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Zykadia
Classes
Small Molecule Antineoplastic Anaplastic Lymphoma Kinase (ALK) Inhibitors
Administration
Hazardous Drugs Classification
NIOSH (Draft) 2020 List: Table 2
Approved by FDA after NIOSH 2016 list published. The manufacturer recommends this drug be handled as a hazardous drug.
Emetic Risk
Moderate/High
Administer routine antiemetic prophylaxis prior to treatment.
Take ceritinib with food.
Swallow whole; do not crush or cut.
Do not take with grapefruit or grapefruit juice.
If a dose is missed, make it up unless the next dose is due within 12 hours. Do not take 2 doses at the same time if a dose is missed.
If vomiting occurs, do not take an additional dose. Take the next dose at the next scheduled time.
Adverse Reactions
elevated hepatic enzymes / Delayed / 13.0-49.0
hyperglycemia / Delayed / 10.0-13.0
visual impairment / Early / 4.0-9.0
hyperamylasemia / Delayed / 7.0-8.0
asthenia / Delayed / 5.0-7.0
fatigue / Early / 5.0-7.0
hypophosphatemia / Delayed / 3.7-7.0
abdominal pain / Early / 1.1-6.0
diarrhea / Early / 1.1-6.0
QT prolongation / Rapid / 1.3-6.0
vomiting / Early / 0-5.0
anemia / Delayed / 4.2-5.0
nausea / Early / 0-4.0
bradycardia / Rapid / 1.1-4.0
infection / Delayed / 0-4.0
renal failure (unspecified) / Delayed / 2.0-4.0
weight loss / Delayed / 0-3.7
neutropenia / Delayed / 2.1-2.1
pericardial effusion / Delayed / 2.0-2.0
back pain / Delayed / 1.6-1.6
pericarditis / Delayed / 1.6-1.6
pneumonitis / Delayed / 1.5-1.5
anorexia / Delayed / 1.0-1.1
rash / Early / 0-1.1
dizziness / Early / 1.1-1.1
hyperbilirubinemia / Delayed / 0.5-1.0
pancreatitis / Delayed / 0-1.0
thrombocytopenia / Delayed / 1.0-1.0
pruritus / Rapid / 0-0.5
musculoskeletal pain / Early / 0.5-0.5
headache / Early / 0.5-0.5
seizures / Delayed / 2.0
dehydration / Delayed / 2.0
GI bleeding / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
constipation / Delayed / 20.0-29.0
dysphagia / Delayed / Incidence not known
dyspnea / Early / Incidence not known
hypotonia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
blurred vision / Early / Incidence not known
photopsia / Delayed / Incidence not known
cough / Delayed / 0-25.0
fever / Early / 19.0-19.0
photosensitivity / Delayed / 1.1-1.2
gastroesophageal reflux / Delayed / Incidence not known
dyspepsia / Early / Incidence not known
acneiform rash / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
paresthesias / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
dysesthesia / Delayed / Incidence not known
weakness / Early / Incidence not known
Common Brand Names
Zykadia
Dea Class
Rx
Description
An oral kinase inhibitor, primarily targeting anaplastic lymphoma kinase (ALK)
Used for the treatment of ALK-positive, metastatic non-small cell lung cancer
Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions
Dosage And Indications
NOTE: Patients should be selected based on the presence of ALK positivity in tumor specimens. Information on FDA-approved tests for the detection of ALK rearrangements is available at www.fda.gov/CompanionDiagnostics.
For the treatment of ALK-positive metastatic NSCLC in patients who have progressed on or are intolerant to crizotinib. Oral dosage Adults
450 mg orally once daily with food until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, single-arm, open-label clinical trial, patients with ALK-positive, metastatic NSCLC who progressed or were intolerant to crizotinib (n = 163) had an objective response rate of 43.6% (partial response, 41.1%; complete response, 2.5%) as evaluated by a blinded independent central review committee. The duration of response was 7.1 months.
450 mg orally once daily with food until disease progression or unacceptable toxicity. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In a multicenter, randomized, open-label phase 3 clinical trial, treatment with ceritinib (n = 175) significantly improved PFS as assessed by a blinded independent review committee in patients with previously untreated ALK-rearranged metastatic NSCLC compared with platinum-based chemotherapy plus pemetrexed, followed by pemetrexed maintenance therapy (n = 189) (16.6 months vs. 8.1 months); the overall response rate was 73% vs. 27%, respectively (partial response, 72% vs. 27%). Overall survival, while not mature, was not significantly improved (not estimable vs. 26.2 months); however, this may have been confounded by 72% of chemotherapy patients receiving treatment with ceritinib after progression. In patients with measurable intracranial disease at baseline, the overall response rate was higher with ceritinib (n = 28) versus chemotherapy (n = 27) (57% vs. 22%), with partial responses in 50% versus 15% of patients, respectively.
Dosing Considerations
Baseline Hepatic Impairment:
Mild to moderate hepatic impairment (Child-Pugh A or B): No dose adjustment is recommended.
Severe hepatic impairment (Child-Pugh C): Reduce the starting dose of ceritinib by approximately one-third, rounded to the nearest multiple of the 150-mg dosage strength.
Treatment-Related Hepatotoxicity:
Total bilirubin 2 times the upper limit of normal (ULN) or less, and ALT/AST greater than 5 times ULN: Hold ceritinib therapy. When ALT/AST levels return to baseline or less than or equal to 3 times ULN, resume ceritinib therapy at the next lower dose; do not resume therapy in patients unable to tolerate 150 mg once daily with food.
Total bilirubin greater than 2 times ULN in the absence of cholestasis or hemolysis, and ALT/AST greater than 3 times ULN: Permanently discontinue ceritinib treatment.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with ceritinib is necessary. Dolutegravir is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Abemaciclib: (Major) If coadministration with ceritinib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If ceritinib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of ceritinib. Abemaciclib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and ceritinib; significantly increased acalabrutinib exposure may occur. Acalabrutinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In healthy subjects, the Cmax and AUC values of acalabrutinib were increased by 3.9-fold and 5.1-fold, respectively, when acalabrutinib was coadministered with another strong inhibitor for 5 days.
Acebutolol: (Major) Avoid concomitant use of ceritinib with acebutolol if possible due to the risk of additive bradycardia. Both ceritinib and acebutolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with ceritinib may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Dihydrocodeine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ceritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with strong CYP3A4 inhibitors like ceritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If ceritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Major) Avoid concomitant use of ceritinib with adagrasib. Concomitant use may increase the concentrations of both drugs and result in additive risk for QT/QTc prolongation. If concomitant use is necessary, avoid administration during adagrasib therapy initiation (approximately 8 days) and decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg. Monitor for side effects from both medications and consider taking steps to minimize the risk for QT/QTc interval prolongation and torsade de pointes (TdP), such as electrolyte monitoring and repletion and ECG monitoring. Both medications are CYP3A substrates and strong CYP3A inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. Concomitant use of a single 200 mg dose of adagrasib with another strong CYP3A inhibitor increased adagrasib exposure by approximately 4-fold, however, no clinically significant differences in pharmacokinetics are predicted once steady state is reached.
Ado-Trastuzumab emtansine: (Major) Avoid coadministration of ceritinib with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until ceritinib has cleared from the circulation (approximately 3 half-lives of ceritinib) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; ceritinib is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
Albuterol; Budesonide: (Major) Avoid coadministration of oral budesonide and ceritinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If ceritinib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Alfuzosin: (Contraindicated) Alfuzosin is contraindicated for use with ceritinib due to the potential for serious/life-threatening reactions, including hypotension. Additive effects on the QT interval may also occur. Alfuzosin is a CYP3A4 substrate that may prolong the QT interval in a dose-dependent manner. Ceritinib is a strong CYP3A4 inhibitor that also causes concentration-dependent QT prolongation. Coadministration of another strong CYP3A4 inhibitor increased the alfuzosin AUC by 2.5-fold to 3.2-fold.
Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with ceritinib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and ceritinib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Alosetron: (Moderate) Concomitant use of alosetron with ceritinib may result in increased serum concentrations of alosetron and increase the risk for adverse reactions. Caution and close monitoring are advised if these drugs are used together. Alosetron is a substrate of hepatic isoenzyme CYP3A4; ceritinib is a strong inhibitor of this enzyme. In a study of healthy female subjects, another strong CYP3A4 inhibitor increased mean alosetron AUC by 29%.
Alprazolam: (Contraindicated) Coadministration of ceritinib and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with ceritinib, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
Amiodarone: (Major) Avoid coadministration of amiodarone with ceritinib if possible due to the risk of QT prolongation; exposure to amiodarone may also be increased. Because amiodarone has an extremely long half-life, an interaction is possible for days to weeks after discontinuation of amiodarone. If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; also consider serial measurement of amiodarone serum concentrations. An interruption of ceritinib therapy, dose reduction, or discontinuation of ceritinib therapy may be necessary if QT prolongation occurs. Amiodarone, a Class III antiarrhythmic agent, is a CYP3A4 substrate associated with a well-established risk of QT prolongation; although the frequency of torsade de pointes (TdP) is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Ceritinib is a strong CYP3A4 inhibitor associated with concentration-dependent QT prolongation.
Amisulpride: (Major) Avoid coadministration of ceritinib with amisulpride if possible due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs and periodically monitor electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration- dependent QT prolongation. Amisulpride causes dose- and concentration-dependent QT prolongation.
Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Atorvastatin: (Major) Consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness) if coadministration of atorvastatin with ceritinib is required, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Ceritinib is a strong CYP3A4 inhibitor and atorvastatin is a CYP3A4 substrate. Coadministration of ceritinib with atorvastatin may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Celecoxib: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of clarithromycin with ceritinib due to the additive risk of QT prolongation and increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg; monitor for ceritinib-related adverse reactions. Periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, further dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. After clarithromycin is discontinued, resume the dose of ceritinib taken prior to initiating clarithromycin. Ceritinib is a CYP3A substrate associated with concentration-dependent QT prolongation; clarithromycin is a strong CYP3A4 inhibitor associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Anagrelide: (Major) Do not use anagrelide with ceritinib due to the risk of QT prolongation. 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. Concentration-dependent QT prolongation has also been reported with ceritinib.
Apalutamide: (Major) Avoid concomitant use of ceritinib with apalutamide as ceritinib exposure may be decreased, which may reduce its efficacy; apalutamide exposure may also increase. Ceritinib is a CYP3A substrate and a strong CYP3A4 inhibitor. Apalutamide is a CYP3A4 substrate and a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%. Coadministration with a strong CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties (unbound apalutamide plus potency-adjusted unbound N-desmethyl apalutamide) by 28%.
Apomorphine: (Major) Avoid coadministration of ceritinib with apomorphine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aprepitant, Fosaprepitant: (Major) Avoid coadministration of ceritinib and aprepitant/fosaprepitant due to substantially increased exposure of aprepitant. Fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction is likely. Aprepitant is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Administration of a strong CYP3A4 inhibitor increased the aprepitant AUC and mean terminal half-life by approximately 5-fold and 3-fold, respectively.
Aripiprazole: (Major) Concomitant use of aripiprazole and ceritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. 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. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ceritinib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and ceritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. 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. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, ceritinib is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Arsenic Trioxide: (Major) Avoid coadministration of arsenic trioxide with ceritinib due to the risk of QT interval prolongation; discontinue ceritinib or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy 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. Ceritinib also causes concentration-dependent prolongation of the QT interval.
Artemether; Lumefantrine: (Major) Avoid coadministration of ceritinib with artemether due to the risk of QT prolongation; plasma concentrations of artemether may also increase. If concomitant use is unavoidable, monitor ECGs for QT prolongation and periodically monitor electrolytes; also watch for artemether-related adverse reactions. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib is a strong CYP3A4 inhibitor that causes a concentration-dependent prolongation of the QT interval. Artemether is a CYP3A4 substrate that has also been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased artemether exposure by 2.3-fold. (Major) Avoid coadministration of ceritinib with lumefantrine due to the risk of QT prolongation; plasma concentrations of lumefantrine may also increase. If concomitant use is unavoidable, monitor ECGs for QT prolongation and periodically monitor electrolytes; also watch for lumefantrine-related adverse reactions. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib is a strong CYP3A4 inhibitor that causes a concentration-dependent prolongation of the QT interval. Lumefantrine is a CYP3A4 substrate that has also been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased lumefantrine exposure by 1.6-fold.
Asciminib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with ceritinib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Asenapine: (Major) Avoid coadministration of asenapine with ceritinib due to the risk of QT prolongation. Asenapine has been associated with QT prolongation. Concentration-dependent QT prolongation has also been reported with ceritinib treatment.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with strong CYP3A4 inhibitors like ceritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If ceritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Major) Avoid concomitant use of ceritinib with atazanavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After atazanavir is discontinued, resume the dose of ceritinib taken prior to initiating atazanavir. Ceritinib is a CYP3A substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of ceritinib with atazanavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After atazanavir is discontinued, resume the dose of ceritinib taken prior to initiating atazanavir. Ceritinib is a CYP3A substrate; atazanavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. (Major) Avoid concomitant use of ceritinib with cobicistat due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; cobicistat exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After cobicistat is discontinued, resume the dose of ceritinib taken prior to initiating cobicistat. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Atenolol: (Major) Avoid concomitant use of ceritinib with atenolol if possible due to the risk of additive bradycardia. Both ceritinib and atenolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Atenolol; Chlorthalidone: (Major) Avoid concomitant use of ceritinib with atenolol if possible due to the risk of additive bradycardia. Both ceritinib and atenolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Atogepant: (Major) Avoid use of atogepant and ceritinib when atogepant is used for chronic migraine. Limit the dose of atogepant to 10 mg PO once daily for episodic migraine if coadministered with ceritinib. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of CYP3A and ceritinib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor resulted in a 5.5-fold increase in atogepant overall exposure and a 2.15-fold increase in atogepant peak concentration.
Atomoxetine: (Major) Avoid coadministration of ceritinib with atomoxetine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Prolongation of the QT interval has occurred during therapeutic use of atomoxetine as well as following overdose.
Atorvastatin: (Major) Consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness) if coadministration of atorvastatin with ceritinib is required, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Ceritinib is a strong CYP3A4 inhibitor and atorvastatin is a CYP3A4 substrate. Coadministration of ceritinib with atorvastatin may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin.
Atorvastatin; Ezetimibe: (Major) Consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness) if coadministration of atorvastatin with ceritinib is required, particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Ceritinib is a strong CYP3A4 inhibitor and atorvastatin is a CYP3A4 substrate. Coadministration of ceritinib with atorvastatin may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin.
