Tagrisso 40mg Tablets

Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that selectively inhibits both EGFR-TKI sensitizing mutations (Exon 19 deletions, L858R) and the EGFR T790M resistance mutation. It has less activity against wild-type EGFR, which may contribute to its improved tolerability profile compared to earlier generation EGFR TKIs.

Urgent Side Effects: Seek Medical Attention Immediately

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical help right away:

Signs of an allergic reaction: 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: mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, change in balance, abnormal heartbeat, seizures, loss of appetite, or severe upset stomach or vomiting.
Signs of high blood sugar: confusion, feeling sleepy, unusual thirst or hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
Signs of a urinary tract infection (UTI): blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
Dizziness.
Changes in eyesight, eye pain, or severe eye irritation.
Sensitivity to bright lights.
Watery eyes.
Purple spots, red skin on the lower arms, lower legs, or buttocks that does not fade when pressed, or hives that do not go away within 24 hours and appear bruised.

Serious Lung and Heart Problems

This medication can cause lung problems, which may be fatal. If you experience any new or worsening symptoms of lung or breathing problems, such as shortness of breath, trouble breathing, cough, or fever, contact your doctor right away.

Heart failure has occurred rarely in people taking this medication, and it can be fatal. If you experience shortness of breath, significant weight gain, swelling in the arms or legs, or bulging neck veins, contact your doctor immediately.

Abnormal Heartbeat and Low Blood Cell Counts

A type of abnormal heartbeat (prolonged QT interval) can occur with this medication. If you experience a fast heartbeat, an irregular heartbeat, or fainting, contact your doctor right away.

Low blood cell counts can also occur, which can lead to bleeding problems, infections, or anemia. In rare cases, a blood disorder called aplastic anemia can occur, which can be fatal. If you experience a new fever or persistent fever, chills, sore throat, or other signs of infection, unexplained bruising or bleeding, pale skin, or extreme fatigue or weakness, contact your doctor right away.

Severe Skin Reactions

This medication can cause severe skin reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and other severe skin reactions. If you experience red, swollen, blistered, or peeling skin, skin irritation (with or without fever), red or irritated eyes, or sores in your mouth, throat, nose, or eyes, seek medical help immediately.

Other Possible Side Effects

While many people may not experience side effects or may only have mild side effects, it is essential to contact your doctor or seek medical help if you experience any of the following:

Dry skin.
Changes in nails, including pain, redness, swelling, and loss of nails.
Constipation, diarrhea, stomach pain, upset stomach, vomiting, or decreased appetite.
Mouth irritation or mouth sores.
Headache.
Feeling tired or weak.
Signs of a common cold.
* Back, bone, joint, muscle, or neck pain.

Reporting Side Effects

If you have questions about side effects or experience any side effects that bother you or do not go away, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the allergic reaction you experienced, including the symptoms that occurred.
If you are taking any medications that can cause an abnormal heartbeat, known as a prolonged QT interval. There are numerous medications that can lead to this condition, so consult your doctor or pharmacist if you are unsure.
If you are taking any prescription or over-the-counter medications, natural products, or vitamins that should not be taken with this medication. Certain medications used to treat HIV, infections, seizures, and other conditions may interact with this drug, so it is crucial to discuss your medication regimen with your doctor.
If you are breastfeeding or plan to breastfeed. It is recommended that you do not breastfeed while taking this medication and for 2 weeks after your last dose, unless your doctor advises otherwise. Be sure to understand the specific guidelines for avoiding breastfeeding.

This list is not exhaustive, and it is crucial to inform your doctor and pharmacist about all your medications, including prescription and over-the-counter medications, natural products, and vitamins, as well as any health problems you may have. This will enable your healthcare team to verify that it is safe for you to take this medication with your existing medications and health conditions. Never start, stop, or change the dose of any medication without consulting your doctor.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Your doctor will instruct you to undergo regular blood tests and other laboratory examinations to monitor your condition. Additionally, some individuals may require an electrocardiogram (ECG) to check their heart rhythm.

If you have diabetes (high blood sugar), it is crucial to closely monitor your blood sugar levels. Elderly patients (65 years or older) should exercise caution when taking this medication, as they may be more susceptible to side effects.

