Posology : מינונים

4.2 Posology and method of administration
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.
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.

Treatment with TAGRISSO should be initiated by a physician experienced in the use of anticancer therapies.
When considering the use of TAGRISSO, EGFR mutation status in tumour or plasma specimens should be determined using a validated test method (see section 4.4).


Posology
The recommended dose is 80 mg osimertinib once a day until disease progression or unacceptable toxicity. 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 
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.

If a dose of TAGRISSO is missed, the dose should be made up unless the next dose is due within 12 hours. TAGRISSO can be taken with or without food at the same time each day.


Dose adjustments
Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. If dose reduction is necessary, then the dose should be reduced to 40 mg taken once daily.

Dose reduction guidelines for adverse reactions toxicities are provided in Table 1.

Table 1. Recommended dose modifications for TAGRISSO


Target organ               Adverse reaction ª                                  Dose modification Pulmonary               ILD/Pneumonitis                          Permanently discontinue TAGRISSO Withhold TAGRISSO until QTc interval is less
QTc interval greater than 500 msec                than 481 msec or recovery to baseline if on at least 2 separate ECGs                baseline QTc is greater than or equal to 481 Cardiac                                                      msec, then restart at a reduced dose (40 mg) QTc interval prolongation with signs/symptoms of serious                     Permanently discontinue TAGRISSO arrhythmia

Stevens-Johnson Syndrome and
Cutaneousb                                                                        Permanently discontinue TAGRISSO Toxic epidermal necrolysis

Blood and lymphatic                      Aplastic anaemia                                   Permanently discontinue TAGRISSO systemb
Grade 3 or higher adverse reaction                           Withhold TAGRISSO for up to 3 weeks If Grade 3 or higher adverse reaction improves to Grade 0-2 after                        TAGRISSO may be restarted at the same dose withholding of TAGRISSO for up to                                (80 mg) or a lower dose (40 mg) Other
3 weeks
Grade 3 or higher adverse reaction that does not improve to Grade 0-2                            Permanently discontinue TAGRISSO after withholding for up to 3 weeks a Note: The intensity of clinical adverse events graded by the National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) version 4.0.
b Refer to Section 4.4 Special warnings and special precautions for use for further details.
ECGs: Electrocardiograms; QTc: QT interval corrected for heart rate

Special populations
No dose adjustment is required due to patient age, body weight, gender, ethnicity and smoking status 
(see section 5.2).

Hepatic impairment
Based on clinical studies, no dose adjustments are necessary in patients with mild hepatic impairment 
(Child Pugh A) or moderate hepatic impairment (Child Pugh B). Similarly, based on population  pharmacokinetic analysis, no dose adjustment is recommended in patients with mild hepatic impairment 
(total bilirubin < ULN or total  bilirubin>1.0 to 1.5x ULN and any AST) or moderate hepatic impairment (total bilirubin between 1.5 to 3  times ULN and any AST). The safety and efficacy of this medicinal product has not been established in  patients with severe hepatic impairment. Until additional data become available, use in patients with  severe hepatic impairment is not recommended (see section 5.2).


Renal impairment
Based on clinical studies and population PK analysis no dose adjustments are necessery in patients with  mild, and moderate or severe, renal impairment. The safety and efficacy of this medicinal product has not  been established in patients with end-stage renal disease [creatinine clearance (CLcr)