No

Stimulant

Improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy

C-IV

C

Currently, there are no studies in humans evaluating its teratogenicity. Embryotoxicity of modafinil has been observed in animal models at dosages above those employed therapeutically. As a result, it should be used cautiously during pregnancy and should be used only when the potential risk of drug therapy is outweighed by the drug's benefits. It remains unknown if modafinil is secreted into human milk and, therefore, should be used cautiously in nursing women.

Hypersensitivity to modafinil or any component

History of angina, ischemic EKG changes, left ventricular hypertrophy, or clinically significant mitral valve prolapse in association with CNS stimulant use; caution should be exercised when modafinil is given to patients with a history of psychosis, recent history of myocardial infarction, and because it has not yet been adequately studied in patients with hypertension, periodic monitoring of hypertensive patients receiving modafinil may be appropriate; caution is warranted when operating machinery or driving, although functional impairment has not been demonstrated with modafinil, all CNS-active agents may alter judgment, thinking and/or motor skills. Efficacy of oral contraceptives may be reduced, therefore, use of alternative contraception should be considered.

Limited to reports that were equal to or greater than placebo-related events:

Cardiovascular: Chest pain (2%), hypertension (2%), hypotension (2%), vasodilation (1%), arrhythmia (1%), syncope (1%)

Central nervous system: Headache (50%, compared to 40% with placebo), nervousness (8%), dizziness (5%), depression (4%), anxiety (4%), cataplexy (3%), insomnia (3%), chills (2%), fever (1%), confusion (1%), amnesia (1%), emotional lability (1%), ataxia (1%)

Dermatologic: Dry skin (1%)

Endocrine & metabolic: Hyperglycemia (1%), albuminuria (1%)

Gastrointestinal: Diarrhea (8%), nausea (13%, compared to 4% with placebo), xerostomia (5%), anorexia (5%), vomiting (1%), mouth ulceration (1%), gingivitis (1%)

Genitourinary: Abnormal urine (1%), urinary retention (1%), ejaculatory disturbance (1%)

Hematologic: Eosinophilia (1%)

Hepatic: Abnormal LFTs (3%)

Neuromuscular & skeletal: Paresthesias (3%), dyskinesia (2%), neck pain (2%), hypertonia (2%), neck rigidity (1%), joint disorder (1%), tremor (1%)

Ocular: Amblyopia (2%), abnormal vision (2%)

Respiratory: Pharyngitis (6%), rhinitis (11%, compared to 8% with placebo), lung disorder (4%), dyspnea (2%), asthma (1%), epistaxis (1%)

Signs and symptoms of an overdose include agitation, irritability, aggressiveness, confusion, nervousness, tremor, sleep disturbance, palpitations, decreased prothrombin time, and slight to moderate elevations of hemodynamic parameters; treatment is symptomatic and supportive, there is no data to suggest the utility of dialysis or urinary pH alteration to enhance elimination; cardiac monitoring is warranted

Modafinil may interact with drugs that inhibit, induce, or are metabolized by cytochrome P-450 isoenzymes; specifically modafinil is a 3A4 isoenzyme substrate and induces CYP1A2, CYP2B6, and CYP3A4 isoenzymes, as a result modafinil may decrease serum concentrations of 3A4 metabolized drugs such as oral contraceptives, cyclosporine, and to a lesser degree, theophylline; agents that induce CYP3A4, including phenobarbital, carbamazepine, and rifampin may result in decreased modafinil levels; there is evidence to suggest that modafinil may induce its own metabolism.

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

Modafinil is a racemic compound (10% d-isomer and 90% l-isomer at steady state), whose enantiomers have different pharmacokinetics

Protein binding: 60%, mostly to albumin

Metabolism: In the liver; multiple pathways including the cytochrome P-450 system

Half-life: Effective half-life: 15 hours; time to steady-state: 2-4 days

Time to peak serum concentration: 2-4 hours

Elimination: Renal, as metabolites (<10% excreted unchanged)

Narcolepsy: Initial: 200 mg as a single daily dose in the morning

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

Dosing adjustment in elderly: Elimination of modafinil and its metabolites may be reduced as a consequence of aging and as a result, lower doses should be considered.

Dosing adjustment in renal impairment: Inadequate data to determine safety and efficacy in severe renal impairment

Dosing adjustment in hepatic impairment: Dose should be reduced to one-half of that recommended for patients with normal liver function

No information available to require special precautions

Dry mouth, mouth ulceration, and gingivitis have been reported

Take exactly as prescribed; do not exceed recommended dosage without consulting prescriber. Maintain healthy sleep hygiene. Do not share medication with anyone else. Void before taking medication. You may experience headache, nervousness, confusion, or dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); diarrhea (yogurt or buttermilk may help); or dry mouth or sore mouth, loss of appetite, or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Diabetics should monitor glucose levels closely. Report chest pain or palpitations; difficulty breathing; excessive insomnia, CNS agitation, depression, or memory disturbances; vision changes; changes in urinary pattern or ejaculation disturbances; or persistent joint pain or stiffness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Tablet: 100 mg, 200 mg

Broughton, RJ, "Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Modafinil in the Treatment of Excessive Daytime Sleepiness in Narcolepsy," Neurology, 1997, 49(2):444-451.

Grozinger M, "Interaction of Modafinil and Clomipramine as Comedication in a Narcoleptic Patient," Clin Neuropharmacol, 1998, 21(2):127-129.

U.S. Modafinil in Narcolepsy Multicenter Study Group, "Randomized Trial of Modafinil for the Treatment of Pathological Somnolence in Narcolepsy," Ann Neurol, 1998, 43(1):88-97.

Wong, YN, "Single-Dose Pharmacokinetics of Modafinil and Methylphenidate Given Alone or in Combination in Healthy Male Volunteers," J Clin Pharmacol, 1998, 38(3):276-282.