Trade Names:Provigil- Tablets 100 mg- Tablets 200 mgAlertec (Canada)
Wakefulness-promoting agent; however, precise mechanism(s) unknown.
T max is 2 to 4 h. Food delays T max approximately 1 h.
Apparent Vd is 0.9 L/kg and protein binding is approximately 60%.
Primary site is hepatic via hydrolytic deamination, S-oxidation, aromatic ring hydroxylation, and glucuronide conjugation. Major inactive metabolites are modafinil acid and modafinil sulfone. Modafinil induces it own metabolism via CYP-450 3A4 after chronic administration.
Approximately 80% (urine) and 1% (feces) are excreted in 11 days. The half-life is approximately 15 h.
Severe chronic renal failure (CrCl 20 mL/min or less) did not influence the pharmacokinetics, but exposure to modafinil was increased 9-fold.Hepatic Function Impairment
In patients with severe hepatic function impairment, Cl is decreased approximately 60%, and steady-state concentrations are doubled. Dose reduction is recommended.Elderly
Decrease of approximately 20% in oral Cl in patients with a mean age of 63 yr, which is not likely to be clinically important.
Improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSA/HS), and shift work sleep disorder (SWSD).
Treatment of fatigue associated with multiple sclerosis.
Hypersensitivity to armodafinil, modafinil, or any component of the product.
PO 200 mg/day as a single dose. Patients with narcolepsy or OSA/HS should take the dose in the morning, while patients with SWSD should take the dose 1 h prior to the start of work shift. Consider dosage adjustment for concomitant medications that are substrates for CYP3A4, such as triazolam and cyclosporine.Elderly
Consider using a lower dose in this population.Hepatic function impairment
A dose reduction of 50% is recommended.
Store tablets at 68° to 77°F.
Plasma levels of certain tricyclic antidepressants may be increased.Clomipramine
Plasma levels may be increased by modafinil.Contraceptives, hormonal
Efficacy may be decreased by modafinil, increasing the risk of unintended pregnancy.Cyclosporine
Blood levels may be decreased by modafinil.CYP3A4 inducers (eg, carbemazepine, phenobarbital, rifampin) or inhibitors (eg, ketoconazole, itraconazole)
Coadministration could alter the plasma levels of modafinil.Dextroamphetamine, methylphenidate
May delay the absorption of modafinil.Drugs eliminated by CYP2C19 metabolism (eg, diazepam, phenytoin, propranolol)
May have prolonged elimination and may require dosage reduction, as well as monitoring for toxicity.MAOIs (eg, isocarboxazid)
Use with caution.Phenytoin
Increased risk of phenytoin toxicity.Triazolam
Triazolam concentration may be decreased, reducing the clinical effect.Warfarin
None well documented.
Hypertension (3%); palpitation, tachycardia, vasodilatation (2%).
Headache (34%); nervousness (7%); anxiety, dizziness, insomnia (5%); depression, paresthesia, somnolence (2%); agitation, confusion, dyskinesia, emotional lability, hyperkinesia, hypertonia, tremor, vertigo (1%); delusions, hallucinations, mania, suicidal ideation (postmarketing).
Herpes simplex, sweating (1%); serious rash including Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) (postmarketing).
Rhinitis (7%); pharyngitis (4%); abnormal vision, amblyopia, epistaxis, eye pain (1%).
Nausea (11%); diarrhea (6%); dyspepsia (5%); anorexia, dry mouth (4%); constipation (2%); flatulence, mouth ulceration, taste perversion, thirst (1%).
Hematuria, pyuria, urine abnormality (1%).
Eosinophilia (1%); agranulocytosis (postmarketing).
Abnormal liver function (2%).
Angioedema, hypersensitivity (with rash, dysphagia, and bronchospasm), multiorgan hypersensitivity with death (postmarketing).
Increased gamma glutamyltransferase and alkaline phosphatase.
Back pain (6%); neck rigidity (1%).
Lung disorder (2%); asthma (1%).
Flu-like syndrome (4%); chest pain (3%); chills (1%).
Monitor for rash, or emergence or exacerbation of psychiatric symptoms. Consider monitoring BP.
Category C .
Safety and efficacy in children younger than 16 yr of age not established.
Safety and efficacy have not been established. Because elimination of modafinil and its metabolites may be reduced, consider using a lower dose.
Dosage reduction is recommended in patients with severe hepatic function impairment.
Psychotic episodes have been reported.
Not recommended for use in patients with history of left ventricular hypertrophy or mitral valve prolapse who have experienced the mitral valve prolapse syndrome when receiving CNS stimulants. Use with caution in patients with a recent history of MI or unstable angina.
Serious rash, which may be life-threatening or require hospitalization (eg, Stevens-Johnson syndrome, TEN), has been reported in postmarketing experience.
Because of psychoactive and euphoric effects, modafinil has potential for abuse.
Rarely, serious angioedema and hypersensitivity, with rash, dysphagia, and bronchospasm, have been reported. Multiorgan hypersensitivity (including 1 fatality) has been reported in postmarketing experience.
Use with caution.
Psychiatric adverse reactions have been reported. Postmarketing adverse reactions have included delusions, hallucinations, mania, and suicidal ideation, some resulting in hospitalization.
May not return to normal in patients taking modafinil.
Aggressiveness, agitation, anxiety, confusion, decreased PT, diarrhea, excitation, insomnia, irritability, nausea, nervousness, palpitations, sleep disturbances, slight to moderate elevations in hemodynamic parameters, tremor.
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