Modafinil Disease Interactions

The use of CNS stimulants is contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc. Sudden death has been reported in adults and children taking CNS stimulant treatment. Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias, and other symptoms have been reported in adults under treatment. A careful assessment of the cardiovascular status should be done in patients being considered for treatment. This includes family history, physical exam, and further cardiac evaluation (EKG and echocardiogram). Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.

CNS stimulants have been shown to increase blood pressure, and their use might be contraindicated in patients with severe/uncontrolled hypertension. Caution should be used when administering to patients with preexisting high blood pressure and other cardiovascular conditions. All patients under treatment should be regularly monitored for changes in blood pressure and heart rate.

In general, CNS stimulants are extensively metabolized by the liver. Their plasma clearance may be decreased and their half-life prolonged in patients with impaired hepatic function. Therapy with CNS stimulants should be administered cautiously in patients with moderate to severe liver disease, and the dosage should be adjusted accordingly. Additionally, postmarketing reports have shown that atomoxetine can cause severe liver injury. Laboratory testing should be done at the first sign or symptom of liver dysfunction (jaundice, dark urine, upper quadrant tenderness) and treatment should be discontinued in patients with evidence of liver injury.

The use of CNS stimulants can cause psychotic or manic symptoms, suicidal ideation, and aggression, and can exacerbate symptoms of behavior disturbance and thought disorder. Psychiatric symptoms have been reported in patients with and without history of psychiatric disorders, and all patients 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. All patients receiving treatment should be screened for bipolar disease prior to initiation. If any psychiatric symptoms emerge or are exacerbated, treatment suspension should be considered. CNS stimulants are contraindicated in patients with marked agitation or anxiety.

CNS stimulants may induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, and depression). Close monitoring is recommended when using these agents in patients with bipolar disorders.

CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. Close monitoring is recommended when using these agents in patients with psychotic disorders.

Overall CNS stimulants should be administered with caution in patients with significantly impaired renal function as the reduction in the rate of elimination may alter the therapeutic response. The dosage should be adjusted accordingly.

Due to general central nervous system stimulation, therapy with CNS stimulant drugs may cause seizures. These drugs may lower the convulsive threshold in patients with prior history of seizures or EEG abnormalities, and very rarely in patients with no previous history of seizures. Therapy with CNS stimulants should be used with caution in patients with or predisposed to seizures. If seizures appear, therapy should be discontinued.

In clinical trials, a few patients treated with modafinil developed chest pain, palpitations, dyspnea and transient ischemic T-wave changes in association with mitral valve prolapse or left ventricular hypertrophy. The manufacturer recommends that modafinil not be used 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 (CNS) stimulant use. In addition, caution is advised in patients with cardiovascular disease due to other causes, particularly hypertension and/or a recent history of myocardial infarction or unstable angina, since the use of modafinil has not been evaluated in such patients.