Osimertinib
Other name
-
International/Other brands
Tagrisso
Groups
Approved
Structure
Prescription products
| Name | Dosage | Strength | Route | Labeller |
|---|---|---|---|---|
| Tagrisso | Tablet, film coated | 40 mg | Oral | Astra Zeneca Ab |
| Tagrisso | Tablet | 80 mg | Oral | Astra Zeneca |
| Tagrisso | Tablet, film coated | 81 | Oral | Astra Zeneca Lp |
| Tagrisso | Tablet | 40 mg | Oral | Astra Zeneca |
| Tagrisso | Tablet, film coated | 80 mg | Oral | Astra Zeneca Ab |
| Tagrisso | Tablet, film coated | 41 | Oral | Astra Zeneca Lp |
Target
Description
Osimertinib is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) drug developed by AstraZeneca Pharmaceuticals. Its use is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in cases where tumour EGFR expression is positive for the T790M mutation as detected by FDA-approved testing and which has progressed following therapy with a first-generation EGFR tyrosine kinase inhibitor. Approximately 10% of patients with NSCLC have a rapid and clinically effective response to EGFR-TKIs due to the presence of specific activating EGFR mutations within the tumour cells. More specifically, deletions around the LREA motif in exon 19 and exon 21 L858R point mutations are correlated with response to therapy.
Indications
Metastatic Non-Small Cell Lung Cancer
Other indications
-
Mechaism of action
-
Absorption
The median time to Cmax was found to be 6 hours.
Metabolism
Osimertinib is metabolized to at least two pharmacologically active metabolites, AZ7550 and AZ5104, that circulate at approximately 10% of the concentration of the parent compound. Biochemical assays have shown that AZ7550 has similar potency and efficacy to osimertinib, while AZ5104 is more potent against mutant and wild-type EGFR. The main metabolic pathways are oxidation (predominantly by CYP3A) and dealkylation.
Toxicity
Across clinical trials, interstitial lung disease (ILD)/pneumonitis occurred in 3.3% of treated patients with 0.5% of these being fatal. There is also a change of QTc interval prolongation; electrocardiogram and electrolytes should be monitored in patients with a history or predisposition for QTc prolongation. Cardiomyopathy occurred in 1.4% of patients, therefore left ventricular ejection fraction (LVEF) should be measured at baseline and then every 3 months during treatment. Osimertinib can cause embryo-fetal toxicity, requiring female patients to take effective birth control during therapy and for 6 weeks after final dose.