Avacopan: (Major) Reduce the dose of avacopan to 30 mg once daily if concomitant use of ceritinib is necessary. Concomitant use may increase avacopan exposure and risk for avacopan-related adverse effects. Avacopan is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased avacopan overall exposure 2.19-fold.
Avanafil: (Major) Do not use avanafil in patients receiving ceritinib due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Avapritinib: (Major) Avoid coadministration of avapritinib with ceritinib due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state.
Axitinib: (Major) Avoid coadministration of axitinib with ceritinib due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after ceritinib is discontinued. Axitinib is a CYP3A4/5 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers.
Azelastine; Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Azithromycin: (Major) Avoid coadministration of azithromycin with ceritinib if possible due to the 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 ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
Bedaquiline: (Major) Concurrent use of bedaquiline and ceritinib should be avoided due to the potential risk of adverse reactions to bedaquiline because of increased systemic exposure; there is also an increased risk of QT prolongation. Bedaquiline is a CYP3A4 substrate that has been reported to prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor associated with concentration-dependent QT prolongation. Concurrent use of another strong CYP3A4 inhibitor increased bedaquiline exposure by 22%.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with ceritinib may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of ceritinib in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Ceritinib is a strong inhibitor of CYP3A4.
Betaxolol: (Major) Avoid concomitant use of ceritinib with betaxolol if possible due to the risk of additive bradycardia. Both ceritinib and betaxolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and ceritinib 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 ceritinib 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.
Bisoprolol: (Major) Avoid concomitant use of ceritinib with bisoprolol if possible due to the risk of additive bradycardia. Both ceritinib and bisoprolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Avoid concomitant use of ceritinib with bisoprolol if possible due to the risk of additive bradycardia. Both ceritinib and bisoprolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Bortezomib: (Moderate) Monitor for signs of bortezomib toxicity and consider a bortezomib dose reduction if coadministration of ceritinib is necessary. Bortezomib exposure may be increased. Bortezomib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased bortezomib exposure by 35%.
Bosentan: (Moderate) Use caution if coadministration of ceritinib with bosentan is necessary, as the systemic exposure of bosentan may be increased resulting in an increase in treatment-related adverse reactions; however, a bosentan dose adjustment is not necessary. Administration of bosentan with both ceritinib and a strong or moderate CYP2C9 inhibitor is not recommended. Ceritinib is a strong CYP3A4 inhibitor and a weak CYP2C9 inhibitor. Bosentan is a CYP3A4 and CYP2C9 substrate.
Bosutinib: (Major) Avoid concomitant use of bosutinib and ceritinib; bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. The Cmax and AUC values of bosutinib were increased 5.2-fold and 8.6-fold, respectively, when a single oral dose of bosutinib 100 mg PO was administered after 5 days of a strong CYP3A4 inhibitor.
Brentuximab vedotin: (Moderate) Closely monitor for an increase in brentuximab-related adverse reactions, including peripheral neuropathy or gastrointestinal side effects, if coadministration with ceritinib is necessary. Monomethyl auristatin E (MMAE), one of the 3 components released from brentuximab vedotin, is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased MMAE exposure by approximately 34%.
Brexpiprazole: (Major) Reduce the brexpiprazole dose to half the usual dose if coadministered with ceritinib. Administer one quarter of the usual brexpiprazole dose if the patient is also receiving a strong or moderate CYP2D6 inhibitor or is a known poor metabolizer of CYP2D6. If ceritinib is discontinued, adjust the brexpiprazole dosage to its original level. Ceritinib is a strong CYP3A4 inhibitor. Brexpiprazole is a CYP3A4 and CYP2D6 substrate. Concomitant use of strong CYP3A4 inhibitors increased the exposure of brexpiprazole compared to use of brexpiprazole alone.
Brigatinib: (Major) Avoid coadministration of brigatinib with ceritinib if possible due to increased plasma exposure of brigatinib. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of ceritinib, resume the brigatinib dose that was tolerated prior to initiation of ceritinib. Brigatinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
Brimonidine; Timolol: (Major) Avoid concomitant use of ceritinib with timolol if possible due to the risk of additive bradycardia. Both ceritinib and timolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Bromocriptine: (Major) When bromocriptine is used for diabetes, avoid coadministration with ceritinib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; ceritinib is a strong inhibitor of CYP3A4.
Budesonide: (Major) Avoid coadministration of oral budesonide and ceritinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Budesonide; Formoterol: (Major) Avoid coadministration of oral budesonide and ceritinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid coadministration of oral budesonide and ceritinib due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In the presence of another strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor; lidocaine is metabolized by CYP3A4 and CYP1A2. Concomitant treatment CYP3A4 inhibitors has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and prolonging the elimination half-life.
Bupivacaine; Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with ceritinib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and ceritinib is a weak CYP2C9 inhibitor.
Buprenorphine: (Major) Avoid coadministration of ceritinib with buprenorphine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved; monitor for respiratory depression and sedation at frequent intervals. When stopping ceritinib, the buprenorphine concentration will decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency; consider increasing buprenorphine dosage until stable drug effects are achieved and monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A4 that has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation.
Buprenorphine; Naloxone: (Major) Avoid coadministration of ceritinib with buprenorphine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved; monitor for respiratory depression and sedation at frequent intervals. When stopping ceritinib, the buprenorphine concentration will decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency; consider increasing buprenorphine dosage until stable drug effects are achieved and monitor for signs of opioid withdrawal. Buprenorphine is a substrate of CYP3A4 that has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation.
Buspirone: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with ceritinib. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering ceritinib with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A4. Ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with ceritinib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and ceritinib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cabotegravir; Rilpivirine: (Major) Avoid coadministration of ceritinib with rilpivirine if possible due to the risk of QT prolongation; plasma concentrations of rilpivirine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Rilpivirine is a CYP3A4 substrate that has been associated with QT prolongation at supratherapeutic doses (75 to 300 mg per day). Ceritinib is a strong CYP3A4 inhibitor that has also been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the AUC of rilpivirine by 1.49-fold.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib and ceritinib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with ceritinib 2 to 3 days after discontinuation of ceritinib. Cabozantinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Capmatinib: (Moderate) Monitor for an increase in capmatinib-related adverse reactions if coadministration with ceritinib is necessary. Capmatinib is a CYP3A substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%.
Carbamazepine: (Major) Avoid concomitant use of ceritinib with carbamazepine as ceritinib exposure may be decreased, which may reduce its efficacy; carbamazepine exposure may also increase. Ceritinib is a CYP3A4 substrate and a strong CYP3A4 inhibitor; carbamazepine is a CYP3A4 substrate with a narrow therapeutic index and a strong CYP3A4 inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Cariprazine: (Major) The dose of cariprazine should be reduced in patients also receiving ceritinib. When ceritinib is initiated in a patient who is on a stable dose of cariprazine, reduce the cariprazine dosage by half. For adult patients taking cariprazine 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For patients taking cariprazine 1.5 mg daily, the dosing frequency should be adjusted to every other day. When initiating cariprazine in a patient who is stable on ceritinib, the patient should be administered 1.5 mg of cariprazine on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, and then increased to a maximum dose of 3 mg daily. When ceritinib is withdrawn, the cariprazine dosage may need to be increased. Cariprazine is metabolized by CYP3A4 to its major active metabolite. Ceritinib is a strong CYP3A4 inhibitor. Concurrent use with another strong CYP3A4 inhibitor increased the exposure of cariprazine by about 4-fold; increased the AUC of DDCAR metabolite by about 1.5-fold; and decreased DCAR metabolite AUC by about one-third.
Carteolol: (Major) Avoid coadministration of ceritinib with carteolol if possible due to the risk of additive bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. Bradycardia has been reported with ceritinib treatment; carteolol also causes bradycardia.
Carvedilol: (Major) Avoid concomitant use of ceritinib with carvedilol if possible due to the risk of additive bradycardia. Both ceritinib and carvedilol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Celecoxib; Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with ceritinib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of ceritinib, a strong CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Chloramphenicol: (Major) Avoid concomitant use of ceritinib with chloramphenicol due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After chloramphenicol is discontinued, resume the dose of ceritinib taken prior to initiating chloramphenicol. Ceritinib is a CYP3A substrate; chloramphenicol is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Chlordiazepoxide: (Moderate) Monitor for an increase in sedation and respiratory depression if coadministration of chlordiazepoxide with ceritinib is necessary. Chlordiazepoxide is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chlordiazepoxide; Amitriptyline: (Moderate) Monitor for an increase in sedation and respiratory depression if coadministration of chlordiazepoxide with ceritinib is necessary. Chlordiazepoxide is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chlordiazepoxide; Clidinium: (Moderate) Monitor for an increase in sedation and respiratory depression if coadministration of chlordiazepoxide with ceritinib is necessary. Chlordiazepoxide is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chloroquine: (Major) Avoid coadministration of chloroquine with ceritinib 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. Interrupt, dose reduce, or discontinue ceritinib if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. 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.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with ceritinib may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Dihydrocodeine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ceritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Chlorpromazine: (Major) Avoid coadministration of ceritinib with chlorpromazine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP).
Chlorthalidone; Clonidine: (Major) Avoid concomitant use of ceritinib with clonidine if possible due to the risk of additive bradycardia. Both ceritinib and clonidine can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
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.
Cilostazol: (Major) Reduce the dose of cilostazol to 50 mg twice daily when coadministered with ceritinib. Monitor for an increase in cilostazol-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor and cilostazol is a CYP3A4 substrate. Coadministration of another strong CYP3A4 inhibitor increased the cilostazol AUC by 117%.
Cinacalcet: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of ceritinib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and ceritinib 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, use of cisapride with ceritinib is contraindicated. QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Ceritinib also prolongs the QT interval.
Citalopram: (Major) Coadministration of citalopram with ceritinib is not recommended due to the risk of QT prolongation; citalopram exposure may also be increased. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Citalopram is a CYP3A4 substrate that causes dose-dependent QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that is also associated with concentration-dependent QT prolongation.
Clarithromycin: (Major) Avoid coadministration of clarithromycin with ceritinib due to the additive risk of QT prolongation and increased cer
Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of ceritinib as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; ceritinib is a strong inhibitor of CYP3A4.
Clofazimine: (Major) Concomitant use of clofazimine and ceritinib 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: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and clomipramine; an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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).
Clonazepam: (Moderate) Monitor for increased sedation and respiratory depression if clonazepam is coadministered with ceritinib; adjust the dose of clonazepam if necessary. The systemic exposure of clonazepam may be increased resulting in increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor and clonazepam is a CYP3A4 substrate.
Clonidine: (Major) Avoid concomitant use of ceritinib with clonidine if possible due to the risk of additive bradycardia. Both ceritinib and clonidine can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Clorazepate: (Moderate) Monitor for an increase in sedation and respiratory depression if coadministration of clorazepate with ceritinib is necessary. Clorazepate is a prodrug whose active metabolite (N-desmethyldiazepam) is a CYP3A4 substrate. Ceritinib is a strong CYP3A4 inhibitor.
Clozapine: (Major) Avoid coadministration of ceritinib with clozapine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Additionally, consider a clozapine dose reduction and monitor for adverse reactions; if ceritinib is discontinued, monitor for lack of clozapine effect and increase dose if necessary. Clozapine is partially metabolized by CYP3A4 and has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use.
Cobicistat: (Major) Avoid concomitant use of ceritinib with cobicistat due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; cobicistat exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After cobicistat is discontinued, resume the dose of ceritinib taken prior to initiating cobicistat. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Cobimetinib: (Major) Avoid coadministration of ceritinib with cobimetinib due to the increased risk of cobimetinib-related adverse reactions. Cobimetinib is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased cobimetinib exposure by 6.7-fold.
Codeine: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and ceritinib 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. (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Codeine; Promethazine: (Major) Concomitant use of promethazine and ceritinib 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. (Moderate) Concomitant use of codeine with ceritinib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of ceritinib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ceritinib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Ceritinib is a strong inhibitor of CYP3A4.
Colchicine: (Major) Avoid concomitant use of colchicine and ceritinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Conivaptan: (Contraindicated) Coadministration of conivaptan and ceritinib is contraindicated due to the potential for increased conivaptan exposure. Conivaptan is a sensitive CYP3A substrate; ceritinib is a strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the exposure of oral conivaptan by 11-fold.
Conjugated Estrogens; Medroxyprogesterone: (Moderate) Use caution if coadministration of ceritinib with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4.
Copanlisib: (Major) Avoid the concomitant use of copanlisib and ceritinib if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; ceritinib is a strong CYP3A inhibitor.
Crizotinib: (Major) Avoid concomitant use of ceritinib and crizotinib due to increased plasma concentrations of crizotinib, which may increase the incidence and severity of adverse reactions; QT prolongation and torsade de pointes (TdP) may also occur. If concomitant use is necessary for adults with non-small cell lung cancer (NSCLC) or inflammatory myofibroblastic tumor (IMT), reduce the dose of crizotinib to 250 mg PO once daily. If concomitant use is necessary for young adult or pediatric patients with anaplastic large cell lymphoma or pediatric patients with IMT, reduce the dose of crizotinib to 250 mg PO twice daily for BSA of 1.7 m2 or more; 200 mg PO twice daily for BSA of 1.17 to 1.69 m2; and 250 mg PO once daily for BSA of 0.81 to 1.16 m2; do not use this combination in patients with a BSA of 0.6 to 0.8 m2. Resume the original crizotinib dose after discontinuation of ceritinib. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Crizotinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with one strong CYP3A inhibitor increased the AUC of single-dose crizotinib by 216%. Concomitant use with another strong CYP3A inhibitor increased the steady-state AUC of crizotinib by 57% compared to crizotinib alone.
Cyclosporine: (Moderate) Monitor serum cyclosporine concentrations when administered concurrently with ceritinib due to potential for elevated cyclosporine concentrations and cyclosporine-related adverse events; cyclosporine dosage adjustment may be necessary. Ceritinib is a strong inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of cyclosporine.
Dabrafenib: (Major) Avoid coadministration of dabrafenib and ceritinib due to increased dabrafenib exposure. If another agent cannot be substituted and coadministration of these agents is unavoidable, monitor patients closely for dabrafenib adverse reactions including skin toxicity, ocular toxicity, and cardiotoxicity. Dabrafenib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the dabrafenib AUC by 71%, hydroxy-dabrafenib AUC by 82%, and desmethyl-dabrafenib AUC by 68%.
Daclatasvir: (Major) Reduce the daclatasvir dose to 30 mg PO once daily if coadministered with ceritinib due to increased daclatasvir exposure; exposure to ceritinib may also increase. Daclatasvir is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the daclatasvir AUC by 3-fold.
Dapagliflozin; Saxagliptin: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with ceritinib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Daridorexant: (Major) Avoid concomitant use of daridorexant and ceritinib. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased daridorexant overall exposure by over 400%.
Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg PO when administered with ceritinib due to increased darifenacin exposure. Darifenacin is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor.
Darunavir: (Major) Avoid concomitant use of ceritinib with darunavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; darunavir exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After darunavir is discontinued, resume the dose of ceritinib taken prior to initiating darunavir. Both drugs are CYP3A substrates and a strong CYP3A4 inhibitosr. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Darunavir; Cobicistat: (Major) Avoid concomitant use of ceritinib with cobicistat due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; cobicistat exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After cobicistat is discontinued, resume the dose of ceritinib taken prior to initiating cobicistat. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. (Major) Avoid concomitant use of ceritinib with darunavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; darunavir exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After darunavir is discontinued, resume the dose of ceritinib taken prior to initiating darunavir. Both drugs are CYP3A substrates and a strong CYP3A4 inhibitosr. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of ceritinib with cobicistat due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; cobicistat exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After cobicistat is discontinued, resume the dose of ceritinib taken prior to initiating cobicistat. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. (Major) Avoid concomitant use of ceritinib with darunavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; darunavir exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After darunavir is discontinued, resume the dose of ceritinib taken prior to initiating darunavir. Both drugs are CYP3A substrates and a strong CYP3A4 inhibitosr. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Dasatinib: (Major) Avoid coadministration of dasatinib and ceritinib due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation. An alternative to ceritinib with no or minimal enzyme inhibition potential is recommended if possible. If concomitant use cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Stop dasatinib during use of ceritinib in patients receiving dasatinib 60 mg or 40 mg PO daily. If dasatinib is not tolerated after dose reduction, either discontinue ceritinib or stop dasatinib until ceritinib is discontinued. Allow a washout of approximately 1 week after ceritinib is stopped before increasing the dasatinib dose or reinitiating dasatinib. Periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for QT prolongation. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; ceritinib is a strong CYP3A4 inhibitor that is associated with concentration-dependent QT prolongation. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with ceritinib. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; ceritinib is a strong inhibitor of CYP3A4. Administration of deflazacort with another strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Degarelix: (Major) Avoid coadministration of ceritinib with degarelix if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Androgen deprivation therapy (i.e., degarelix) is also associated with QT prolongation.
Delavirdine: (Major) Avoid concomitant use of ceritinib with delavirdine due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After delavirdine is discontinued, resume the dose of ceritinib taken prior to initiating delavirdine. Ceritinib is a CYP3A substrate; delavirdine is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Desflurane: (Major) Avoid coadministration of ceritinib with halogenated anesthetics if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Halogenated anesthetics can also prolong the QT interval.
Desipramine: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and desipramine; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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).
Desogestrel; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Deutetrabenazine: (Major) Avoid coadministration of ceritinib with deutetrabenazine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. 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.
Dexamethasone: (Moderate) Monitor for steroid-related adverse reactions if coadministration of ceritinib with dexamethasone is necessary, due to increased dexamethasone exposure; Cushings syndrome and adrenal suppression could potentially occur with long-term use. Consider the use of corticosteroids such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A inhibitors, especially for long-term use. Ceritinib is a strong CYP3A4 inhibitor and dexamethasone is primarily metabolized by CYP3A. Another strong CYP3A inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Dexlansoprazole: (Moderate) Monitor for dexlansoprazole-related adverse reactions (e.g., GI effects) if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor, while dexlansoprazole is a CYP3A4 substrate. Plasma concentrations of dexlansoprazole may be elevated when administered concurrently with ceritinib.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and ceritinib 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.
Dextromethorphan; Quinidine: (Major) Avoid coadministration of ceritinib with quinidine if possible due to the risk of QT prolongation; plasma concentrations of quinidine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Quinidine is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Diazepam: (Moderate) Monitor for an increase in sedation and respiratory depression if coadministration of diazepam with ceritinib is necessary. At low concentrations, diazepam is a CYP2C19 substrate but at high concentrations, CYP3A4 is also involved. Ceritinib is a strong CYP3A4 inhibitor.
Diclofenac: (Moderate) Monitor for an increase in diclofenac-related adverse reactions if coadministration with ceritinib is necessary; adjust the dose of diclofenac if needed. Diclofenac is a CYP2C9 substrate and ceritinib is a weak CYP2C9 inhibitor.
Diclofenac; Misoprostol: (Moderate) Monitor for an increase in diclofenac-related adverse reactions if coadministration with ceritinib is necessary; adjust the dose of diclofenac if needed. Diclofenac is a CYP2C9 substrate and ceritinib is a weak CYP2C9 inhibitor.
Digoxin: (Major) Avoid concomitant use of ceritinib with digoxin if possible due to the risk of additive bradycardia. Both ceritinib and digoxin can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Dihydroergotamine: (Contraindicated) Concomitant use of ergotamine with ceritinib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Diltiazem: (Major) Avoid concomitant use of ceritinib with diltiazem if possible due to the risk of additive bradycardia; diltiazem exposure may also increase. Both ceritinib and diltiazem can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. Monitor blood pressure and heart rate. Diltiazem is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Disopyramide: (Major) Avoid coadministration of ceritinib with disopyramide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Additionally, closely monitor for disopyramide-related adverse reactions. Disopyramide is a CYP3A4 substrate that has been associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when administered with another strong CYP3A4 inhibitor.
Docetaxel: (Major) Avoid coadministration of docetaxel with ceritinib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
Dofetilide: (Major) Avoid coadministration of ceritinib with dofetilide due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Dofetilide is a CYP3A4 substrate that is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that is also associated with concentration-dependent QT prolongation.
Dolasetron: (Major) Avoid coadministration of ceritinib with dolasetron if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Dolasetron has also 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 ceritinib is necessary. Dolutegravir is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with ceritinib is necessary. Dolutegravir is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Dolutegravir; Rilpivirine: (Major) Avoid coadministration of ceritinib with rilpivirine if possible due to the risk of QT prolongation; plasma concentrations of rilpivirine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Rilpivirine is a CYP3A4 substrate that has been associated with QT prolongation at supratherapeutic doses (75 to 300 mg per day). Ceritinib is a strong CYP3A4 inhibitor that has also been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the AUC of rilpivirine by 1.49-fold. (Moderate) Monitor for an increase in dolutegravir-related adverse reactions if coadministration with ceritinib is necessary. Dolutegravir is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Donepezil: (Major) Avoid coadministration of ceritinib with donepezil if possible due to the risk of QT prolongation; plasma concentrations of donepezil may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Also, monitor for donepezil-related adverse reactions (e.g., GI or cholinergic effects). Donepezil is a CYP3A4 substrate that has had case reports of QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Donepezil; Memantine: (Major) Avoid coadministration of ceritinib with donepezil if possible due to the risk of QT prolongation; plasma concentrations of donepezil may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Also, monitor for donepezil-related adverse reactions (e.g., GI or cholinergic effects). Donepezil is a CYP3A4 substrate that has had case reports of QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Doravirine: (Minor) Monitor for an increase in doravirine-related adverse reactions if coadministration with ceritinib is necessary; increased doravirine plasma concentrations may occur. Doravirine is a CYP3A4 substrate; ceritinib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Monitor for an increase in doravirine-related adverse reactions if coadministration with ceritinib is necessary; increased doravirine plasma concentrations may occur. Doravirine is a CYP3A4 substrate; ceritinib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Dorzolamide; Timolol: (Major) Avoid concomitant use of ceritinib with timolol if possible due to the risk of additive bradycardia. Both ceritinib and timolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Doxepin: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and doxepin; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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).
Doxorubicin Liposomal: (Major) Avoid coadministration of ceritinib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of ceritinib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Moderate) Monitor for an increase in dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, feeling high, dizziness, somnolence) if coadministration with ceritinib is necessary. Concomitant use may result in elevated plasma concentrations of dronabinol. Ceritinib is a strong CYP3A4 inhibitor and a weak inhibitor of CYP2C9. Dronabinol is a CYP2C9 and 3A4 substrate.
Dronedarone: (Contraindicated) The concomitant use of dronedarone with ceritinib is contraindicated due to the risk of QT prolongation and torsade de pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval; the increase is approximately 10 msec at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 msec at doses of 1,600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, such as ceritinib, coadministration of such drugs may result in additive QT prolongation. Additionally, dronedarone is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as ceritinib. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect. Conduct periodic monitoring with electrocardiograms (ECGs) and electrolytes. Concentration-dependent QT prolongation has been reported with ceritinib. 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.
Drospirenone; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Dutasteride: (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with ceritinib is necessary. Dutasteride is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Although the effect of strong CYP3A4 inhibitors on dutasteride has not been studied, dutasteride exposure may increase.
Dutasteride; Tamsulosin: (Major) Concurrent use of tamsulosin and ceritinib is not recommended due to the potential for elevated tamsulosin concentrations. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension, dizziness, and vertigo. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 like ceritinib are expected to significantly raise tamsulosin concentrations. Concomitant treatment with another strong CYP3A4 inhibitor increased the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively. (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with ceritinib is necessary. Dutasteride is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Although the effect of strong CYP3A4 inhibitors on dutasteride has not been studied, dutasteride exposure may increase.
Duvelisib: (Major) Reduce the duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ceritinib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ceritinib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ceritinib.
Efavirenz: (Major) Avoid coadministration of ceritinib with efavirenz if possible due to the risk of QT prolongation; plasma concentrations of efavirenz may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Monitor for an increase in efavirenz-related adverse reactions. Efavirenz is a CYP3A4 substrate that has been associated with QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of ceritinib with efavirenz if possible due to the risk of QT prolongation; plasma concentrations of efavirenz may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Monitor for an increase in efavirenz-related adverse reactions. Efavirenz is a CYP3A4 substrate that has been associated with QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of ceritinib with efavirenz if possible due to the risk of QT prolongation; plasma concentrations of efavirenz may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Monitor for an increase in efavirenz-related adverse reactions. Efavirenz is a CYP3A4 substrate that has been associated with QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Elacestrant: (Major) Avoid concomitant use of elacestrant and ceritinib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Elagolix: (Major) Concomitant use of elagolix 200 mg twice daily and ceritinib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ceritinib to 6 months. Elagolix is a CYP3A substrate and ceritinib is a strong inhibitor of CYP3A. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Elagolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of elagolix 200 mg twice daily and ceritinib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and ceritinib to 6 months. Elagolix is a CYP3A substrate and ceritinib is a strong inhibitor of CYP3A. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Elbasvir; Grazoprevir: (Moderate) Monitor for an increase in elbasvir-related adverse reactions if coadministration with ceritinib is necessary. Elbasvir is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased elbasvir exposure by 3-fold. (Moderate) Monitor for an increase in grazoprevir-related adverse reactions if coadministration with ceritinib is necessary. Grazoprevir is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased grazoprevir exposure by 3-fold.
Eletriptan: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of ceritinib due to the potential for increased eletriptan exposure. Eletriptan is a sensitive substrate of CYP3A4; ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
Elexacaftor; tezacaftor; ivacaftor: (Major) If ceritinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to twice a week in the morning, approximately 3 to 4 days apart (i.e., Day 1 and Day 4) when coadministered with ceritinib; omit the evening dose of ivacaftor. Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; ceritinib is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with ceritinib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, give one tezacaftor/ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of ceritinib and eliglustat is contraindicated. The coadministration of eliglustat with both ceritinib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. In other patients, avoid coadministration of ceritinib and eliglustat if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Additionally, reduce the dose of eliglustat to 84 mg PO once daily in extensive CYP2D6 metabolizers (EMs). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Eliglustat is a CYP3A and CYP2D6 substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Coadministration of eliglustat with CYP3A inhibitors such as ceritinib increases eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
Eluxadoline: (Moderate) Monitor for an increase in eluxadoline-related adverse reactions including impaired mental or physical abilities if coadministration with ceritinib is necessary. The metabolism of eluxadoline by CYP pathways has not been clearly established, but strong CYP inhibitors such as ceritinib have the potential to increase eluxadoline exposure.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of ceritinib with cobicistat due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; cobicistat exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After cobicistat is discontinued, resume the dose of ceritinib taken prior to initiating cobicistat. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of ceritinib with cobicistat due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; cobicistat exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After cobicistat is discontinued, resume the dose of ceritinib taken prior to initiating cobicistat. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid coadministration of ceritinib with rilpivirine if possible due to the risk of QT prolongation; plasma concentrations of rilpivirine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Rilpivirine is a CYP3A4 substrate that has been associated with QT prolongation at supratherapeutic doses (75 to 300 mg per day). Ceritinib is a strong CYP3A4 inhibitor that has also been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the AUC of rilpivirine by 1.49-fold.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of ceritinib with rilpivirine if possible due to the risk of QT prolongation; plasma concentrations of rilpivirine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Rilpivirine is a CYP3A4 substrate that has been associated with QT prolongation at supratherapeutic doses (75 to 300 mg per day). Ceritinib is a strong CYP3A4 inhibitor that has also been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the AUC of rilpivirine by 1.49-fold.
Encorafenib: (Major) Avoid coadministration of encorafenib and ceritinib due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of ceritinib; monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. If ceritinib is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of ceritinib. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; ceritinib is a strong CYP3A4 inhibitor that can also cause concentration-dependent QT prolongation. Coadministration of a strong CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 3-fold and 68%, respectively.
Entrectinib: (Major) Avoid coadministration of entrectinib with ceritinib due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If ceritinib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of ceritinib. Additionally, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for ceritinib if QT prolongation occurs. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; ceritinib is a strong CYP3A4 inhibitor that is associated with concentration-dependent QT prolongation. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Enzalutamide: (Major) Avoid concomitant use of ceritinib with enzalutamide as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Eplerenone: (Contraindicated) Eplerenone is contraindicated for use with ceritinib due to increased eplerenone exposure which increases the risk of developing hyperkalemia and hypotension. Ceritinib is a strong CYP3A4 inhibitor; eplerenone is a sensitive CYP3A4 substrate. Another strong CYP3A4 inhibitor increased serum eplerenone concentrations by roughly 5-fold.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and ceritinib due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If ceritinib is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
Ergotamine: (Contraindicated) Concomitant use of ergotamine with ceritinib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Ergotamine; Caffeine: (Contraindicated) Concomitant use of ergotamine with ceritinib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Eribulin: (Major) Avoid coadministration of ceritinib with eribulin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, closely monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Eribulin is also associated with QT prolongation.
Erlotinib: (Major) Avoid coadministration of erlotinib with ceritinib if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
Erythromycin: (Major) Avoid coadministration of ceritinib with erythromycin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Erythromycin is associated with QT prolongation and torsade de pointes (TdP).
Escitalopram: (Major) Avoid coadministration of ceritinib with escitalopram if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Escitalopram has also been associated with a risk of QT prolongation and torsade de pointes (TdP).
