Active Ingredient and Strength	OSIMERTINIB MESYLATE 95.4 MG EQV OSIMERTINIB - 80 MG
Dosage Form	TABLET, FILM COATED
Manufacturer and Country	ASTRAZENECA AB - SWEDEN
Registration Number	SIN15139P
Licence Holder	ASTRAZENECA SINGAPORE PTE LTD
Forensic Classification	PRESCRIPTION ONLY MEDICINES
Anatomical Therapeutic Chemical (ATC) code	L01XE35

4.1 Therapeutic indications

TAGRISSO (osimertinib) as monotherapy is indicated for:

the adjuvant treatment after tumour resection in patients with non-small cell lung cancer (NSCLC) whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.
the first-line treatment of patients with locally advanced or metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.
the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC whose disease has progressed on or after EGFR TKI therapy. (See Clinical efficacy and safety section – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

TAGRISSO (osimertinib) is indicated in combination with:

pemetrexed and platinum-based chemotherapy for the first-line treatment of patients with locally advanced or metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

4.2 Posology and method of administration

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 should be determined using a validated test method (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information) for:

exon 19 deletions or exon 21 (L858R) substitution mutations (in tumour specimens for adjuvant treatment and tumour or plasma specimens for first-line treatment).
T790M mutations (in tumour or plasma specimens following progression on or after EGFR TKI therapy).

Posology

Monotherapy

The recommended dose of TAGRISSO is 80 mg osimertinib once a day.

Combination therapy

The recommended dose of TAGRISSO is 80 mg osimertinib once a day when taken with pemetrexed and platinum-based chemotherapy.

Refer to the Product Information for pemetrexed and cisplatin or carboplatin for the respective dosing information.

Duration of treatment

Patients in the adjuvant setting should receive treatment until disease recurrence or unacceptable toxicity or up to a maximum of 3 years. Treatment duration for more than 3 years was not studied.

Patients with locally advanced or metastatic lung cancer should receive TAGRISSO treatment until disease progression or unacceptable toxicity.

Missed dose

If a dose of TAGRISSO is missed, make up the dose 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 of TAGRISSO should be reduced to 40 mg taken once daily. Dose reduction guidelines for adverse reactions toxicities are provided in Table 1.

Combination therapy

When TAGRISSO is used in combination with pemetrexed and platinum-based chemotherapy, any one of the treatments should be dose modified, as appropriate. For TAGRISSO dose modification instructions, see Table 1. Pemetrexed, cisplatin or carboplatin should be withheld, dose reduced, or discontinued in accordance with the instructions in the pemetrexed, cisplatin or carboplatin Product Information, respectively.

Special patient populations

No dosage adjustment is required due to patient age, body weight, gender, ethnicity and smoking status (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Paediatric and adolescents

The safety and efficacy of TAGRISSO in children or adolescents aged less than 18 years have not been established. No data are available.

Method of administration

This medicinal product is for oral use. The tablet should be swallowed whole with water. The tablet should not be crushed, split or chewed.

If the patient is unable to swallow the tablet, it may first be dispersed in 50 mL of non-carbonated water. The tablet should be dropped in the water, without crushing, stirred until dispersed and immediately swallowed. An additional half a glass of water should be added to ensure that no residue remains and then immediately swallowed. No other liquids should be added.

If administration via nasogastric tube is required, the same process as above should be followed but using volumes of 15 mL for the initial dispersion and 15 mL for the residue rinses. The resulting 30 mL of liquid should be administered as per the naso-gastric tube manufacturer’s instructions with appropriate water flushes. The dispersion and residues should be administered within 30 minutes of the addition of the tablets to water.

Elderly (>65 years)

Population pharmacokinetic (PK) analysis indicated that age did not have an impact on the exposure of osimertinib and hence, osimertinib can be used in adults without regard to age.

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 PK analysis, no dose adjustment is recommended in patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin between 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 appropriate dose of TAGRISSO has not been established in patients with severe hepatic impairment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Renal impairment

Based on clinical studies and population PK analysis, no dose adjustments are necessary in patients with mild, moderate, or severe renal impairment. The safety and efficacy of TAGRISSO has not been established in patients with end-stage renal disease [Creatinine clearance (CLcr) less than 15 mL/min, calculated by the Cockcroft and Gault equation], or on dialysis. Caution should be exercised when treating patients with severe and end-stage renal impairment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3 Contraindications

None.