Interactions between Armodafinil and Ceritinib
1 drug interaction and 22 additional warnings found for the following 2 drugs:
- armodafinil
- ceritinib
Drug interactions
Moderate drug interactions
Moderate:
armodafinil ceritinib
Applies to: armodafinil and ceritinib
Monitor
Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ceritinib, which is a substrate of the isoenzyme. In 19 healthy subjects, administration of a single 750 mg dose of ceritinib with the potent CYP450 3A4 inducer rifampin (600 mg daily for 14 days) decreased ceritinib peak plasma concentration (Cmax) by 44% and systemic exposure (AUC) by 70%. Data are not available for ceritinib in combination with other, less potent CYP450 3A4 inducers.
Management
Patients receiving ceritinib with CYP450 3A4 inducers should be monitored for potentially diminished pharmacologic response to ceritinib. Concomitant use should be avoided if an interaction is suspected.
References (1)
- (2014) "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
ceritinib Food/Lifestyle
Applies to: ceritinib
Generally avoid
Grapefruit juice may increase the plasma concentrations of ceritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ceritinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia, and bradycardia may also increase.
Adjust dosing interval
Food increases the oral bioavailability of ceritinib. The mechanism of interaction is unknown. Compared to the fast state, administration of a single 500 mg dose of ceritinib with a high-fat meal (approximately 1000 calories; 58 grams of fat) increased ceritinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 41% and 73%, respectively, and administration with a low-fat meal (approximately 330 calories; 9 grams of fat) increased ceritinib Cmax and AUC by 43% and 58%, respectively. A dose of 600 mg or higher taken with a meal is expected to produce systemic exposure exceeding that from a 750 mg dose taken in the fasted state, which may lead to increased adverse effects.
Management
Patients treated with ceritinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ceritinib should be administered on an empty stomach (i.e., avoid administration within 2 hours of a meal).
References (1)
- (2014) "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals
Minor food/lifestyle interactions
Minor:
armodafinil Food/Lifestyle
Applies to: armodafinil
Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.
References (2)
- (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
- (2007) "Product Information. Nuvigil (armodafinil)." Cephalon Inc
Disease interactions
20 potential interactions Applies to: 17 conditions, including Depression, Diarrhea, Psychosis, Diabetes Mellitus, and Liver Disease.
Alcoholism
Moderate:
armodafinil
Armodafinil has a moderate potential interaction with Alcoholism.
Patients with excessive sleepiness, including those taking armodafinil, should be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity. Patients should refrain from drinking alcohol while taking armodafinil as any drug affecting the central nervous system (CNS) may alter judgment, thinking or motor skills.
Cardiovascular Conditions and Disorders
Moderate:
armodafinil
Armodafinil has a moderate potential interaction with Cardiovascular Conditions and Disorders.
Armodafinil may cause ECG changes, chest pain, or arrhythmia. Armodafinil should be used with caution in patients with cardiovascular complications. Armodafinil should not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced the mitral valve prolapse syndrome when previously receiving CNS stimulants. It is recommended to monitor heart rate and blood pressure during treatment with armodafinil. Caution should be exercised when prescribing armodafinil to patients with known cardiovascular disease.
Depression
Major:
armodafinil
Armodafinil has a major potential interaction with Depression.
The use of CNS stimulants can cause psychotic symptoms, suicidal ideation, and aggression, and can exacerbate symptoms of behavior disturbance and thought disorder; CNS stimulants may induce a manic or mixed episode in patients with bipolar disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders. All patients (particularly those with psychotic or bipolar disorders) should be monitored closely, especially during treatment initiation and at times of dose changes. Extreme caution should be exercised when CNS stimulants are given to patients with a history of psychosis, depression, mania, or bipolar disorder. Prior to initiating therapy, all patients should be screened for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or family history of suicide, bipolar disease, or depression). If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. Some CNS stimulants are contraindicated in patients with marked agitation or anxiety.
Moderate:
armodafinil
Armodafinil has a moderate potential interaction with Depression.
