Osimertinib

What is osimertinib used for?

Osimertinib is a prescription medicine that is used to treat lung cancer.

Description

Osimertinib is a kinase inhibitor for oral use. The molecular formula for osimertinib mesylate is C28H33N7O2•CH4O3S, and the molecular weight is 596 g/mol. The chemical name is N-(2-{2-dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino}phenyl)prop-2-enamide mesylate salt. Osimertinib has the following structural formula (as osimertinib mesylate):

TAGRISSO tablets contain 40 or 80 mg of osimertinib, equivalent to 47.7 and 95.4 mg of osimertinib mesylate, respectively. Inactive ingredients in the tablet core are mannitol, microcrystalline cellulose, low-substituted hydroxypropyl cellulose and sodium stearyl fumarate. The tablet coating consists of polyvinyl alcohol, titanium dioxide, macrogol 3350, talc, ferric oxide yellow, ferric oxide red and ferric oxide black.

 Mechanism of Action

Osimertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletions) at approximately 9-fold lower concentrations than wild-type. Two pharmacologically-active metabolites (AZ7550 and AZ5104 circulating at approximately 10% of the parent) with similar inhibitory profiles to osimertinib have been identified in the plasma after oral administration of osimertinib. AZ7550 showed a similar potency to osimertinib, while AZ5104 showed greater potency against exon 19 deletion and T790M mutants (approximately 8-fold) and wild-type (approximately 15-fold) EGFR. In vitro, osimertinib also inhibited the activity of HER2, HER3, HER4, ACK1, and BLK at clinically relevant concentrations.

In cultured cells and animal tumor implantation models, osimertinib exhibited anti-tumor activity against NSCLC lines harboring EGFR-mutations (T790M/L858R, L858R, T790M/exon 19 deletion, and exon 19 deletion) and, to a lesser extent, wild-type EGFR amplifications. Osimertinib distributed to the brain in multiple animal species (monkey, rat, and mouse) with brain to plasma AUC ratios of approximately 2 following oral dosing. These data are consistent with observations of tumor regression and increased survival in osimertinib- versus control-treated animals in a pre-clinical mutant-EGFR intracranial mouse metastasis xenograft model (PC9; exon 19 deletion).

Before taking osimertinib, tell your doctor:

• If you are allergic to osimertinib; any part of this medicine; or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
• If you are breast-feeding. Do not breast-feed while you take osimertinib and for 2 weeks after your last dose.

This is not a list of all drugs or health problems that interact with osimertinib.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take osimertinib with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some things I need to know or do while I take osimertinib?

• Tell all of your health care providers that you take osimertinib. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You may need to have your heart checked before starting osimertinib and while taking it. This includes an ECG.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely. Tell your doctor if you get signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Low blood cell counts have happened with osimertinib. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. Call your doctor right away if you have signs of infection like fever, chills, or sore throat; any unexplained bruising or bleeding; or if you feel very tired or weak.
• If you are 65 or older, use osimertinib with care. You could have more side effects.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child. In women, this may go back to normal. In men, it is not known if this will go back to normal. If you have questions, talk with the doctor.
• This medicine may cause harm to an unborn baby. A pregnancy test will be done before you start osimertinib to show that you are NOT pregnant.
• Women must use birth control while taking osimertinib and for some time after the last dose. Ask your doctor how long to use birth control. If you get pregnant, call your doctor right away.
• Men with a partner who may get pregnant must use birth control while taking osimertinib and for some time after the last dose. Ask your doctor how long to use birth control. If your partner gets pregnant, call the doctor right away.

How is osimertinib best taken?

Use osimertinib as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Keep taking osimertinib as you have been told by your doctor or other health care provider, even if you feel well.
• If you have trouble swallowing, the tablet may be mixed in 2 ounces (60 mL) of water. Do not use carbonated water or other liquids. Stir well until the tablet is in small pieces. Do not crush or heat. Swallow right away.
• After drinking, rinse the container with 4 to 8 ounces (120 to 240 mL) of water and drink right away.
• Those who have feeding tubes may use osimertinib. Use as you have been told. Flush the feeding tube after osimertinib is given.

What do I do if I miss a dose?

• Skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

What are the side effects of osimertinib that I need to call my doctor about immediately?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Signs of a severe skin reaction (Stevens-Johnson syndrome, erythema multiforme) like red, swollen, blistered, or peeling skin (with or without fever); skin reaction that looks like rings; red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
• Dizziness.
• Change in eyesight, eye pain, or very bad eye irritation.
• If bright lights bother your eyes.
• Watery eyes.
• Very bad and sometimes deadly lung or breathing problems have happened with osimertinib. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.
• Heart failure has rarely happened in people taking osimertinib. Sometimes, this has been deadly. Call your doctor right away if you have shortness of breath, a big weight gain, or swelling in the arms or legs.
• A type of abnormal heartbeat (prolonged QT interval) can happen with osimertinib. Call your doctor right away if you have a fast heartbeat, a heartbeat that does not feel normal, or if you pass out.

What are some other side effects of osimertinib?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dry skin.
• Change in nails.
• Diarrhea or constipation.
• Upset stomach or throwing up.
• Not hungry.
• Mouth irritation or mouth sores.
• Headache.
• Feeling tired or weak.
• Signs of a common cold.
• Back pain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-332-1088. You may also report side effects at https://www.fda.gov/medwatch.

If overdose is suspected:

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out osimertinib?

• Store at room temperature in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.

Label

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 40 MG

• NDC 0310-1349-30          30 Tablets
• Tagrisso®
• (osimertinib) tablets
• 40 mg per tablet
• Rx only
• AstraZeneca

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL – 80 MG

• NDC 0310-1350-30          30 Tablets
• Tagrisso®
• (osimertinib) tablets
• 80 mg per tablet
• Rx only
• AstraZeneca

SRC: NLM .