this medicine be used?

Lorlatinib comes as a tablet to take by mouth. It is usually taken with or without food once daily. Take lorlatinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take lorlatinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

If you vomit after taking the medication, do not take another dose. Continue your regular dosing schedule.

Swallow the tablets whole; do not split, chew, or crush them. Do not take tablets that are already broken or cracked.

Your doctor may decrease your dose or temporarily or permanently stop your treatment depending on if you experience any side effects. Be sure to tell your doctor how you are feeling during your treatment with lorlatinib.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

What SPECIAL PRECAUTIONS should I follow?

Before taking lorlatinib,

• tell your doctor and pharmacist if you are allergic to lorlatinib, any other medications, or any of the ingredients in lorlatinib tablets. Ask your pharmacist for a list of the ingredients.

• tell your doctor if you are taking carbamazepine (Epitol, Equetro, Carbatrol, Tegretol, Teril), efavirenz (Sustiva, in Atripla), nevirapine (Viramune), phenobarbital, phenytoin (Dilantin, Phenytek), pioglitazone (Actos, in Actoplus, Duetact), rifabutin (Mycobutin), rifampin (Rifadin, Rimactane, in Rifamate, Rifater), or St. John's wort. Your doctor will probably tell you not to take lorlatinib if you are taking one or more of these medications.

• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: alprazolam (Xanax); calcium channel blockers such as amlodipine (Norvasc), diltiazem (Cardizem, Dilacor, Tiazac), felodipine (Plendil), nifedipine (Adalat, Procardia), nisoldipine (Sular), and verapamil (Calan, Covera); certain medications to treat high cholesterol such as atorvastatin (Lipitor) and lovastatin (Mevacor); clarithromycin (Biaxin, in Prevpac); cyclosporine (Gengraf, Neoral, Sandimmune); diazepam (Valium); erythromycin (E.E.S, Erytab, Eryped); certain medications to treat HIV including atazanavir (Reyataz, in Evotaz), indinavir (Crixivan), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, in Kaletra, in Technivie), or saquinavir (Invirase); fluconazole; itraconazole (Onmel, Sporanox); ketoconazole; midazolam; nefazodone; oral contraceptives (birth control pills); quinidine (in Nuedexta); sildenafil (Revatio, Viagra); sirolimus (Rapamune); tacrolimus (Prograf); tadalafil (Adcirca, Cialis); trazodone; triazolam (Halcion); or vardenafil (Levitra, Staxyn). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with lorlatinib, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.

• tell your doctor if you have or have ever had high blood pressure, an irregular heartbeat, diabetes or high blood sugar levels, depression, seizures, high levels of cholesterol and other fatty substances in the blood, or kidney or lung disease.

• tell your doctor if you are pregnant, plan to become pregnant, or plan to father a child. Lorlatinib may interfere with the action of hormonal contraceptives (birth control pills, patches, rings, implants, or injections), so you should not use these as your only method of birth control during your treatment. You must use a non-hormonal birth control such as a barrier method (device that blocks sperm from entering the uterus such as a condom or a diaphragm). Ask your doctor to help you choose a method of birth control that will work for you. If you are female, you will need to take a pregnancy test before you start treatment and should use non-hormonal birth control to prevent pregnancy during your treatment and for 6 months after your final dose. If you are male, you and your female partner should use birth control during your treatment and for 3 months after your final dose. Talk to your doctor about birth control methods that you can use during your treatment. If you or your partner become pregnant while taking lorlatinib, call your doctor immediately. Lorlatinib may harm the fetus.

• tell your doctor if you are breast-feeding. You should not breast-feed while you are taking lorlatinib and for 7 days after your final dose.

• you should know that this medication may temporarily decrease fertility in men. Talk to your doctor about the risks of taking lorlatinib.

What SPECIAL DIETARY instructions should I follow?

Talk to your doctor about eating grapefruit and drinking grapefruit juice while taking this medication.

What should I do IF I FORGET to take a dose?

Take the missed dose as soon as you remember it. However, if it is within 4 hours of the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

What SIDE EFFECTS can this medicine cause?

Lorlatinib may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• weight gain
• muscle, joint, or back pain
• diarrhea
• constipation
• nausea
• vomiting
• tiredness
• headache
• vision changes
• rash or itching

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or get emergency medical treatment:

• swelling in your arms, legs, hands and feet
• difficulty breathing
• shortness of breath, cough, or fever
• numbness and tingling feeling in your joints or arms and legs
• difficulty thinking or confusion
• seizures
• seeing things or hearing voices that do not exist
• changes in mood, feeling sad or anxious
• problems with speech
• difficulty falling asleep or staying asleep
• unusual dreams or nightmares
• headache, dizziness, blurred vision, feeling faint, chest pain, or shortness of breath
• feeling more hungry or thirsty than usual, increased urination, extreme tiredness, weakness, confusion, or breath that smells fruity

Lorlatinib may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What should I know about STORAGE and DISPOSAL of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

What should I do in case of OVERDOSE?

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.

What OTHER INFORMATION should I know?

Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests and an electrocardiogram (ECG; test that measures the electrical activity in the heart) before and during your treatment to check your body's response to lorlatinib. Your doctor will also check your blood pressure before and during your treatment. Your doctor will also order a lab test before you begin your treatment to see whether your cancer can be treated with lorlatinib.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.