Esmolol: (Major) Avoid concomitant use of ceritinib with esmolol if possible due to the risk of additive bradycardia. Both ceritinib and esmolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Estazolam: (Moderate) Monitor for estazolam-related adverse reactions, including sedation and respiratory depression, if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and estazolam is primarily metabolized by CYP3A4. In vivo drug-drug interaction studies were not conducted between estazolam and inhibitors of CYP3A.
Estradiol; Progesterone: (Moderate) Use caution if coadministration of ceritinib with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Eszopiclone: (Major) The total dose of eszopiclone should not exceed 2 mg when administered with ceritinib. Coadministration may increase eszopiclone exposure resulting in increased risk of next-day psychomotor or memory impairment and decreased ability to perform tasks requiring full mental alertness such as driving. CYP3A4 is a primary metabolic pathway for eszopiclone; ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased eszopiclone exposure by 2.2-fold.
Ethinyl Estradiol; Norelgestromin: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Ethinyl Estradiol; Norgestrel: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Ethosuximide: (Moderate) Monitor for an increase in ethosuximide-related adverse reactions if coadministration with ceritinib is necessary. Ethosuximide is a CYP3A4 substrate with a narrow therapeutic index and ceritinib is a strong CYP3A4 inhibitor.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Etonogestrel; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Etravirine: (Moderate) Monitor for an increase in etravirine-related adverse reactions if coadministration with ceritinib is necessary. Etravirine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased etravirine exposure by 1.42-fold.
Everolimus: (Major) Avoid coadministration of everolimus with ceritinib due to the risk of increased everolimus-related adverse reactions. If concomitant use is unavoidable in patients receiving everolimus for either kidney or liver transplant, closely monitor everolimus whole blood trough concentrations. Everolimus is a sensitive CYP3A4 substrate and P-glycoprotein (P-gp) substrate. Ceritinib is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4/P-gp inhibitor increased the AUC of everolimus by 15-fold.
Ezetimibe; Simvastatin: (Contraindicated) Concurrent use of simvastatin and ceritinib is contraindicated due to an increased risk of developing myopathy, rhabdomyolysis, and acute renal failure. Simvastatin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Fedratinib: (Major) Avoid coadministration of fedratinib with ceritinib as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If ceritinib is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
Felodipine: (Moderate) Concurrent use of felodipine and ceritinib should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and ceritinib i s a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased felodipine AUC and half-life by approximately 8-fold and 2-fold, respectively.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If ceritinib is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with ceritinib. Avoid use of fesoterodine and ceritinib in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
Finasteride; Tadalafil: (Major) Avoid coadministration of tadalafil and ceritinib for the treatment of pulmonary hypertension. For the treatment of erectile dysfunction, do not exceed 10 mg tadalafil within 72 hours of ceritinib for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Tadalafil is metabolized predominantly by CYP3A4. Potent inhibitors of CYP3A4, such as ceritinib, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.
Finerenone: (Contraindicated) Concomitant use of finerenone and ceritinib is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
Fingolimod: (Major) Avoid coadministration of ceritinib with fingolimod if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Initiation of other drugs during the 2 months after fingolimod discontinuation warrants the same considerations needed for concomitant administration because fingolimod remains in the blood and has pharmacodynamic effects for up to 2 months after the last dose. Ceritinib causes concentration-dependent prolongation of the QT interval. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. 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) Avoid coadministration of ceritinib with flecainide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsade de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors such as ceritinib is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of ceritinib, start flibanserin at least 2 weeks after the last dose of ceritinib. If initiating ceritinib following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating ceritinib therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Fluconazole: (Contraindicated) The concurrent use of fluconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as ceritinib, is contraindicated. Fluconazole has been associated with QT prolongation and concentration-dependent QT prolongation has been reported with ceritinib.
Fluoxetine: (Major) Avoid coadministration of ceritinib with fluoxetine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. QT prolongation and torsade de pointes (TdP) have also been reported in patients treated with fluoxetine.
Fluphenazine: (Minor) Fluphenazine is 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 such as ceritinib.
Flurazepam: (Moderate) Monitor for an increase in sedation and respiratory depression if coadministration of flurazepam with ceritinib is necessary. Flurazepam is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Salmeterol: (Major) Avoid concomitant use of salmeterol with ceritinib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Umeclidinium; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Vilanterol: (Major) Coadministration of inhaled fluticasone propionate and ceritinib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone propionate exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluvoxamine: (Major) Avoid coadministration of ceritinib with fluvoxamine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Prolongation of the QT interval and torsade de pointes (TdP) has also been reported during postmarketing experience with fluvoxamine.
Food: (Major) Advise patients to avoid cannabis use during ceritinib treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A substrates and ceritinib is a strong CYP3A inhibitor. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inhibitor increased THC, 11-OH-THC, and CBD peak exposures by 1.3-, 3-, and 1.9-fold respectively.
Formoterol; Mometasone: (Moderate) Coadministration of mometasone with ceritinib may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; ceritinib is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Fosamprenavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with ceritinib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Foscarnet: (Major) Avoid coadministration of foscarnet with ceritinib due to the risk of QT prolongation. Ceritinib causes concentration-dependent prolongation of the QT interval. If coadministration cannot be avoided, conduct periodic monitoring with electrocardiograms (ECGs) and electrolytes. Both QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of foscarnet.
Fosphenytoin: (Major) Avoid concomitant use of ceritinib with fosphenytoin as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and fosphenytoin is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Fostamatinib: (Moderate) Monitor for an increase in fostamatinib-related adverse reactions if coadministration with ceritinib is necessary. Fostamatinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to R406 (the major active metabolite of fostamatinib) by 102%.
Fostemsavir: (Major) Avoid coadministration of ceritinib with fostemsavir if possible due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes dose-dependent QT prolongation. 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.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with ceritinib is necessary. Gefitinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
Gemifloxacin: (Major) Avoid coadministration of ceritinib with gemifloxacin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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. 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 ceritinib with gemtuzumab if possible due to the risk of QT prolongation. If concomitant use is unavoidable, obtain an ECG and serum electrolytes prior to starting concomitant therapy and periodically monitor ECGs and electrolytes during therapy; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Major) Consider an alternative to ceritinib during treatment with gilteritinib due to increased gilteritinib exposure and the potential for additive QT prolongation. If coadministration is required, monitor for gilteritinib-related adverse reactions as well as monitoring periodic ECGs and serum electrolytes. Interrupt therapy, dose reduce, or discontinue treatment if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study. In addition, both drugs have been associated with QT prolongation.
Glasdegib: (Major) Consider an alternative to ceritinib during treatment with glasdegib. Concurrent use may increase glasdegib exposure resulting in treatment-related adverse events including QT prolongation. If coadministration cannot be avoided, monitor for increased adverse events; more frequent ECG monitoring is recommended, as well as monitoring electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Glasdegib is a CYP3A4 substrate that causes QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study.
Glyburide: (Moderate) Monitor for glyburide-related adverse reactions including hypoglycemia if coadministered with ceritinib; glyburide exposure may increase. Ceritinib is a weak CYP2C9 inhibitor and glyburide is primarily metabolized by CYP2C9.
Glyburide; Metformin: (Moderate) Monitor for glyburide-related adverse reactions including hypoglycemia if coadministered with ceritinib; glyburide exposure may increase. Ceritinib is a weak CYP2C9 inhibitor and glyburide is primarily metabolized by CYP2C9.
Goserelin: (Major) Avoid coadministration of ceritinib with goserelin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval.
Granisetron: (Major) Avoid coadministration of ceritinib with granisetron if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Granisetron has also been associated with QT prolongation.
Grapefruit juice: (Major) Patients should not consume grapefruit and grapefruit juice during ceritinib therapy. Avoid coadministration of ceritinib with grapefruit or grapefruit juice due to increased ceritinib exposure. Ceritinib is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ceritinib AUC by 2.9-fold and the Cmax by 22%.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ceritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) If coadministration of ceritinib with extended-release (ER) guanfacine is necessary, reduce the guanfacine dosage to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. If ceritinib is discontinued, the guanfacine ER dosage should be increased back to the recommended dose. Guanfacine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Ceritinib may significantly increase guanfacine plasma concentrations.
Halogenated Anesthetics: (Major) Avoid coadministration of ceritinib with halogenated anesthetics if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Halogenated anesthetics can also prolong the QT interval.
Haloperidol: (Major) Avoid coadministration of ceritinib with haloperidol if possible due to the risk of QT prolongation; plasma concentrations of haloperidol may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Monitor for haloperidol-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent prolongation of the QT interval. Haloperidol is a CYP3A4 substrate that has caused QT prolongation and torsade de pointes (TdP) during treatment; excessive doses (particularly in the overdose setting) or IV administration may be associated with a higher risk. In clinical trials, mild to moderately increased haloperidol concentrations have been reported when haloperidol was given concomitantly with CYP3A4 inhibitors.
Histrelin: (Major) Avoid coadministration of ceritinib with histrelin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ceritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ceritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ceritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like ceritinib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If ceritinib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydroxychloroquine: (Major) Avoid coadministration of ceritinib and hydroxychloroquine due to the risk of increased 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 ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Hydroxychloroquine also prolongs the QT interval.
Hydroxyzine: (Major) Avoid coadministration of ceritinib with hydroxyzine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Postmarketing data indicate that hydroxyzine also causes QT prolongation and torsade de pointes (TdP).
Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with ceritinib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ibrutinib: (Major) Avoid concomitant use of ibrutinib and ceritinib; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased ibrutinib exposure by 5.7-fold to 24-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with strong CYP3A4 inhibitors like ceritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If ceritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ibutilide: (Major) Avoid coadministration of ceritinib with ibutilide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Ibutilide administration can cause QT prolongation and torsade de pointes (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.
Idelalisib: (Major) Avoid concomitant use of ceritinib with idelalisib due to increased exposure to both drugs which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for treatment-related adverse reactions. After idelalisib is discontinued, resume the dose of ceritinib taken prior to initiating idelalisib. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. Coadministration with another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with ceritinib is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Ceritinib is a strong CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) Avoid coadministration of iloperidone with ceritinib due to the risk of QT prolongation; plasma concentrations of iloperidone may also increase. Iloperidone is a CYP3A4 substrate that has been associated with QT prolongation. Concentration-dependent QT prolongation has also been reported with ceritinib, a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to iloperidone and its metabolites P88 and P95 by 57%, 55%, and 35%, respectively.
Imatinib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with ceritinib is necessary. Imatinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased imatinib exposure by 40%.
Imipramine: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and imipramine; an interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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).
Indinavir: (Major) Avoid concomitant use of ceritinib with indinavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; indinavir exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for treatment-related adverse reactions. Although specific recommendations are unavailable for use with ceritinib, a reduced indinavir dose of 600 mg PO every 8 hours is recommended when coadministered with other strong CYP3A4 inhibitors. Both drugs are CYP3A substrates and strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Infigratinib: (Major) Avoid concomitant use of infigratinib and ceritinib. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with ceritinib due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Inotuzumab has been associated with QT interval prolongation. Concentration-dependent QT prolongation has been reported with ceritinib.
Irinotecan Liposomal: (Major) Discontinue ceritinib at least 1 week prior to starting irinotecan therapy; do not administer ceritinib with irinotecan unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to both irinotecan and SN-38.
Irinotecan: (Major) Discontinue ceritinib at least 1 week prior to starting irinotecan therapy; do not administer ceritinib with irinotecan unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to both irinotecan and SN-38.
Isavuconazonium: (Contraindicated) Coadministration of isavuconazonium with ceritinib is contraindicated due to the risk of increased isavuconazole exposure. Isavuconazole is a sensitive substrate of CYP3A4 and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased isavuconazole exposure by 422%.
Isoflurane: (Major) Avoid coadministration of ceritinib with halogenated anesthetics if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Halogenated anesthetics can also prolong the QT interval.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concomitant use of ceritinib with rifampin as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased ceritinib exposure by 70%.
Isoniazid, INH; Rifampin: (Major) Avoid concomitant use of ceritinib with rifampin as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased ceritinib exposure by 70%.
Isradipine: (Moderate) Monitor for hypotension if coadministration of ceritinib with isradipine is necessary. Ceritinib is a strong CYP3A4 inhibitor and isradipine is metabolized by CYP3A4. Concomitant use may increase isradipine exposure, increasing the risk for isradipine-related adverse reactions.
Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with ceritinib as istradefylline exposure and adverse effects may increase. Ceritinib is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
Itraconazole: (Major) Avoid concomitant use of ceritinib during and for 2 weeks after itraconazole due to increased exposure to ceritinib which may increase the incidence and severity of adverse reactions as well as an additive risk of QT prolongation; itraconazole exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg; monitor for treatment-related adverse reactions. Periodically monitor electrolytes and ECGs; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. After itraconazole is discontinued, resume the dose of ceritinib taken prior to initiating itraconazole. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. Ceritinib also causes concentration-dependent prolongation of the QT interval and itraconazole is associated with QT prolongation. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Ivabradine: (Contraindicated) Coadministration of ceritinib with ivabradine is contraindicated due to an increase in plasma concentrations of ivabradine, which may exacerbate bradycardia and conduction disturbances. Ivabradine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivabradine exposure by 7.7-fold.
Ivacaftor: (Major) If ceritinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with ceritinib due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If ceritinib is discontinued, wait at least 5 half-lives of ceritinib before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate that has been associated with QTc prolongation and ventricular arrhythmias. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and ceritinib due to increased ixabepilone exposure, which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of ixabepilone to 20 mg/m2. Ixabepilone is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ixabepilone exposure by 79%.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and ceritinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of both drugs, further increasing the risk for adverse events. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. Coadministration with ketoconazole increased ceritinib exposure by 2.9-fold.
Labetalol: (Major) Avoid concomitant use of ceritinib with labetolol if possible due to the risk of additive bradycardia. Both ceritinib and labetolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with ceritinib due to the additive risk of QT prolongation and increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg; monitor for ceritinib-related adverse reactions. Periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, further dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. After clarithromycin is discontinued, resume the dose of ceritinib taken prior to initiating clarithromycin. Ceritinib is a CYP3A substrate associated with concentration-dependent QT prolongation; clarithromycin is a strong CYP3A4 inhibitor associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Lapatinib: (Major) Avoid coadministration of lapatinib with ceritinib due to increased plasma concentrations of lapatinib and the risk of QT prolongation. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily. Monitor ECGs for QT prolongation and monitor electrolytes; correct any electrolyte abnormalities prior to treatment. If ceritinib is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Ceritinib is a strong CYP3A4 inhibitor that also causes concentration-dependent QT prolongation. Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold.
