CONTRAINDICATIONS / PRECAUTIONS
Cardiac disease, cardiomyopathy, heart failure
Cardiomyopathy, including heart failure, congestive heart failure, pulmonary edema, or decreased ejection fraction, has been reported with osimertinib therapy; some cases have been fatal. Patients with a history of cardiac disease may be at increased risk. In patients with cardiac risk factors, conduct cardiac monitoring including an assessment of the left ventricular ejection fraction (LVEF) before initiation of therapy and during treatment. Also assess the LVEF in patients who develop cardiac signs or symptoms during treatment. Permanently discontinue therapy for symptomatic congestive heart failure. Of note, cardiomyopathy and heart failure may increase the risk of prolonging the QT interval when using osimertinib.
Apheresis, AV block, bradycardia, celiac disease, electrolyte imbalance, females, fever, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)
Prolongation of the heart rate-corrected QT (QTc) interval has occurred in patients treated with osimertinib; patients with a baseline QTc interval of 470 milliseconds or greater were excluded from clinical trials. No QTc-related arrhythmias have been reported with osimertinib treatment. Periodically monitor ECGs and electrolytes of patients at increased risk. If the QTc interval is greater than 500 milliseconds on 2 separate ECGs, withhold osimertinib therapy; a dose reduction may be necessary when the QTc decreases to less than 481 milliseconds or baseline. Permanently discontinue therapy in patients with QTc prolongation and signs or symptoms of a life-threatening arrhythmia. Use osimertinib with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalance. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.
Pneumonitis, pulmonary disease
Use osimertinib with caution in patients with pre-existing pulmonary disease. Interstitial pulmonary disease/interstitial lung disease (ILD) or pneumonitis, including fatalities, have been reported with osimertinib therapy. Hold osimertinib therapy in patients who develop new or worsening pulmonary symptoms such as cough, dyspnea, fever, hypoxia, pleural effusion, or pulmonary infiltrates. Permanently discontinue therapy in patients with confirmed, treatment related ILD or pneumonitis.
Keratitis, ocular inflammation, visual impairment
Keratitis has been reported in patients treated with osimertinib in clinical trials. Promptly refer patients with signs and symptoms of keratitis (ocular inflammation, lacrimation, light sensitivity, visual impairment, eye pain, and/or red eye) to an ophthalmologist for evaluation.
Serious rash, vasculitis
Serious rash such as erythema multiforme and Stevens-Johnson syndrome (SJS) and cutaneous vasculitis (e.g., leukocytoclastic, urticarial, and IgA vasculitis) have been reported with osimertinib therapy. Hold osimertinib if erythema multiforme major (EMM) or SJS is suspected; permanently discontinue osimertinib if EMM or SJS is confirmed. Signs and symptoms of cutaneous vasculitis may include nonblanching red papules on the forearms, lower legs, or buttocks or large hives on the trunk that do not go away within 24 hours and develop a bruised appearance. Hold osimertinib if cutaneous vasculitis is suspected and evaluate for systemic involvement; consider a dermatology consult. Discontinuation of osimertinib therapy may be necessary, based on severity, if no other etiology is identified.
Aplastic anemia
Aplastic anemia, including some fatal cases, has been reported in patients treated with osimertinib in clinical trials and in postmarketing experience. Monitor complete blood counts with differential at baseline and periodically during treatment. Advise patients to report any new or persistent fevers, bruising, bleeding, or pallor. Interrupt osimertinib therapy if aplastic anemia is suspected and obtain a hematology consultation; permanently discontinue osimertinib if aplastic anemia is confirmed.
Geriatric
Monitor geriatric patients (older than 65 years) for an increased incidence of serious adverse reactions, as grade 3 and 4 adverse reactions occurred more often in this age group compared to patients younger than age 65 in an exploratory analysis (13.4% vs. 9.3%); more frequent dose modifications for adverse reactions (13.4% vs. 7.6%) also occurred. Geriatric patients may be at increased risk of developing a prolonged QT interval when using osimertinib.
Pregnancy
Although there are no adequate and well-controlled studies in pregnant women, osimertinib can cause fetal harm if used by humans during pregnancy. When administered to pregnant rats prior to implantation through the end of organogenesis at exposures 1.5 times the exposure at the recommended human dose, post-implantation loss, embryo-lethality, and reduced fetal growth occurred. When administered to pregnant rats from implantation through the closure of the hard palate at exposures greater than or equal to 0.1 times the AUC observed in humans at the recommended dose, an equivocal increase in the rate of fetal malformations and variations was observed in treated litters compared to controls. In pregnant dams at doses of 30 mg/kg/day during organogenesis through lactation day 6, an increase in total litter loss and postnatal death occurred. At a dose of 20 mg/kg/day, increased postnatal death and a slight reduction in mean pup weight at birth occurred.
