Note: Select patients for treatment based on the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations in tumor specimen (for adjuvant therapy) or in tumor or plasma specimen (for first-line treatment), or based on the presence of a T790M EGFR mutation (in previously treated patients) in tumor sample (preferred) or plasma specimen.
Non–small cell lung cancer, adjuvant therapy, EGFR exon 19 deletion- or exon 21 L858R mutation-positive: Oral: 80 mg once daily until disease progression or unacceptable toxicity, or for up to 3 years (Ref).
Non–small cell lung cancer, metastatic, first-line treatment, EGFR exon 19 deletion- or exon 21 L858R mutation-positive: Oral: 80 mg once daily until disease progression or unacceptable toxicity (Ref).
Non–small cell lung cancer, metastatic, previously treated, T790M EGFR mutation-positive: Oral: 80 mg once daily until disease progression or unacceptable toxicity (Ref).
Non–small cell lung cancer, adenocarcinoma, with brain or leptomeningeal metastases, EGFR mutation-positive (off-label dose): Oral: 160 mg once daily until disease progression or unacceptable toxicity; may continue beyond disease progression if deriving clinical benefit (Ref).
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.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment; increased mean exposure of the parent drug was reported in patients with advanced kidney impairment, although there was variability and overlap in reported concentrations across all degrees of kidney dysfunction (Ref). Closer monitoring for toxicity may be warranted (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzed (high protein binding and large Vd): No dosage adjustment likely to be necessary. Several cases of successful use in patients with end-stage kidney disease have been reported (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (high protein binding and large Vd) (Ref): No dosage adjustment likely to be necessary (Ref).
CRRT: No dosage adjustment likely to be necessary (Ref).
PIRRT (eg, slow, low efficiency hemodiafiltration): No dosage adjustment likely to be necessary (Ref).
Mild to moderate impairment (Child-Pugh class A or B) or total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 3 times ULN and any AST: No dosage adjustment necessary.
Severe impairment (total bilirubin 3 to 10 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling (a recommended dose has not been established).
Target organ |
Adverse reaction |
Dose modification |
---|---|---|
Blood and bone marrow |
Aplastic anemia |
Withhold osimertinib treatment if suspected; obtain hematology consultation. If aplastic anemia is confirmed, permanently discontinue osimertinib. |
Cardiotoxicity |
QTc interval >500 msec on at least 2 separate ECGs |
Withhold osimertinib until QTc interval is <481 msec or recovery to baseline if baseline QTc is ≥481 msec, then resume osimertinib at 40 mg once daily. |
QTc interval prolongation with signs/symptoms of life-threatening arrhythmia |
Permanently discontinue osimertinib. | |
Symptomatic heart failure |
Permanently discontinue osimertinib. | |
Cutaneous toxicity |
Stevens-Johnson syndrome; erythema multiforme major; toxic epidermal necrolysis |
Withhold osimertinib treatment if suspected; permanently discontinue if confirmed. |
Cutaneous vasculitis (including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis) |
Withhold osimertinib treatment if suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology is identified, consider permanent osimertinib discontinuation (based on severity). | |
Ocular toxicity |
Signs/symptoms of keratitis (eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) |
If signs/symptoms of keratitis develop, promptly refer for ophthalmologic evaluation. |
Pulmonary toxicity |
Interstitial lung disease/pneumonitis |
Withhold osimertinib treatment for worsening respiratory symptoms (eg, dyspnea, cough, fever). Permanently discontinue osimertinib if interstitial lung disease/pneumonitis is confirmed. |
Other adverse reactions |
≥ grade 3 adverse reaction |
Withhold osimertinib for up to 3 weeks. |
If improvement to grade 0 to 2 within 3 weeks |
Resume osimertinib at 80 mg or 40 mg once daily. | |
If no improvement within 3 weeks |
