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The following serious adverse reactions are described below and elsewhere in the labeling:
- Serious Dermatologic Reactions [see WARNINGS AND PRECAUTIONS]
- Drug Reaction with Eosinophilia and System Symptoms (DRESS)/Multiorgan Hypersensitivity [see WARNINGS AND PRECAUTIONS]
- Angioedema and Anaphylaxis Reactions [see WARNINGS AND PRECAUTIONS]
- Persistent Sleepiness [see WARNINGS AND PRECAUTIONS]
- Psychiatric Symptoms [see WARNINGS AND PRECAUTIONS]
- Effects on Ability to Drive and Use Machinery [see WARNINGS AND PRECAUTIONS]
- Cardiovascular Events [see WARNINGS AND PRECAUTIONS]
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.
Most Common Adverse Reactions
In the placebo-controlled clinical trials, the most common adverse reactions ( ≥ 5%) associated with the use of NUVIGIL more frequently than in placebo-treated patients were headache, nausea, dizziness, and insomnia. The adverse reaction profile was similar across the studies.
Table 1 presents the adverse reactions that occurred at a rate of 1% or more and were more frequent in NUVIGIL-treated patients than in placebo-treated patients in the placebo-controlled clinical trials.
Table 1: Adverse Reactions in Pooled
Placebo-Controlled Clinical Trials* in OSA, Narcolepsy, and SWD with NUVIGIL
(150 mg and 250 mg)
|Upper Abdominal Pain||2||1|
|Disturbance In Attention||1||0|
|Increased Heart Rate||1||0|
|* Adverse reactions that occurred in ≥ 1% of NUVIGIL-treated patients and greater incidence than that of placebo.|
Dose-Dependent Adverse Reactions
In the placebo-controlled clinical trials which compared doses of 150 mg/day and 250 mg/day of NUVIGIL and placebo, the following adverse reactions were dose-related: headache, rash, depression, dry mouth, insomnia, and nausea. See Table 2 for additional information.
Table 2: Dose-Dependent Adverse Reactions in Pooled
Placebo-Controlled Clinical Trials in OSA, Narcolepsy and SWD
|NUVIGIL 250 mg (%)
|NUVIGIL 150 mg (%)
|NUVIGIL Combined (%)
|Dry Mouth||7||2||4||< 1|
Adverse Reactions Resulting In Discontinuation Of Treatment
In placebo-controlled clinical trials, 44 of the 645 patients (7%) who received NUVIGIL discontinued due to an adverse reaction compared to 16 of the 445 (4%) of patients that received placebo. The most frequent reason for discontinuation was headache (1%).
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 NUVIGIL, but not placebo. Few patients, however, had GGT or AP elevations outside of the normal range. No differences were apparent in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, or total bilirubin, although there were rare cases of isolated elevations of AST and/or ALT. A single case of mild pancytopenia was observed after 35 days of treatment and resolved with drug discontinuation. A small mean decrease from baseline in serum uric acid compared to placebo was seen in clinical trials. The clinical significance of this finding is unknown.
The following adverse reactions have been identified during post approval use of NUVIGIL. 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.
Gastrointestinal Disorders: Mouth Sores (including mouth blistering and ulceration)
Read the Nuvigil (armodafinil) Side Effects Center for a complete guide to possible side effects
Effects Of NUVIGIL 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 NUVIGIL 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 NUVIGIL [see CLINICAL PHARMACOLOGY].
The effectiveness of steroidal contraceptives may be reduced when used with NUVIGIL 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 NUVIGIL and for one month after discontinuation of NUVIGIL treatment.
Blood levels of cyclosporine may be reduced when used with NUVIGIL. Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when used concomitantly with NUVIGIL.
Effects Of NUVIGIL On CYP2C19 Substrates
Elimination of drugs that are substrates for CYP2C19 (e.g., phenytoin, diazepam, propranolol, omeprazole, and clomipramine) may be prolonged by NUVIGIL via inhibition of metabolic enzymes, with resultant higher systemic exposure. Dose reduction of these drugs may be required when these drugs are used concomitantly with NUVIGIL.
Monoamine Oxidase (MAO) Inhibitors
Caution should be used when concomitantly administering MAO inhibitors and NUVIGIL.
Drug Abuse And Dependence
NUVIGIL contains armodafinil, a Schedule IV controlled substance.
Abuse of NUVIGIL has been reported in patients treated with NUVIGIL. Patterns of abuse have included euphoric mood and use of increasingly large doses or recurrent use of NUVIGIL for a desired effect. Drug diversion has also been noted. During the postmarketing period, misuse of NUVIGIL has been observed (e.g., taking NUVIGIL against a physician's advice, and obtaining NUVIGIL from multiple physicians).
Abuse of armodafinil, the active ingredient of NUVIGIL, poses a risk of overdosage similar to that seen for modafinil, which may lead to tachycardia, insomnia, agitation, dizziness, anxiety, nausea, headache, dystonia, tremor, chest pain, hypertension, seizures, delirium, or hallucinations. Other signs and symptoms of CNS stimulant abuse include tachypnea, sweating, dilated pupils, hyperactivity, restlessness, decreased appetite, loss of coordination, flushed skin, vomiting, and abdominal pain.
In humans, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking and feelings, typical of other CNS stimulants. In in vitro binding studies, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. Modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine. In some studies, modafinil was also partially discriminated as stimulant-like.
Physicians should follow patients closely, especially those with a history of drug and/or stimulant (e.g., methylphenidate, amphetamine, or cocaine) abuse. Patients should be observed for signs of misuse or abuse (e.g., incrementation of doses or drug-seeking behavior).
The abuse potential of modafinil (200, 400, and 800 mg) was assessed relative to methylphenidate (45 and 90 mg) in an inpatient study in individuals experienced with drugs of abuse. Results from this clinical study demonstrated that modafinil produced psychoactive and euphoric effects and feelings consistent with other scheduled CNS stimulants (methylphenidate).
Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.
Physical dependence can occur in patients treated with NUVIGIL. Abrupt cessation or dose reduction following chronic use can result in withdrawal symptoms, including shaking, sweating, chills, nausea, vomiting, confusion, aggression, and atrial fibrillation.
Drug withdrawal convulsions, suicidality, fatigue, insomnia, aches, depression and headache have also been observed during the postmarketing period. Also, abrupt withdrawal has caused deterioration of psychiatric symptoms such as depression.
Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Multiple cases of development of tolerance to NUVIGIL have been reported during the postmarketing period.
Read the Nuvigil Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 2/27/2017
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Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
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