Osimertinib

SOURCE: UK SPC for TAGRISSO 40 mg film-coated tablets (https://www.medicines.org.uk/emc/product/1985/smpc), indicated in EGFR mutation-positive non-small cell lung cancer. PRESCRIBING RESTRICTION: treatment should be initiated by a physician experienced in the use of anticancer therapies, and EGFR mutation status should be determined using a validated test method before use (tumour specimens for adjuvant treatment or for locally advanced unresectable tumours; tumour or plasma specimens in the locally advanced or metastatic setting). TREATMENT DURATION: patients in the adjuvant setting should receive treatment until disease recurrence or unacceptable toxicity (treatment duration for more than 3 years was not studied); patients with locally advanced or metastatic lung cancer should receive treatment until disease progression or unacceptable toxicity. MISSED DOSE: the dose should be made up unless the next dose is due within 12 hours. DOSE REDUCTION: dosing interruption and/or dose reduction may be required based on individual safety and tolerability; if dose reduction is necessary, the dose should be reduced to 40 mg taken once daily. DOSE MODIFICATIONS (CTCAE v5.0): ILD/pneumonitis — discontinue; ILD/pneumonitis following definitive platinum-based chemoradiation therapy — if asymptomatic (Grade 1) continue or interrupt and restart as appropriate, if Grade 2 or higher permanently discontinue. QTc interval greater than 500 msec on at least 2 separate ECGs — withhold until the QTc interval is less than 481 msec, or recovery to baseline if baseline QTc is 481 msec or greater, then restart at the reduced 40 mg dose; QTc prolongation with signs/symptoms of serious arrhythmia — permanently discontinue. Stevens-Johnson syndrome and toxic epidermal necrolysis — permanently discontinue. Aplastic anaemia — permanently discontinue. Other Grade 3 or higher adverse reaction — withhold for up to 3 weeks; if it improves to Grade 0-2 within that time, restart at the same dose (80 mg) or a lower dose (40 mg); if it does not improve to Grade 0-2 after withholding for up to 3 weeks, permanently discontinue. COMBINATION THERAPY: refer to the SPCs for pemetrexed and cisplatin or carboplatin for their dosing; cisplatin and/or carboplatin should be used for up to 4 cycles; any of the treatment components should be dose modified as appropriate. NASOGASTRIC TUBE: follow the same dispersion process but using 15 mL for the initial dispersion and 15 mL for the residue rinse, administering the resulting 30 mL as per the nasogastric tube manufacturer's instructions with appropriate water flushes; the dispersion and residues should be administered within 30 minutes of adding the tablets to water. SPECIAL POPULATIONS: no dose adjustment is required due to patient age, body weight, gender, ethnicity or smoking status. HEPATIC: no dose adjustment is necessary in mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment; safety and efficacy have not been established in severe hepatic impairment and use is not recommended there. PAEDIATRIC: safety and efficacy in children or adolescents aged less than 18 years have not been established and no data are available. Verify any under-18 use against a children's formulary. US LABELLING DIFFERENCE (not in the fetched UK §4.2): the US label states that if concurrent use with a strong CYP3A4 inducer is unavoidable, the TAGRISSO dosage should be increased to 160 mg daily — confirm against the UK SPC §4.5 before applying, as that section was not retrieved in this bundle.