Larotrectinib: (Major) Avoid coadministration of larotrectinib with ceritinib due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If ceritinib is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of ceritinib. Larotrectinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study.
Lasmiditan: (Major) Avoid concomitant use of ceritinib with lasmiditan if possible due to the risk of additive bradycardia. Both ceritinib and lasmiditan can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. In a drug interaction study, addition of a single 200 mg dose of lasmiditan to another heart rate lowering drug decreased heart rate by an additional 5 beats per minute.
Lefamulin: (Major) Avoid coadministration of lefamulin with ceritinib 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. Lefamulin is a CYP3A4 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. Ceritinib is a strong CYP3A4 that can cause concentration-dependent QT prolongation. Coadministration of a strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and ceritinib as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of lemborexant with a strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Leniolisib: (Major) Avoid concomitant use of leniolisib and ceritinib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with ceritinib due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Ceritinib causes concentration-dependent QT prolongation.
Letermovir: (Moderate) Avoid coadministration of ceritinib with letermovir if the patient is also taking cyclosporine. If this combination (ceritinib/letermovir/cyclosporine) is unavoidable, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg; monitor for ceritinib-related adverse reactions. No dose adjustment or special precautions are necessary if ceritinib and letermovir are coadministered without cyclosporine. Ceritinib is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor, but the combined effect when given with cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ceritinib exposure by 2.9-fold after a single dose in healthy subjects.
Leuprolide: (Major) Avoid coadministration of ceritinib with leuprolide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Major) Avoid coadministration of ceritinib with leuprolide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval.
Levamlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Levobunolol: (Major) Avoid coadministration of ceritinib with levobunolol if possible due to the risk of additive bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. Bradycardia has been reported with ceritinib treatment; levobunolol also causes bradycardia.
Levofloxacin: (Major) Concomitant use of levofloxacin and ceritinib 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 ceritinib due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of both drugs, further increasing the risk for adverse events. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. Coadministration with ketoconazole increased ceritinib exposure by 2.9-fold.
Levomilnacipran: (Major) Do not exceed a levomilnacipran dose of 80 mg once daily if coadministration with ceritinib is necessary. Levomilnacipran is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased levomilnacipran exposure by about 50%.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor; lidocaine is metabolized by CYP3A4 and CYP1A2. Concomitant treatment CYP3A4 inhibitors has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and prolonging the elimination half-life.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor; lidocaine is metabolized by CYP3A4 and CYP1A2. Concomitant treatment CYP3A4 inhibitors has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and prolonging the elimination half-life.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor; lidocaine is metabolized by CYP3A4 and CYP1A2. Concomitant treatment CYP3A4 inhibitors has the potential to increase lidocaine plasma levels by decreasing lidocaine clearance and prolonging the elimination half-life.
Lithium: (Major) Avoid coadministration of ceritinib with lithium if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Lithium is also associated with QT prolongation.
Lofexidine: (Major) Avoid coadministration of ceritinib with lofexidine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Lofexidine prolongs the QT interval. Ceritinib also causes concentration-dependent prolongation of the QT interval.
Lomitapide: (Contraindicated) Concomitant use of ceritinib and lomitapide is contraindicated; if treatment with ceritinib is unavoidable, lomitapide should be stopped during treatment. Ceritinib is a strong CYP3A4 inhibitor and lomitapide is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased lomitapide exposure approximately 27-fold.
Lonafarnib: (Contraindicated) Concomitant use of lonafarnib and ceritinib is contraindicated and may increase the exposure and risk of adverse effects from both drugs. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg. Lonafarnib is a CYP3A and CYP2C9 substrate and strong CYP3A4 inhibitor; ceritinib is a CYP3A4 substrate and strong CYP3A4 and weak CYP2C9 inhibitor. Strong CYP3A4 inhibitors are expected to increase lonafarnib exposure by 425% and ceritinib exposure by 190%.
Loperamide: (Major) Concomitant use of loperamide and ceritinib 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 CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and ceritinib 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 CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with ceritinib 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, dose reduce, or discontinue ceritinib if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Lopinavir is also associated with QT prolongation. (Major) Avoid concomitant use of ceritinib with ritonavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After ritonavir is discontinued, resume the dose of ceritinib taken prior to initiating ritonavir. Ceritinib is a CYP3A substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Lorlatinib: (Major) Avoid coadministration of lorlatinib with ceritinib due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If ceritinib is discontinued, resume the original dose of lorlatinib after 3 half-lives of ceritinib. Lorlatinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%.
Lovastatin: (Contraindicated) Coadministration of lovastatin and ceritinib is contraindicated due to the risk of elevated plasma concentrations of lovastatin leading to myopathy and rhabdomyolysis. Lovastatin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lovastatin exposure by 11 to 36-fold.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of ceritinib with lumacaftor; ivacaftor as ceritinib exposure may be decreased, which may reduce its efficacy; ivacaftor exposure may also increase. Ceritinib is a CYP3A substrate and a strong CYP3A4 inhibitor. Lumacaftor is a strong CYP3A inducer and ivacaftor is a CYP3A substrate. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) If ceritinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of ceritinib with lumacaftor; ivacaftor as ceritinib exposure may be decreased, which may reduce its efficacy; ivacaftor exposure may also increase. Ceritinib is a CYP3A substrate and a strong CYP3A4 inhibitor. Lumacaftor is a strong CYP3A inducer and ivacaftor is a CYP3A substrate. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Lumateperone: (Major) Reduce the dose of lumateperone to 10.5 mg once daily if concomitant use of ceritinib is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold.
Lurasidone: (Contraindicated) Coadministration of lurasidone with ceritinib is contraindicated due to increased plasma concentrations of lurasidone. Lurasidone is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lurasidone exposure by 9-fold.
Lurbinectedin: (Major) Avoid concomitant use of lurbinectedin and ceritinib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as ceritinib. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of ceritinib prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Concentration-dependent QT prolongation has been reported with ceritinib.
Macitentan: (Major) Avoid coadministration of macitentan with ceritinib due to the risk of increased plasma concentrations of macitentan. Macitentan is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor approximately doubled macitentan exposure.
Maprotiline: (Major) Avoid coadministration of ceritinib with maprotiline if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Maprotiline has 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 torsade de pointes (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: (Major) Reduce the dose of maraviroc when coadministered with strong CYP3A inhibitors such as ceritinib; coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCL less than 30 mL/min. Adjust the maraviroc dosage as follows when administered with ceritinib (with or without a concomitant CYP3A inducer): adults and children weighing 40 kg or more: 150 mg PO twice daily; children weighing 30 to 39 kg: 100 mg PO twice daily; children weighing 20 to 29 kg: 75 mg PO twice daily (or 80 mg PO twice daily for solution); children weighing 10 to 19 kg: 50 mg PO twice daily; children weighing 2 to 9 kg: use not recommended. The AUC of maraviroc was increased by up to approximately 10-fold in the presence of strong CYP3A4 inhibitors.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with ceritinib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Medroxyprogesterone: (Moderate) Use caution if coadministration of ceritinib with medroxyprogesterone is necessary, as the systemic exposure of medroxyprogesterone may be increased resulting in an increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor. Medroxyprogesterone is metabolized primarily by hydroxylation via a CYP3A4.
Mefloquine: (Major) Avoid coadministration of ceritinib with mefloquine if possible due to the risk of QT prolongation; plasma concentrations of mefloquine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Mefloquine is a CYP3A4 substrate. 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. Ceritinib is a strong CYP3A4 inhibitor that has been reported to cause concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased mefloquine exposure by 79%.
Meloxicam: (Moderate) Consider a meloxicam dose reduction and monitor for adverse reactions if coadministration with ceritinib is necessary. Concurrent use may increase meloxicam exposure. Meloxicam is a CYP2C9 substrate and ceritinib is a weak CYP2C9 inhibitor.
Metformin; Repaglinide: (Moderate) A dose reduction of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with ceritinib is necessary. Repaglinide is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased repaglinide exposure by up to 1.5-fold.
Metformin; Saxagliptin: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with ceritinib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Methadone: (Major) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary; carefully assess the benefits of treatment with the risks of therapy, including QT prolongation. Periodically monitor ECGs for QT prolongation and monitor electrolytes. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary for QT prolongation. If ceritinib is discontinued, consider increasing the methadone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Methadone is a CYP3A4 substrate, and coadministration with strong CYP3A4 inhibitors like ceritinib can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone. If ceritinib is discontinued, methadone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Additionally, concentration-dependent QT prolongation has been reported with ceritinib therapy. Methadone is considered to be associated with an increased risk for QT prolongation and torsade de pointes (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.
Methylprednisolone: (Moderate) Monitor for steroid-related adverse reactions if coadministration of ceritinib with methylprednisolone is necessary, due to increased methylprednisolone exposure; Cushings syndrome and adrenal suppression could potentially occur with long-term use. Ceritinib is a strong CYP3A4 inhibitor and methylprednisolone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Metoprolol: (Major) Avoid concomitant use of ceritinib with metoprolol if possible due to the risk of additive bradycardia. Both ceritinib and metoprolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Avoid concomitant use of ceritinib with metoprolol if possible due to the risk of additive bradycardia. Both ceritinib and metoprolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Metronidazole: (Major) Concomitant use of metronidazole and ceritinib 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.
Midazolam: (Moderate) Monitor for increased sedation and respiratory depression if coadministration of midazolam with ceritinib is necessary. Midazolam is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Daily administration of ceritinib increased the AUC and Cmax of single-dose midazolam by 5.4-fold and 1.8-fold, respectively.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and ceritinib due to the risk of increased midostaurin exposure which may increase the incidence and severity of adverse reactions; concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). If concomitant use cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity, particularly during the first week of midostaurin therapy for those with systemic mastocytosis/mast cell leukemia and during the first week of each cycle for those with acute myeloid leukemia. 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 is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration of one strong CYP3A4 inhibitor with a single dose of midostaurin increased the exposure of midostaurin and its active metabolites CGP62221 and CGP52421 by 10.4-fold, 3.5-fold, and 1.2-fold, respectively. Coadministration of another strong CYP3A4 inhibitor with twice daily doses of midostaurin increased Day 28 trough concentrations of midostaurin, CGP62221, and CGP52421 by 2.1-fold, 1.2-fold, and 1.3-fold respectively compared with day 21 trough levels with midostaurin alone.
Mifepristone: (Major) Avoid concomitant use of mifepristone with ceritinib due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use is necessary for the treatment of Cushings syndrome, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. If mifepristone therapy is added for the treatment of Cushing's syndrome in a patient already receiving ceritinib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ceritinib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ceritinib are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Mirtazapine: (Major) Avoid coadministration of ceritinib with mirtazapine if possible due to the risk of QT prolongation; plasma concentrations of mirtazapine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Mirtazapine is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; torsade de pointes (TdP) has also been reported in postmarketing experience, primarily in overdose or in patients with other risk factors for QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that is also associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the Cmax and AUC of a single dose of mirtazapine by approximately 40% and 50%, respectively.
Mirvetuximab Soravtansine: (Moderate) Closely monitor for mirvetuximab soravtansine-related adverse reactions if concomitant use of ceritinib is necessary. DM4, the cytotoxic component of mirvetuximab soravtansine, is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use may increase unconjugated DM4 exposure.
Mitapivat: (Major) Avoid coadministration of mitapivat with ceritinib due to increased risk of adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with other strong CYP3A inhibitors increased mitapivat overall exposure by 3.6 to 4.9-fold.
Mitotane: (Major) Avoid concomitant use of ceritinib with mitotane as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and mitotane is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and ceritinib. Concomitant use increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may increase mobocertinib exposure and the risk for mobocertinib-related adverse reactions. Mobocertinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Use of a strong CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 374% to 419%.
Modafinil: (Moderate) Monitor for an increase in modafinil-related adverse reactions if coadministration with ceritinib is necessary. Modafinil has multiple pathways for metabolism including non-CYP-related pathways; however, due to partial involvement of the CYP3A enzymes, concomitant use of strong CYP3A4 inhibitors such as ceritinib could increase plasma concentrations of modafinil.
Mometasone: (Moderate) Coadministration of mometasone with ceritinib may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; ceritinib is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Moxifloxacin: (Major) Avoid coadministration of ceritinib with moxifloxacin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Quinolones have also been associated with a risk of QT prolongation. Although extremely rare, torsade de pointes (TdP) has been reported during postmarketing experience with moxifloxacin; these reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
Nadolol: (Major) Avoid concomitant use of ceritinib with nadolol if possible due to the risk of additive bradycardia. Both ceritinib and nadolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Naldemedine: (Moderate) Monitor for potential naldemedine-related adverse reactions if coadministered with ceritinib. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor.
Naloxegol: (Contraindicated) Concomitant use of naloxegol with ceritinib is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as ceritinib, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with ceritinib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and ceritinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Nateglinide: (Moderate) More frequent monitoring of blood glucose may be necessary during coadministration of nateglinide and ceritinib due to the potential for increased nateglinide exposure. A nateglinide dose reduction may be necessary. Ceritinib is a weak CYP2C9 inhibitor and nateglinide is primarily metabolized by CYP2C9.
Nebivolol: (Major) Avoid coadministration of ceritinib with nebivolol if possible due to the risk of additive bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. Bradycardia has been reported with ceritinib treatment; nebivolol also causes bradycardia.
Nebivolol; Valsartan: (Major) Avoid coadministration of ceritinib with nebivolol if possible due to the risk of additive bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. Bradycardia has been reported with ceritinib treatment; nebivolol also causes bradycardia.
Nefazodone: (Major) Avoid concomitant use of ceritinib with nefazodone due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After nefazodone is discontinued, resume the dose of ceritinib taken prior to initiating nefazodone. Ceritinib is a CYP3A substrate; nefazodone is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Nelfinavir: (Major) Avoid concomitant use of ceritinib with nelfinavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; nelfinavir exposure may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After nelfinavir is discontinued, resume the dose of ceritinib taken prior to initiating nelfinavir. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. Coadministration with another strong CYP3A4 inhibitor increased the exposure of nelfinavir by 35%.
Neratinib: (Major) Avoid concomitant use of ceritinib with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for netupitant-related adverse reactions if coadministration with ceritinib is necessary; however, a dosage adjustment is not necessary. Ceritinib is a strong CYP3A4 inhibitor and netupitant is primarily metabolized by CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased the mean Cmax and AUC of netupitant by 25% and 140%, respectively.
