Provigil Side Effects
Generic Name: modafinil
Please note - some side effects for Provigil may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).
Side Effects of Provigil - for the Consumer
Provigil
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Provigil:
Seek medical attention right away if any of these SEVERE side effects occur when using Provigil:Back pain; diarrhea; dizziness; headache; nausea; nervousness; stomach upset; stuffy nose; trouble sleeping.
TopSevere allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thinking; chest pain; confusion; dark urine; fever, chills, or sore throat; irregular heartbeat; mental or mood changes (eg, anxiety, depression, exaggerated sense of well-being, hallucinations); mouth sores; red, swollen, blistered, or peeling skin; shortness of breath; suicidal thoughts or actions; unusual bruising or bleeding; unusual weakness; yellowing of the skin or eyes.
Provigil Side Effects - for the Professional
Provigil
Modafinil has been evaluated for safety in over 3500 patients, of whom more than 2000 patients with excessive sleepiness associated with primary disorders of sleep and wakefulness were given at least one dose of modafinil. In clinical trials, modafinil has been found to be generally well tolerated and most adverse experiences were mild to moderate.
The most commonly observed adverse events (≥5%) associated with the use of Provigil more frequently than placebo-treated patients in the placebo-controlled clinical studies in primary disorders of sleep and wakefulness were headache, nausea, nervousness, rhinitis, diarrhea, back pain, anxiety, insomnia, dizziness, and dyspepsia. The adverse event profile was similar across these studies.
In the placebo-controlled clinical trials, 74 of the 934 patients (8%) who received Provigil discontinued due to an adverse experience compared to 3% of patients that received placebo. The most frequent reasons for discontinuation that occurred at a higher rate for Provigil than placebo patients were headache (2%), nausea, anxiety, dizziness, insomnia, chest pain and nervousness (each <1%). In a Canadian clinical trial, a 35 year old obese narcoleptic male with a prior history of syncopal episodes experienced a 9-second episode of asystole after 27 days of modafinil treatment (300 mg/day in divided doses).
Incidence in Controlled Trials
The following table (Table 3) presents the adverse experiences that occurred at a rate of 1% or more and were more frequent in adult patients treated with Provigil than in placebo-treated patients in the principal, placebo-controlled clinical trials.
The prescriber should be aware that the figures provided below cannot be used to predict the frequency of adverse experiences in the course of usual medical practice, where patient characteristics and other factors may differ from those occurring during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. Review of these frequencies, however, provides prescribers with a basis to estimate the relative contribution of drug and non-drug factors to the incidence of adverse events in the population studied.
| Body System |
Preferred Term |
Modafinil (n = 934) |
Placebo (n = 567) |
|
* Six double-blind, placebo-controlled clinical studies in narcolepsy, OSAHS, and SWSD. 1 Events reported by at least 1% of patients treated with Provigil that were more frequent than in the placebo group are included; incidence is rounded to the nearest 1%. The adverse experience terminology is coded using a standard modified COSTART Dictionary. Events for which the Provigil incidence was at least 1%, but equal to or less than placebo are not listed in the table. These events included the following: infection, pain, accidental injury, abdominal pain, hypothermia, allergic reaction, asthenia, fever, viral infection, neck pain, migraine, abnormal electrocardiogram, hypotension, tooth disorder, vomiting, periodontal abscess, increased appetite, ecchymosis, hyperglycemia, peripheral edema, weight loss, weight gain, myalgia, leg cramps, arthritis, cataplexy, thinking abnormality, sleep disorder, increased cough, sinusitis, dyspnea, bronchitis, rash, conjunctivitis, ear pain, dysmenorrhea4, urinary tract infection.
4 Incidence adjusted for gender. |
|||
| Body as a Whole | Headache | 34% | 23% |
| Back Pain | 6% | 5% | |
| Flu Syndrome | 4% | 3% | |
| Chest Pain | 3% | 1% | |
| Chills | 1% | 0% | |
| Neck Rigidity | 1% | 0% | |
| Cardiovascular | Hypertension | 3% | 1% |
| Tachycardia | 2% | 1% | |
| Palpitation | 2% | 1% | |
| Vasodilatation | 2% | 0% | |
| Digestive | Nausea | 11% | 3% |
| Diarrhea | 6% | 5% | |
| Dyspepsia | 5% | 4% | |
| Dry Mouth | 4% | 2% | |
| Anorexia | 4% | 1% | |
| Constipation | 2% | 1% | |
| Abnormal Liver Function2 | 2% | 1% | |
| Flatulence | 1% | 0% | |
| Mouth Ulceration | 1% | 0% | |
| Thirst | 1% | 0% | |
| Hemic/Lymphatic | Eosinophilia | 1% | 0% |
| Metabolic/Nutritional | Edema | 1% | 0% |
| Nervous | Nervousness | 7% | 3% |
| Insomnia | 5% | 1% | |
| Anxiety | 5% | 1% | |
| Dizziness | 5% | 4% | |
| Depression | 2% | 1% | |
| Paresthesia | 2% | 0% | |
| Somnolence | 2% | 1% | |
| Hypertonia | 1% | 0% | |
| Dyskinesia3 | 1% | 0% | |
| Hyperkinesia | 1% | 0% | |
| Agitation | 1% | 0% | |
| Confusion | 1% | 0% | |
| Tremor | 1% | 0% | |
| Emotional Lability | 1% | 0% | |
| Vertigo | 1% | 0% | |
| Respiratory | Rhinitis | 7% | 6% |
| Pharyngitis | 4% | 2% | |
| Lung Disorder | 2% | 1% | |
| Epistaxis | 1% | 0% | |
| Asthma | 1% | 0% | |
| Skin/Appendages | Sweating | 1% | 0% |
| Herpes Simplex | 1% | 0% | |
| Special Senses | Amblyopia | 1% | 0% |
| Abnormal Vision | 1% | 0% | |
| Taste Perversion | 1% | 0% | |
| Eye Pain | 1% | 0% | |
| Urogenital | Urine Abnormality | 1% | 0% |
| Hematuria | 1% | 0% | |
| Pyuria | 1% | 0% | |
Dose Dependency of Adverse Events
In the adult placebo-controlled clinical trials which compared doses of 200, 300, and 400 mg/day of Provigil and placebo, the only adverse events that were clearly dose related were headache and anxiety.
