英文版
Tagrisso (osimertinib)
药品使用说明书
用于有特定表皮生长因子受体（EGFR）T790M突变及其它 EGFR 抑制剂耐药的晚期
非小细胞肺癌患者
HAOEYOU ( 好医友)非洲地理位置
HIGHLIGHTS OF PRESCRIBING INFORMATION
The highlights do not include all the information needed to u TAGRISSO safely and effectively. See full prescribing information for TAGRISSO.
TAGRISSO™ (osimertinib) tablet, for oral u
Initial U.S. Approval: 2015
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-------------------------- INDICATIONS AND USAGE -------------------------- TAGRISSO is a kina 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 progresd on or after EGFR TKI therapy. (1)
This indication is approved under accelerated approval bad on tumor respon rate and duration of respon. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. (1)
---------------------- DOSAGE AND ADMINISTRATION ---------------------- •Confirm the prence of T790M mutation in tumor specimens prior to initiation of treatment with TAGRISSO. (2.1)
•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 ---------------------- •Interstitial Lung Dia (IL
D)/Pneumonitis: Occurred in 3.3% of patients. Permanently discontinue TAGRISSO in patients diagnod
with ILD/Pneumonitis. (5.1) •QTc Interval Prolongation: Monitor electrocardiograms and electrolytes in patients who have a history or predisposition for QTc prolongation, or tho who are taking medications that are known to prolong the QTc
interval. Withhold then restart at a reduced do or permanently
discontinue TAGRISSO. (2.4, 5.2)
•Cardiomyopathy: Occurred in 1.4% of patients. Asss left ventricular ejection fraction (LVEF) before treatment and then every 3 months
thereafter. (2.4, 5.3)
•Embryo-Fetal Toxicity: TAGRISSO can cau fetal harm. Advi females of potential risk to the fetus and to u effective contraception
during treatment with TAGRISSO and for 6 weeks after final do.
Advi males to u effective contraception for 4 months, after the last
do of TAGRISSO. (5.3, 8.1, 8.3)
------------------------------ ADVERSE REACTIONS ----------------------------- Most common adver 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 or FDA at 1-800-FDA-1088 or v/medwatch.
------------------------------ DRUG INTERACTIONS ----------------------------- •Strong CYP3A Inhibitors: Avoid concurrent administration with TAGRISSO if possible. If no alternative exists, the patient should be
cloly monitored for signs of toxicity. (7.1)
•Strong CYP3A Inducers: Avoid if possible becau concomitant u may decrea 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.
Revid: 11/2015
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Patient Selection
2.2 Recommended Dosage Regimen
2.3 Administration to Patients Who Have Difficulty Swallowing Solids
2.4 Do Modification for Adver Reactions
3 DOSAGE FORMS AND STRENGTHS
摩羯男和射手女4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Interstitial Lung Dia/Pneumonitis
5.2 QTc Interval Prolongation
5.3 Cardiomyopathy
5.4 Embryo-Fetal Toxicity
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
7 DRUG INTERACTIONS
7.1 Effect of Other Drugs on Osimertinib
7.2 Effect of Osimertinib on Other Drugs
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.3 Females and Males of Reproductive Potential
8.4 Pediatric U
8.5 Geriatric U
8.6 Renal Impairment
8.7 Hepatic Impairment
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
典韦王者荣耀13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subctions omitted from the full prescribing information are not listed.
3182209 11/15
FULL PRESCRIBING INFORMATION
1 INDICATIONS 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 progresd on or after EGFR tyrosine kina inhibitor (TKI) therapy.
This indication is approved under accelerated approval bad on tumor respon rate and duration of respon [e 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
2.1 Patient Selection
Confirm the prence of a T790M EGFR mutation in tumor specimens prior to initiation of treatment with TAGRISSO [e Indications and Usage (1) and Clinical Studies (14)]. Information on FDA-approved tests for the detection of T790M mutations is available at
v/companiondiagnostics.
2.2 Recommended Dosage Regimen
The recommended do of TAGRISSO is 80 mg tablet once a day until dia progression or unacceptable toxicity. TAGRISSO can be taken with or without food.
If a do of TAGRISSO is misd, do not make up the misd do and take the next do as scheduled.
2.3 Administration to Patients Who Have Difficulty Swallowing Solids
Disper tablet in 4 tablespoons (approximately 50 mL) of non-carbonated water only. Stir until tablet is completely disperd and swallow or administer through naso-gastric tube immediately. Do not crush, heat, or ultrasonicate during preparation. Rin the container with 4 to 8 ounces of water and immediately drink or administer through the naso-gastric tube [e Clinical Pharmacology (12.3)].
2.4 Do Modification for Adver Reactions
Table 1 Recommended Do Modifications for TAGRISSO Target
Organ Adver Reaction a Do Modification
Pulmonary Interstitial lung dia
(ILD)/Pneumonitis
Permanently discontinue TAGRISSO.
Cardiac QTc† interval greater than 500
mc on at least 2 parate ECGs b
Withhold TAGRISSO until QTc interval is less
than 481 mc or recovery to baline if baline
QTc is greater than or equal to 481 mc, then
resume at 40 mg do.
QTc interval prolongation with
signs/symptoms of life threatening
arrhythmia
Permanently discontinue TAGRISSO.
Asymptomatic, absolute decrea
in LVEF c of 10% from baline
and below 50%
Withhold TAGRISSO for up to 4 weeks.
• If improved to baline LVEF, resume.
• If not improved to baline, permanently
discontinue.
Symptomatic congestive heart
failure
画画素材图片Permanently discontinue TAGRISSO.
Other Grade 3 or higher adver reaction 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.
a Adver reactions graded by the National Cancer Institute Common Terminology Criteria for Adver Events
笑忘书version 4.0 (NCI CTCAE v4.0).
b ECGs = Electrocardiograms
c LVEF = Left Ventricular Ejection Fraction
†QTc = QT interval corrected for heart rate
3 DOSAGE FORMS AND STRENGTHS
80 mg tablets: beige, oval and biconvex tablet marked with “AZ 80” on one side and plain on the rever.
40 mg tablets: beige, round and biconvex tablet marked with “AZ 40” on one side and plain on the rever.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Interstitial Lung Dia/Pneumonitis
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Across clinical trials, interstitial lung dia (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 prents with worning of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed [e Dosage and Administration (2.4) and Adver Reactions (6)].
阜师院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 mc, and 11 patients (2.7%) had an increa from baline QTc greater than 60 mc [e Clinical Pharmacology (12.2)].
In Study 1 and 2, patients with baline QTc of 470 mc or greater were excluded. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or tho 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[e Dosage and Administration (2.4)].
5.3 Cardiomyopathy
Across clinical trials, cardiomyopathy (defined as cardiac failure, pulmonary edema, ejection fraction decread 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 baline and at least one follow up LVEF asssment. Asss 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 decreas 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 [e Dosage and Administration (2.4)].
后妈5.4 Embryo-Fetal Toxicity
Bad on data from animal studies and its mechanism of action, TAGRISSO can cau fetal harm when administered to a pregnant woman. In animal reproduction studies, osimertinib caud post-implantation fetal loss when administered during early development at a do exposure 1.5 times the exposure at the
