Drug Interactions between modafinil and palovarotene

Grapefruit, pomelo, and juices or supplements containing these fruits may increase the blood levels of palovarotene, which may increase the risk and/or severity of side effects such as dry skin, dry lips, hair loss, skin rash, itching, skin and nail infection, dry eyes, night blindness, depression, and mood changes. It may also increase the risk of a rare, but potentially serious, condition called pseudotumor cerebri caused by increased pressure in the brain. Palovarotene should be taken with food at approximately the same time each day. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact. 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.

New or worsening psychiatric events have been reported with the use of palovarotene. Patients with a history of psychiatric illness may be more susceptible to the adverse effects including depression, anxiety, mood alterations, and suicidal thoughts and behaviors. Patients should be monitored for the development of new or worsening psychiatric symptoms during treatment with palovarotene.

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.

New or worsening psychiatric events have been reported with the use of palovarotene. Patients with a history of psychiatric illness may be more susceptible to the adverse effects including depression, anxiety, mood alterations, and suicidal thoughts and behaviors. Patients should be monitored for the development of new or worsening psychiatric symptoms during treatment with palovarotene.

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.

The use of palovarotene in patients with moderate or severe liver dysfunction (Child-Pugh B and C) is not recommended. No dose adjustment of palovarotene is recommended for patients with mild liver dysfunction (Child-Pugh A). The effect of moderate or severe liver dysfunction on palovarotene pharmacokinetics has not been evaluated.

New or worsening psychiatric events have been reported with the use of palovarotene. Patients with a history of psychiatric illness may be more susceptible to the adverse effects including depression, anxiety, mood alterations, and suicidal thoughts and behaviors. Patients should be monitored for the development of new or worsening psychiatric symptoms during treatment with palovarotene.

The use of palovarotene in patients with severe renal dysfunction (CrCl 15 to 29 mL/min) is not recommended. No dose adjustment of palovarotene is recommended for patients with mild or moderate renal dysfunction (CrCl 30 to 89 mL/min). The effect of renal dysfunction on palovarotene pharmacokinetics has not been evaluated.