Drug Interactions between mazindol and modafinil

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.

CNS stimulants (especially amphetamines) have a high potential for abuse and misuse, which can lead to development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants can result in overdose and death; this risk is increased with higher doses or unapproved methods of administration (e.g., snorting, injection). Before prescribing a CNS stimulant, each patient's risk for abuse, misuse, and addiction should be assessed. Throughout therapy, it is recommended to reassess each patient's risk and frequently monitor for signs/symptoms of abuse, misuse, and addiction. Therapy with CNS stimulants should be administered cautiously, if at all, in patients with a history of alcohol or substance abuse. The use of some agents is contraindicated in patients with a history of drug abuse.

Some CNS stimulants are contraindicated in patients with marked agitation and/or anxiety since these symptoms may be aggravated. CNS stimulants may also exacerbate symptoms of behavior disturbance and thought disorder in psychotic patients, particularly children. Therapy with CNS stimulants should be administered cautiously in patients with a history of psychosis or a predisposition to agitated states.

Many amphetamines and amphetamine-like drugs are contraindicated in patients with advanced arteriosclerosis, symptomatic or unstable cardiac or cerebrovascular disease, moderate to severe hypertension, or hyperthyroidism. Like other sympathomimetic amines, amphetamines may cause cardiovascular adverse effects such as palpitation, tachycardia, cardiac arrhythmias, and elevation of blood pressure. Rarely, cardiomyopathy manifested as ventricular hypertrophy and/or congestive heart failure has been reported during chronic amphetamine use. In addition, sudden death has been reported in association with amphetamine therapy at usual dosages in children with structural cardiac abnormalities. In general, amphetamines should not be used in patients with structural cardiac abnormalities. If not otherwise contraindicated, therapy with amphetamines should be administered cautiously in patients with a current or past history of cardiovascular or cerebrovascular disease.

Many amphetamines and amphetamine-like drugs are contraindicated in patients with advanced arteriosclerosis, symptomatic or unstable cardiac or cerebrovascular disease, moderate to severe hypertension, or hyperthyroidism. Like other sympathomimetic amines, amphetamines may cause cardiovascular adverse effects such as palpitation, tachycardia, cardiac arrhythmias, and elevation of blood pressure. Rarely, cardiomyopathy manifested as ventricular hypertrophy and/or congestive heart failure has been reported during chronic amphetamine use. In addition, sudden death has been reported in association with amphetamine therapy at usual dosages in children with structural cardiac abnormalities. In general, amphetamines should not be used in patients with structural cardiac abnormalities. If not otherwise contraindicated, therapy with amphetamines should be administered cautiously in patients with a current or past history of cardiovascular or cerebrovascular disease.

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 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 (especially amphetamines) have a high potential for abuse and misuse, which can lead to development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants can result in overdose and death; this risk is increased with higher doses or unapproved methods of administration (e.g., snorting, injection). Before prescribing a CNS stimulant, each patient's risk for abuse, misuse, and addiction should be assessed. Throughout therapy, it is recommended to reassess each patient's risk and frequently monitor for signs/symptoms of abuse, misuse, and addiction. Therapy with CNS stimulants should be administered cautiously, if at all, in patients with a history of alcohol or substance abuse. The use of some agents is contraindicated in patients with a history of drug abuse.

Some amphetamines and amphetamine-like drugs are contraindicated in patients with narrow-angle glaucoma or anatomically narrow angles. Like other sympathomimetic amines, amphetamines can induce transient mydriasis. In patients with narrow angles, pupillary dilation can provoke an acute attack of angle-closure glaucoma. If possible, these agents should also be avoided in patients with other forms of glaucoma since mydriasis may occasionally increase intraocular pressure.

Many CNS stimulants are 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 patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 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.

Many amphetamines and amphetamine-like drugs are contraindicated in patients with advanced arteriosclerosis, symptomatic or unstable cardiac or cerebrovascular disease, moderate to severe hypertension, or hyperthyroidism. Like other sympathomimetic amines, amphetamines may cause cardiovascular adverse effects such as palpitation, tachycardia, cardiac arrhythmias, and elevation of blood pressure. Rarely, cardiomyopathy manifested as ventricular hypertrophy and/or congestive heart failure has been reported during chronic amphetamine use. In addition, sudden death has been reported in association with amphetamine therapy at usual dosages in children with structural cardiac abnormalities. In general, amphetamines should not be used in patients with structural cardiac abnormalities. If not otherwise contraindicated, therapy with amphetamines should be administered cautiously in patients with a current or past history of cardiovascular or cerebrovascular disease.

