Modafinil

Today's med: Modafinil (moe DAF i nil) (brand name: Provigil)

Drug Class: CNS stimulant, sympathomimetic: Schedule IV controlled substance

Action: The exact mechanism of action is unclear, it does not appear to alter the release of dopamine or norepinephrine, it may exert its stimulant effects by decreasing GABA-mediated neurotransmission, although this theory has not yet been fully evaluated; several studies also suggest that an intact central alpha-adrenergic system is required for modafinil's activity; the drug increases high-frequency alpha waves while decreasing both delta and theta wave activity, and these effects are consistent with generalized increases in mental alertness

Indications: Improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy and shift work sleep disorder (SWSD); adjunctive therapy for obstructive sleep apnea/hypopnea syndrome (OSAHS)

Use: Unlabeled

Attention-deficit/hyperactivity disorder (ADHD); treatment of fatigue in MS and other disorders

Contraindications: Hypersensitivity to modafinil, armodafinil, or any component of the formulation

Adverse Effects: >10%: Central nervous system: Headache (adults 34%; children 20%; dose related)

Gastrointestinal: Appetite decreased (children 16%), abdominal pain (children 12%), nausea (11%)

1% to 10%:

Cardiovascular: Chest pain (3%), hypertension (3%), palpitation (2%), tachycardia (2%), vasodilation (2%), edema (1%)

Central nervous system: Nervousness (7%), dizziness (5%), anxiety (5%; dose related), insomnia (5%), depression (2%), somnolence (2%), chills (1%), agitation (1%), confusion (1%), emotional lability (1%), vertigo (1%)

Dermatologic: Rash (1%; includes some severe cases requiring hospitalization)

Gastrointestinal: Diarrhea (6%), dyspepsia (5%), weight loss (children 5%), xerostomia (4%), anorexia (4%), constipation (2%), flatulence (1%), mouth ulceration (1%), taste perversion (1%)

Genitourinary: Abnormal urine (1%), hematuria (1%), pyuria (1%)

Hematologic: Eosinophilia (1%)

Hepatic: LFTs abnormal (2%)

Neuromuscular & skeletal: Back pain (6%), paresthesia (2%), dyskinesia (1%), hyperkinesia (1%), hypertonia (1%), neck rigidity (1%), tremor (1%)

Ocular: Amblyopia (1%), eye pain (1%), vision abnormal (1%)

Respiratory: Rhinitis (7%), pharyngitis (4%), lung disorder (2%), asthma (1%), epistaxis (1%)

Miscellaneous: Flu-like syndrome (4%), thirst (1%), diaphoresis (1%), herpes simplex infection (1%)

Postmarketing and/or case reports: Agranulocytosis, anaphylactic reaction, angioedema, DRESS syndrome, erythema multiforme, hypersensitivity syndrome (multiorgan), mania, psychosis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Concerns related to adverse effects:

• CNS effects: May impair the ability to engage in potentially hazardous activities. The degree of sleepiness should be reassessed frequently; some patients may not return to a normal level of wakefulness.

• Dermatologic effects (severe): Serious and life-threatening rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with modafinil. Although initially reported in children during clinical trials, postmarketing cases have occurred in both children and adults. Most cases have occurred within the first 5 weeks of therapy; however, rare cases have occurred after long-term use. No risk factors have been identified to predict occurrence or severity. Patients should be advised to discontinue at first sign of rash. As a result of these serious dermatologic adverse events, approval for the use of modafinil in children for ADHD was denied by the FDA.

• Hypersensitivity reactions: Rare cases of multiorgan hypersensitivity reactions in association with modafinil use and lone cases of angioedema and anaphylactoid reactions with armodafinil have been reported. Signs and symptoms are diverse, reflecting the involvement of specific organs. Patients typically present with fever and rash associated with organ-system dysfunction. Patients should be advised to report any signs and symptoms related to these effects; discontinuation of therapy is recommended.

Standard Dosing:  Oral: Adults: ADHD (unlabeled use): 100-400 mg/day (Taylor, 2000)

Narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS): Initial: 200 mg as a single daily dose in the morning

Shift work sleep disorder (SWSD): Initial: 200 mg as a single dose taken ~1 hour prior to start of work shift

Note: Doses of 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit.

Elderly: Elimination of modafinil and its metabolites may be reduced as a consequence of aging and as a result, consider initiating at lower doses in this patient population.

Administration

For the treatment of narcolepsy and obstructive sleep apnea/hypopnea syndrome (OSAHS), administer dose in the morning. For the treatment of shift work sleep disorder (SWSD), administer dose ~1 hour prior to start of work shift

Drug interactions: Link: http://www.drugs.com/drug-interactions/modafinil.html

A total of 391 drugs (1692 brand and generic names) are known to interact with modafinil.

• 4 major drug interactions (8 brand and generic names)
• 177 moderate drug interactions (823 brand and generic names)
• 210 minor drug interactions (861 brand and generic names)

Show all medications in the database that may interact with modafinil.

May have mild interaction with alcohol and food.

Disease interactions: Liver Disease, CVD, Psychosis, Renal Dysfunction

Tourette's syndrome: Use with caution in patients with Tourette's syndrome; stimulants may unmask tics.

Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Management: Consider avoiding CYP3A4 inducing herbs in order to avoid therapeutic failure of the substrate. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modificationCYP2C19 Substrates: CYP2C19 Inhibitors (Strong) may decrease the metabolism of CYP2C19 Substrates. Consider therapy modification

Modafinil, awake to smell the daffodils...