Interactions between Larotrectinib and Modafinil
1 drug interaction and 15 additional warnings found for the following 2 drugs:
- larotrectinib
- modafinil
Drug interactions
Major drug interactions
Major:
modafinil larotrectinib
Applies to: modafinil and larotrectinib
Adjust dose
Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of larotrectinib, which is primarily metabolized by the isoenzyme. When coadministered with efavirenz, a moderate CYP450 3A4 inducer, larotrectinib peak plasma concentration (Cmax) is predicted to decrease by 60% and systemic exposure (AUC) by 72% compared to larotrectinib administered alone. Reduced efficacy of larotrectinib may occur.
Management
When coadministered with moderate CYP450 3A4 inducers, the manufacturer recommends doubling the larotrectinib dose. After the inducer has been discontinued for 3 to 5 elimination half-lives, the larotrectinib dose that was taken prior to initiating the inducer may be resumed.
References (2)
- (2022) "Product Information. Vitrakvi (larotrectinib)." Bayer Pharmaceutical Inc
- (2022) "Product Information. Vitrakvi (larotrectinib)." Bayer Inc
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
larotrectinib Food/Lifestyle
Applies to: larotrectinib
Generally avoid
Grapefruit juice may increase the plasma concentrations of larotrectinib. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of larotrectinib by certain compounds present in grapefruit. When a single 100 mg dose of larotrectinib was coadministered with itraconazole, a potent CYP450 3A4 inhibitor, larotrectinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.8- and 4.3-fold, respectively, compared to administration of larotrectinib alone. The interaction has not been studied with grapefruit juice. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to larotrectinib may increase the risk of adverse effects such as neurotoxicity (delirium, dysarthria, dizziness, gait disturbance, paraesthesia, encephalopathy, memory impairment, tremor) and hepatotoxicity (elevations in liver transaminases). Food does not alter the pharmacokinetics of larotrectinib to a clinically significant extent. When a single 100 mg dose of larotrectinib was administered with a high-fat meal (approximately 900 calories; 58 g carbohydrate, 56 g fat, 43 g protein) in healthy study subjects, larotrectinib peak plasma concentration (Cmax) was reduced by 35% while systemic exposure (AUC) was similar compared to administration in the fasted state.
Management
Larotrectinib may be taken with or without food. Patients should avoid the consumption of grapefruit and grapefruit juice during treatment.
References (1)
- (2018) "Product Information. Vitrakvi (larotrectinib)." Bayer Pharmaceutical Inc
Minor food/lifestyle interactions
Minor:
modafinil Food/Lifestyle
Applies to: modafinil
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
13 potential interactions Applies to: 11 conditions, including High Blood Pressure, Depression, Angina, Arrhythmia, and Psychosis.
Alcoholism
Moderate:
modafinil
Modafinil has a moderate potential interaction with Alcoholism.
Patients with a history of drug and/or stimulant abuse should be closely followed during treatment with modafinil. Observe patients for signs of misuse and abuse. Clinical studies indicate modafinil produces psychoactive and euphoric effects/feelings consistent with other CNS stimulants.
Angina
Moderate:
modafinil
Modafinil has a moderate potential interaction with Angina.
Modafinil is not recommended for use in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with central nervous system stimulant use. Increased monitoring of heart rate and blood pressure is recommended in patients taking modafinil. Caution is advised in patients with known cardiovascular disease and increased monitoring is recommended in patients with a recent history of myocardial infarction or unstable angina.
Arrhythmia
Moderate:
modafinil
Modafinil has a moderate potential interaction with Arrhythmia.
Modafinil is not recommended for use in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with central nervous system stimulant use. Increased monitoring of heart rate and blood pressure is recommended in patients taking modafinil. Caution is advised in patients with known cardiovascular disease and increased monitoring is recommended in patients with a recent history of myocardial infarction or unstable angina.
Cardiovascular Conditions and Disorders
Moderate:
modafinil
Modafinil has a moderate potential interaction with Cardiovascular Conditions and Disorders.
