Tagrisso

1st-line treatment of patients w/ locally advanced or metastatic NSCLC w/ activating epidermal growth factor receptor (EGFR) mutations. Adults w/ locally advanced or metastatic EGFR T790M mutation-+ve NSCLC. In combination w/ pemetrexed & platinum-based chemotherapy for 1st-line treatment of adults w/ advanced NSCLC, or as adjuvant therapy after tumour resection in patients w/ NSCLC, whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.

80 mg once daily. May be reduced to 40 mg once daily if necessary.

May be taken with or without food: Take at the same time each day. Swallow whole w/ water, do not crush/split/chew. For patients w/ swallowing difficulties, disperse tab in 50 mL non-carbonated water & stir w/o crushing then, 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, administered w/in 30 min. Flush tube w/ water after administration.

Hypersensitivity. Concomitant use w/ St. John's wort.

Discontinue treatment if ILD, SJS or TEN is diagnosed; in patients w/ confirmed aplastic anaemia. Permanently discontinue treatment in patients who develop QTc interval prolongation in combination w/ Torsade de Pointes, polymorphic ventricular tachycardia, signs/symptoms of serious arrhythmia. Interrupt use if signs & symptoms suggestive of SJS or TEN appear. Withhold treatment in patients who develop QTc interval of >500 msec on at least 2 separate ECGs until QTc interval is <481 msec or recovery to baseline if QTc interval is ≥481 msec, then resume treatment at reduced dose. Consider drug interruption or discontinuation if signs & symptoms suggestive of aplastic anaemia develop. Severe, life-threatening or fatal ILD or ILD-like adverse reactions (eg, pneumonitis). QTc interval prolongation. Keratitis. Avoid use in patients w/ congenital long QT syndrome. Patients w/ low body wt <50 kg. Determine EGFR mutation +ve status. Perform careful assessment of all patients w/ acute onset &/or unexplained worsening of pulmonary symptoms eg, dyspnoea, cough & fever to exclude ILD; interrupt treatment pending investigation of pulmonary symptoms. Advise patients of signs & symptoms of SJS & TEN; aplastic anaemia prior to treatment. Periodically monitor ECGs & electrolytes in patients w/ CHF, electrolyte abnormalities or those taking QTc interval prolonging medicinal products. Consider cardiac monitoring & left ventricular ejection fraction assessment in patients who develop relevant cardiac signs/symptoms during treatment. Refer to ophthalmology specialist if patients present w/ signs & symptoms suggestive of keratitis eg, acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain &/or red eye. Not recommended in severe hepatic impairment. Mild (total bilirubin ≤ULN & AST >ULN or total bilirubin >1-1.5x ULN & any AST) or moderate (total bilirubin between 1.5-3x ULN & any AST) hepatic impairment. ESRD patients (CrCl <15 mL/min) or patients on dialysis. Patients of childbearing potential should use effective contraception at least 2 mth for females & at least 4 mth for males after treatment completion. Not to be used during pregnancy. Discontinue breastfeeding during treatment. Childn or adolescents <18 yr. Elderly >65 yr.

Decreased appetite; diarrhoea, stomatitis; rash, paronychia, dry skin, pruritus; decreased leucocytes, lymphocytes, platelet count & neutrophils; increased blood creatinine; leukopenia, lymphopenia, thrombocytopenia, neutropenia. Cardiac failure; epistaxis, ILD; alopecia, palmar-plantar erythrodysaesthesia syndrome, urticaria, skin hyperpigmentation, erythema multiforme; decreased left ventricular ejection fraction, QTc interval prolongation, increased blood creatine phosphokinase. SJS, TEN.

Increased exposure of BCRP & P-gp substrates; medications w/ disposition dependent upon P-gp & w/ narrow therapeutic index (eg, digoxin, dabigatran, aliskiren). Reduced steady-state AUC w/ rifampicin. Decreased exposure w/ strong (eg, phenytoin, rifampicin & carbamazepine) & moderate (eg, bosentan, efavirenz, etravirine, modafinil) CYP3A4 inducers. Decreased exposure of hormonal contraceptive. Increased AUC & C_max of rosuvastatin & fexofenadine.

Targeted Cancer Therapy

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

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