Modafinil is a wakefulness-promoting agent (eugeroic) used primarily for the treatment of excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), and shift work sleep disorder (SWSD). It is a racemic compound with a mechanism distinct from traditional stimulants like amphetamines. In India, it is increasingly used off-label for cognitive enhancement and fatigue management in various conditions, though this is not an approved indication.
Adult: For Narcolepsy/OSAHS: 200mg once daily in the morning. For SWSD: 200mg taken approximately 1 hour prior to the start of the work shift.
Note: Take orally, with or without food. Taking with a high-fat meal may delay onset of action. For SWSD, timing is critical—take 1 hour before work shift. Do not take dose late in the day to avoid insomnia.
The exact mechanism is not fully elucidated. Modafinil promotes wakefulness without generalized CNS stimulation. It is believed to inhibit dopamine reuptake by binding to the dopamine transporter (DAT), leading to increased extracellular dopamine in specific brain regions like the nucleus accumbens and hypothalamus. This action is distinct from amphetamines, which cause dopamine release. It also interacts with other neurotransmitter systems, including norepinephrine, serotonin, glutamate, GABA, orexin (hypocretin), and histamine, contributing to its wakefulness effects.
Pregnancy: Category C: Animal studies show adverse effects. No adequate, well-controlled studies in pregnant women. Use only if potential benefit justifies potential fetal risk. Modafinil may reduce the effectiveness of hormonal contraceptives.
Driving: May impair ability to engage in potentially hazardous activities (driving, operating machinery). Patients should be cautioned until they know how the drug affects them. Despite promoting wakefulness, it does not replace the need for sleep.
| Cyclosporine | Decreased cyclosporine levels due to CYP3A4 induction; risk of transplant rejection. | Major |
| Ethinyl Estradiol (Oral Contraceptives) | Decreased contraceptive efficacy; risk of unintended pregnancy. Use alternative non-hormonal methods. | Major |
| Midazolam, Triazolam | Decreased benzodiazepine levels and efficacy due to CYP3A4 induction. | Moderate |
| Warfarin | Decreased warfarin (S-warfarin) levels due to CYP2C9 induction; requires frequent INR monitoring. | Major |
| Phenytoin, Carbamazepine | Mutual induction; decreased levels of both drugs. Monitor levels. | Moderate |
| Clomipramine | Increased levels of clomipramine due to possible CYP2C19 inhibition; risk of toxicity. | Moderate |
| Monoamine Oxidase Inhibitors (MAOIs) | Theoretical risk of hypertensive crisis; avoid combination. | Major |
| Ketoconazole, Itraconazole | Increased modafinil levels due to CYP3A4 inhibition. | Moderate |