Modafinil is not recommended for use in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with central nervous system stimulant use. Increased monitoring of heart rate and blood pressure is recommended in patients taking modafinil. Caution is advised in patients with known cardiovascular disease and increased monitoring is recommended in patients with a recent history of myocardial infarction or unstable angina.
Depression
Major:
modafinil
Modafinil 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.
Drug Dependence
Moderate:
modafinil
Modafinil has a moderate potential interaction with Drug Dependence.
Patients with a history of drug and/or stimulant abuse should be closely followed during treatment with modafinil. Observe patients for signs of misuse and abuse. Clinical studies indicate modafinil produces psychoactive and euphoric effects/feelings consistent with other CNS stimulants.
Heart Disease
Moderate:
modafinil
Modafinil has a moderate potential interaction with Heart Disease.
Modafinil is not recommended for use in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with central nervous system stimulant use. Increased monitoring of heart rate and blood pressure is recommended in patients taking modafinil. Caution is advised in patients with known cardiovascular disease and increased monitoring is recommended in patients with a recent history of myocardial infarction or unstable angina.
High Blood Pressure
Major:
modafinil
Modafinil has a major potential interaction with High Blood Pressure.
CNS stimulants increase blood pressure and heart rate; the use of some agents may be contraindicated in patients with severe/uncontrolled hypertension. Caution should be used when administering to patients with preexisting high blood pressure (even mild hypertension) and other cardiovascular conditions. All patients under treatment should be regularly monitored for potential tachycardia and hypertension.
Moderate:
modafinil
Modafinil has a moderate potential interaction with High Blood Pressure.
Modafinil is not recommended for use in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with central nervous system stimulant use. Increased monitoring of heart rate and blood pressure is recommended in patients taking modafinil. Caution is advised in patients with known cardiovascular disease and increased monitoring is recommended in patients with a recent history of myocardial infarction or unstable angina.
History - Myocardial Infarction
Moderate:
modafinil
Modafinil has a moderate potential interaction with History - Myocardial Infarction.
Modafinil is not recommended for use in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse in association with central nervous system stimulant use. Increased monitoring of heart rate and blood pressure is recommended in patients taking modafinil. Caution is advised in patients with known cardiovascular disease and increased monitoring is recommended in patients with a recent history of myocardial infarction or unstable angina.
Liver Disease
Moderate:
larotrectinib
Larotrectinib has a moderate potential interaction with Liver Disease.
Forty- five percent of the patients receiving larotrectinib had increased hepatic parameters, including Grade 3 increased AST or ALT in 6% of patients. Monitor liver tests, including ALT and AST, every 2 weeks during the first month of treatment, then monthly thereafter, and as clinically indicated. Treatment should be withheld or permanently discontinued based on the severity of hepatic toxicity. Caution is advised in patients with moderate to severe hepatic impairment as the drug clearance was reduced in these patients (Child-Pugh B and C). Dose should be reduced on these patients as recommended by the manufacturers (refer to prescribing information).
Moderate:
modafinil
Modafinil has a moderate potential interaction with Liver Disease.
Exposure to modafinil is increased in patients with liver dysfunction. In patients with severe liver dysfunction, reduce the dose of modafinil to one-half the dose recommended dose.
Psychosis
Major:
modafinil
Modafinil 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.
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More resources
larotrectinib
A total of 536 drugs are known to interact with larotrectinib.
- Larotrectinib is in the drug class multikinase inhibitors.
- Larotrectinib is used to treat Solid Tumors.
modafinil
A total of 551 drugs are known to interact with modafinil.
- Modafinil is in the drug class CNS stimulants.
-
Modafinil is used to treat the following conditions:
- ADHD (off-label)
- Chronic Fatigue Syndrome (off-label)
- Depression (off-label)
- Fatigue (off-label)
- Idiopathic Hypersomnia (off-label)
- Narcolepsy
- Obstructive Sleep Apnea/Hypopnea Syndrome
- Shift Work Sleep Disorder
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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