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Non-small cell lung cancer, metastatic: Treatment of metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an approved test, in patients who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy
There are no contraindications listed in the manufacturers US labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to osimertinib or any component of the formulation.
Note: T790M EGFR mutation status of tumor specimen should be confirmed prior to treatment initiation.
Non-small cell lung cancer, metastatic (T790M EGFR mutation-positive): Oral: 80 mg once daily until disease progression or unacceptable toxicity
Missed doses: If a dose is missed, do not make up the missed dose, take the next dose as scheduled.
Refer to adult dosing.
CrCl 30 to 89 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute and end stage renal disease: There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).
Mild impairment (total bilirubin <ULN and AST 1 to 1.5 times ULN or total bilirubin 1 to 1.5 times ULN and any AST): No dosage adjustment necessary.
Moderate (total bilirubin 1.5 to 3 times ULN and any AST) or severe impairment (total bilirubin 3 to 10 times ULN and any AST): There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied).
Hazardous agent; use appropriate precautions for handling and disposal (meets NIOSH 2014 criteria). For patients who have difficulty swallowing tablets, disperse tablet in ~50 mL of noncarbonated water (only), stir until tablet is completely dispersed and use immediately; rinse container with 120 to 240 mL water and drink or administer immediately. Do not crush, heat, or ultrisonicate during preparation. When it is necessary to manipulate the tablets (eg, to prepare an oral liquid), it is recommended to double glove, wear a protective gown, and prepare in a controlled device (NIOSH 2014).
Oral: May be administered with or without food.
For patients who have difficulty swallowing tablets, disperse tablet in ~50 mL of noncarbonated water (only), stir until tablet is completely dispersed and immediately swallow or administer through NG tube. Rinse container with 120 to 240 mL water and immediately drink or administer through NG tube. Do not crush, heat, or ultrasonicate during preparation.
Hazardous agent; use appropriate precautions for handling and disposal (meets NIOSH 2014 criteria). NIOSH recommends single gloving for administration of intact tablets (NIOSH 2014). Avoid exposure to crushed tablets. When it is necessary to manipulate the tablets (eg, to prepare an oral liquid), it is recommended to double glove, wear a protective gown, and prepare in a controlled device (NIOSH 2014).
Store at 25 ‚ °C (77 ‚ °F); excursions are permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tagrisso: 40 mg, 80 mg
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
CYP1A2 Substrates: Osimertinib may decrease the serum concentration of CYP1A2 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Osimertinib. Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Osimertinib. Avoid combination
CYP3A4 Substrates: Osimertinib may increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Highest Risk QTc-Prolonging Agents: Moderate Risk QTc-Prolonging Agents may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Ivabradine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination
Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Moderate Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
St Johns Wort: May decrease the serum concentration of Osimertinib. Avoid combination
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Vinflunine: May enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Avoid combination
T790M epidermal growth factor receptor (EGFR) mutation status (prior to treatment). Monitor ECG and electrolytes periodically (in patients with a history of long QTc syndrome, heart failure, electrolyte abnormalities, and/or those taking concurrent medications known to prolong the QTc interval). Assess LVEF (by echocardiogram or multigated acquisition [MUGA] scan) prior to treatment and then every 3 months while on treatment. Monitor for signs/symptoms of interstitial lung disease or pneumonitis, dermatologic, and gastrointestinal toxicity.
>10%:
Central nervous system: Fatigue (14%), headache (10%)
Dermatologic: Skin rash (41%, including erythematous rash, macular rash, maculopapular rash, papular rash, pustular rash, erythema, folliculitis, acne vulgaris, dermatitis, dermatitis acneiform), xeroderma (31%), nail disease (25%), pruritus (14%)
Endocrine & metabolic: Hyponatremia (26%), hypermagnesemia (20%)
Gastrointestinal: Diarrhea (42%), nausea (17%), decreased appetite (16%), constipation (15%), stomatitis (12%)
Hematologic & oncologic: Lymphopenia (63%, grades 3/4: 3%), thrombocytopenia (54%, grades 3/4: 1%), anemia (44%, grades 3/4: <1%), neutropenia (33%, grades 3/4: 3%)
Neuromuscular & skeletal: Back pain (13%)
Ophthalmic: Eye disorder (19%, including dry eyes, blurred vision, keratitis, cataract, eye irritation, blepharitis, eye pain, increased lacrimation, vitreous floaters, <1% other ocular toxicity)
Respiratory: Cough (14%)
1% to 10%:
Cardiovascular: Venous thromboembolism (7%, including deep vein thrombosis, internal jugular thrombosis), cerebrovascular accident (3%), prolonged Q-T interval on EKG ( ≤3%; prolonged from baseline), pulmonary embolism ( ≤2%), reduced ejection fraction (<2%), cardiomyopathy ( ≤1%)
Respiratory: Pneumonia ( ≤4%; grade 3/4: 2%), interstitial pneumonitis (3%)
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, 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% and a drop to below 50% was noted. Assess LVEF (by echocardiogram or multigated acquisition [MUGA] scan) prior to treatment and then every 3 months while on treatment. Withhold treatment if ejection fraction decreases by 10% from baseline and is <50%. Permanently discontinue for symptomatic heart failure or persistent, asymptomatic left ventricular dysfunction that does not resolve within 4 weeks. Prolongation of the QTc interval may occur; QTc >500 msec and an increase from baseline of >60 msec 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 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.
- Dermatologic toxicity: Skin reactions, including rash, dry skin, and itching may occur. Nail toxicity may also occur.
- Gastrointestinal toxicity: Diarrhea (usually grades 1 and 2) was observed in almost half the patients receiving osimertinib.
- Pulmonary toxicity: Interstitial lung disease (ILD) and pneumonitis was 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.
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.
Special handling:
- Hazardous agent: Use appropriate precautions for handling and disposal (meets NIOSH 2014 criteria).
Other warnings/precautions:
- Appropriate use: Confirm the presence of a T790M epidermal growth factor receptor (EGFR) mutation prior to treatment initiation. Information on diagnostic tests approved for detection of T790M EGFR mutations may be found at www.fda.gov/companiondiagnostics.
Based on data from animal reproduction studies and the mechanism of action, use during pregnancy is expected to cause fetal harm. Women of reproductive potential should use effective contraception during therapy and for 6 weeks after the last dose. Males with female partners of reproductive potential should also use effective contraception during therapy and for 4 months after the last dose.
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 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).
Vss/F: 986 L
Hepatic; predominantly oxidation (via CYP3A4) and dealkylation to 2 active metabolites (AZ7550 and AZ5104)
Feces (68%; ~2% as unchanged drug); Urine (14%; ~2% as unchanged drug)
Median: 6 hours (range: 3 to 24 hours)
Mean (estimated): 48 hours
Binding is likely high.
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, dry skin, nail changes, nausea, lack of appetite, constipation, mouth sores, back pain, or headache. Have patient report immediately to prescriber signs of low sodium (headache, difficulty focusing, memory impairment, confusion, weakness, seizures, or change in balance), signs of high magnesium levels (confusion, feeling sluggish, slow movements, shortness of breath, nausea, severe dizziness, or passing out), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of heart problems (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), signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), dizziness, passing out, tachycardia, abnormal heartbeat, coughing up blood, angina, severe loss of strength and energy, chills, pharyngitis, bruising, or bleeding (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.