Drug Interactions between modafinil and ribociclib

Patients should not consume pomegranates, pomegranate juice, grapefruit, or grapefruit juice during treatment with ribociclib unless directed otherwise by your doctor. Pomegranate juice or grapefruit juice can increase the blood levels of ribociclib. You may be more likely to experience side effects such as nausea; vomiting; diarrhea; loss of appetite; abdominal pain; mouth sores; hair loss; weakness; and impaired bone marrow function resulting in low numbers of different types of blood cells, which can increase the risk of anemia, bleeding problems, and infections. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Information for this minor interaction is available on the professional version.

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.

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.

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.

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.

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.

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.

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.

Patients receiving ribociclib have developed severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. This drug must not be reintroduced in patients who have experienced SCARs or other life-threatening cutaneous reactions during ribociclib treatment.

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.

Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. This drug should be avoided in patients who are at significant risk of developing torsade de pointes, including those with: congenital long QT syndrome; uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism; electrolyte abnormalities. ECG should be performed in all patients prior to initiation of treatment; ribociclib should be started only in patients with QTcF (QT corrected for heart rate using Fridericia's formula) values less than 450 milliseconds. ECG should be repeated at Day 14 of the first cycle, and as clinically indicated. Serum electrolytes (including potassium, calcium, phosphorous, and magnesium) should be monitored before the initiation of treatment, at the beginning of the first 6 cycles, and as clinically indicated; any electrolyte abnormality should be corrected before starting this drug. Ribociclib may require dose interruption, dose reduction, or discontinuation according to observed QT prolongation during therapy.

Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. This drug should be avoided in patients who are at significant risk of developing torsade de pointes, including those with: congenital long QT syndrome; uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism; electrolyte abnormalities. ECG should be performed in all patients prior to initiation of treatment; ribociclib should be started only in patients with QTcF (QT corrected for heart rate using Fridericia's formula) values less than 450 milliseconds. ECG should be repeated at Day 14 of the first cycle, and as clinically indicated. Serum electrolytes (including potassium, calcium, phosphorous, and magnesium) should be monitored before the initiation of treatment, at the beginning of the first 6 cycles, and as clinically indicated; any electrolyte abnormality should be corrected before starting this drug. Ribociclib may require dose interruption, dose reduction, or discontinuation according to observed QT prolongation during therapy.

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.

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.

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.

Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. This drug should be avoided in patients who are at significant risk of developing torsade de pointes, including those with: congenital long QT syndrome; uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism; electrolyte abnormalities. ECG should be performed in all patients prior to initiation of treatment; ribociclib should be started only in patients with QTcF (QT corrected for heart rate using Fridericia's formula) values less than 450 milliseconds. ECG should be repeated at Day 14 of the first cycle, and as clinically indicated. Serum electrolytes (including potassium, calcium, phosphorous, and magnesium) should be monitored before the initiation of treatment, at the beginning of the first 6 cycles, and as clinically indicated; any electrolyte abnormality should be corrected before starting this drug. Ribociclib may require dose interruption, dose reduction, or discontinuation according to observed QT prolongation during therapy.

Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. This drug should be avoided in patients who are at significant risk of developing torsade de pointes, including those with: congenital long QT syndrome; uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmias, uncontrolled hypertension, high degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism; electrolyte abnormalities. ECG should be performed in all patients prior to initiation of treatment; ribociclib should be started only in patients with QTcF (QT corrected for heart rate using Fridericia's formula) values less than 450 milliseconds. ECG should be repeated at Day 14 of the first cycle, and as clinically indicated. Serum electrolytes (including potassium, calcium, phosphorous, and magnesium) should be monitored before the initiation of treatment, at the beginning of the first 6 cycles, and as clinically indicated; any electrolyte abnormality should be corrected before starting this drug. Ribociclib may require dose interruption, dose reduction, or discontinuation according to observed QT prolongation during therapy.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with ribociclib. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis, which may include hypoxia, cough, and dyspnea. Ribociclib should be interrupted immediately and patients should be evaluated if new or worsening respiratory symptoms suspected to be due to ILD or pneumonitis develop. This drug should be permanently discontinued in patients with any recurrent symptomatic or severe ILD/pneumonitis.

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.

Ribociclib undergoes extensive hepatic metabolism mainly via CYP450 3A4 in humans. Increases in transaminases and drug-induced liver injury have occurred in clinical studies. The starting dose of ribociclib should be reduced to 400 mg in patients with advanced or metastatic breast cancer who have moderate or severe liver dysfunction (Child-Pugh B or C). Liver function tests (LFTs) should be performed before initiating therapy; LFTs should be monitored every 2 weeks for the first 2 cycles, at the beginning of each subsequent 4 cycles, and as clinically indicated. Dose interruption, dose reduction, or drug discontinuation may be necessary based on the severity of transaminase elevations. No dose adjustment is necessary in patients with breast cancer who have mild liver dysfunction (Child-Pugh A).

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with ribociclib. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis, which may include hypoxia, cough, and dyspnea. Ribociclib should be interrupted immediately and patients should be evaluated if new or worsening respiratory symptoms suspected to be due to ILD or pneumonitis develop. This drug should be permanently discontinued in patients with any recurrent symptomatic or severe ILD/pneumonitis.

The starting dose of ribociclib should be reduced to 200 mg in patients with severe renal dysfunction. No dose adjustment is necessary in patients with mild or moderate renal dysfunction (estimated GFR 30 to 89 mL/min/1.73 m2).