Modafinil
Generic: MODAFINIL
Basic Information
Manufacturer
Alembic Pharmaceuticals Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
5b8496fe-b647-4ce6-aeef-71245712e46f
Indications & Usage
1 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.
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).
(1) Limitations of Use In OSA, modafinil tablets are indicated to treat excessive sleepiness and not as treatment for the underlying obstruction.
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.
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).
(1) Limitations of Use In OSA, modafinil tablets are indicated to treat excessive sleepiness and not as treatment for the underlying obstruction.
Adverse Reactions
6 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)] Multiorgan 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)] Most common adverse reactions (≥5%): headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Modafinil has been evaluated for safety in over 3,500 patients, of whom more than 2,000 patients with excessive sleepiness associated with OSA, SWD, and narcolepsy.
Most Common Adverse Reactions In placebo-controlled clinical trials, the most common adverse reactions (≥ 5%) associated with the use of modafinil more frequently than placebo-treated patients were headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.
The adverse reaction profile was similar across these studies.
Table 1 presents the adverse reactions that occurred at a rate of 1% or more and were more frequent in modafinil-treated patients than in placebo-treated patients in the placebo-controlled clinical trials.
Table 1.
Adverse Reactions in Pooled Placebo-Controlled Trials * in Narcolepsy, OSA, and SWD Preferred Term Modafinil (%) (n = 934) Placebo (%) (n = 567) Headache Nausea Nervousness Rhinitis Back Pain Diarrhea Anxiety Dizziness Dyspepsia Insomnia Anorexia Dry Mouth Pharyngitis Chest Pain Hypertension Abnormal Liver Function Constipation Depression Palpitation Paresthesia Somnolence Tachycardia Vasodilatation Abnormal Vision Agitation Asthma Chills Confusion Dyskenesia Edema Emotional Lability Eosinophilia Epistaxis Flatulence Hyperkinesia Hypertonia Mouth Ulceration Sweating Taste Perversion Thirst Tremor Urine Abnormality Vertigo 34 11 7 7 6 6 5 5 5 5 4 4 4 3 3 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 23 3 3 6 5 5 1 4 4 1 1 2 2 1 1 1 1 1 1 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 * Adverse Reactions that occurred in > 1% of modafinil-treated patients (either 200, 300, or 400 mg once daily) and greater incidence than placebo Dose-Dependent Adverse Reactions In the placebo-controlled clinical trials which compared doses of 200, 300, and 400 mg/day of modafinil and placebo, the following adverse reactions were dose related: headache and anxiety.
Adverse Reactions Resulting in Discontinuation of Treatment In placebo-controlled clinical trials, 74 of the 934 patients (8%) who received modafinil discontinued due to an adverse reaction compared to 3% of patients that received placebo.
The most frequent reasons for discontinuation that occurred at a higher rate for modafinil than placebo patients were headache (2%), nausea, anxiety, dizziness, insomnia, chest pain, and nervousness (each <1%).
Laboratory Abnormalities Clinical chemistry, hematology, and urinalysis parameters were monitored in the studies.
Mean plasma levels of gamma glutamyltransferase (GGT) and alkaline phosphatase (AP) were found to be higher following administration of modafinil, but not placebo.
Few patients, however, had GGT or AP elevations outside of the normal range.
Shifts to higher, but not clinically significantly abnormal, GGT and AP values appeared to increase with time in the population treated with modafinil in the placebo-controlled clinical trials.
No differences were apparent in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, or total bilirubin.
6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of modafinil.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hematologic: agranulocytosis Psychiatric disorders: psychomotor hyperactivity
(6.1) To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Modafinil has been evaluated for safety in over 3,500 patients, of whom more than 2,000 patients with excessive sleepiness associated with OSA, SWD, and narcolepsy.
Most Common Adverse Reactions In placebo-controlled clinical trials, the most common adverse reactions (≥ 5%) associated with the use of modafinil more frequently than placebo-treated patients were headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia.
The adverse reaction profile was similar across these studies.
Table 1 presents the adverse reactions that occurred at a rate of 1% or more and were more frequent in modafinil-treated patients than in placebo-treated patients in the placebo-controlled clinical trials.
Table 1.
Adverse Reactions in Pooled Placebo-Controlled Trials * in Narcolepsy, OSA, and SWD Preferred Term Modafinil (%) (n = 934) Placebo (%) (n = 567) Headache Nausea Nervousness Rhinitis Back Pain Diarrhea Anxiety Dizziness Dyspepsia Insomnia Anorexia Dry Mouth Pharyngitis Chest Pain Hypertension Abnormal Liver Function Constipation Depression Palpitation Paresthesia Somnolence Tachycardia Vasodilatation Abnormal Vision Agitation Asthma Chills Confusion Dyskenesia Edema Emotional Lability Eosinophilia Epistaxis Flatulence Hyperkinesia Hypertonia Mouth Ulceration Sweating Taste Perversion Thirst Tremor Urine Abnormality Vertigo 34 11 7 7 6 6 5 5 5 5 4 4 4 3 3 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 23 3 3 6 5 5 1 4 4 1 1 2 2 1 1 1 1 1 1 0 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 * Adverse Reactions that occurred in > 1% of modafinil-treated patients (either 200, 300, or 400 mg once daily) and greater incidence than placebo Dose-Dependent Adverse Reactions In the placebo-controlled clinical trials which compared doses of 200, 300, and 400 mg/day of modafinil and placebo, the following adverse reactions were dose related: headache and anxiety.
Adverse Reactions Resulting in Discontinuation of Treatment In placebo-controlled clinical trials, 74 of the 934 patients (8%) who received modafinil discontinued due to an adverse reaction compared to 3% of patients that received placebo.
The most frequent reasons for discontinuation that occurred at a higher rate for modafinil than placebo patients were headache (2%), nausea, anxiety, dizziness, insomnia, chest pain, and nervousness (each <1%).
Laboratory Abnormalities Clinical chemistry, hematology, and urinalysis parameters were monitored in the studies.
Mean plasma levels of gamma glutamyltransferase (GGT) and alkaline phosphatase (AP) were found to be higher following administration of modafinil, but not placebo.
Few patients, however, had GGT or AP elevations outside of the normal range.
Shifts to higher, but not clinically significantly abnormal, GGT and AP values appeared to increase with time in the population treated with modafinil in the placebo-controlled clinical trials.
No differences were apparent in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, or total bilirubin.
6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of modafinil.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hematologic: agranulocytosis Psychiatric disorders: psychomotor hyperactivity