Many amphetamines and amphetamine-like drugs are contraindicated in patients with advanced arteriosclerosis, symptomatic or unstable cardiac or cerebrovascular disease, moderate to severe hypertension, or hyperthyroidism. Like other sympathomimetic amines, amphetamines may cause cardiovascular adverse effects such as palpitation, tachycardia, cardiac arrhythmias, and elevation of blood pressure. Rarely, cardiomyopathy manifested as ventricular hypertrophy and/or congestive heart failure has been reported during chronic amphetamine use. In addition, sudden death has been reported in association with amphetamine therapy at usual dosages in children with structural cardiac abnormalities. In general, amphetamines should not be used in patients with structural cardiac abnormalities. If not otherwise contraindicated, therapy with amphetamines should be administered cautiously in patients with a current or past history of cardiovascular or cerebrovascular disease.

Many amphetamines and amphetamine-like drugs are contraindicated in patients with advanced arteriosclerosis, symptomatic or unstable cardiac or cerebrovascular disease, moderate to severe hypertension, or hyperthyroidism. Like other sympathomimetic amines, amphetamines may cause cardiovascular adverse effects such as palpitation, tachycardia, cardiac arrhythmias, and elevation of blood pressure. Rarely, cardiomyopathy manifested as ventricular hypertrophy and/or congestive heart failure has been reported during chronic amphetamine use. In addition, sudden death has been reported in association with amphetamine therapy at usual dosages in children with structural cardiac abnormalities. In general, amphetamines should not be used in patients with structural cardiac abnormalities. If not otherwise contraindicated, therapy with amphetamines should be administered cautiously in patients with a current or past history of cardiovascular or cerebrovascular disease.

Many CNS stimulants are 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 patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 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 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.

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.

Many amphetamines and amphetamine-like drugs are contraindicated in patients with advanced arteriosclerosis, symptomatic or unstable cardiac or cerebrovascular disease, moderate to severe hypertension, or hyperthyroidism. Like other sympathomimetic amines, amphetamines may cause cardiovascular adverse effects such as palpitation, tachycardia, cardiac arrhythmias, and elevation of blood pressure. Rarely, cardiomyopathy manifested as ventricular hypertrophy and/or congestive heart failure has been reported during chronic amphetamine use. In addition, sudden death has been reported in association with amphetamine therapy at usual dosages in children with structural cardiac abnormalities. In general, amphetamines should not be used in patients with structural cardiac abnormalities. If not otherwise contraindicated, therapy with amphetamines should be administered cautiously in patients with a current or past history of cardiovascular or cerebrovascular disease.

Many CNS stimulants are 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 patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 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.

Some CNS stimulants are contraindicated in patients with marked agitation and/or anxiety since these symptoms may be aggravated. CNS stimulants may also exacerbate symptoms of behavior disturbance and thought disorder in psychotic patients, particularly children. Therapy with CNS stimulants should be administered cautiously in patients with a history of psychosis or a predisposition to agitated states.

Many CNS stimulants are 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 patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 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.

Many CNS stimulants are 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 patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended dosages for attention deficit hyperactivity disorder; use of these agents should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 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.

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 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.

Some CNS stimulants are contraindicated in patients with marked agitation and/or anxiety since these symptoms may be aggravated. CNS stimulants may also exacerbate symptoms of behavior disturbance and thought disorder in psychotic patients, particularly children. Therapy with CNS stimulants should be administered cautiously in patients with a history of psychosis or a predisposition to agitated states.

CNS stimulants have been reported to worsen Tourette's syndrome and exacerbate motor and verbal tics. Before initiating therapy, it is recommended to assess family history and clinically evaluate patients for tics or Tourette's syndrome. Therapy with CNS stimulants, if necessary, should be administered cautiously in patients with tic disorders or family history of Tourette's syndrome. The manufacturers of the CNS stimulants, methylphenidate (racemic) and dexmethylphenidate (the more pharmacologically active d-enantiomer), consider their use to be contraindicated in such patients.

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.

Obese, type 2 diabetic patients who achieve weight loss may demonstrate improved metabolic control of their disease as a result of their reduced weight. Therefore, patients with type 2 diabetes mellitus should be monitored during weight-reduction therapy (or therapy that may be expected to induce significant weight loss as a secondary effect) for hypoglycemia and reduced need for oral hypoglycemic medication or insulin, and the dosages of these agents adjusted accordingly. Patients should be apprised of the risk of hypoglycemia and be alert to potential signs and symptoms such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, and palpitation.

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.

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 in certain agents. Additionally, postmarketing reports have shown that atomoxetine can cause severe liver injury; laboratory testing should be done at the first sign/symptom of liver dysfunction (jaundice, dark urine, upper quadrant tenderness) and treatment should be discontinued in patients with evidence of liver injury.

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.

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 in certain agents.

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 history of seizures, with prior electroencephalogram (EEG) abnormalities without seizures, and very rarely, without history of seizures and no prior EEG evidence of seizures. Therapy with CNS stimulants should be used with caution in patients with or predisposed to seizures. If seizures occur, therapy should be discontinued.

The recommended maximum number of medicines in the 'stimulants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'stimulants' category:

• mazindol
• modafinil

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

The recommended maximum number of medicines in the 'cerebral stimulants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'cerebral stimulants' category:

• mazindol
• modafinil

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.