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TAGRISSO(osimertinib) tablet
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TAGRISSO safely and effectively. See full prescribing information for TAGRISSO.
TAGRISSO™ (osimertinib) tablet, for oral use
Initial U.S. Approval: 2015
INDICATIONS AND USAGE
TAGRISSO is a kinase inhibitor indicated for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR TKI therapy. (1)
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (1)
DOSAGE AND ADMINISTRATION
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Confirm the presence of T790M mutation in tumor specimens prior to initiation of treatment with TAGRISSO. ( 2.1)
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80 mg orally once daily, with or without food. ( 2.2)
DOSAGE FORMS AND STRENGTHS
Tablets: 80 mg and 40 mg (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
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Interstitial Lung Disease (ILD)/Pneumonitis: Occurred in 3.3% of patients. Permanently discontinue TAGRISSO in patients diagnosed with ILD/Pneumonitis. ( 5.1)
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QTc Interval Prolongation: Monitor electrocardiograms and electrolytes in patients who have a history or predisposition for QTc prolongation, or those who are taking medications that are known to prolong the QTc interval. Withhold then restart at a reduced dose or permanently discontinue TAGRISSO. ( 2.4, 5.2)
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Cardiomyopathy: Occurred in 1.4% of patients. Assess left ventricular ejection fraction (LVEF) before treatment and then every 3 months thereafter. ( 2.4, 5.3)
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Embryo-Fetal Toxicity: TAGRISSO can cause fetal harm. Advise females of potential risk to the fetus and to use effective contraception during treatment with TAGRISSO and for 6 weeks after final dose. Advise males to use effective contraception for 4 months, after the last dose of TAGRISSO. ( 5.3, 8.1, 8.3)
ADVERSE REACTIONS
Most common adverse reactions (≥25%) were diarrhea, rash, dry skin, and nail toxicity. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or www.TAGRISSO.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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Strong CYP3A Inhibitors: Avoid concurrent administration with TAGRISSO if possible. If no alternative exists, the patient should be closely monitored for signs of toxicity. ( 7.1)
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Strong CYP3A Inducers: Avoid if possible because concomitant use may decrease osimertinib plasma concentrations. ( 7.1)
USE IN SPECIFIC POPULATIONS
Lactation: Do not breastfeed. (8.2)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 11/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICTIONS AND USAGE
TAGRISSO is indicated for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.
This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies (14)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
2 DOSAGE AND ADMINISTRATION
2.2 Recommended Dosage Regimen
The recommended dose of TAGRISSO is 80 mg tablet once a day until disease progression or unacceptable toxicity. 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.
2.3 Administration to Patients Who Have Difficulty Swallowing Solids
Disperse tablet in 4 tablespoons (approximately 50 mL) of non-carbonated water only. Stir until tablet is completely dispersed and swallow or administer through naso-gastric tube immediately. Do not crush, heat, or ultrasonicate during preparation. Rinse the container with 4 to 8 ounces of water and immediately drink or administer through the naso-gastric tube [see Clinical Pharmacology (12.3)].
2.4 Dose Modification for Adverse Reactions
3 DOSAGE FORMS AND STRENGTHS
80 mg tablets: beige, oval and biconvex tablet marked with “AZ 80” on one side and plain on the reverse.
40 mg tablets: beige, round and biconvex tablet marked with “AZ 40” on one side and plain on the reverse.
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Interstitial Lung Disease/Pneumonitis
Across clinical trials, interstitial lung disease (ILD)/pneumonitis occurred in 3.3% (n=27) of TAGRISSO treated patients (n=813); 0.5% (n=4) were fatal.
Withhold TAGRISSO and promptly investigate for ILD in any patient who presents with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed [see Dosage and Administration (2.4) and Adverse Reactions (6)].
5.2 QTc Interval Prolongation
The heart rate-corrected QT (QTc) interval prolongation occurs in patients treated with TAGRISSO. Of the 411 patients in Study 1 and Study 2, one patient (0.2%) was found to have a QTc greater than 500 msec, and 11 patients (2.7%) had an increase from baseline QTc greater than 60 msec [see Clinical Pharmacology (12.2)].
