Modafinil (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- MODAFINIL
- PROVIGIL
Indications and Usage
Modafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD). Limitations of Use In OSA, modafinil tablets are indicated to treat excessive sleepiness and not as treatment for the underlying obstruction. If continuous positive airway pressure (CPAP) is the treatment of choice for a patient, a maximal effort to treat with CPAP for an adequate period of time should be made prior to initiating and during treatment with modafinil tablets for excessive sleepiness.
Contraindications
Modafinil tablets are contraindicated in patients with known hypersensitivity to modafinil or armodafinil or its inactive ingredients [see Warnings and Precautions ( 5.1, 5.2, 5.3)] .
Adverse Reactions
The following serious adverse reactions are described elsewhere in the labeling: Serious Rash, including Stevens-Johnson Syndrome [see Warnings and Precautions ( 5.1)] Angioedema and Anaphylaxis Reactions [see Warnings and Precautions ( 5.2)] Multi-organ Hypersensitivity Reactions [see Warnings and Precautions ( 5.3)] Persistent Sleepiness [see Warnings and Precautions ( 5.4)] Psychiatric Symptoms [see Warnings and Precautions ( 5.5)] Effects on Ability to Drive and Use Machinery [see Warnings and Precautions ( 5.6)] Cardiovascular Events [see Warnings and Precautions ( 5.7)]
Drug Interactions
Effects of Modafinil Tablets on CYP3A4/5 Substrates The clearance of drugs that are substrates for CYP3A4/5 (e.g., steroidal contraceptives, cyclosporine, midazolam, and triazolam) may be increased by modafinil tablets via induction of metabolic enzymes, which results in lower systemic exposure. Dosage adjustment of these drugs should be considered when these drugs are used concomitantly with modafinil tablets [see Clinical Pharmacology ( 12.3)] . The effectiveness of steroidal contraceptives may be reduced when used with modafinil tablets and for one month after discontinuation of therapy. Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives (e.g., ethinyl estradiol) when treated concomitantly with modafinil tablets and for one month after discontinuation of modafinil tablets treatment. Blood levels of cyclosporine may be reduced when used with modafinil tablets. Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when used concomitantly with modafinil tablets. Effects of Modafinil Tablets on CYP2C19 Substrates Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by modafinil tablets via inhibition of metabolic enzymes, with resultant higher systemic exposure. In individuals deficient in the CYP2D6 enzyme, the levels of CYP2D6 substrates which have ancillary routes of elimination through CYP2C19, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may be increased by co-administration of modafinil tablets. Dose adjustments of these drugs and other drugs that are substrates for CYP2C19 may be necessary when used concomitantly with modafinil tablets [see Clinical Pharmacology ( 12.3)] . Warfarin More frequent monitoring of prothrombin times/INR should be considered whenever modafinil tablets are coadministered with warfari
Overdosage
In clinical trials, a total of 151 protocol-specified doses ranging from 1000 to 1600 mg/day (5 to 8 times the recommended daily dose of modafinil tablets) have been administered to 32 subjects, including 13 subjects who received doses of 1000 or 1200 mg/day for 7 to 21 consecutive days. In addition, several intentional acute overdoses occurred; the two largest being 4500 mg and 4000 mg taken by two subjects participating in foreign depression studies. None of these study subjects experienced any unexpected or life-threatening effects. Adverse reactions that were reported at these doses included excitation or agitation, insomnia, and slight or moderate elevations in hemodynamic parameters. Other observed high-dose effects in clinical studies have included anxiety, irritability, aggressiveness, confusion, nervousness, tremor, palpitations, sleep disturbances, nausea, diarrhea, and decreased prothrombin time. From postmarketing experience, there have been reports of fatal overdoses involving modafinil alone or in combination with other drugs. Symptoms most often accompanying modafinil tablets overdose, alone or in combination with other drugs have included insomnia; central nervous system symptoms such as restlessness, disorientation, confusion, agitation, anxiety, excitation, and hallucination; digestive changes such as nausea and diarrhea; and cardiovascular changes such as tachycardia, bradycardia, hypertension, and chest pain. Cases of accidental ingestion/overdose have been reported in children as young as 11 months of age. The highest reported accidental ingestion on a mg/kg basis occurred in a three-year-old boy who ingested 800 to 1000 mg (50 to 63 mg/kg) of modafinil tablets. The child remained stable. The symptoms associated with overdose in children were similar to those observed in adults. No specific antidote exists for the toxic effects of a modafinil tablets overdose. Such overdoses should be managed with primarily supportive care, including cardiovascu