Contraception requirements, infertility, male-mediated teratogenicity, pregnancy testing, reproductive risk
Counsel patients about the reproductive risk and contraception requirements during osimertinib treatment. Osimertinib can be teratogenic and embryotoxic if taken by the mother during pregnancy. Females should avoid pregnancy and use effective contraception during and for at least 6 weeks after treatment with osimertinib. Due to the risk of male-mediated teratogenicity, males with female partners of reproductive potential should use effective contraception during and for 4 months after the last dose of osimertinib. Females of reproductive potential should undergo pregnancy testing prior to initiation of therapy. Women who become pregnant while receiving osimertinib should be apprised of the potential hazard to the fetus. In addition, based on animal data, osimertinib may cause impaired fertility or infertility. The effects on female fertility showed a trend toward reversibility; it is not known whether the effects on male fertility are reversible. In male rats, degenerative changes were present in the testes of rats and dogs exposed to osimertinib for 1 month or more, with evidence of reversibility in the rat. Additionally, after 10 weeks of exposure to male rats at 0.5 times the AUC in humans at the recommended dose, increased pre-implantation loss occurred in untreated females. In repeat-dose toxicity studies, histological evidence of anestrus, corpora lutea degeneration in the ovaries, and epithelial thinning in the uterus and vagina were seen in female rats after greater than or equal to 1 month of exposure at 0.3 times the AUC observed in humans at the recommended dose, with evidence of reversibility. In a female fertility study, rats treated at approximately 1.5 times the human Cmax at the recommended dose had no effects on cycling or becoming pregnant, but caused early embryonic deaths; these findings showed evidence of reversibility 1 month after treatment discontinuation.
Breast-feeding
It is not known whether osimertinib is present in human milk. Many drugs are excreted in human milk including antibodies. Due to the potential for serious adverse reactions in nursing infants from osimertinib, advise women to discontinue breast-feeding during treatment and for 2 weeks after the final dose.
DRUG INTERACTIONS
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase dolutegravir plasma concentrations. Dolutegravir is a BCRP and P-glycoprotein (P-gp) substrate and osimertinib is a BCRP and P-gp inhibitor.
Adagrasib: (Major) Concomitant use of adagrasib and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Afatinib: (Moderate) If the concomitant use of osimertinib and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of osimertinib. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate. Osimertinib inhibits P-gp. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Alfuzosin: (Major) Avoid coadministration of alfuzosin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Based on electrophysiology studies performed by the manufacturer, alfuzosin may also prolong the QT interval in a dose-dependent manner.
Alpelisib: (Major) Avoid coadministration of alpelisib with osimertinib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and osimertinib is a BCRP inhibitor.
Amiodarone: (Major) Concomitant use of osimertinib and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Avoid coadministration of amisulpride with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Amisulpride causes dose- and concentration- dependent QT prolongation.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Anagrelide: (Major) Do not use anagrelide with other drugs that prolong the QT interval. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Torsade de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects who received anagrelide.
Apalutamide: (Major) Avoid coadministration of apalutamide with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If apalutamide is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Apomorphine: (Major) Avoid coadministration of apomorphine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) Concomitant use of osimertinib and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with other drugs that may cause QT interval prolongation such as osimertinib; discontinue osimertinib or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant use is unavoidable, frequently monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Concomitant use may increase the risk of QT prolongation.
Artemether; Lumefantrine: (Major) Avoid coadministration of artemether with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Artemether is also associated with prolongation of the QT interval. Concomitant use may increase the risk of QT prolongation. (Major) Avoid coadministration of lumefantrine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Artemether is also associated with prolongation of the QT interval. Concomitant use may increase the risk of QT prolongation.
Asenapine: (Major) The manufacturer of asenapine recommends avoiding coadministration with other agents known to prolong the QT interval, such as osimertinib. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Asenapine has also been associated with QT prolongation. Concomitant use may increase the risk of QT prolongation.
Atomoxetine: (Major) Concomitant use of osimertinib and atomoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Azithromycin: (Major) Concomitant use of osimertinib and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Avoid coadministration of bedaquiline with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Bedaquiline has been reported to prolong the QT interval. Coadministration with other QT prolonging drugs may result in additive or synergistic prolongation of the QT interval.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking osimertinib. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp and BCRP substrate and osimertinib is a P-gp and BCRP inhibitor. Coadministration with another P-gp and BCRP inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving osimertinib. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving osimertinib. Concurrent use may increase betrixaban exposure resulting in an increased bleeding risk; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a P-gp substrate; osimertinib is a P-gp inhibitor. Coadministration of other P-gp inhibitors increased betrixaban exposure by 2 to 3 fold.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine: (Major) Concomitant use of osimertinib and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of osimertinib and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cabotegravir; Rilpivirine: (Major) Avoid coadministration of rilpivirine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Carbamazepine: (Major) Avoid coadministration of carbamazepine with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If carbamazepine is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Ceritinib: (Major) Avoid coadministration of ceritinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in ceritinib-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes. An interruption of therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, and has also been reported with ceritinib. Additionally, ceritinib is a substrate of P-glycoprotein (P-gp) and osimertinib is a P-gp inhibitor.
Chloroquine: (Major) Avoid coadministration of chloroquine with osimertinib due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. An interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses.
Chlorpromazine: (Major) Avoid coadministration of chlorpromazine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Major) Concomitant use of osimertinib and ciprofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of osimertinib with cisapride is contraindicated. QT prolongation and ventricular arrhythmias, including TdP and death, have been reported with cisapride. Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib. Concomitant use may increase the risk of QT prolongation.
Citalopram: (Major) Concomitant use of osimertinib and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Avoid coadministration of clarithromycin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Clofazimine: (Major) Concomitant use of clofazimine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clomipramine: (Major) If possible, avoid coadministration of clomipramine and osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Clozapine: (Major) Avoid coadministration of clozapine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death.