Armodafinil may cause adverse psychiatric reactions. Caution should be exercised when using this agent in patients with a history of psychosis, depression, or mania. If psychiatric symptoms develop in association with armodafinil administration, consider discontinuing armodafinil. Close monitoring of psychiatric symptoms is recommended.
Diabetes Mellitus
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Diabetes Mellitus.
The use of ceritinib causes hyperglycemia. It is recommended to monitor fasting serum glucose prior to the start of therapy and periodically thereafter as clinically indicated. Initiate or optimize antihyperglycemic medications as clinically appropriate, and withhold therapy until hyperglycemia is adequately controlled, then resume at a reduced dose as clinically appropriate. If adequate hyperglycemic control cannot be achieved with optimal medical management, permanently discontinue treatment with ceritinib. Care should be exercised when using this agent in diabetic patients.
Diarrhea
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Diarrhea.
Severe gastrointestinal toxicity has been reported in patients treated with ceritinib. It is recommended to monitor and manage patients using standards of care, or withhold ceritinib with resumption at a reduced dose as per clinical guidelines. Care and close monitoring is recommended in patients reporting diarrhea, vomiting, or abdominal pain.
Electrolyte Abnormalities
Major:
ceritinib
Ceritinib has a major potential interaction with Electrolyte Abnormalities.
Ceritinib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. When possible, avoid use of ceritinib in patients with congenital long QT syndrome. It is recommended to conduct periodic monitoring with electrocardiograms (ECGs) in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold ceritinib in patients who develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume therapy at a reduced dose as clinically indicated. Permanently discontinue ceritinib in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.
Heart Block
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Heart Block.
The use of ceritinib may cause bradycardia. It is recommended to monitor heart rate and blood pressure regularly and in cases of symptomatic bradycardia that is not life-threatening, withhold therapy until recovery and adjust the dose of ceritinib. It might be necessary to permanently discontinue ceritinib for life-threatening bradycardia if no contributing concomitant medication is identified; however, if associated with a concomitant medication known to cause bradycardia or hypotension, withhold therapy until recovery and resume therapy at a reduced dose with frequent monitoring. Care and close monitoring is recommended.
Interstitial Lung Disease
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Interstitial Lung Disease.
The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.
Liver Disease
Moderate:
armodafinil
Armodafinil has a moderate potential interaction with Liver Disease.
In a study to determine the pharmacokinetics and metabolism of armodafinil in patients with cirrhosis, the oral clearance of armodafinil was decreased by about 60%, and the steady state concentration was doubled compared to healthy patients. The dosage of armodafinil should be reduced in patients with severe hepatic impairment. Close monitoring is recommended.
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Liver Disease.
Ceritinib is eliminated primarily via the liver. Patients with hepatic impairment may have increased exposure and drug-induced hepatotoxicity. Based on results of population pharmacokinetic analysis no dose adjustment is needed for patients with mild hepatic impairment. The pharmacokinetics of ceritinib has not been studied in patients with moderate to severe hepatic impairment; therefore, a recommended dose has not been determined for these patients. It is recommended to monitor liver function tests including ALT, AST, and total bilirubin once a month and as clinically indicated, with more frequent testing in patients who develop transaminase elevations. In some cases, it might be necessary to withhold ceritinib and resume therapy at a reduced dose, or permanently discontinue treatment.
Long QT Syndrome
Major:
ceritinib
Ceritinib has a major potential interaction with Long QT Syndrome.
Ceritinib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. When possible, avoid use of ceritinib in patients with congenital long QT syndrome. It is recommended to conduct periodic monitoring with electrocardiograms (ECGs) in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold ceritinib in patients who develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume therapy at a reduced dose as clinically indicated. Permanently discontinue ceritinib in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.
Pancreatitis
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Pancreatitis.
Pancreatitis, including a fatal case has occurred in patients receiving ceritinib. It is recommended to monitor lipase and amylase prior to the start of therapy with ceritinib and periodically thereafter as clinically indicated. It might be necessary to withhold the dose of ceritinib based on the severity of the laboratory abnormalities and resume therapy at a reduced dose per clinical guidelines. Care is recommended when using this agent in patients at risk.
