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Osimertinib

Medically reviewed by Drugs.com. Last updated on Oct 12, 2020.

Pronunciation

(oh si mer ti nib)

Index Terms

  • AZD9291

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Tagrisso: 40 mg, 80 mg

Brand Names: U.S.

  • Tagrisso

Pharmacologic Category

  • Antineoplastic Agent, Epidermal Growth Factor Receptor (EGFR) Inhibitor
  • Antineoplastic Agent, Tyrosine Kinase Inhibitor

Pharmacology

Osimertinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which binds to select mutant forms of EGFR, including T790M, L858R, and exon 19 deletion at lower concentrations than wild-type. Osimertinib exhibits less activity against wild-type EGFR (as compared to other EGFR inhibitors) and is selective for sensitizing mutations and the T790M resistance mutation, which is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors (Janne 2015).

Distribution

Vss/F: 918 L

Metabolism

Hepatic; predominantly oxidation (via CYP3A) and dealkylation to 2 active metabolites (AZ7550 and AZ5104)

Excretion

Feces (68%; ~2% as unchanged drug); Urine (14%; ~2% as unchanged drug)

Time to Peak

Median: 6 hours (range: 3 to 24 hours)

Half-Life Elimination

Mean (estimated): 48 hours

Protein Binding

95%

Use: Labeled Indications

Non-small cell lung cancer, metastatic:

First-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations as detected in tumor or plasma specimen by an approved test

Treatment of metastatic EGFR T790M mutation-positive (as detected in tumor or plasma specimen by an approved test) NSCLC in patients whose disease has progressed on or after EGFR tyrosine kinase inhibitor therapy

Contraindications

There are no contraindications listed in the US manufacturer's labeling.

Canadian labeling: Hypersensitivity to osimertinib or any component of the formulation.

Dosing: Adult

Note: Prior to treatment, test tumor or plasma specimen to confirm tumor epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations (first-line treatment) or T790M EGFR mutation status (previously treated).

Non-small cell lung cancer, metastatic, first-line (EGFR exon 19 deletion- or exon 21 L858R mutation-positive): Oral: 80 mg once daily until disease progression or unacceptable toxicity (Soria 2018)

Non-small cell lung cancer, metastatic, previously treated (T790M EGFR mutation-positive): Oral: 80 mg once daily until disease progression or unacceptable toxicity (Jänne 2015; Mok 2017)

Missed doses: If a dose is missed, do not make up the missed dose, take the next dose as scheduled.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult Drug Interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Cardiotoxicity:

QTc interval >500 msec on at least 2 separate ECGs: Withhold treatment until QTc interval is <481 msec or recovers to baseline (if baseline QTc ≥481 msec) and then resume at a dose of 40 mg once daily.

QTc interval prolongation with signs/symptoms of life-threatening arrhythmia: Permanently discontinue.

Symptomatic heart failure: Permanently discontinue.

Cutaneous: Stevens-Johnson syndrome, erythema multiforme major: Withhold treatment if suspected; permanently discontinue if confirmed.

Pulmonary toxicity: Interstitial lung disease/pneumonitis: Permanently discontinue.

Other toxicities: Grade 3 or higher adverse reaction: Withhold treatment for up to 3 weeks. If improves to ≤ grade 2 within 3 weeks, resume at either 80 mg once daily or 40 mg once daily. If not improved within 3 weeks, permanently discontinue.

Reconstitution

For patients who have difficulty swallowing tablets, disperse tablet in 60 mL of noncarbonated water (only), stir until tablet is dispersed into small pieces (will not dissolve completely) and use immediately; rinse container with 120 to 240 mL water and drink or administer immediately. For nasogastric administration, disperse the tablet in 15 mL of noncarbonated water; use an additional 15 mL of water to transfer residue to the syringe. Administer the 30 mL of liquid via the nasogastric tube and flush appropriately (with ~30 mL of water). Do not crush, heat, or ultrasonicate during preparation.

Administration

Oral: May be administered with or without food.