Cobimetinib: (Moderate) Monitor for an increase in cobimetinib-related adverse reactions if coadministration with osimertinib is necessary. Cobimetinib is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of cobimetinib.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Codeine; Promethazine: (Major) Concomitant use of promethazine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and osimertinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Osimertinib can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken osimertinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
Crizotinib: (Major) Avoid coadministration of crizotinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib; crizotinib has been associated with concentration-dependent QT prolongation.
Cyclosporine: (Moderate) Monitor cyclosporine levels if coadministration with osimertinib is necessary; adjust the dose of cyclosporine if clinically appropriate. Cyclosporine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase cyclosporine exposure.
Dabigatran: (Moderate) Monitor for an increase in dabigatran-related adverse reactions if coadministration with osimertinib is necessary. When dabigatran is administered for treatment or reduction in risk of recurrence of deep venous thrombosis (DVT) or pulmonary embolism (PE) or prophylaxis of DVT or PE following hip replacement surgery, avoid coadministration with osimertinib in patients with CrCL less than 50 mL/minute. When dabigatran is used in patients with non-valvular atrial fibrillation and severe renal impairment (CrCL less than 30 mL/minute), avoid coadministration with osimertinib, as serum concentrations of dabigatran are expected to be higher than when administered to patients with normal renal function. Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein (P-gp) substrate, is coadministered with osimertinib, a P-gp inhibitor; P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. Coadministration of dabigatran and a single oral dose of another P-gp inhibitor increased the dabigatran AUC and Cmax by 58% and 50%, respectively; there was additionally a 65% increase in renal clearance of dabigatran.
Darunavir: (Moderate) Monitor for an increase in darunavir-related adverse reactions if coadministration with osimertinib is necessary. Darunavir may be a P-glycoprotein (P-gp) substrate; osimertinib is a P-gp inhibitor. Coadministration with drugs that inhibit P-gp may decrease the clearance of darunavir, resulting in increased plasma concentrations.
Darunavir; Cobicistat: (Moderate) Monitor for an increase in darunavir-related adverse reactions if coadministration with osimertinib is necessary. Darunavir may be a P-glycoprotein (P-gp) substrate; osimertinib is a P-gp inhibitor. Coadministration with drugs that inhibit P-gp may decrease the clearance of darunavir, resulting in increased plasma concentrations.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for an increase in darunavir-related adverse reactions if coadministration with osimertinib is necessary. Darunavir may be a P-glycoprotein (P-gp) substrate; osimertinib is a P-gp inhibitor. Coadministration with drugs that inhibit P-gp may decrease the clearance of darunavir, resulting in increased plasma concentrations.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in dasabuvir-related adverse reactions during coadministration of osimertinib. Dasabuvir exposure may be increased. Dasabuvir is a substrate of BCRP and P-glycoprotein (P-gp). Osimertinib is a BCRP and P-gp inhibitor. (Moderate) Monitor for an increase in ombitasvir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase plasma concentrations of ombitasvir. Ombitasvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor. (Moderate) Monitor for an increase in paritaprevir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase plasma concentrations of paritaprevir. Paritaprevir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Dasatinib: (Major) Avoid coadministration of dasatinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. In vitro studies have shown that dasatinib also has the potential to prolong the QT interval.
Degarelix: (Major) Avoid coadministration of degarelix with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval.
Desflurane: (Major) Avoid coadministration of halogenated anesthetics with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Halogenated anesthetics can also prolong the QT interval.
Desipramine: (Major) If possible, avoid coadministration of desipramine and osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Deutetrabenazine: (Major) Avoid coadministration of deutetrabenazine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dextromethorphan; Quinidine: (Major) Avoid coadministration of quinidine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in quinidine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Quinidine administration is associated with both QT prolongation and TdP. Additionally, quinidine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Disopyramide: (Major) Avoid coadministration of disopyramide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Disopyramide administration is associated with QT prolongation and TdP.
Dofetilide: (Major) Avoid coadministration of dofetilide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Dolasetron: (Major) Avoid coadministration of dolasetron with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase dolutegravir plasma concentrations. Dolutegravir is a BCRP and P-glycoprotein (P-gp) substrate and osimertinib is a BCRP and P-gp inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase dolutegravir plasma concentrations. Dolutegravir is a BCRP and P-glycoprotein (P-gp) substrate and osimertinib is a BCRP and P-gp inhibitor.
Dolutegravir; Rilpivirine: (Major) Avoid coadministration of rilpivirine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase dolutegravir plasma concentrations. Dolutegravir is a BCRP and P-glycoprotein (P-gp) substrate and osimertinib is a BCRP and P-gp inhibitor.
Donepezil: (Major) Avoid coadministration of donepezil with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Donepezil; Memantine: (Major) Avoid coadministration of donepezil with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Case reports indicate that QT prolongation and TdP can occur during donepezil therapy.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Doxepin: (Major) If possible, avoid coadministration of doxepin and osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Doxorubicin Liposomal: (Major) Avoid coadministration of osimertinib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Osimertinib is a P-gp inhibitor and doxorubicin is a P-gp substrate. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of osimertinib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Osimertinib is a P-gp inhibitor and doxorubicin is a P-gp substrate. Concurrent use of P-gp inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronedarone: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of osimertinib with dronedarone is contraindicated. Dronedarone is associated with a risk for QT prolongation and TdP. Osimertinib causes concentration dependent prolongation of the QT interval at recommended dosing. Additive QT prolongation is possible.
Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as osimertinib. If coadministration cannot be avoided, use extreme caution; monitor electrolytes and ECGs for QT prolongation. Initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. An interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib.
Edoxaban: (Moderate) Monitor for an increase in edoxaban-related adverse reactions if coadministration with osimertinib is necessary. Dosage reduction may be considered for patients being treated for deep venous thrombosis (DVT) or pulmonary embolism. Edoxaban is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Increased concentrations of edoxaban may occur during concomitant use.
Efavirenz: (Major) Avoid coadministration of efavirenz with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QTc prolongation has been observed with the use of efavirenz.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of efavirenz with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QTc prolongation has been observed with the use of efavirenz. (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of efavirenz with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QTc prolongation has been observed with the use of efavirenz. (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Eliglustat: (Major) Avoid coadministration of eliglustat with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of rilpivirine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of rilpivirine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation. (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Encorafenib: (Major) Avoid coadministration of encorafenib and osimertinib due to the potential for additive QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Encorafenib is associated with dose-dependent prolongation of the QT interval. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Entrectinib: (Major) Avoid coadministration of entrectinib with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Entrectinib has been associated with QT prolongation.
Enzalutamide: (Major) Avoid coadministration of osimertinib with enzalutamide due to the risk of decreased osimertinib exposure, resulting in decreased efficacy. If concomitant use is unavoidable, increase the daily dose of osimertinib to 160 mg. Resume normal dosing of osimertinib (80 mg once daily) 3 weeks after discontinuation of enzalutamide. Osimertinib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Eribulin: (Major) Avoid coadministration of eribulin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Eribulin has also been associated with QT prolongation.
Erythromycin: (Major) Concomitant use of osimertinib and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Major) Concomitant use of osimertinib and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with osimertinib is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Fingolimod: (Major) Avoid coadministration of fingolimod with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Fingolimod initiation results in decreased heart rate and may prolong the QT interval; after the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of TdP. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
Flecainide: (Major) Concomitant use of osimertinib and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Major) Concomitant use of osimertinib and fluconazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluoxetine: (Major) Concomitant use of osimertinib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) Use osimertinib and fluphenazine together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Fluphenazine is also associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Monitor for an increase in umeclidinium-related adverse reactions if coadministration with osimertinib is necessary. Umeclidinium is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased umeclidinium exposure by 1.4-fold.
Fluvoxamine: (Major) Avoid coadministration of fluvoxamine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation and TdP has been reported during fluvoxamine post-marketing use.
Foscarnet: (Major) Avoid the use of foscarnet with other drugs known to prolong the QT interval such as osimertinib. If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet; concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib.
Fosphenytoin: (Major) Avoid coadministration of fosphenytoin with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If fosphenytoin is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Fostemsavir: (Major) Avoid coadministration of fostemsavir with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Gemifloxacin: (Major) Avoid coadministration of gemifloxacin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Major) Avoid coadministration of gemtuzumab with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, obtain an ECG and serum electrolytes prior to the start of combination therapy, and periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Major) Avoid coadministration of gilteritinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Gilteritinib has also been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with osimertinib due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring and monitoring of electrolytes. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and osimertinib as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). Osimertinib is a BCRP and P-gp inhibitor. (Moderate) Monitor for an increase in pibrentasvir-related adverse reactions if coadministration with osimertinib is necessary. Pibrentasvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor. Concomitant use may increase plasma concentrations of pibrentasvir.
Glyburide: (Moderate) Monitor for an increase in glyburide-related adverse reactions, including hypoglycemia, if coadministration with osimertinib is necessary. Glyburide is a P-glycoprotein (P-gp) substrate. Osimertinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates.
Glyburide; Metformin: (Moderate) Monitor for an increase in glyburide-related adverse reactions, including hypoglycemia, if coadministration with osimertinib is necessary. Glyburide is a P-glycoprotein (P-gp) substrate. Osimertinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates.
Goserelin: (Major) Avoid coadministration of goserelin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., goserelin) may also prolong the QT/QTc interval.
Granisetron: (Major) Avoid coadministration of granisetron with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Granisetron has also been associated with QT prolongation.
Halogenated Anesthetics: (Major) Avoid coadministration of halogenated anesthetics with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Halogenated anesthetics can also prolong the QT interval.
Haloperidol: (Major) Avoid coadministration of haloperidol with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation and TdP have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation.
Histrelin: (Major) Avoid coadministration of histrelin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., histrelin) may also prolong the QT/QTc interval.
Hydroxychloroquine: (Major) Concomitant use of osimertinib and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of osimertinib and hydroxyzine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibutilide: (Major) Avoid coadministration of ibutilide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Ibutilide administration can also cause QT prolongation and TdP; proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval.
Iloperidone: (Major) According to the manufacturer of iloperidone, coadministration with other agents known to prolong the QT interval, such as osimertinib, should be avoided. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, and iloperidone has also been associated with QT prolongation.
Imatinib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with osimertinib is necessary. Imatinib is a BCRP substrate and osimertinib is a BCRP inhibitor.