Nevirapine: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with ceritinib is necessary. Nevirapine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
Niacin; Simvastatin: (Contraindicated) Concurrent use of simvastatin and ceritinib is contraindicated due to an increased risk of developing myopathy, rhabdomyolysis, and acute renal failure. Simvastatin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Nifedipine: (Moderate) Monitor blood pressure if coadministration of nifedipine with ceritinib is necessary; consider decreasing the dose of nifedipine if appropriate. Nifedipine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Concomitant use may increase nifedipine exposure.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and ceritinib due to increased plasma concentrations of nilotinib which may result in QT prolongation. If coadministration is required, monitor patients closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in patients with resistant or intolerant Ph+ CML or to 200 mg once daily in patients with newly diagnosed Ph+ CML. Periodically monitor electrolytes as well. If ceritinib is discontinued, a washout period should be allowed before adjusting the nilotinib dosage upward to the indicated dose. Nilotinib is a substrate of CYP3A4 and ceritinib is a strong inhibitor of CYP3A4. Concentration-dependent QT prolongation has been reported with ceritinib therapy. Sudden death and QT interval prolongation have occurred in patients who received nilotinib treatment.
Nimodipine: (Major) Avoid coadministration of nimodipine with ceritinib due to the risk of significant hypotension. If concomitant use is unavoidable, monitor blood pressure and reduce the dose of nimodipine as clinically appropriate. Nimodipine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of ceritinib with ritonavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After ritonavir is discontinued, resume the dose of ceritinib taken prior to initiating ritonavir. Ceritinib is a CYP3A substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with ceritinib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Norethindrone; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Norgestimate; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Nortriptyline: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and nortriptyline; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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).
Ofloxacin: (Major) Concomitant use of ofloxacin and ceritinib 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 ceritinib with olanzapine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval.
Olanzapine; Fluoxetine: (Major) Avoid coadministration of ceritinib with fluoxetine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. QT prolongation and torsade de pointes (TdP) have also been reported in patients treated with fluoxetine. (Major) Avoid coadministration of ceritinib with olanzapine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval.
Olanzapine; Samidorphan: (Major) Avoid coadministration of ceritinib with olanzapine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Limited data, including some case reports, suggest that olanzapine may also be associated with a significant prolongation of the QTc interval.
Olaparib: (Major) Avoid coadministration of olaparib with ceritinib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after ceritinib is discontinued. Olaparib is a CYP3A substrate and ceritinib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and ceritinib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and ceritinib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If ceritinib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Olopatadine; Mometasone: (Moderate) Coadministration of mometasone with ceritinib may cause elevated mometasone serum concentrations, potentially resulting in Cushing's syndrome and adrenal suppression. Mometasone is a CYP3A4 substrate; ceritinib is a strong inhibitor of CYP3A4. Corticosteroids, such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A4 inhibitors, should be considered, especially for long-term use.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and ceritinib. If concomitant use is necessary, decrease omaveloxolone dose to 50 mg once daily. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased omaveloxolone overall exposure by 4-fold.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Monitor for an increase in rifabutin-related adverse reactions if coadministration with ceritinib is necessary; a dosage adjustment may be necessary. Ceritinib is a strong CYP3A4 inhibitor and rifabutin is primarily metabolized by CYP3A4. Concomitant medications that competitively inhibit the CYP3A activity may increase plasma concentrations of rifabutin.
Ondansetron: (Major) Concomitant use of ondansetron and ceritinib 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 ceritinib with osilodrostat if possible due to the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of osilodrostat by one-half and periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Osilodrostat is a CYP3A4 substrate that is associated with dose-dependent QT prolongation; ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Osimertinib: (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.
Ospemifene: (Major) Monitor for an increase in ospemifene-related adverse reactions if coadministration with ceritinib is necessary. Ospemifene is a CYP3A4 and CYP2C9 substrate. Ceritinib is a strong CYP3A4 inhibitor and a weak CYP2C9 inhibitor. Coadministration of another strong inhibitor increased ospemifene systemic exposure by 1.4-fold. Coadministration with drugs known to inhibit both CYP3A4 and CYP2C9 may increase the risk of ospemifene-related adverse reactions.
Oxaliplatin: (Major) Avoid coadministration of ceritinib with oxaliplatin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
Oxybutynin: (Moderate) Monitor for an increase in oxybutynin-related adverse reactions if coadministration with ceritinib is necessary. Oxybutynin is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased mean oxybutynin plasma concentrations by approximately 2-fold.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with strong CYP3A4 inhibitors like ceritinib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If ceritinib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Ozanimod: (Major) Avoid coadministration of ceritinib with ozanimod if possible due to the risk of QT prolongation. If concomitant use is unavoidable, consult cardiology, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with torsade de pointes in patients with bradycardia.
Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and paclitaxel is metabolized by CYP3A4. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with ceritinib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Palbociclib: (Major) Avoid coadministration of palbociclib with ceritinib if possible due to the risk of increased palbociclib exposure. If concomitant use is unavoidable, decrease the dose of palbociclib to 75 mg once daily; the original dose of palbociclib may be resumed after 3 to 5 half-lives of the discontinuation of ceritinib. Palbociclib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased palbociclib exposure by 87%.
Paliperidone: (Major) Avoid coadministration of paliperidone with ceritinib if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor electrolytes for QT prolongation and monitor electrolytes; close monitoring is essential if the patient has known risk factors for cardiac disease or arrhythmia. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Paliperidone has been associated with QT prolongation; torsade de pointes and ventricular fibrillation have been reported in the setting of overdose. Concentration-dependent QT prolongation has been reported with ceritinib therapy.
Palovarotene: (Major) Avoid concomitant use of palovarotene and ceritinib due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. Palovarotene is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased palovarotene overall exposure by 3-fold.
Panobinostat: (Major) Coadministration of panobinostat and ceritinib is not recommended due to the potential for QT prolongation; increased panobinostat exposure is also possible. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent prolongation of the QT interval. Panobinostat is primarily metabolized by CYP3A4 and is also associated with QT prolongation. Coadministration with a strong CYP3A4 inhibitor increased the Cmax and AUC of panobinostat by 62% and 73%, respectively.
Paricalcitol: (Moderate) Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with both paricalcitol and ceritinib, or during periods of dose titration. If hypercalcemia occurs, the dose of paricalcitol should be reduced or withheld until these parameters are normalized. Ceritinib is a strong CYP3A4 inhibitor and paricalcitol is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor approximately doubled the exposure of paricalcitol.
Pasireotide: (Major) Avoid coadministration of ceritinib with pasireotide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Pasireotide is also associated with QT prolongation; coadministration may have additive effects.
Pazopanib: (Major) Avoid coadministration of pazopanib and ceritinib due to the potential for increased pazopanib exposure; QT prolongation may also occur. If concurrent use is unavoidable, reduce the pazopanib dose to 400 mg PO once daily; further dose adjustments may be necessary if adverse effects occur. Closely monitor ECGs for QT prolongation; also monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Pazopanib is a CYP3A4 substrate that has been reported to prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has had reports of concentration-dependent QT prolongation. Concurrent use of another strong CYP3A4 inhibitor increased the Cmax and AUC of pazopanib by 1.5-fold and 1.7-fold, respectively.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and ceritinib due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If ceritinib is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of ceritinib. Pemigatinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%.
Pentamidine: (Major) Avoid coadministration of ceritinib with systemic pentamidine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Systemic pentamidine has been associated with QT prolongation.
Perindopril; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Perphenazine: (Minor) Perphenazine is 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 such as ceritinib.
Perphenazine; Amitriptyline: (Minor) Perphenazine is 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 such as ceritinib.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and ceritinib due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If ceritinib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of ceritinib. Pexidartinib is a CYP3A substrate; ceritinib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Phenobarbital: (Major) Avoid concomitant use of ceritinib with phenobarbital as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and phenobarbital is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concomitant use of ceritinib with phenobarbital as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and phenobarbital is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Phenytoin: (Major) Avoid concomitant use of ceritinib with phenytoin as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and phenytoin is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Pimavanserin: (Major) Pimavanserin should generally be avoided in patients receiving ceritinib due to the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of pimavanserin to 10 mg PO once daily and monitor for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, and loss of balance or coordination. Monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Pimavanserin is a CYP3A4 substrate that may cause QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. In drug interaction studies, coadministration with a strong CYP3A4 inhibitor increased exposure to pimavanserin by 3-fold.
Pimozide: (Contraindicated) Because of the potential for torsade de pointes, coadministration of pimozide with ceritinib is contraindicated. Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Ceritinib also prolongs the QT interval.
Pindolol: (Major) Avoid concomitant use of ceritinib with pindolol if possible due to the risk of additive bradycardia. Both ceritinib and pindolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Pirtobrutinib: (Major) Avoid concomitant use of pirtobrutinib and ceritinib due to the risk of increased pirtobrutinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pirtobrutinib dose by 50 mg. If the current pirtobrutinib dosage is 50 mg once daily, interrupt pirtobrutinib treatment for the duration of ceritinib use. Resume the previous dose of pirtobrutinib after ceritinib is discontinued for 5 half-lives. Pirtobrutinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant with another strong CYP3A inhibitor increased pirtobrutinib overall exposure by 49%.
Pitolisant: (Major) Avoid coadministration of pitolisant with ceritinib as concurrent use may increase the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Pitolisant also prolongs the QT interval.
Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ceritinib due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ceritinib is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Ponatinib: (Major) Avoid coadministration of ponatinib and ceritinib due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of ceritinib and consider alternative therapy. After ceritinib has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting ceritinib. Ponatinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%.
Ponesimod: (Major) Avoid concomitant use of ponesimod and ceritinib due to the risk of severe bradycardia and heart block, 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, monitor ECGs, electrolytes, and for signs and symptoms of infection; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. 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: (Contraindicated) The concurrent use of posaconazole with drugs that are associated with QT prolongation and are also CYP3A4 substrates, such as ceritinib, is contraindicated. Posaconazole is a strong CYP3A4 inhibitor that has been associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation. If concomitant use is unavoidable, the manufacturer of ceritinib recommends decreasing the dose of ceritinib by approximately one-third when administered in combination with strong CYP3A4 inhibitors, rounding to the nearest multiple of 150 mg and monitoring for ceritinib-related adverse reactions. After posaconazole is discontinued, resume the dose of ceritinib taken prior to initiating posaconazole. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Pralsetinib: (Major) Avoid concomitant use of ceritinib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Prednisolone: (Minor) Monitor for steroid-related adverse reactions if coadministration of ceritinib with prednisolone is necessary, due to increased prednisolone exposure. Ceritinib is a strong CYP3A4 inhibitor and prednisolone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects; however, plasma concentrations of prednisolone are less affected by strong CYP3A4 inhibitors, especially for long-term use.
Prednisone: (Minor) Monitor for steroid-related adverse reactions if coadministration of ceritinib with prednisone is necessary, due to increased prednisone exposure. Ceritinib is a strong CYP3A4 inhibitor and prednisolone, the active metabolite of prednisone, is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects; however, plasma concentrations of prednisolone are less affected by strong CYP3A4 inhibitors, especially for long-term use.
Primaquine: (Major) Avoid coadministration of ceritinib with primaquine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Primaquine is also associated with QT prolongation.
Primidone: (Major) Avoid concomitant use of ceritinib with primidone as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and primidone is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and ceritinib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Procainamide: (Major) Avoid coadministration of ceritinib with procainamide if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Procainamide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP).
Prochlorperazine: (Minor) 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 such as ceritinib.
Progesterone: (Moderate) Use caution if coadministration of ceritinib with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Promethazine: (Major) Concomitant use of promethazine and ceritinib 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 ceritinib 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 ceritinib 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) Avoid coadministration of ceritinib with propafenone if possible due to the risk of QT prolongation; plasma concentrations of propafenone may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Avoid coadministration altogether if the patient either has CYP2D6 deficiency or is taking a concomitant CYP2D6 inhibitor, as the risk of proarrhythmia and other adverse events is increased. Propafenone is a CYP2D6 and CYP3A4 substrate as well as a Class IC antiarrhythmic which increases the QT interval, largely due to prolongation of the QRS interval. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Propranolol: (Major) Avoid concomitant use of ceritinib with propranolol if possible due to the risk of additive bradycardia. Both ceritinib and propranolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Avoid concomitant use of ceritinib with propranolol if possible due to the risk of additive bradycardia. Both ceritinib and propranolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Protriptyline: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and protriptyline; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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).
Quazepam: (Moderate) Monitor for an increase in quazepam-related adverse reactions including sedation and respiratory depression if coadministration with ceritinib is necessary; reduce the dose of quazepam if clinically appropriate. Quazepam is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Quetiapine: (Major) Avoid coadministration of ceritinib with quetiapine due to an increased risk for QT prolongation. Systemic exposure of quetiapine may also be increased resulting in increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may also be associated with a significant prolongation of the QTc interval in rare instances. Coadministration with another strong CYP3A4 inhibitor significantly increased quetiapine exposure; the manufacturer recommends a large dose reduction when coadministered with strong CYP3A4 inhibitors that do not cause QT prolongation.
Quinidine: (Major) Avoid coadministration of ceritinib with quinidine if possible due to the risk of QT prolongation; plasma concentrations of quinidine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Quinidine is a CYP3A4 substrate that is associated with QT prolongation and torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Quinine: (Major) Avoid coadministration of quinine with ceritinib due to the risk of QT prolongation; plasma concentrations of quinine may also increase. Quinine is a CYP3A4 substrate that is associated with QT prolongation and rare cases of torsade de pointes (TdP). Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the mean AUC of quinine by 45%.
Quizartinib: (Major) Avoid concomitant use of ceritinib with quizartinib due to the risk of increased quizartinib exposure which may increase the risk of adverse reactions. Concomitant use may also increase the risk for torsade de pointes (TdP) and QT/QTc prolongation. If concomitant use is necessary, reduce the dose of quizartinib to 26.5 mg for patients taking a daily dose of 53 mg, and to 17.7 mg for patients taking a daily dose of 35.4 mg or 26.5 mg; interrupt quizartinib therapy for the duration of the strong CYP3A inhibitor use for patients already taking a daily dose of 17.7 mg. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Quizartinib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of quizartinib by 94%.
Ramelteon: (Moderate) Monitor for an increase in ramelteon-related adverse reactions if coadministration with ceritinib is necessary. Ramelteon is a CYP3A4 and CYP2C9 substrate. Ceritinib is a strong CYP3A4 inhibitor and a weak CYP2C9 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ramelteon exposure by 84%.
Ranolazine: (Contraindicated) Coadministration of ranolazine with ceritinib is contraindicated due to increased plasma concentrations of ranolazine; QT prolongation may also occur. Ranolazine is a CYP3A4 substrate that is associated with dose- and plasma concentration-dependent increases in the QTc interval. Ceritinib is a strong CYP3A4 inhibitor that also causes concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased ranolazine exposure by 220%.
Regorafenib: (Major) Avoid coadministration of ceritinib with regorafenib due to increased plasma concentrations of regorafenib and decreased exposure to the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each.