For patients who have difficulty swallowing tablets, disperse tablet in 60 mL of noncarbonated water (only), stir until tablet is dispersed into small pieces (will not dissolve completely) and immediately swallow. Rinse container with 120 to 240 mL of water and immediately drink. For nasogastric administration, disperse the tablet in 15 mL of noncarbonated water; use an additional 15 mL of water to transfer residue to the syringe. Administer the 30 mL of liquid via the nasogastric tube and flush appropriately (with ~30 mL of water). Do not crush, heat, or ultrasonicate during preparation.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Consider therapy modification

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Monitor therapy

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification

Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCRP/ABCG2 Substrates: Osimertinib may increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30 mL/min). Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Consider therapy modification

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and strong CYP3A4 inducers if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after discontinuation of the strong CYP3A4 inducer. Consider therapy modification

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digitoxin. Monitor therapy

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Avoid combination

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: Exceptions to this monograph are discussed in separate Lexi-Interact monographs. Monitor therapy

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Haloperidol: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Monitor therapy

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Ozanimod: BCRP/ABCG2 Inhibitors may increase serum concentrations of the active metabolite(s) of Ozanimod. Avoid combination

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Consider therapy modification

QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: CloZAPine; Pimozide. Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone. Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Osimertinib may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Consider therapy modification

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

Rimegepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Sirolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus. Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Consider therapy modification

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tolvaptan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tolvaptan. Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Adverse Reactions

>10%:

Dermatologic: Skin rash (58%), xeroderma (36%), nail disease (35%), pruritus (17%)

Endocrine & metabolic: Hypermagnesemia (30%), hypokalemia (16%)

Gastrointestinal: Diarrhea (58%), stomatitis (29%; grades 3/4: <1%), decreased appetite (20%), constipation (15%), nausea (14%), vomiting (11%)

Hematologic & oncologic: Lymphocytopenia (63%, grades 3/4: 6%), anemia (59%; grades 3/4: <1%), thrombocytopenia (51%, grades 3/4: <1%), neutropenia (41%, grades 3/4: 3%)

Hepatic: Increased serum aspartate aminotransferase (22%), increased serum alanine aminotransferase (21%), hyperbilirubinemia (14%)

Nervous system: Fatigue (21%), headache (12%)

Respiratory: Cough (17%), dyspnea (13%)

1% to 10%:

Cardiovascular: Prolonged QT interval on ECG (≤10%), decreased left ventricular ejection fraction (4%), cardiomyopathy (3%)

Respiratory: Upper respiratory tract infection (10%), interstitial pneumonitis (2% to 4%), pneumonia (3%), pulmonary embolism (2%)

Miscellaneous: Fever (10%)

<1%: Hyponatremia (Goss 2016), keratitis

Frequency not defined:

Dermatologic: Eczema, erythema of skin, leukonychia, nail bed changes, nail discoloration, nail hyperpigmentation, onychoclasis, onycholysis, onychomadesis, paronychia, skin erosion, skin fissure

Neuromuscular & skeletal: Asthenia

Ophthalmic: Eyelid pruritus

Postmarketing: Erythema multiforme, Stevens-Johnson syndrome

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Lymphopenia, thrombocytopenia, neutropenia, and anemia may occur (usually grades 1 and 2) with osimertinib.

• Cardiovascular toxicity: Cardiomyopathy (cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema, decreased ejection fraction, or stress cardiomyopathy) has been observed; some events were fatal. In patients who had baseline and at least one follow up assessment, a left ventricular ejection fraction (LVEF) decline of ≥10% from baseline to below 50% was noted. Assess LVEF prior to treatment, while on treatment in patients with cardiac risk factors, and in patients who develop cardiac signs/symptoms during treatment. Permanently discontinue for symptomatic heart failure. Prolongation of the QTc interval may occur; QTc >500 msec and an increase from baseline of >60 msec have been reported, although no QTc-related arrhythmias have been reported. Patients with a baseline QTc of ≥470 were excluded from clinical trials. Monitor ECG and electrolytes periodically in patients with a history of congenital long QTc syndrome, heart failure, electrolyte abnormalities, and/or those taking concurrent medications known to prolong the QTc interval. Permanently discontinue in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

• Cutaneous toxicity: Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported; withhold treatment if SJS or EMM is suspected and permanently discontinue if confirmed. Other skin reactions, including rash, dry skin, and itching may occur. Nail toxicity may also occur.