Psychosis
Major:
armodafinil
Armodafinil has a major potential interaction with Psychosis.
The use of CNS stimulants can cause psychotic symptoms, suicidal ideation, and aggression, and can exacerbate symptoms of behavior disturbance and thought disorder; CNS stimulants may induce a manic or mixed episode in patients with bipolar disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders. All patients (particularly those with psychotic or bipolar disorders) should be monitored closely, especially during treatment initiation and at times of dose changes. Extreme caution should be exercised when CNS stimulants are given to patients with a history of psychosis, depression, mania, or bipolar disorder. Prior to initiating therapy, all patients should be screened for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or family history of suicide, bipolar disease, or depression). If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. Some CNS stimulants are contraindicated in patients with marked agitation or anxiety.
Moderate:
armodafinil
Armodafinil has a moderate potential interaction with Psychosis.
Armodafinil may cause adverse psychiatric reactions. Caution should be exercised when using this agent in patients with a history of psychosis, depression, or mania. If psychiatric symptoms develop in association with armodafinil administration, consider discontinuing armodafinil. Close monitoring of psychiatric symptoms is recommended.
Pulmonary Impairment
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Pulmonary Impairment.
The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.
Renal Dysfunction
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Renal Dysfunction.
Based on results of population pharmacokinetic analyses ceritinib exposures are similar between patients with mild to moderate renal impairment and patients with normal renal function. No dose adjustment is needed for these patients. Caution and monitoring is needed when using this agent in patients with severe renal impairment as no information is available.
Sinus Node Dysfunction
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Sinus Node Dysfunction.
The use of ceritinib may cause bradycardia. It is recommended to monitor heart rate and blood pressure regularly and in cases of symptomatic bradycardia that is not life-threatening, withhold therapy until recovery and adjust the dose of ceritinib. It might be necessary to permanently discontinue ceritinib for life-threatening bradycardia if no contributing concomitant medication is identified; however, if associated with a concomitant medication known to cause bradycardia or hypotension, withhold therapy until recovery and resume therapy at a reduced dose with frequent monitoring. Care and close monitoring is recommended.
Valvular Heart Disease
Moderate:
armodafinil
Armodafinil has a moderate potential interaction with Valvular Heart Disease.
Armodafinil may cause ECG changes, chest pain, or arrhythmia. Armodafinil should be used with caution in patients with cardiovascular complications. Armodafinil should not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced the mitral valve prolapse syndrome when previously receiving CNS stimulants. It is recommended to monitor heart rate and blood pressure during treatment with armodafinil. Caution should be exercised when prescribing armodafinil to patients with known cardiovascular disease.
Vomiting
Moderate:
ceritinib
Ceritinib has a moderate potential interaction with Vomiting.
Severe gastrointestinal toxicity has been reported in patients treated with ceritinib. It is recommended to monitor and manage patients using standards of care, or withhold ceritinib with resumption at a reduced dose as per clinical guidelines. Care and close monitoring is recommended in patients reporting diarrhea, vomiting, or abdominal pain.
More resources
armodafinil
A total of 527 drugs are known to interact with armodafinil.
- Armodafinil is in the drug class CNS stimulants.
-
Armodafinil is used to treat the following conditions:
- ADHD (off-label)
- Bipolar Disorder (off-label)
- Chronic Fatigue Syndrome (off-label)
- Depression (off-label)
- Fibromyalgia (off-label)
- Idiopathic Hypersomnia (off-label)
- Jet Lag (off-label)
- Narcolepsy
- Obstructive Sleep Apnea/Hypopnea Syndrome
- Shift Work Sleep Disorder
ceritinib
A total of 779 drugs are known to interact with ceritinib.
- Ceritinib is in the drug class multikinase inhibitors.
- Ceritinib is used to treat Non Small Cell Lung Cancer.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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