Imipramine: (Major) If possible, avoid coadministration of imipramine and osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Indinavir: (Moderate) Monitor for an increase in indinavir-related adverse reactions if coadministration with osimertinib is necessary. Indinavir is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase indinavir exposure.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab with osimertinib due to the potential for additive QT prolongation and torsade de pointes (TdP). If coadministration is unavoidable, obtain ECGs and prior to the start of treatment and periodically during treatment; monitor electrolytes. An interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Inotuzumab has been associated with QT interval prolongation, and concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Isoflurane: (Major) Avoid coadministration of halogenated anesthetics with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Halogenated anesthetics can also prolong the QT interval.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of rifampin with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If rifampin is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased osimertinib exposure by 78%.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of rifampin with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If rifampin is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased osimertinib exposure by 78%.
Itraconazole: (Major) Avoid coadministration of itraconazole with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in itraconazole-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Itraconazole has also been associated with prolongation of the QT interval. Additionally, itraconazole is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with osimertinib due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib and/or osimertinib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and osimertinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Lapatinib: (Major) Avoid coadministration of lapatinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP); exposure to lapatinib may also increase. If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Correct electrolyte abnormalities prior to treatment. Lapatinib is a P-glycoprotein (P-gp) substrate that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely when administered with P-gp inhibitors.
Ledipasvir; Sofosbuvir: (Moderate) Monitor for an increase in sofosbuvir-related adverse reactions if coadministration with osimertinib is necessary. Sofosbuvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Lefamulin: (Major) Avoid coadministration of lefamulin with osimertinib as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. If coadministration cannot be avoided, monitor ECG and electrolytes during treatment; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Additionally, monitor for lefamulin-related adverse effects if oral lefamulin is administered. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Osimertinib is a P-gp inhibitor that has been associated with concentration-dependent QTc prolongation.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with osimertinib due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Leuprolide: (Major) Avoid coadministration of leuprolide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., leuprolide) may also prolong the QT/QTc interval.
Levofloxacin: (Major) Concomitant use of osimertinib and levofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and osimertinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lithium: (Major) Concomitant use of osimertinib and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Major) Avoid coadministration of lofexidine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Loperamide: (Major) Concomitant use of loperamide and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a P-gp substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with osimertinib due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Interrupt or dose reduce osimertinib if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Lopinavir is associated with QT prolongation.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If lumacaftor; ivacaftor is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of lumacaftor; ivacaftor with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If lumacaftor; ivacaftor is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and lumacaftor is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as osimertinib. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Maprotiline: (Major) Avoid coadministration of maprotiline with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Maprotiline has also been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and TdP tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with osimertinib is necessary. Maraviroc is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase maraviroc exposure.
Mefloquine: (Major) Avoid coadministration of mefloquine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for increased mefloquine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation; however, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval. Additionally, mefloquine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Meperidine; Promethazine: (Major) Concomitant use of promethazine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Methadone: (Major) Avoid coadministration of methadone with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, use extreme caution; monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Methadone is considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses (greater than 200 mg/day but averaging approximately 400 mg/day in adult patients). Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Methotrexate: (Moderate) Monitor for an increase in methotrexate-related adverse reactions if coadministration with osimertinib is necessary. Methotrexate is a BCRP substrate and osimertinib is a BCRP inhibitor.
Metronidazole: (Major) Concomitant use of metronidazole and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midostaurin: (Major) Avoid coadministration of midostaurin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation was also reported in patients who received midostaurin in clinical trials.
Mifepristone: (Major) Concomitant use of osimertinib and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirtazapine: (Major) Concomitant use of osimertinib and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mitotane: (Major) Avoid coadministration of mitotane with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If mitotane is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and mitotane is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Mitoxantrone: (Moderate) Monitor for an increase in mitoxantrone-related adverse reactions if coadministration with osimertinib is necessary. Mitoxantrone is a BCRP substrate and osimertinib is a BCRP inhibitor.
Mobocertinib: (Major) Concomitant use of mobocertinib and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Morphine: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death, if coadministration with osimertinib is necessary; decrease the dose of morphine as clinically appropriate. Morphine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. The concomitant use of P-gp inhibitors can increase the exposure to morphine by about 2-fold.
Morphine; Naltrexone: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death, if coadministration with osimertinib is necessary; decrease the dose of morphine as clinically appropriate. Morphine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. The concomitant use of P-gp inhibitors can increase the exposure to morphine by about 2-fold.
Moxifloxacin: (Major) Avoid coadministration of moxifloxacin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Quinolones have also been associated with a risk of QT prolongation; although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
Naldemedine: (Moderate) Monitor for an increase in naldemedine-related adverse reactions if coadministration with osimertinib is necessary. Naldemedine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase naldemedine exposure.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid coadministration of sirolimus with osimertinib as concurrent use may increase sirolimus exposure and risk of toxicity. Alternative agents with lesser interaction potential with sirolimus should be considered. Sirolimus is a P-gp substrate and osimertinib is a P-gp inhibitor.
Nelfinavir: (Moderate) Monitor for an increase in nelfinavir-related adverse reactions if coadministration with osimertinib is necessary. Nelfinavir is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase nelfinavir exposure.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and osimertinib; significant prolongation of the QT interval may occur. If concomitant use is unavoidable, closely monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Nortriptyline: (Major) If possible, avoid coadministration of nortriptyline and osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Ofloxacin: (Major) Concomitant use of osimertinib and ofloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Avoid coadministration of olanzapine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of olanzapine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. (Major) Concomitant use of osimertinib and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine; Samidorphan: (Major) Avoid coadministration of olanzapine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval.
Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Monitor for an increase in ombitasvir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase plasma concentrations of ombitasvir. Ombitasvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor. (Moderate) Monitor for an increase in paritaprevir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase plasma concentrations of paritaprevir. Paritaprevir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Ondansetron: (Major) Concomitant use of osimertinib and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Major) Avoid coadministration of osilodrostat with osimertinib due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Osilodrostat is associated with dose-dependent QT prolongation.
Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, correct electrolyte abnormalities prior to administration of oxaliplatin. Periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation and ventricular arrhythmias including fatal TdP have been reported with oxaliplatin use in postmarketing experience.
Ozanimod: (Major) Concomitant use of ozanimod and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Pacritinib: (Major) Concomitant use of pacritinib and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) According to the manufacturer of paliperidone, coadministration with other agents that prolong the QT interval, such as osimertinib, should be avoided. If concomitant use is unavoidable, closely monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Paliperidone has been associated with QT prolongation; torsade de pointes and ventricular fibrillation have been reported in the setting of overdose.
Panobinostat: (Major) According to the manufacturer of panobinostat, coadministration with other agents that prolong the QT interval, such as osimertinib, is not recommended. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, and QT prolongation has also been reported with panobinostat. Additionally, panobinostat is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor; concomitant use may increase panobinostat exposure.
Pasireotide: (Major) Avoid coadministration of pasireotide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation has also occurred with pasireotide at therapeutic and supra-therapeutic doses.
Pazopanib: (Major) According to the manufacturer of pazopanib, coadministration with other medications that prolong the QT interval, such as osimertinib, is not advised. If concomitant use is unavoidable, monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Additionally, monitor for an increase in pazopanib related adverse reactions if coadministration with osimertinib is necessary. Pazopanib is a BCRP and P-glycoprotein (P-gp) substrate that has been reported to prolong the QT interval. Osimertinib is a BCRP and P-gp inhibitor that is associated with concentration-dependent QT prolongation.
Pentamidine: (Major) Avoid coadministration of pentamidine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Systemic pentamidine has also been associated with QT prolongation.
Perphenazine: (Minor) Use osimertinib and perphenazine together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Perphenazine is also associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Perphenazine; Amitriptyline: (Minor) Use osimertinib and perphenazine together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Perphenazine is also associated with a possible risk for QT prolongation. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Phenobarbital: (Major) Avoid coadministration of phenobarbital with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If phenobarbital is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of phenobarbital with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If phenobarbital is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and phenobarbital is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Phenytoin: (Major) Avoid coadministration of phenytoin with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If phenytoin is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Pimavanserin: (Major) Avoid coadministration of pimavanserin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Pimavanserin may also cause QT prolongation.
Pimozide: (Contraindicated) Concomitant use of osimertinib and pimozide is contraindicated because there is an increased risk of QT prolongation and torsade de pointes (TdP). Pimozide is associated with a well-established risk of QT prolongation and TdP. Osimertinib causes concentration dependent prolongation of the QT interval at recommended dosing.
Pitolisant: (Major) Avoid coadministration of pitolisant with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Pitolisant prolongs the QT interval.
Ponesimod: (Major) Avoid coadministration of ponesimod with osimertinib if possible due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If concomitant use is unavoidable, periodically monitor ECGs, electrolytes, and for signs and symptoms of infection; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia.
Posaconazole: (Major) Avoid coadministration of posaconazole with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in posaconazole-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Posaconazole is a P-glycoprotein (P-gp) substrate that has been associated with prolongation of the QT interval as well as rare cases of TdP. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, which is also a P-gp inhibitor.
Primaquine: (Major) Avoid coadministration of primaquine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Primaquine may also cause QT interval prolongation.
Primidone: (Major) Avoid coadministration of primidone with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If primidone is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and primidone is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Probenecid; Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and osimertinib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Osimertinib can inhibit colchicine's metabolism via P-glycoprotein (P-gp), resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken osimertinib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
Procainamide: (Major) Avoid coadministration of procainamide with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Procainamide is associated with a well-established risk of QT prolongation and TdP.
Prochlorperazine: (Minor) Use osimertinib and prochlorperazine together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Promethazine: (Major) Concomitant use of promethazine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of propafenone and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Protriptyline: (Major) If possible, avoid coadministration of protriptyline and osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Quetiapine: (Major) Concomitant use of quetiapine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinidine: (Major) Avoid coadministration of quinidine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in quinidine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Quinidine administration is associated with both QT prolongation and TdP. Additionally, quinidine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Quinine: (Major) Avoid coadministration of quinine with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, monitor for an increase in quinine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Quinine is a P-glycoprotein (P-gp) substrate that has been associated with QT prolongation and rare cases of TdP. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, which is also a P-gp inhibitor.
Ranolazine: (Major) Avoid coadministration of ranolazine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in ranolazine-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Ranolazine is a P-glycoprotein (P-gp) substrate that is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration may result in additive QT prolongation. Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib, which is a P-gp inhibitor.
Relugolix: (Major) Avoid concomitant use of relugolix and oral osimertinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer osimertinib at least 6 hours after relugolix and monitor for adverse reactions as well as periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Relugolix is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral osimertinib. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer osimertinib at least 6 hours after relugolix and monitor for adverse reactions as well as periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Relugolix is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Ribociclib: (Major) Avoid coadministration of ribociclib with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). Both drugs have been shown to prolong the QT interval in a concentration-dependent manner. For ribociclib, these ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). Both drugs have been shown to prolong the QT interval in a concentration-dependent manner. For ribociclib, these ECG changes occurred within the first four weeks of treatment and were reversible with dose interruption.
