Drug Interactions between efavirenz and modafinil

Taking efavirenz with food increases the amount of medicine in your body, which may increase the frequency of side effects. You should take efavirenz once a day on an empty stomach, preferably at bedtime. Taking it at bedtime may make some side effects such as dizziness, trouble sleeping, drowsiness, trouble concentrating, and/or unusual dreams less bothersome. However, these symptoms may be more severe if efavirenz is used with alcohol or mood-altering (street) drugs. You should avoid driving or operating hazardous machinery until you know how the medication affects you. 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.

During clinical trials, efavirenz was associated with an increase in the occurrence of serious psychiatric events, including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions. Other factors associated with an increased occurrence of these psychiatric symptoms were history of injectable drug use, psychiatric history, or use of psychiatric medications at study entry; similar associations were observed in the efavirenz and control groups. Therapy with efavirenz should be administered cautiously in patients with current/history of psychiatric illness, emotional instability, or substance abuse. Patients with serious psychiatric adverse reactions should receive prompt medical evaluation to assess the possibility that symptoms are related to efavirenz use, and if so, to determine whether the risks of continued therapy outweigh the benefits.

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.

During clinical trials, efavirenz was associated with an increase in the occurrence of serious psychiatric events, including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions. Other factors associated with an increased occurrence of these psychiatric symptoms were history of injectable drug use, psychiatric history, or use of psychiatric medications at study entry; similar associations were observed in the efavirenz and control groups. Therapy with efavirenz should be administered cautiously in patients with current/history of psychiatric illness, emotional instability, or substance abuse. Patients with serious psychiatric adverse reactions should receive prompt medical evaluation to assess the possibility that symptoms are related to efavirenz use, and if so, to determine whether the risks of continued therapy outweigh the benefits.

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.

During clinical trials, efavirenz was associated with an increase in the occurrence of serious psychiatric events, including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions. Other factors associated with an increased occurrence of these psychiatric symptoms were history of injectable drug use, psychiatric history, or use of psychiatric medications at study entry; similar associations were observed in the efavirenz and control groups. Therapy with efavirenz should be administered cautiously in patients with current/history of psychiatric illness, emotional instability, or substance abuse. Patients with serious psychiatric adverse reactions should receive prompt medical evaluation to assess the possibility that symptoms are related to efavirenz use, and if so, to determine whether the risks of continued therapy outweigh the benefits.

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.

During clinical trials, efavirenz was associated with an increase in the occurrence of serious psychiatric events, including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions. Other factors associated with an increased occurrence of these psychiatric symptoms were history of injectable drug use, psychiatric history, or use of psychiatric medications at study entry; similar associations were observed in the efavirenz and control groups. Therapy with efavirenz should be administered cautiously in patients with current/history of psychiatric illness, emotional instability, or substance abuse. Patients with serious psychiatric adverse reactions should receive prompt medical evaluation to assess the possibility that symptoms are related to efavirenz use, and if so, to determine whether the risks of continued therapy outweigh the benefits.

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.

Efavirenz is not recommended for patients with moderate or severe liver dysfunction; insufficient data are available to determine whether dose adjustment is needed. Patients with mild liver dysfunction may receive efavirenz without dose adjustment. Due to extensive CYP450-mediated metabolism and limited clinical experience in patients with liver dysfunction, therapy with efavirenz should be administered cautiously in patients with mild liver dysfunction; careful monitoring is recommended for these patients. In addition, postmarketing cases of hepatitis (including fulminant hepatitis progressing to liver failure requiring transplantation or resulting in death) have occurred during therapy with efavirenz; reports have included patients with underlying liver disease (including coinfection with hepatitis B or C). Monitoring of liver enzymes before and during therapy is recommended for all patients.

QTc prolongation has been observed with the use of efavirenz. Alternatives to efavirenz should be considered when administered to patients at higher risk of torsade de pointes or when coadministered with a medication with known risk of torsade de pointes.

During clinical trials, efavirenz was associated with an increase in the occurrence of serious psychiatric events, including severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions, and manic reactions. Other factors associated with an increased occurrence of these psychiatric symptoms were history of injectable drug use, psychiatric history, or use of psychiatric medications at study entry; similar associations were observed in the efavirenz and control groups. Therapy with efavirenz should be administered cautiously in patients with current/history of psychiatric illness, emotional instability, or substance abuse. Patients with serious psychiatric adverse reactions should receive prompt medical evaluation to assess the possibility that symptoms are related to efavirenz use, and if so, to determine whether the risks of continued therapy outweigh the benefits.

Convulsions have been observed in adult and pediatric patients receiving efavirenz, generally in the presence of known medical history of seizures. Caution should be taken with any patient with history of seizures. Anticonvulsant medications primarily metabolized by the liver (e.g., phenytoin, phenobarbital) may require periodic monitoring of plasma levels.