Modafinil

left-ventricular hypertrophy, uncontrolled hypertension, unstable angina, recent myocardial infarction, mitral valve prolapse

Cardiovascular disease including left-ventricular hypertrophy, uncontrolled hypertension, unstable angina, and recent MI are relative contraindications. Modafinil produces sympathomedullary activation that may exacerbate pre-existing cardiac pathology.

Pre-existing psychotic disorders, including schizophrenia and schizoaffective disorder, represent a relative contraindication. Post-marketing surveillance has documented psychosis and hallucinations at therapeutic doses.

Bipolar disorder is a relative contraindication due to risk of precipitating mania. Adjunctive use for bipolar depression has been studied in RCTs with benefit (Nunez 2020 meta-analysis), but only under careful psychiatric supervision and mood stabilizer coverage.

Maximum dose is 100 mg/day in severe hepatic impairment (50% of standard dose). Moderate impairment may also require dose reduction.

Caution is advised in renal insufficiency. Specific dose adjustment guidelines have not been established, but elevated modafinil acid levels warrant monitoring.

Any prior hypersensitivity reaction to modafinil or armodafinil is an absolute contraindication. Re-challenge is not recommended due to the unpredictable and potentially fatal nature of SJS/TEN/DRESS reactions.

Modafinil is contraindicated in pregnancy due to documented teratogenic risk. Women of childbearing potential must use effective non-hormonal contraception or supplement hormonal contraception with barrier methods during treatment and for one month after stopping.

Modafinil is not FDA-approved for any indication in children. The elevated risk of serious dermatological reactions in pediatric populations led to the FDA's rejection of ADHD approval despite demonstrated efficacy in RCTs.