Rifampin: (Major) Avoid coadministration of rifampin with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If rifampin is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and rifampin is a strong CYP3A4 inducer. Coadministration with rifampin decreased osimertinib exposure by 78%.
Rifapentine: (Major) Avoid coadministration of rifapentine with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If rifapentine is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) Avoid coadministration of rilpivirine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have also caused QT prolongation.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with osimertinib; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and osimertinib is a P-gp inhibitor.
Risperidone: (Major) Avoid coadministration of risperidone with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in risperidone-related adverse reactions, periodically monitor ECGs for QT prolongation, and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Reports of QT prolongation and TdP during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting.
Romidepsin: (Major) Avoid coadministration of romidepsin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor for an increase in romidepsin-related adverse reactions, monitor electrolytes, and monitor ECGs for QT prolongation at baseline and periodically during treatment; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Romidepsin is a P-glycoprotein (P-gp) substrate that has been reported to prolong the QT interval. Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib, which is a P-gp inhibitor.
Rosuvastatin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including rhabdomyolysis and myopathy, if coadministration with osimertinib is necessary. Rosuvastatin is a BCRP substrate and osimertinib is a BCRP inhibitor. Concomitant use increased the AUC of rosuvastatin by 35% and the Cmax by 72%.
Rosuvastatin; Ezetimibe: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including rhabdomyolysis and myopathy, if coadministration with osimertinib is necessary. Rosuvastatin is a BCRP substrate and osimertinib is a BCRP inhibitor. Concomitant use increased the AUC of rosuvastatin by 35% and the Cmax by 72%.
Saquinavir: (Major) Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as osimertinib. If concomitant use is unavoidable, monitor for an increase in saquinavir-related adverse reactions, monitor electrolytes, and monitor ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Saquinavir is a P-glycoprotein (P-gp) substrate that, when boosted with ritonavir, increases the QT interval in a dose-dependent fashion which may increase the risk for serious arrhythmias such as TdP. Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib, which is a P-gp inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Major) Avoid coadministration of selpercatinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QT prolongation has been observed with osimertinib and selpercatinib therapy.
Sertraline: (Major) Concomitant use of sertraline and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Avoid coadministration of halogenated anesthetics with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Halogenated anesthetics can also prolong the QT interval.
Simeprevir: (Moderate) Monitor for an increase in simeprevir-related adverse reactions if coadministration with osimertinib is necessary. Simeprevir is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase simeprevir exposure.
Siponimod: (Major) Avoid coadministration of siponimod and osimertinib due to the potential for additive QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib.
Sirolimus: (Major) Avoid coadministration of sirolimus with osimertinib as concurrent use may increase sirolimus exposure and risk of toxicity. Alternative agents with lesser interaction potential with sirolimus should be considered. Sirolimus is a P-gp substrate and osimertinib is a P-gp inhibitor.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sofosbuvir: (Moderate) Monitor for an increase in sofosbuvir-related adverse reactions if coadministration with osimertinib is necessary. Sofosbuvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Sofosbuvir; Velpatasvir: (Moderate) Monitor for an increase in sofosbuvir-related adverse reactions if coadministration with osimertinib is necessary. Sofosbuvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Monitor for an increase in sofosbuvir-related adverse reactions if coadministration with osimertinib is necessary. Sofosbuvir is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Solifenacin: (Major) Avoid coadministration of solifenacin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Solifenacin has also been associated with dose-dependent prolongation of the QT interval; TdP has been reported with postmarketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with osimertinib due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Sorafenib is associated with QTc prolongation.
Sotalol: (Major) Concomitant use of sotalol and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of St. John's Wort with osimertinib due to decreased plasma concentrations of osimertinib which may lead to reduced efficacy. If concomitant use is unavoidable, increase the dose of osimertinib to 160 mg once daily. If St. John's Wort is discontinued, reduce the dose of osimertinib to 80 mg once daily after a washout period of 3 weeks. Osimertinib is a CYP3A4 substrate and St. John's Wort is a strong CYP3A4 inducer, although the effect varies widely and is preparation-dependent. Coadministration with another strong CYP3A4 inducer decreased osimertinib exposure by 78%.
Sulfasalazine: (Moderate) Monitor for an increase in sulfasalazine-related adverse reactions if coadministration with osimertinib is necessary. Sulfasalazine is a BCRP substrate and osimertinib is a BCRP inhibitor.
Sunitinib: (Major) Avoid coadministration of sunitinib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Sunitinib can also prolong the QT interval.
Tacrolimus: (Major) Avoid coadministration of tacrolimus with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Tacrolimus also causes QT prolongation.
Talazoparib: (Major) Avoid coadministration of osimertinib with talazoparib due to increased talazoparib exposure. If concomitant use is unavoidable, monitor for an increase in talazoparib-related adverse reactions. Talazoparib is a BCRP substrate and osimertinib is a BCRP inhibitor. The effect of concomitant administration of BCRP inhibitors on the pharmacokinetics of talazoparib has not been studied; however, BCRP inhibitors may increase talazoparib exposure.