In Study 1 and 2, patients with baseline QTc of 470 msec or greater were excluded. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life threatening arrhythmia [see Dosage and Administration (2.4)].
5.3 Cardiomyopathy
Across clinical trials, cardiomyopathy (defined as cardiac failure, pulmonary edema, ejection fraction decreased or stress cardiomyopathy) occurred in 1.4% (n=11) of TAGRISSO treated patients (n=813); 0.2% (n=2) were fatal.
In Study 1 and Study 2, Left Ventricular Ejection Fraction (LVEF) decline >10% and a drop to <50% occurred in 2.4% (9/375) of patients who had baseline and at least one follow up LVEF assessment.
Assess LVEF by echocardiogram or multigated acquisition (MUGA) scan before initiation of TAGRISSO and then at 3 month intervals while on treatment. Withhold treatment with TAGRISSO if ejection fraction decreases by 10% from pretreatment values and is less than 50%. For symptomatic congestive heart failure or persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks, permanently discontinue TAGRISSO [see Dosage and Administration (2.4)].
5.4 Embryo-Fetal Toxicity
Based on data from animal studies and its mechanism of action, TAGRISSO can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, osimertinib caused post-implantation fetal loss when administered during early development at a dose exposure 1.5 times the exposure at the recommended human dose. When males were treated prior to mating with untreated females, there was an increase in preimplantation embryonic loss at plasma exposures of approximately 0.5-times those observed in patients at the 80 mg dose level.
Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose [see Use in Specific Populations (8.1), (8.3) and Clinical Pharmacology (12.3)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.1)]
QTc Interval Prolongation [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to TAGRISSO (80 mg daily) in 411 patients with EGFR T790M mutation-positive non-small cell lung cancer who received prior EGFR TKI therapy, in two single arm studies, Study 1 and Study 2. Patients with a past medical history of ILD or radiation pneumonitis that required steroid treatment, serious arrhythmia or baseline QTc interval greater than 470 ms were excluded from Study 1 and Study 2. Baseline patient and disease characteristics were: median age 63 years, 13% of patients were ≥75 years old, female (68%), White (36%), Asian (60%), metastatic (96%), sites of brain metastases (39%), World Health Organization (WHO) performance status of 0 (37%) or 1 (63%), 1 prior line of therapy [EGFR-TKI treatment only, second line, chemotherapy-naïve (31%)], 2 or more prior lines of therapy (69%). Of the 411 patients, 333 patients were exposed to TAGRISSO for at least 6 months; 97 patients were exposed for at least 9 months; however no patient was exposed to TAGRISSO for 12 months.
In Studies 1 and 2, the most common (>20%) adverse reactions (all grades) observed in TAGRISSO-treated patients were diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Dose reductions occurred in 4.4% of patients treated with TAGRISSO. The most frequent adverse reactions that led to dose reductions or interruptions were: electrocardiogram QTc prolonged (2.2%) and neutropenia (1.9%). Serious adverse reactions reported in 2% or more patients were pneumonia and pulmonary embolus. There were 4 patients (1%) treated with TAGRISSO who developed fatal adverse reactions of ILD/pneumonitis. Other fatal adverse reactions occurring in more than 1 patient included pneumonia (4 patients) and CVA/cerebral hemorrhage (2 patients). Discontinuation of therapy due to adverse reactions occurred in 5.6% of patients treated with TAGRISSO. The most frequent adverse reactions that led to discontinuation were ILD/pneumonitis and cerebrovascular accidents/infarctions.
Tables 2 and 3 summarize the common adverse reactions and laboratory abnormalities observed in TAGRISSO-treated patients.
Additional clinically significant adverse reactions occurring in 2% or more of patients treated with TAGRISSO included cerebrovascular accident (2.7%).
7 DRUG INTERACTIONS
Drug interaction studies with inhibitors, inducers or substrates of CYP enzymes and transporters have not been conducted with TAGRISSO.
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