Osimertinib


Concise Prescribing Info
Indications/Uses
Locally advanced or metastatic non-small cell lung carcinoma.
Dosage/Direction for Use
Adult : In patient with activating EGFR mutations or EGFR T790M mutation-positive: 80 mg once daily continued until disease progression or unacceptable toxicity occurs. Dose may be reduced to 40 mg daily, as required based on patient safety and tolerability.
Dosage Details
Oral
Locally advanced or metastatic non-small cell lung carcinoma
Adult: In patient with activating EGFR mutations or EGFR T790M mutation-positive: 80 mg once daily continued until disease progression or unacceptable toxicity occurs. Dose reduction and/or dose interruption may be required according to individual safety and tolerability (refer to detailed product guideline). May reduce dose to 40 mg daily, as required.
Special Patient Group
Patient taking strong CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine): Increase dose to 160 mg daily. Resume dose at 80 mg daily after 3 weeks of discontinuation of strong CYP3A4 inducer.
Administration
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.
Special Precautions
Patient with interstitial lung disease, cardiac disease or at risk for QT prolongation. Elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Leucopenia, lymphopenia, neutropenia, thrombocytopenia, anaemia, QT prolongation, keratitis, decreased left ventricular ejection fraction.
Gastrointestinal disorders: Diarrhoea, stomatitis.
Infections and infestations: Paronychia, pneumonia.
Skin and subcutaneous tissue disorders: Rash, dry skin, pruritus.
Potentially Fatal: Interstitial lung disease, pneumonitis, cardiomyopathy.
MonitoringParameters
Determine EGFR mutation status and pregnancy test (in females of reproductive potential) prior to therapy. Monitor ECG and electrolytes periodically. Assess for signs/symptoms of interstitial lung disease or pneumonitis, dermatologic and gastrointestinal toxicity.
Drug Interactions
Decreased serum concentration and efficacy with strong and moderate CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine, bosentan, efavirenz, etravirine, modafinil). May increase serum concentration and risk of toxicity of breast cancer resistant protein (BCRP) and P-glycoprotein (P-gp) substrates. May enhance QT prolongation effect and may increase cardiovascular risk with QT prolonging agents.
Food Interaction
Decreased serum concentration with St. John’s wort.
Action
Description: Osimertinib is a tyrosine kinase inhibitor which irreversibly inhibits epidermal growth factor receptor (EGFR) by binding to its selected mutant forms (T790M, L858R, exon 19 deletion) at lower concentrations. Osimertinib is selective for sensitising mutations and the T790M resistance mutation, it also exhibits less activity against wild-type EGFR.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: 6 hours (range: 3-24 hours).
Distribution: Volume of distribution: 918 L. Plasma protein binding: 95%.
Metabolism: Metabolised predominantly via CYP3A oxidation and dealkylation to AZ7550 and AZ5104 (active metabolites).
Excretion: Via faeces (68%; approx 2% as unchanged drug), urine (14%; approx 2% as unchanged drug). Elimination half-life: 48 hours.
Chemical Structure

Chemical Structure Image
Osimertinib

Source: National Center for Biotechnology Information. PubChem Database. Osimertinib, CID=71496458, https://pubchem.ncbi.nlm.nih.gov/compound/Osimertinib (accessed on Jan. 22, 2020)

Storage
Store between 15-30°C.
ATC Classification
L01XE35 - osimertinib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. Used in the treatment of cancer.
References
Anon. Osimertinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/03/2019.

Buckingham R (ed). Osimertinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/03/2019.

Tagrisso Tablet, film-coated (AstraZeneca Pharmaceuticals LP). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/03/2019.

Disclaimer: This information is independently developed by MIMS based on Osimertinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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