• Fertility effects: Osimertinib may impair fertility; effects may be reversible in females.

• GI toxicity: Diarrhea (usually grades 1 and 2) was observed in almost half the patients receiving osimertinib.

• Ocular toxicity: Keratitis has been reported (rarely) in clinical trials. Promptly refer patients for ophthalmologic evaluation if signs/symptoms of keratitis (eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) develop.

• Pulmonary toxicity: Interstitial lung disease (ILD) and pneumonitis were observed in clinical studies; some events were fatal. Withhold treatment with worsening respiratory symptoms (dyspnea, cough, fever) which may be indicative of ILD; permanently discontinue if ILD is confirmed. Cases of transient asymptomatic pulmonary opacities (TAPOs; apparent clinically benign areas of localized ground-glass opacities) have been observed with osimertinib. TAPOs may be mistaken for isolated pulmonary progression of disease or the beginning of more severe pneumonitis. Some TAPOs cases resolved during continued osimertinib treatment; monitor closely (Noonan 2016).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Confirm the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations in tumor or plasma specimen (if mutation is not detected in plasma, test tumor tissue if feasible) for first-line treatment of metastatic non-small cell lung cancer. Confirm the presence of a T790M EGFR mutation in tumor sample (preferred) or plasma specimen prior to treatment initiation in patients receiving treatment following progression on or after EGFR tyrosine kinase inhibitor therapy (mutation status should be determined from tumor sample; if tumor was not biopsied, a plasma sample may be used). Circulating tumor cells from plasma sample may be used as a surrogate marker for detection of T790M in tumor tissue (Remon 2017). If mutation is not detected in plasma sample, re-evaluate the feasibility of tumor biopsy for tissue testing. Information on diagnostic tests approved for detection of EGFR mutations may be found at www.fda.gov/companiondiagnostics.

Monitoring Parameters

Prior to treatment, test tumor or plasma specimen to determine epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutation status (first-line treatment) or T790M EGFR mutation status (previously treated). Pregnancy test (in females of reproductive potential prior to therapy initiation). Monitor ECG and electrolytes periodically (in patients with a history of congenital long QTc syndrome, heart failure, electrolyte abnormalities, and/or those taking concurrent medications known to prolong the QTc interval). Assess left ventricular ejection fraction prior to treatment, while on treatment in patients with cardiac risk factors, and assess in patients who develop cardiac signs/symptoms. Monitor for signs/symptoms of interstitial lung disease or pneumonitis, dermatologic, and gastrointestinal toxicity. Monitor adherence.

Reproductive Considerations

Verify pregnancy status in females of reproductive potential prior to initiating osimertinib. Females of reproductive potential should use effective contraception during therapy and for 6 weeks after the last osimertinib dose. Males with female partners of reproductive potential should also use effective contraception during therapy and for 4 months after the last osimertinib dose.

Pregnancy Considerations

Based on data from animal reproduction studies and the mechanism of action, use during pregnancy is expected to cause fetal harm.

Patient Education

What is this drug used for?

• It is used to treat lung cancer.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Dry skin

• Nail changes

• Nausea

• Vomiting

• Lack of appetite

• Constipation

• Mouth sores

• Mouth irritation

• Headache

• Common cold symptoms

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes

• Lung problems like shortness of breath or other trouble breathing, cough that is new or worse

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out

• Vision changes

• Eye pain

• Severe eye irritation

• Sensitivity to light

• Watery eyes

• Dizziness

• Passing out

• Fast heartbeat

• Abnormal heartbeat

• Bruising

• Bleeding

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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