Relugolix: (Major) Avoid coadministration of ceritinib with relugolix if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid coadministration of ceritinib with relugolix if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Repaglinide: (Moderate) A dose reduction of repaglinide and increased frequency of blood glucose monitoring may be required if coadministration with ceritinib is necessary. Repaglinide is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased repaglinide exposure by up to 1.5-fold.
Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as ceritinib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ribociclib: (Major) Avoid concomitant use of ceritinib with ribociclib due to the risk of additive QT prolongation and increased exposure to both drugs which may increase the incidence and severity of adverse reactions. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors that are also associated with concentration-dependent QT prolongation. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. Coadministration with a strong inhibitor increased ribociclib exposure by 3.2-fold.
Ribociclib; Letrozole: (Major) Avoid concomitant use of ceritinib with ribociclib due to the risk of additive QT prolongation and increased exposure to both drugs which may increase the incidence and severity of adverse reactions. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors that are also associated with concentration-dependent QT prolongation. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. Coadministration with a strong inhibitor increased ribociclib exposure by 3.2-fold.
Rifabutin: (Moderate) Monitor for an increase in rifabutin-related adverse reactions if coadministration with ceritinib is necessary; a dosage adjustment may be necessary. Ceritinib is a strong CYP3A4 inhibitor and rifabutin is primarily metabolized by CYP3A4. Concomitant medications that competitively inhibit the CYP3A activity may increase plasma concentrations of rifabutin.
Rifampin: (Major) Avoid concomitant use of ceritinib with rifampin as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Coadministration with rifampin decreased ceritinib exposure by 70%.
Rifapentine: (Major) Avoid concomitant use of ceritinib with rifapentine as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Rilpivirine: (Major) Avoid coadministration of ceritinib with rilpivirine if possible due to the risk of QT prolongation; plasma concentrations of rilpivirine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discont inuation of therapy may be necessary if QT prolongation occurs. Rilpivirine is a CYP3A4 substrate that has been associated with QT prolongation at supratherapeutic doses (75 to 300 mg per day). Ceritinib is a strong CYP3A4 inhibitor that has also been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased the AUC of rilpivirine by 1.49-fold.
Rimegepant: (Major) Avoid coadministration of rimegepant with ceritinib; concurrent use may significantly increase rimegepant exposure. Rimegepant is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration of rimegepant with another strong CYP3A4 inhibitor increased rimegepant exposure by 4-fold.
Ripretinib: (Moderate) Monitor patients more frequently for ripretinib-related adverse reactions if coadministered with ceritinib. Coadministration may increase the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions. Ripretinib and DP-5439 are metabolized by CYP3A4 and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ripretinib and DP-5439 exposure by 99%.
Risperidone: (Major) Avoid coadministration of ceritinib with risperidone if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Reports of QT prolongation and torsade de pointes (TdP) during risperidone therapy are also noted by the manufacturer, primarily in the overdose setting.
Ritonavir: (Major) Avoid concomitant use of ceritinib with ritonavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After ritonavir is discontinued, resume the dose of ceritinib taken prior to initiating ritonavir. Ceritinib is a CYP3A substrate; ritonavir is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Roflumilast: (Moderate) Carefully weigh the risks of increased roflumilast exposure against the benefits of therapy if coadministration with ceritinib is necessary; monitor for roflumilast-related adverse reactions. Roflumilast is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Romidepsin: (Major) Avoid coadministration of ceritinib with romidepsin if possible due to the risk of QT prolongation; plasma concentrations of romidepsin may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Monitor for romidepsin-related adverse reactions and follow dose modifications for toxicity during initial administration. Romidepsin is a CYP3A4 substrate that has been reported to prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. In a pharmacokinetic drug interaction trial a strong CYP3A4 inhibitor increased romidepsin AUC by approximately 25%.
Ruxolitinib: (Major) Reduce the ruxolitinib dosage when coadministered with ceritinib in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur. No dose adjustments are necessary for patients with graft-versus-host disease; however, monitor blood counts more frequently for toxicity and adjust ruxolitinib dosage for adverse reactions. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Avoid the use of ceritinib in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. Ruxolitinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Salmeterol: (Major) Avoid concomitant use of salmeterol with ceritinib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Saquinavir: (Contraindicated) Coadministration of saquinavir with ceritinib is contraindicated due to the risk of QT prolongation; increased exposure to both drugs is also possible. Ceritinib is a CYP3A4 substrate and a strong CYP3A4 inhibitor that causes concentration-dependent prolongation of the QT interval. Saquinavir is a sensitive CYP3A4 substrate, as well as a strong CYP3A4 inhibitor. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). If concomitant use is unavoidable, the manufacturer of ceritinib recommends decreasing the dose of ceritinib by approximately one-third when administered in combination with strong CYP3A4 inhibitors, rounding to the nearest multiple of 150 mg and monitoring for ceritinib-related adverse reactions. After posaconazole is discontinued, resume the dose of ceritinib taken prior to initiating posaconazole. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
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.
Saxagliptin: (Major) Limit the dose of saxagliptin to 2.5 mg PO once daily when administered with ceritinib due to significantly increased saxagliptin exposure. Saxagliptin is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 100 mg dose of saxagliptin and a single 20 mg dose of saxagliptin increased the saxagliptin AUC by 2.45-fold and 3.67-fold, respectively.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Monitor for an increase in estrogenic-related adverse reactions (e.g., nausea, breast tenderness) if coadministration of ethinyl estradiol with ceritinib is necessary. Ceritinib is a strong CYP3A4 inhibitor and ethinyl estradiol is a CYP3A4 substrate.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and ceritinib due to the risk of additive QT prolongation and increased selpercatinib exposure resulting in increased treatment-related adverse effects. If coadministration is unavoidable, reduce the dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily, and to 80 mg PO twice daily if original dose was 160 mg twice daily. Monitor electrolytes and ECGs for QT prolongation more frequently. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. If ceritinib is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of ceritinib. Selpercatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Coadministration with another strong CYP3A inhibitor increased selpercatinib exposure by 133%.
Selumetinib: (Major) Avoid coadministration of selumetinib and ceritinib due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If ceritinib is discontinued, resume the original selumetinib dose after 3 elimination half-lives of ceritinib. Selumetinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selumetinib exposure by 49%.
Sertraline: (Major) Concomitant use of sertraline and ceritinib 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 ceritinib with halogenated anesthetics if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Halogenated anesthetics can also prolong the QT interval.
Sildenafil: (Major) Coadministration with ceritinib is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving ceritinib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Ceritinib is a strong CYP3A4 inhibitor and sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Silodosin: (Contraindicated) Concurrent use of silodosin and ceritinib is contraindicated due to increased plasma concentrations of silodosin resulting in an increase of treatment-related adverse reactions. Silodosin is extensively metabolized by CYP3A4 and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased silodosin exposure by 2.9-fold to 3.2-fold.
Simvastatin: (Contraindicated) Concurrent use of simvastatin and ceritinib is contraindicated due to an increased risk of developing myopathy, rhabdomyolysis, and acute renal failure. Simvastatin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving ceritinib due to the potential for 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. Ceritinib causes concentration-dependent prolongation of the QT interval. Additionally, concomitant use of siponimod and ceritinib may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor and a weak CYP2C9 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Major) Avoid concomitant use of sirolimus and ceritinib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and ceritinib 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.
Solifenacin: (Major) Avoid coadministration of ceritinib with solifenacin if possible due to the risk of QT prolongation and increased exposure to solifenacin. If concomitant use is unavoidable, do not administer more than solifenacin 5 mg per day in adults; do not exceed the initial starting dose in pediatric patients. Periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Solifenacin is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased solifenacin exposure by 2.7-fold. Both drugs have been associated with dose- or concentration-dependent QT prolongation, and torsade de pointes (TdP) was reported in postmarketing experience with solifenacin although causality was not determined.
Sonidegib: (Major) Avoid coadministration of sonidegib with ceritinib due to increased plasma concentrations of sonidegib which may increase the risk of treatment-related adverse reactions. Sonidegib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased sonidegib exposure by 2.2-fold.
Sorafenib: (Major) Avoid coadministration of sorafenib with ceritinib 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. Sorafenib is associated with QTc prolongation. Ceritinib causes concentration-dependent QT prolongation.
Sotalol: (Major) Avoid concomitant use of sotalol and ceritinib due to the risk of additive QT prolongation and bradycardia. Ceritinib causes concentration-dependent QT prolongation. Sotalol administration is associated with QT prolongation and torsade de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Both ceritinib and timolol can cause bradycardia.
Sparsentan: (Major) Avoid concomitant use of sparsentan and ceritinib. Concomitant use may increase sparsentan exposure and the risk for sparsentan-related adverse effects. Sparsentan is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased sparsentan overall exposure by 174%.
St. John's Wort, Hypericum perforatum: (Major) Avoid concomitant use of ceritinib with St. Johns Wort as ceritinib exposure may be decreased, which may reduce its efficacy. Ceritinib is a CYP3A substrate and St. Johns Wort is a strong CYP3A inducer. Coadministration with a strong CYP3A inducer decreased ceritinib exposure by 70%.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if ceritinib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of ceritinib is necessary. If ceritinib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If ceritinib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Sunitinib: (Major) Avoid coadministration of ceritinib with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
Suvorexant: (Major) Coadministration of suvorexant and ceritinib is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
Tacrolimus: (Major) Avoid coadministration of ceritinib with tacrolimus if possible due to the risk of QT prolongation; plasma concentrations of tacrolimus may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Decrease tacrolimus dose and closely monitor tacrolimus serum concentrations if coadministration is necessary; additional dosage reductions may be required. Concurrent use may increase tacrolimus serum concentrations and increase the risk of toxicity. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range that can cause QT prolongation. Ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor significantly increased oral bioavailability of tacrolimus (14% vs. 30%) and decreased oral clearance (0.43 L/hour/kg vs. 0.148 L/hour/kg) compared to tacrolimus alone. Overall, intravenous clearance of tacrolimus was not significantly changed by coadministration with a strong CYP3A4 inhibitor, although it was highly variable between patients.
Tadalafil: (Major) Avoid coadministration of tadalafil and ceritinib for the treatment of pulmonary hypertension. For the treatment of erectile dysfunction, do not exceed 10 mg tadalafil within 72 hours of ceritinib for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Tadalafil is metabolized predominantly by CYP3A4. Potent inhibitors of CYP3A4, such as ceritinib, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.
Tamoxifen: (Major) Concomitant use of tamoxifen and ceritinib 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.
Tamsulosin: (Major) Concurrent use of tamsulosin and ceritinib is not recommended due to the potential for elevated tamsulosin concentrations. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension, dizziness, and vertigo. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes, and strong inhibitors of CYP3A4 like ceritinib are expected to significantly raise tamsulosin concentrations. Concomitant treatment with another strong CYP3A4 inhibitor increased the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with ceritinib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telavancin: (Major) Avoid coadministration of ceritinib with telavancin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Telavancin is also associated with QT prolongation.
Telmisartan; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with ceritinib is necessary; adjust the dose of amlodipine as clinically appropriate. Ceritinib is a strong CYP3A inhibitor and amlodipine is a CYP3A substrate. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Temsirolimus: (Major) Avoid coadministration of ceritinib with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week and monitor for temsirolimus-related adverse reactions. Allow a washout period of approximately 1 week after discontinuation of ceritinib before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively.
Terbinafine: (Major) Monitor for an increase in terbinafine-related adverse reactions if coadministration with ceritinib is necessary. Terbinafine is a CYP3A4 and CYP2C9 substrate. Ceritinib is a strong CYP3A4 inhibitor and a weak CYP2C9 inhibitor. Coadministration with a moderate CYP3A4 and CYP2C9 inhibitor increased the Cmax and AUC of terbinafine by 52% and 69%, respectively.
Tetrabenazine: (Major) Avoid coadministration of tetrabenazine with ceritinib due to the risk of QT prolongation. Tetrabenazine causes a small increase in the corrected QT interval (QTc). Concentration-dependent QT prolongation has been reported with ceritinib treatment.
Tezacaftor; Ivacaftor: (Major) If ceritinib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with ceritinib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, give one tezacaftor/ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Theophylline, Aminophylline: (Major) Avoid the use of ceritinib, a time-dependent inhibitor of CYP3A4, with CYP3A4 substrates that have a narrow therapeutic index, such as theophylline, aminophylline as theophylline exposure may be increased. If co-administration is unavoidable, consider a theophylline dose reduction and monitor for theophylline toxicity.
Thioridazine: (Contraindicated) Thioridazine is contraindicated for use along with agents such as ceritinib that may prolong the QT interval and increase the risk of torsades de pointes (TdP), and/or cause orthostatic hypotension when combined with a phenothiazine. Thioridazine is associated with a well-established risk of QT prolongation and TdP, and ceritinib is associated with concentration-dependent QT prolongation.
Thiotepa: (Major) Avoid the concomitant use of thiotepa and ceritinib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; ceritinib is a strong CYP3A4 inhibitor.
Ticagrelor: (Major) Avoid coadministration of ticagrelor with ceritinib due to increased plasma concentrations of ticagrelor resulting in an increased risk of dyspnea, bleeding, and other treatment-related adverse reactions. Ticagrelor is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ticagrelor exposure by 7.32-fold.
Timolol: (Major) Avoid concomitant use of ceritinib with timolol if possible due to the risk of additive bradycardia. Both ceritinib and timolol can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Tinidazole: (Moderate) Monitor for an increase in tinidazole-related adverse reactions if coadministration with ceritinib is necessary. Tinidazole is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Tipranavir: (Major) Avoid concomitant use of ceritinib with tipranavir due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions; exposure to tipranavir may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After tipranavir is discontinued, resume the dose of ceritinib taken prior to initiating tipranavir. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Tisotumab Vedotin: (Moderate) Monitor for tisotumab vedotin-related adverse reactions if concomitant use with ceritinib is necessary due to increased monomethyl auristatin E (MMAE) exposure which may increase the incidence and severity of adverse reactions. MMAE, the active component of tisotumab vedotin, is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Clinical drug interaction studies have not been conducted for tisotumab vedotin. However, coadministration of another antibody-drug conjugate that contains MMAE with a strong CYP3A inhibitor increased unconjugated MMAE exposure by 34%.
Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with ceritinib. In patients receiving 5 mg or less twice daily, reduce to once daily dosing; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 22 mg once daily of the extended-release (XR) formulation, switch to 11 mg XR once daily; in patients receiving 11 mg XR once daily, switch to the immediate-release formulation at a dose of 5 mg once daily. Tofacitinib is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold.
Tolterodine: (Major) Avoid coadministration of ceritinib with tolterodine if possible due to the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily. Periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation. Tolterodine is a CYP3A4 substrate that can also cause concentration-dependent QT prolongation, especially in CYP2D6 poor metabolizers. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers.
