Tagrisso

1st-line treatment of patients w/ locally advanced or metastatic NSCLC whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. Patients w/ locally advanced or metastatic EGFR T790M mutation +ve NSCLC whose disease has progressed on or after EGFR TKI therapy. Adjuvant treatment after tumour resection in patients w/ NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

Recommended dose: 80 mg once daily. May be reduced to 40 mg once daily if necessary. Patient in adjuvant setting Treatment duration: Until disease recurrence or unacceptable toxicity; max: 3 yr. Patient w/ locally advanced or metastatic lung cancer Treatment duration: Until disease progression or unacceptable toxicity.

May be taken with or without food: Take at the same time each day. Swallow whole, do not crush/split/chew. For patients w/ swallowing difficulties, tab may be dispersed in 50 mL non-carbonated water & stir w/o crushing until dispersed. Drink immediately. Rinse glass w/ another ½ glass of water & drink. Dispersed liqd may also be administered via nasogastric tube by using 15 mL for initial dispersion & 15 mL for residue rinses. The tube should be flushed w/ water after administration. Soln should be administered w/in 30 min of the addition of tab to water.

Perform a validated test using tumour tissue DNA from diagnostic tumour biopsy specimen or tumour tissue taken during surgery when considering use as an adjuvant therapy after tumour resection in patients w/ NSCLC, EGFR mutation +ve status; using either tumour tissue DNA or circulating tumour DNA obtained from a plasma sample when considering use for locally advanced or metastatic NSCLC. Determine +ve EGFR mutation status [exon 19 deletions or exon 21 (L858R) substitution mutations] for 1st-line treatment or T790M mutations following progression on or after EGFR TKI therapy. Permanently discontinue use if ILD is confirmed; & in those who develop QTc interval prolongation in combination w/ Torsade de pointes, polymorphic ventricular tachycardia, signs & symptoms of serious arrhythmia. Closely monitor & consider drug interruption or discontinuation if signs & symptoms suggestive of erythema multiforme develop. Immediately interrupt or discontinue use if signs & symptoms suggestive of SJS appear. Avoid use in patients w/ congenital long QT syndrome. Consider periodic monitoring w/ ECG & electrolytes in patients w/ CHF, electrolyte abnormalities or those who are taking known QTc interval-prolonging medications. W/hold treatment in patients who develop a QTc interval >500 msec on at least 2 separate ECGs until the QTc interval is <481 msec or recovery to baseline if the QTc interval is ≥481 msec, resume treatment at a reduced dose. Consider cardiac monitoring including left ventricular ejection fraction (LVEF) assessment at baseline & during treatment in patients w/ cardiac risk factors & those w/ conditions that can affect LVEF. Promptly refer to an ophthalmologist if patient presents w/ signs & symptoms suggestive of keratitis (eg, acute or worsening of eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain &/or red eye). Consider close patient monitoring, drug interruption or discontinuation if signs & symptoms suggestive of aplastic anaemia develop. Severe hepatic & renal impairment; ESRD (CrCl <15 mL/min). Advise women of childbearing potential to avoid becoming pregnant while receiving treatment; use effective contraception after completion of treatment (for at least 6 wk for females; 4 mth for males). Not recommended during pregnancy & in women of childbearing potential not using contraception. Discontinue breast-feeding during treatment. Childn & adolescents <18 yr.

Diarrhoea, stomatitis; rash, paronychia, dry skin, pruritus; decreased leukocytes, lymphocytes, platelet count & neutrophils. Epistaxis, ILD; alopecia, urticaria, palmar-plantar erythrodysaesthesia syndrome; increased blood creatinine. Potentially, SJS.

Exposure may be decreased by strong CYP3A4 inducers. May increase exposure of BCRP & P-gp substrates. Avoid concomitant use w/ strong CYP3A inducers (eg, phenytoin, rifampicin, carbamazepine, St. John's wort). Increased AUC & C_max of rosuvastatin & fexofenadine. Decreased AUC & C_max of simvastatin. Increased exposure of medications w/ disposition dependent upon P-gp & w/ narrow therapeutic index (eg, digoxin, dabigatran, aliskiren).

Targeted Cancer Therapy

L01EB04 - osimertinib ; Belongs to the class of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Used in the treatment of cancer.

POM