Permanently discontinue osimertinib. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Dermatologic: Nail disease (35% to 37%; including leukonychia, nail bed changes, nail discoloration, nail hyperpigmentation, onychoclasis, onycholysis, onychomadesis, paronychia), pruritus (17% to 19%), skin rash (40% to 58%), xeroderma (29% to 36%)
Endocrine & metabolic: Hypermagnesemia (24% to 30%), hypokalemia (16%), hyponatremia (20% to 26%)
Gastrointestinal: Abdominal pain (12%), constipation (15%), decreased appetite (13% to 20%), diarrhea (47% to 58%; grades 3/4: 2%; including enterocolitis), nausea (14%), stomatitis (32%; grades 3/4: ≤2%), vomiting (11%)
Hematologic & oncologic: Anemia (30% to 59%; grades 3/4: <1%), leukopenia (54%), lymphocytopenia (44% to 63%, grades 3/4: 3% to 6%), neutropenia (26% to 41%, grades 3/4: ≤3%), thrombocytopenia (47% to 51%, grades 3/4: <1%)
Hepatic: Hyperbilirubinemia (14%), increased serum alanine aminotransferase (21%), increased serum aspartate aminotransferase (22%)
Nervous system: Fatigue (13% to 21%; including asthenia), headache (12%)
Neuromuscular & skeletal: Musculoskeletal pain (18%)
Respiratory: Cough (17% to 19%), dyspnea (13%), nasopharyngitis (14%), upper respiratory tract infection (10% to 13%)
1% to 10%:
Cardiovascular: Cardiomyopathy (≤3%), decreased left ventricular ejection fraction (2%), prolonged QT interval on ECG (≤10%), pulmonary embolism (2%)
Dermatologic: Alopecia (6% to 7%), palmar-plantar erythrodysesthesia (1% to 2%), urticaria (2%)
Genitourinary: Urinary tract infection (10%)
Nervous system: Dizziness (10%)
Renal: Increased serum creatinine (9% to 10%)
Respiratory: Epistaxis (6%), interstitial lung disease (3% to 4%), pneumonia (2% to 3%), pneumonitis (≤2%)
Miscellaneous: Fever (10%)
<1%:
Dermatologic: Erythema multiforme
Hematologic & oncologic: Aplastic anemia
Ophthalmic: Keratitis
Frequency not defined: Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen
Postmarketing:
Dermatologic: Stevens-Johnson syndrome
Hematologic & oncologic: Henoch-Schönlein purpura
Hypersensitivity: Hypersensitivity angiitis (including urticarial vasculitis)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to osimertinib or any component of the formulation.
Concerns related to adverse effects:
• Aplastic anemia: Aplastic anemia has been reported in a small number of patients; some cases were fatal. Signs/symptoms of aplastic anemia may include new or persistent fevers, bruising, bleeding, and/or pallor.
• Cardiovascular toxicity: Cardiomyopathy (cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema, or decreased ejection fraction) has been observed; some events were fatal. In some studies, a left ventricular ejection fraction (LVEF) decline of ≥10% from baseline or a drop to <50% were noted in a small number of patients. 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.
• Cutaneous toxicity: Cases of Stevens-Johnson syndrome, erythema multiforme major, toxic epidermal necrolysis, and cutaneous vasculitis (including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis) have been reported.
• 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. Respiratory symptoms which may be indicative of ILD include dyspnea, cough, and/or fever. 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).
Other warnings/precautions:
• Appropriate use: Confirm the presence of epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations in tumor specimen (for adjuvant therapy) or 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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tagrisso: 40 mg, 80 mg
No
Tablets (Tagrisso Oral)
40 mg (per each): $664.75
80 mg (per each): $664.75
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Tagrisso: 40 mg, 80 mg
Available through specialty pharmacies and distributors. Further information may be obtained from the manufacturer, Astra Zeneca, at 1-844-275-2360 or at https://www.tagrisso.com.
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.
Non-small cell lung cancer, adjuvant treatment: Adjuvant therapy following tumor resection for non-small cell lung cancer (NSCLC) in adults whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations as detected by an approved test.
Non-small cell lung cancer, metastatic:
First-line treatment of metastatic NSCLC in adults whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations as detected by an approved test.