Vital Sign Changes
While there was no consistent change in mean values of heart rate or systolic and diastolic blood pressure, the requirement for antihypertensive medication was slightly greater in patients on Provigil compared to placebo.
Weight Changes
There were no clinically significant differences in body weight change in patients treated with Provigil compared to placebo-treated patients in the placebo-controlled clinical trials.
Laboratory Changes
Clinical chemistry, hematology, and urinalysis parameters were monitored in Phase 1, 2, and 3 studies. In these studies, mean plasma levels of gamma glutamyltransferase (GGT) and alkaline phosphatase (AP) were found to be higher following administration of Provigil, but not placebo. Few subjects, 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 Provigil in the Phase 3 clinical trials. No differences were apparent in alanine aminotransferase, aspartate aminotransferase, total protein, albumin, or total bilirubin.
ECG Changes
No treatment-emergent pattern of ECG abnormalities was found in placebo-controlled clinical trials following administration of Provigil.
Postmarketing Reports
The following adverse reactions have been identified during post-approval use of Provigil. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of the reporting, or (3) strength of causal connection to Provigil.
Hematologic: agranulocytosis
TopSide Effects by Body System
General
General side effects including headache (50% vs 40% in placebo), chest pain (2%), neck pain (2%), chills (2%), rigid neck (1%), and fever/chills (1%) have been reported.
Dermatologic
Some cases of rash were serious or life-threatening requiring hospitalization and discontinuation of treatment. Some cases have occurred after prolonged treatment (e.g., 3 months), while others have been reported within 1 to 5 weeks of initiation of treatment. Although benign rashes may also occur, modafinil should be discontinued at the first sign of rash unless the rash is definitely not drug-related.
Dermatologic side effects including rash, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms have been reported. In addition, herpes simplex (1%) and dry skin (1%) have been reported.
Hypersensitivity
Hypersensitivity reactions including rare cases of angioedema have been observed in patients treated with the racemic mixture of modafinil. Although no such cases were observed in modafinil clinical trials, angioedema has been reported in postmarketing experience. Patients should be advised to immediately discontinue therapy and promptly report any signs or symptoms suggesting angioedema or anaphylaxis to their physician (e.g., swelling of face, eyes, lips, tongue or larynx; difficulty in swallowing or breathing; hoarseness).
Multi-organ hypersensitivity reactions have occurred in close temporal association to the initiation of modafinil, including at least one fatality in postmarketing experience.
Multi-organ hypersensitivity reactions have occurred in close temporal association to the initiation of modafinil, including at least one fatality in postmarketing experience. Multi-organ hypersensitivity reactions may result in hospitalization or be life-threatening. Patients typically present with fever and rash associated with other organ system involvement. Myocarditis, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, leukopenia, thrombocytopenia), pruritus, and asthenia may also occur. If multi-organ hypersensitivity is suspected at any time, modafinil should be discontinued.
Psychiatric
Psychiatric side effects, some resulting in hospitalization, have been reported. These include mania, delusions, hallucinations, and suicidal ideation. Many, but not all, patients had a prior psychiatric history. Caution should be exercised when modafinil is given to patients with a history of psychosis, depression, or mania. Clinicians should consider discontinuation if psychiatric symptoms develop in association with modafinil therapy.
Cardiovascular
Cardiovascular side effects including hypotension (2%), hypertension (2%), vasodilation (1%), arrhythmia (1%), and syncope (1%) have been reported. One case of modafinil-induced premature ventricular contractions ((PVCs), ventricular ectopic beats) has been reported and confirmed by rechallenge. Following discontinuation of modafinil, PVCs continued for 14 to 20 days before finally subsiding.
Gastrointestinal
Gastrointestinal side effects including nausea (13%), diarrhea (8%), dry mouth (5%), anorexia (5%), abnormal liver function (3% vs 2% placebo), vomiting (2%), mouth ulcer (1%), gingivitis (1%), thirst (1%), and hypersalivation have been reported.
Respiratory
Respiratory side effects including rhinitis (11% vs 8% placebo), pharyngitis (6%), lung disorder (4%), dyspnea (2%), asthma (1%), and epistaxis (1%) have been reported.
Nervous system
Nervous system side effects including nervousness (8% vs 6% placebo), dizziness (5% vs 4% placebo), depression (4% vs 3% placebo), anxiety (4%), cataplexy (3% vs 2% placebo), insomnia (3%), paresthesia (3%), dyskinesia (2%), hypertonia (2%), confusion (1%), amnesia (1%), emotional lability (1%), ataxia (1%), and tremor (1%) have been reported.
Hematologic
Hematologic side effects including eosinophilia (2%) have been reported.
Ocular
Ocular side effects including amblyopia (2%), and abnormal vision (2%) have been reported.
Metabolic
Metabolic side effects including hyperglycemia (1%) and albuminuria (1%) have been reported.
Musculoskeletal
Musculoskeletal side effects including joint disorder (1%) have been reported.
Genitourinary
Genitourinary side effects including abnormal urine (1%), urinary retention (1%), and abnormal ejaculation (1%) have been reported.
TopMore resources:
Provigil - Includes detailed dosage instructions.
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