What are the biggest side effects of Modafinil (Provigil)?

Major Side Effects of Modafinil

The most serious side effects of modafinil include life-threatening Stevens-Johnson syndrome, serious rash or allergic reactions affecting the liver or blood cells, and potential for psychological dependence. 1

Common Side Effects

Modafinil commonly causes several side effects that patients should be aware of:

• Headache (34% of patients vs 23% with placebo) 2
• Insomnia 3
• Nausea (11% vs 3% with placebo) 2
• Diarrhea 3
• Dry mouth 3
• Nervousness and anxiety 1
• Dizziness 1

Serious Side Effects

Modafinil can cause potentially severe adverse effects that require immediate medical attention:

• Serious skin reactions: Stevens-Johnson syndrome has been reported, particularly in pediatric patients, which is why modafinil is not approved for use in individuals under 17 years of age 3
• Serious allergic reactions affecting multiple body systems including:
  • Skin rash, hives, mouth sores, blistering and peeling skin 1
  • Swelling of face, eyes, lips, tongue, or throat 1
  • Trouble swallowing or breathing 1
  • Fever, shortness of breath 1
• Liver problems: Yellowing of the skin or whites of the eyes, dark urine 1
• Psychiatric symptoms:
  • Depression 1
  • Anxiety 1
  • Hallucinations (hearing, seeing, feeling, or sensing things that aren't real) 1
  • Mania (extreme increase in activity and talking) 1
  • Suicidal thoughts 1
  • Aggressive behavior 1

Cardiovascular Effects

• Increased blood pressure 3, 4
• Increased heart rate 3, 4
• Palpitations 3

Special Considerations

Pregnancy and Breastfeeding

• Based on animal data, modafinil may cause fetal harm 3
• Human data are insufficient to determine risk 3
• A 2018 report showed higher rates of major congenital anomalies in children exposed to modafinil in utero 3

Drug Interactions

• Modafinil may reduce the effectiveness of hormonal birth control methods 3, 1
• Women using hormonal contraception may have a higher chance of getting pregnant while taking modafinil and for one month after stopping 1
• Modafinil induces and inhibits several cytochrome P450 isoenzymes, creating potential for interactions with many drug classes 5

Abuse Potential

• Modafinil is classified as a Schedule IV controlled substance due to potential for abuse or dependency 3
• However, it has lower abuse potential compared to amphetamines and methylphenidate 6, 5
• Physical and psychological dependence is possible but uncommon 3, 4

Dosing Considerations

• Dose should be reduced in elderly patients and those with hepatic disease 5
• Caution is needed in patients with severe renal insufficiency due to substantial increases in modafinil acid levels 5
• Typical dosing is 200-400 mg daily, taken in the morning or divided between morning and midday 3, 6

Monitoring Recommendations

• More frequent follow-up is necessary when starting or adjusting doses 3
• Monitor for adverse effects including hypertension, palpitations, arrhythmias, and irritability 3
• Be vigilant for any signs of skin reactions, especially in the first few weeks of treatment 1

Always discuss any concerning symptoms with a healthcare provider immediately, particularly skin reactions or psychiatric symptoms, as these may require prompt medical attention.