This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. In females, fertility may return to normal, but in males, it is unclear if fertility will be restored. If you have concerns, discuss them with your doctor.

There is a risk of harm to an unborn baby if you become pregnant while taking this medication. To confirm you are not pregnant, a pregnancy test will be conducted before initiating treatment. If you may become pregnant, use birth control during treatment and for 6 weeks after the final dose, unless otherwise instructed by your doctor. It is vital to understand the duration of birth control use. If you become pregnant, notify your doctor immediately.

If your partner may become pregnant, use birth control during treatment and for 4 months after the last dose. If your partner becomes pregnant, contact the doctor right away.

• Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, St. John's Wort): May significantly decrease osimertinib plasma concentrations, reducing efficacy. Avoid co-administration.
• QT-prolonging drugs (e.g., amiodarone, disopyramide, sotalol, quinidine, chloroquine, haloperidol, methadone, moxifloxacin, ondansetron, pimozide): Increased risk of QTc prolongation. Avoid or use with caution and monitor ECG.

• Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin): May decrease osimertinib exposure. Consider alternative or monitor for reduced efficacy.
• Strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin, ritonavir, indinavir, nelfinavir, saquinavir, telithromycin, voriconazole): May increase osimertinib plasma concentrations. Monitor for increased adverse reactions. No dose adjustment typically needed for osimertinib, but caution is advised.

• New or worsening respiratory symptoms (e.g., dyspnea, cough, fever) for Interstitial Lung Disease (ILD)
• Cardiac symptoms (e.g., shortness of breath, edema, palpitations, chest pain) for cardiomyopathy/LVEF reduction
• Dermatologic reactions (e.g., rash, acneiform dermatitis, dry skin, nail changes)
• Ocular symptoms (e.g., blurred vision, dry eyes, photophobia, eye pain) for keratitis or other ocular toxicities
• Diarrhea
• Fatigue
• Stomatitis

Osimertinib can cause fetal harm when administered to a pregnant woman. Based on animal studies and its mechanism of action, it is expected to cause adverse developmental effects. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the last dose.

It is not known whether osimertinib or its metabolites are present in human milk. Due to the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed during treatment with osimertinib and for 6 weeks after the last dose.

The safety and effectiveness of osimertinib in pediatric patients have not been established. Its use is not recommended in this population.

No overall differences in safety or effectiveness were observed between patients ≥65 years of age and younger patients. No dose adjustment is required based on age.

• Osimertinib is a third-generation EGFR TKI, designed to overcome the T790M resistance mutation that often develops after first- or second-generation EGFR TKI treatment.
• It has demonstrated efficacy in patients with CNS metastases due to its ability to cross the blood-brain barrier.
• Patients should be educated on the importance of reporting any new or worsening respiratory symptoms immediately, as ILD/pneumonitis can be life-threatening.
• Cardiac monitoring (ECG, LVEF) is crucial due to the risk of QTc prolongation and cardiomyopathy.
• Common side effects include diarrhea, rash, dry skin, nail changes, and stomatitis, which often require proactive management (e.g., anti-diarrheals, moisturizers, topical steroids).
• The 40mg dose is typically used for dose reduction due to toxicity or as an alternative for adjuvant therapy if the 80mg dose is not tolerated, though 80mg is the standard for most indications.

• First-generation EGFR TKIs (e.g., erlotinib, gefitinib) for EGFR-mutated NSCLC (though osimertinib is often preferred first-line or for T790M resistance).
• Second-generation EGFR TKIs (e.g., afatinib, dacomitinib) for EGFR-mutated NSCLC.
• Chemotherapy (e.g., platinum-based doublet chemotherapy) for NSCLC.
• Immunotherapy (e.g., pembrolizumab, nivolumab) for NSCLC (often in different settings or for different molecular profiles).
• Other targeted therapies depending on specific molecular alterations (e.g., ALK inhibitors, ROS1 inhibitors, BRAF inhibitors).

If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more details. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider for clarification. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide information about the medication taken, the amount, and the time it happened.