Treatment of metastatic EGFR T790M mutation-positive (as detected by an approved test) NSCLC in adults with disease progression on or after EGFR tyrosine kinase inhibitor therapy.
Non-small cell lung cancer, adenocarcinoma, with brain or leptomeningeal metastases, EGFR mutation-positive
Osimertinib may be confused with dacomitinib, olaparib, ospemifene.
Tagrisso may be confused with Targretin, Tasigna.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, P-glycoprotein/ABCB1
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: 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. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Azithromycin (Systemic): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). 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. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Osimertinib may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: 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. Risk C: 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: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Osimertinib. Risk C: 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. Risk D: Consider therapy modification
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Dabrafenib: Osimertinib may enhance the QTc-prolonging effect of Dabrafenib. Dabrafenib may decrease the serum concentration of Osimertinib. Management: Monitor for decreased osimertinib efficacy, QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Risk C: 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. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: 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. Risk D: Consider therapy modification
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Encorafenib: Osimertinib may enhance the QTc-prolonging effect of Encorafenib. Encorafenib may decrease the serum concentration of Osimertinib. Management: Avoid coadministration of osimertinib and encorafenib if possible. If coadministration is unavoidable, increase osimertinib to 160 mg daily. Reduce osimertinib to 80 mg daily 3 weeks after encorafenib discontinuation. Monitor for QTc interval prolongation Risk D: Consider therapy modification
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Fluorouracil Products: 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. Risk C: Monitor therapy
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: 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. Risk C: Monitor therapy
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: 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. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Midostaurin: 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. Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
OLANZapine: 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. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: 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. Risk C: Monitor therapy
PAZOPanib: Osimertinib may enhance the QTc-prolonging effect of PAZOPanib. Osimertinib may increase the serum concentration of PAZOPanib. Risk X: 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. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: 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. Risk D: 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. Risk C: 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. Risk C: 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. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (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. Risk C: 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. Risk C: 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. Risk C: 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). Risk C: 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. Risk C: 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. Risk D: Consider therapy modification
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
RisperiDONE: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of RisperiDONE. 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. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Rosuvastatin: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Conventional). 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. Risk D: Consider therapy modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: 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. Risk D: 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. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Verify pregnancy status prior to initiating osimertinib in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for 6 weeks after the last osimertinib dose. Patients with partners who could become pregnant should use effective contraception during therapy and for 4 months after the last osimertinib dose.
Based on data from animal reproduction studies and the mechanism of action, use during pregnancy is expected to cause fetal harm.
It is not known if osimertinib (or its active metabolites) are present in breast milk. Because of the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 2 weeks after the last osimertinib dose.
Prior to treatment, test for EGFR exon 19 deletions or exon 21 L858R mutations in tumor specimen (for adjuvant therapy) or in tumor or plasma specimen (for first-line treatment), or for T790M EGFR mutation status in tumor sample (preferred) or plasma specimen (in previously treated patients). CBC with differential (baseline and periodically; more frequently if indicated). Evaluate pregnancy status (prior to therapy initiation in patients who could become pregnant). 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, aplastic anemia, dermatologic, ocular toxicity, and gastrointestinal toxicity. Monitor adherence.
The American Society of Clinical Oncology hepatitis B screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends hepatitis B virus (HBV) screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Additional cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]; ESC [Lyon 2022]). Obtain echocardiography at baseline and every 3 months (ESC [Lyon 2022]).
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; penetrates blood brain barrier (Soria 2018; Yang 2020).
Protein binding: 95%.
Metabolism: Hepatic; predominantly oxidation (via CYP3A) and dealkylation to 2 active metabolites (AZ7550 and AZ5104).
Bioavailability: AUC is increased by 19% with a high-fat, high-calorie meal.
Half-life, elimination: Mean (estimated): 48 hours.
Time to peak: Median: 6 hours (range: 3 to 24 hours).
Excretion: Feces (68%; ~2% as unchanged drug); Urine (14%; ~2% as unchanged drug).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