Tolvaptan: (Contraindicated) The concomitant use of tolvaptan and ceritinib is contraindicated. Concurrent use is expected to increase tolvaptan exposure. Tolvaptan is a sensitive CYP3A4 substrate; ceritinib is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
Toremifene: (Major) Avoid coadministration of ceritinib with toremifene if possible due to increased plasma concentrations of toremifene which may result in QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to treatment. Toremifene is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner. Ceritinib is a strong CYP3A4 inhibitor that has also been reported to cause concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased toremifene exposure by 2.9-fold; exposure to N-demethyltoremifene was reduced by 20%.
Torsemide: (Moderate) Monitor diuretic effect and blood pressure if torsemide is used in combination with ceritinib; adjust the dose of torsemide if necessary. Ceritinib is a weak CYP2C9 inhibitor and torsemide is primarily metabolized by CYP2C9.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with ceritinib due to the risk of increased trabectedin exposure. Trabectedin is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with ceritinib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of ceritinib, a strong CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Tramadol; Acetaminophen: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with ceritinib is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of ceritinib, a strong CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Trandolapril; Verapamil: (Major) Avoid concomitant use of ceritinib with verapamil if possible due to the risk of additive bradycardia; verapamil exposure may also increase. Both ceritinib and verapamil can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. Monitor blood pressure and heart rate. Diltiazem is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Trazodone: (Major) Avoid coadministration of ceritinib with trazodone due to an increased risk for QT prolongation and torsade de pointes (TdP). Systemic exposure of trazodone may also be increased resulting in increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Trazodone is a CYP3A4 substrate that can also prolong the QT/QTc interval at therapeutic doses; in addition, there are postmarketing reports of TdP. Concomitant use may increase the risk for QT prolongation.
Triamcinolone: (Moderate) Ceritinib, a strong CYP3A4 inhibitor, may inhibit the CYP3A4 metabolism of triamcinolone, resulting in increased plasma triamcinolone concentrations and reduced serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients receiving another strong CYP3A4 inhibitor with triamcinolone, resulting in systemic corticosteroid effects including, but not limited to, Cushing syndrome and adrenal suppression. Consider the benefit-risk of concomitant use and monitor for systemic corticosteroid side effects. Consider using an alternative treatment to triamcinolone, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). In some patients, a corticosteroid dose adjustment may be needed. If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
Triazolam: (Contraindicated) Concomitant use of ceritinib with triazolam is contraindicated due to the risk of serious adverse events, such as prolonged hypnotic and/or sedative effects. Triazolam is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Consider safer alternatives if a benzodiazepine must be administered in combination with ceritinib. Benzodiazepines not metabolized by the CYP3A4 enzyme (e.g., lorazepam, oxazepam) are less likely to be affected by strong CYP3A4 inhibitors.
Triclabendazole: (Major) Concomitant use of triclabendazole and ceritinib 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) 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, such a ceritinib.
Trimipramine: (Minor) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and trimipramine; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. 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).
Triptorelin: (Major) Avoid coadministration of ceritinib with triptorelin if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may also prolong the QT/QTc interval.
Tucatinib: (Major) Avoid concomitant use of ceritinib with tucatinib due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. After tucatinib is discontinued, resume the dose of ceritinib taken prior to initiating tucatinib. Ceritinib is a CYP3A substrate; tucatinib is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Ubrogepant: (Contraindicated) Coadministration of ubrogepant and ceritinib is contraindicated as concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor resulted in a 9.7-fold increase in the exposure of ubrogepant.
Ulipristal: (Minor) Concomitant use of ulipristal and ceritinib may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events; however, this is not likely to be significant for single-dose emergency contraceptive use. Ulipristal is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ulipristal overall exposure by 5.9-fold and increased the overall exposure if ulipristal's active metabolite, monodemethyl-ulipristal acetate, by 2.4-fold.
Upadacitinib: (Major) During concomitant use of upadacitinib and ceritinib reduce the upadacitinib dosage to 15 mg once daily. During induction for ulcerative colitis and Crohn's disease reduce the upadacitinib dosage to 30 mg once daily. Concomitant use may increase upadacitinib exposure and risk for adverse effects. Concomitant use with another strong CYP3A inhibitor increased upadacitinib overall exposure 1.75-fold.
Valbenazine: (Major) Reduce the dose of valbenazine to 40 mg once daily if coadministration with ceritinib is necessary. Prolongation of the QT interval is not clinically significant at valbenazine concentrations expected with recommended dosing; however, valbenazine concentrations may be higher in patients taking a strong CYP3A4 inhibitor and QT prolongation may become clinically significant. Valbenazine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased both valbenazine and NBI-98782 exposure by approximately 2-fold.
Vandetanib: (Major) Avoid coadministration of vandetanib with ceritinib due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to treatment. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for QT prolongation. Both drugs can prolong the QT interval in a concentration-dependent manner; sudden death and TdP have been reported in patients receiving vandetanib.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with ceritinib due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A; ceritinib is a strong CYP3A inhibitor. Use of vardenafil with other strong CYP3A inhibitors increased the AUC of vardenafil by 10 to 16-fold. There may also be an increased potential for QT prolongation. Vardenafil can produce an increase in QTc interval at both therapeutic and supratherapeutic doses. Ceritinib has been reported to cause concentration-dependent QT prolongation. Periodically monitor ECGs and electrolytes during concurrent use of ceritinib and vardenafil oral tablets.
Vemurafenib: (Major) Avoid vemurafenib in patients receiving medications known to prolong the QT interval such as ceritinib. Vemurafenib has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. Ceritinib causes concentration-dependent QT prolongation. Additionally, coadministration may result in increased vemurafenib exposure and an increased risk of adverse events, including QT prolongation. Vemurafenib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of vemurafenib by 40%.
Venetoclax: (Contraindicated) Coadministration of ceritinib with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of ceritinib. Specific venetoclax dosage adjustments are as follows: CLL/SLL patients at steady daily dose: 100 mg/day. AML patients: 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, then 100 mg/day starting on day 4. Venetoclax is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. Coadministration of strong CYP3A4 inhibitors increased the venetoclax AUC by 90% to 690% in drug interaction studies.
Venlafaxine: (Major) Avoid coadministration of ceritinib with venlafaxine if possible due to the risk of QT prolongation; plasma concentrations of venlafaxine may also increase. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Monitor for venlafaxine-related adverse reactions. Venlafaxine is a CYP3A4 substrate that is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has been reported with postmarketing use. Ceritinib is a strong CYP3A4 inhibitor that causes concentration-dependent QT prolongation.
Verapamil: (Major) Avoid concomitant use of ceritinib with verapamil if possible due to the risk of additive bradycardia; verapamil exposure may also increase. Both ceritinib and verapamil can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs. Monitor blood pressure and heart rate. Diltiazem is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Vilazodone: (Major) Do not exceed a vilazodone dose of 20 mg once daily if coadministration with ceritinib is necessary; the original dose of vilazodone can be resumed if ceritinib is discontinued. Vilazodone is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased vilazodone exposure by 50%.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ceritinib is necessary. Vinblastine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Vincristine Liposomal: (Major) Avoid coadministration of vincristine with ceritinib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Vincristine: (Major) Avoid coadministration of vincristine with ceritinib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with ceritinib is necessary. Vinorelbine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Voclosporin: (Contraindicated) Concomitant use of voclosporin and ceritinib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor that has been associated with concentration-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of clarithromycin with ceritinib due to the additive risk of QT prolongation and increased ceritinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg; monitor for ceritinib-related adverse reactions. Periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, further dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. After clarithromycin is discontinued, resume the dose of ceritinib taken prior to initiating clarithromycin. Ceritinib is a CYP3A substrate associated with concentration-dependent QT prolongation; clarithromycin is a strong CYP3A4 inhibitor associated with an established risk for QT prolongation and torsade de pointes (TdP). Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Vorapaxar: (Major) Avoid coadministration of vorapaxar with ceritinib due to increased plasma concentrations of vorapaxar and the risk of treatment-related adverse reactions. Vorapaxar is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased vorapaxar exposure by 2-fold; the bleeding risk for a change in exposure of this magnitude is not known.
Voriconazole: (Major) Avoid concomitant use of ceritinib with voriconazole due to increased ceritinib exposure which may increase the incidence and severity of adverse reactions as well as an additive risk of QT prolongation; exposure to voriconazole may also increase. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for treatment-related adverse reactions. Periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. After voriconazole is discontinued, resume the dose of ceritinib taken prior to initiating voriconazole. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. Ceritinib causes concentration-dependent QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes.
Vorinostat: (Major) Avoid coadministration of ceritinib with vorinostat if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Vorinostat is also associated with QT prolongation.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with ceritinib is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Ceritinib is a strong CYP3A4 and the R-enantiomer of warfarin is a CYP3A4 substrate. Ceritinib is also a weak CYP2C9 inhibitor and the S-enantiomer, the active metabolite of warfarin, is a CYP2C9 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zaleplon: (Moderate) Monitor for an increase in zaleplon-related adverse reactions if coadministration with ceritinib is necessary. Zaleplon is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with ceritinib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of ceritinib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; ceritinib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Ziprasidone: (Major) Concomitant use of ziprasidone and ceritinib should be avoided due to the 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 QT prolongation has been reported with ceritinib.
Zolpidem: (Moderate) Consider decreasing the dose of zolpidem if coadministration with ceritinib is necessary. Zolpidem is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of zolpidem by 34% to 70%.
How Supplied
Zykadia Oral Tab: 150mg
Maximum Dosage
450 mg PO once daily with food.
Geriatric450 mg PO once daily with food.
AdolescentsSafety and efficacy have not been established.
ChildrenSafety and efficacy have not been established.
InfantsSafety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Ceritinib is an oral kinase inhibitor primarily targeting anaplastic lymphoma kinase (ALK); additional targets include insulin-like growth factor 1 (IFG-1) receptor, insulin receptor (InsR), and ROS1. The inhibition of IGF-1 receptor is 50 times less potent than inhibition of ALK. In in vitro and in vivo assays, ceritinib inhibits autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells. Ceritinib inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice and rats. Ceritinib also exhibited dose-dependent anti-tumor activity in mice bearing EML4-ALK-positive NSCLC xenografts with resistance to crizotinib. Unlike crizotinib, ceritinib does not inhibit the kinase activity of MET.
Pharmacokinetics
Ceritinib is administered orally. Ceritinib is approximately 97% protein bound in serum, independent of drug concentration. The geometric mean apparent volume of distribution is 4,230 L after a single 750-mg dose of ceritinib was given under fasted conditions. There is a preferential distribution to red blood cells relative to plasma, with a mean in vitro blood-to-plasma ratio of 1.35. The geometric mean apparent plasma terminal half-life of ceritinib was 41 hours, with steady-state reached by approximately day 15 and a geometric mean accumulation ratio of 6.2 after 3 weeks. The pharmacokinetics of ceritinib are nonlinear, with a geometric mean apparent clearance of 88.5 L/hour after a single dose and 33.2 L/hour after daily dosing. Ceritinib crossed the blood-brain barrier in rats with a blood-to-brain exposure ratio of approximately 15%. After oral administration of a radiolabeled dose, fecal elimination comprises 92% of a radiolabeled dose (68% as unchanged drug) while 1.3% of a dose is recovered in the urine.[57094]
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP2C9
Ceritinib is primarily metabolized by CYP3A4; the parent drug is the main circulating component (82%) in human plasma following oral administration of a single radiolabeled dose. Ceritinib is also a strong CYP3A4 inhibitor and a weak inhibitor of CYP2C9. Ceritinib is a substrate of P-glycoprotein (P-gp) in vitro.[57094]
After a single oral dose of ceritinib, peak plasma levels (Cmax) were achieved at approximately 4 to 6 hours; the AUC and Cmax increased in a dose-proportional manner after a single dose of 50 mg to 750 mg on an empty stomach. Systemic exposure increased in a greater than dose proportional manner after repeat doses of 50 mg to 750 mg once daily on an empty stomach.[57094]
Food increases the systemic exposure of ceritinib. In healthy subjects, administration with a high-fat meal (approximately 1,000 calories and 58 g fat) increased the AUC and Cmax of ceritinib capsules (500 mg) by 73% and 41%, respectively, compared to fasting conditions; the AUC and Cmax of ceritinib tablets (750 mg) increased by 64% and 58%, respectively, when administered with a high-fat meal. Administration with a low-fat meal (approximately 330 calories and 9 g fat) increased the AUC and Cmax of ceritinib capsules (500 mg) by 58% and 43%, respectively, compared to fasting conditions; the AUC and Cmax of ceritinib tablets (750 mg) increased by 39% and 42%, respectively, when administered with a low-fat meal. In a dose-optimization study (ASCEND-8), there was no clinically meaningful difference in the systemic steady-state AUC of ceritinib capsules at a dose of 450 mg once daily with food (100 to 500 calories and 1.5 to 15 g fat) or 750 mg once daily on an empty stomach.[57094]
Pregnancy And Lactation
Pregnancy should be avoided by females of reproductive potential during ceritinib treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant animals or humans, ceritinib can cause fetal harm when administered during pregnancy based on its mechanism of action and animal studies. Women who become pregnant while receiving ceritinib should be apprised of the potential hazard to the fetus. An embryo-fetal development study in pregnant rats and rabbits found dose-related skeletal anomalies including delayed ossifications and skeletal variations after ceritinib exposure less than 0.5-fold and 0.015-fold the human exposure by AUC at the recommended dose, respectively. At 0.13-fold the human exposure by AUC at the recommended dose, a low incidence of visceral anomalies including absent or malpositioned gallbladder and retroesophageal subclavian cardiac artery occurred in pregnant rabbits. Maternal toxicity, abortion, and embryolethality were also reported with higher exposures in animal studies.
Counsel patients about the reproductive risk and contraception requirements during ceritinib treatment. Ceritinib can be teratogenic if taken by the mother during pregnancy. Females of reproductive potential should avoid pregnancy and use effective contraception during and for at least 6 months after treatment with ceritinib. Females of reproductive potential should undergo pregnancy testing prior to initiation of ceritinib. Based on the potential for male-mediated teratogenicity, males with female partners of reproductive potential should use condoms during treatment with ceritinib and for 3 months after the last dose. Women who become pregnant while receiving ceritinib or while their partner is receiving ceritinib should be apprised of the potential hazard to the fetus. There are no data regarding the effect of ceritinib on human fertility. In general toxicology studies conducted in monkeys and rats at exposures greater than or equal to 0.5-fold and 1.5-fold, respectively of the human exposure at the recommended dose, there were no adverse effects on male or female reproductive organs.