What are the contraindications for prescribing Modafinil (provigil) to patients, particularly those with a history of cardiovascular disease, hepatic impairment, psychosis, or geriatric patients with impaired liver function?

Modafinil Contraindications

Modafinil is absolutely contraindicated in patients with known hypersensitivity to modafinil or armodafinil, and should be used with extreme caution—or avoided entirely—in patients with cardiovascular disease, severe hepatic impairment, or a history of psychosis. 1

Absolute Contraindications

• Known hypersensitivity to modafinil or armodafinil is the only FDA-labeled absolute contraindication 1
• Serious rash history, including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), represents a de facto contraindication given the risk of recurrence 1

Critical Warnings and High-Risk Populations

Cardiovascular Disease

Patients with known cardiovascular disease require increased monitoring and may not be suitable candidates for modafinil. 1 The FDA label specifically advises consideration of increased monitoring in this population, though it stops short of absolute contraindication 1. This is particularly important because:

• Modafinil can cause hypertension and tachycardia 2
• Common adverse effects include elevated heart rate and blood pressure 2
• The drug should be used with extreme caution in patients with moderate to severe hypertension 3

Hepatic Impairment

In patients with severe hepatic impairment, the dose must be reduced to one-half of the standard dose (i.e., 100 mg instead of 200 mg daily) 1. This is critical because:

• Modafinil is extensively metabolized in the liver 3
• Both maximum plasma concentration and elimination half-life are increased in hepatic impairment 3
• The pharmacokinetics are significantly altered, requiring dose adjustment 1

Psychiatric Conditions and Psychosis History

Modafinil should be used with extreme caution—or avoided—in patients with a history of psychosis, depression, or mania. 1 The evidence is compelling:

• The FDA label explicitly states to "use caution in patients with a history of psychosis, depression, or mania" and to "consider discontinuing modafinil if psychiatric symptoms develop" 1
• Case reports document psychosis occurring even at low doses (100 mg/day) in previously healthy individuals 4
• In patients with schizophrenia, modafinil may worsen psychosis, though the evidence quality is low 5
• Psychiatric monitoring is essential even in previously healthy individuals 4

Geriatric Patients

Consideration should be given to using lower doses and implementing close monitoring in geriatric patients. 1 This recommendation is particularly important when combined with hepatic impairment, as:

• The FDA label specifically recommends lower doses in elderly patients 1
• Geriatric patients may have age-related hepatic function decline 3
• The combination of advanced age and impaired liver function creates compounded risk 1

Additional Precautions and Relative Contraindications

Renal Impairment

• Severe renal insufficiency requires caution due to substantial increases in levels of modafinil acid (the inactive metabolite) 6
• Dose adjustment may be necessary, though specific recommendations are not provided in the FDA label 3

Dermatologic Risk

• Discontinue modafinil immediately at the first sign of rash unless the rash is clearly not drug-related 1
• Nearly all cases of serious rash occur within 1 to 5 weeks after treatment initiation, though isolated cases have occurred after 3 months 1
• The reporting rate of TEN and SJS with modafinil exceeds background incidence rates 1

Drug Interactions Creating Relative Contraindications

• Steroidal contraceptives: Modafinil reduces efficacy; alternative or additional contraception is required during treatment and for one month after discontinuation 1
• Cyclosporine: Blood concentrations may be reduced 1
• CYP2C19 substrates (omeprazole, phenytoin, diazepam): Exposure may be increased 1
• Modafinil induces and inhibits several cytochrome P450 isoenzymes, creating potential for interactions across all drug classes 6

Common Pitfalls to Avoid

• Do not assume modafinil is safe in "mild" cardiovascular disease—the FDA specifically calls out the need for increased monitoring in known cardiovascular disease 1
• Do not use standard dosing in severe hepatic impairment—this is a mandatory dose reduction, not optional 1
• Do not dismiss early psychiatric symptoms—psychosis can develop even at low doses and in previously healthy individuals 4
• Do not continue modafinil if any rash develops—the risk of progression to life-threatening conditions is too high 1