Tamoxifen: (Major) Concomitant use of tamoxifen and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telavancin: (Major) Avoid coadministration of telavancin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Telavancin has also been associated with QT prolongation.
Temsirolimus: (Moderate) Monitor for an increase in temsirolimus-related adverse reactions if coadministration with osimertinib is necessary. Temsirolimus is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of temsirolimus.
Tenofovir Alafenamide: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir alafenamide is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an increase in tenofovir-related adverse reactions if coadministration with osimertinib is necessary. Concomitant use may result in increased tenofovir absorption. Tenofovir disoproxil is a BCRP and P-glycoprotein (P-gp) substrate. Osimertinib is a BCRP and P-gp inhibitor.
Tetrabenazine: (Major) Avoid coadministration of tetrabenazine with osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib.
Thioridazine: (Contraindicated) Concomitant use of osimertinib and thioridazine is contraindicated because there is an increased risk of QT prolongation and torsade de pointes (TdP). Osimertinib causes concentration dependent prolongation of the QT interval at recommended dosing. In addition, thioridazine is associated with a well-established risk of QT prolongation and TdP. Coadministration may further increase the risk of QT prolongation.
Ticagrelor: (Moderate) Monitor for an increase in ticagrelor-related adverse reactions, including bleeding, if coadministration with osimertinib is necessary. Ticagrelor is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Tipranavir: (Moderate) Monitor for an increase in tipranavir-related adverse reactions if coadministration with osimertinib is necessary. Tipranavir is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Tolterodine: (Major) Avoid coadministration of tolterodine with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Topotecan: (Major) Avoid coadministration of osimertinib with oral topotecan due to increased topotecan exposure; osimertinib may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP); osimertinib is a P-gp and BCRP inhibitor. Following escalating doses of a dual inhibitor of BCRP and P-gp, the AUC of topotecan lactone and total topotecan increased by approximately 2.5-fold compared to topotecan alone. Coadministration of a dual P-gp/BCRP inhibitor with intravenous topotecan increased total topotecan exposure by 1.2-fold and exposure to topotecan lactone by 1.1-fold.
Toremifene: (Major) Avoid coadministration of osimertinib with toremifene due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Both drugs have been shown to prolong the QTc interval in a dose- and concentration-related manner.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with osimertinib is necessary. Verapamil is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase verapamil exposure.
Trazodone: (Major) Concomitant use of trazodone and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triclabendazole: (Major) Concomitant use of triclabendazole and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) Use osimertinib and trifluoperazine together with caution due to the risk of QT prolongation. The manufacturer of osimertinib recommends avoiding coadministration with other drugs that prolong the QT, if possible; if unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Trimipramine: (Major) If possible, avoid coadministration of trimipramine and osimertinib due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor electrolytes and ECGs for QT prolongation; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Concentration-dependent QTc prolongation also occurred during clinical trials of osimertinib.
Triptorelin: (Major) Avoid coadministration of triptorelin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with osimertinib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the BCRP and P-gp drug transporters; osimertinib is a BCRP and P-gp inhibitor.
Umeclidinium: (Moderate) Monitor for an increase in umeclidinium-related adverse reactions if coadministration with osimertinib is necessary. Umeclidinium is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased umeclidinium exposure by 1.4-fold.
Umeclidinium; Vilanterol: (Moderate) Monitor for an increase in umeclidinium-related adverse reactions if coadministration with osimertinib is necessary. Umeclidinium is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased umeclidinium exposure by 1.4-fold.
Vandetanib: (Major) Avoid coadministration of vandetanib with vandetanib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor electrolytes and ECGs for QT prolongation; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of therapy or dose reduction for both drugs may be necessary for QT prolongation. Both osimertinib and vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have also been reported in patients receiving vandetanib.
Vardenafil: (Major) Concomitant use of vardenafil and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Avoid coadministration of vemurafenib with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Vemurafenib has also been associated with QT prolongation.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with osimertinib due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of osimertinib. Venetoclax is a P-glycoprotein (P-gp) substrate; osimertinib is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Venlafaxine: (Major) Concomitant use of venlafaxine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verapamil: (Moderate) Monitor blood pressure and heart rate if coadministration of verapamil with osimertinib is necessary. Verapamil is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. Concomitant use may increase verapamil exposure.
Vincristine Liposomal: (Moderate) Monitor for an increase in vincristine-related adverse reactions if coadministration with osimertinib is necessary. Vincristine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Vincristine: (Moderate) Monitor for an increase in vincristine-related adverse reactions if coadministration with osimertinib is necessary. Vincristine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Voclosporin: (Major) Avoid concomitant use of osimertinib and voclosporin if possible due to the risk of additive QT prolongation and torsade de pointes (TdP). If concomitant use is necessary, periodically monitor ECGs and electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Voclosporin has been associated with QT prolongation at supratherapeutic doses.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Clarithromycin is associated with an established risk for QT prolongation and TdP.
Voriconazole: (Major) Avoid coadministration of voriconazole with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Voriconazole has also been associated with QT prolongation and rare cases of TdP.
Vorinostat: (Major) Avoid coadministration of vorinostat with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Vorinostat therapy is also associated with a risk of QT prolongation.
Ziprasidone: (Major) Concomitant use of ziprasidone and osimertinib should be avoided due to a potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Concentration-dependent QTc prolongation has also occurred during clinical trials of osimertinib.