Drug Interactions between eliglustat and modafinil

Do not consume grapefruit or grapefruit juice during treatment with eliglustat unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of eliglustat to dangerous levels. This may increase the risk of serious and potentially life-threatening cardiac side effects such as irregular heart rhythm, heart block, and cardiac arrest. Talk to your doctor if you have any questions or concerns. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, slow heart rate, weak pulse, or heart palpitations during treatment. 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.

The use of eliglustat is contraindicated in patients who are CYP2D6 extensive metabolizers or intermediate metabolizers taking a strong or moderate CYP2D6 inhibitor concomitantly with a strong or moderate CYP3A inhibitor or those who are intermediate metabolizers or poor metabolizers taking a strong CYP3A inhibitor due to the risk of a significant increase in drug plasma concentrations. Eliglustat is predicted to cause increases in EKG intervals (PR, QTc, and QRS) at high plasma concentrations and could result in arrhythmias; therefore, its use is not recommended in patients with preexisting cardiac disease (congestive heart failure, recent myocardial infarction, heart block, arrhythmias), or long QT syndrome.

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 drugs eliglustat is contraindicated in patients with moderate or severe hepatic impairment and in those patients, who are CYP450 2D6 extensive metabolizers with mild hepatic impairment and taking a strong or moderate CYP450 2D6 inhibitor due to the risk of cardiac arrhythmias from prolongation of the PR, QTc, and/or QRS cardiac intervals. This agent is contraindicated in patients who are CYP450 2D6 extensive metabolizers, intermediate metabolizers and taking a strong or moderate CYP450 2D6 inhibitor concomitantly with a strong or moderate CYP450 3A inhibitor. In the case of CYP450 2D6 intermediate metabolizers, or poor metabolizers, eliglustat is contraindicated in those patients with any degree of hepatic impairment or those taking a strong CYP450 3A inhibitor.

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.

The use of drugs eliglustat should be avoided in patients with end-stage renal disease (estimated creatinine clearance (eCrCl) less than 15 mL/min not on dialysis or requiring dialysis). No dosage adjustment is recommended in patients with mild, moderate, or severe renal impairment (eCrCl at least 15 mL/min). In the case of CYP450 2D6 intermediate metabolizers, or poor metabolizers, eliglustat should be avoided in those patients with any degree of renal impairment.

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 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.

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.