Tagrisso (osimertinib)

Tagrisso may cause serious side effects, including:

• lung problems. Tagrisso may cause lung problems that may lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you have any new or worsening lung symptoms, including trouble breathing, shortness of breath, cough, or fever.
• heart problems, including heart failure. Tagrisso may cause heart problems that may lead to death. Your healthcare provider should check your heart function before you start taking Tagrisso and during treatment as needed.
• severe blistering or peeling of skin. Seek medical attention right away if you develop these symptoms.
• target lesions, which are skin reactions that look like rings. Seek medical attention right away if you develop these symptoms.

The most common side effects of Tagrisso are:

• low white blood cell counts
• low platelet counts
• diarrhea
• muscle, bone, or joint pain
• changes in your nails, including: redness, tenderness, pain, inflammation, brittleness,
• dry skin
• mouth sores
• tiredness
• cough
• low red blood cell counts (anemia)
• rash separation from the nailbed, and shedding of nail

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Tagrisso. 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 1-800FDA-1088. 

First-line Treatment Of EGFR Mutation-Positive Metastatic NSCLC

• Tagrisso is indicated for the first-line treatment of adult patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

Previously Treated EGFR T790M Mutation-Positive Metastatic NSCLC

• Tagrisso is indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

Patient Selection

• Select patients with resectable tumors for the adjuvant treatment of NSCLC with Tagrisso based on the presence of EGFR exon 19 deletions or exon 21 L858R mutations in tumor specimens.
• Select patients for the first-line treatment of metastatic EGFR-positive NSCLC with Tagrisso based on the presence of EGFR exon 19 deletions or exon 21 L858R mutations in tumor or plasma specimens. If these mutations are not detected in a plasma specimen, test tumor tissue if feasible.
• Select patients for the treatment of metastatic EGFR T790M mutation-positive NSCLC with Tagrisso following progression on or after EGFR TKI therapy based on the presence of an EGFR T790M mutation in tumor or plasma specimens.
• Testing for the presence of the T790M mutation in plasma specimens is recommended only in patients for whom a tumor biopsy cannot be obtained. If this mutation is not detected in a plasma specimen, re-evaluate the feasibility of biopsy for tumor tissue testing.
• Information on FDA-approved tests for the detection of EGFR mutations is available at http://www.fda.gov/companiondiagnostics.

Recommended Dosage Regimen

• The recommended dosage of Tagrisso is 80 mg tablet once a day. Tagrisso can be taken with or without food.
• If a dose of Tagrisso is missed, do not make up the missed dose and take the next dose as scheduled.
• Treat patients in the adjuvant setting until disease recurrence, or unacceptable toxicity, or for up to 3 years.
• Treat patients with metastatic lung cancer until disease progression or unacceptable toxicity.

Administration To Patients Who Have Difficulty Swallowing Solids

• Disperse tablet in 60 mL (2 ounces) of non-carbonated water only.
• Stir until tablet is dispersed into small pieces (the tablet will not completely dissolve) and swallow immediately.
• Do not crush, heat, or ultrasonicate during preparation. Rinse the container with 120 mL to 240 mL (4 to 8 ounces) of water and immediately drink.
• If administration via nasogastric tube is required, disperse the tablet as above in 15 mL of non-carbonated water, and then use an additional 15 mL of water to transfer any residues to the syringe.
• The resulting 30 mL liquid should be administered as per the nasogastric tube instructions with appropriate water flushes (approximately 30 mL).

Dosage Modifications

Adverse Reactions

Table 1: Recommended Dosage Modifications for Tagrisso

Target Organ	Adverse Reaction*	Dosage Modification
Pulmonary	Interstitial lung disease (ILD)/Pneumonitis s	Permanently discontinue Tagrisso.
Cardiac	QTc† interval greater than 500 msec on at least 2 separate ECGs‡	Withhold Tagrisso until QTc interval is less than 481 msec or recovery to baseline if baseline QTc is greater than or equal to 481 msec, then resume at 40 mg dose.
	QTc interval prolongation with signs/symptoms of life-threatening arrhythmia	Permanently discontinue Tagrisso.
	Symptomatic congestive heart failure	Permanently discontinue Tagrisso.
Cutaneous	Stevens-Johnson syndrome (SJS), Erythema Multiforme Major (EMM)	Withhold Tagrisso if suspected and permanently discontinue if confirmed.
Other	Adverse reaction of Grade 3 or greater severity	Withhold Tagrisso for up to 3 weeks.
	If improvement to Grade 0-2 within 3 weeks	Resume at 80 mg or 40 mg daily.
	If no improvement within 3 weeks	Permanently discontinue Tagrisso.
*Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0). †QTc = QT interval corrected for heart rate ‡ECGs = Electrocardiogram

Drug Interactions

Strong CYP3A4 Inducers

• If concurrent use is unavoidable, increase Tagrisso dosage to 160 mg daily when co-administering with a strong CYP3A inducer. Resume Tagrisso at 80 mg 3 weeks after discontinuation of the strong CYP3A4 inducer.

Effect Of Other Drugs On Osimertinib

Strong CYP3A Inducers

• Co-administering Tagrisso with a strong CYP3A4 inducer decreased the exposure of osimertinib compared to administering Tagrisso alone. Decreased osimertinib exposure may lead to reduced efficacy.
• Avoid co-administering Tagrisso with strong CYP3A inducers. Increase the Tagrisso dosage when co-administering with a strong CYP3A4 inducer if concurrent use is unavoidable. No dose adjustments are required when Tagrisso is used with moderate and/or weak CYP3A inducers.

Effect Of Osimertinib On Other Drugs

• Co-administering Tagrisso with a breast cancer-resistant protein (BCRP) or P-glycoprotein (P-gp) substrate increased the exposure of the substrate compared to administering it alone.
• Increased BCRP or P-gp substrate exposure may increase the risk of exposure-related toxicity.
• Monitor for adverse reactions of the BCRP or P-gp substrate, unless otherwise instructed in its approved labeling, when co-administered with Tagrisso.

Drugs That Prolong The QTc Interval

• The effect of co-administering medicinal products known to prolong the QTc interval with Tagrisso is unknown.
• When feasible, avoid concomitant administration of drugs known to prolong the QTc interval with known risk of Torsades de pointes.
• If not feasible to avoid concomitant administration of such drugs, conduct periodic ECG monitoring.