What is Provigil?
Provigil is used to help people who have narcolepsy, obstructive sleep apnea/hypopnea syndrome (OSAHS), or shift work sleep disorder (SWSD) to stay awake during the day. Provigil does not cure these conditions and will only work as long as you continue to take it.
Provigil is available only with your doctor's prescription.
Provigil tablets, USP 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, Provigil tablets, USP 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 Provigil tablets, USP for excessive sleepiness.
How should I use Provigil?
Use Provigil as directed by your doctor. Check the label on the medicine for exact dosing instructions.
- Provigil comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Provigil refilled.
- Provigil comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Provigil refilled.
- Take Provigil by mouth with or without food.
- Take Provigil in the morning unless otherwise directed by your doctor.
- If you miss a dose of Provigil, take it as soon as possible. If you do not remember until late afternoon or evening, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.
Ask your health care provider any questions you may have about how to use Provigil.
Uses of Provigil in details
Provigil is used to treat excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea (problems in breathing while asleep) and chronic shift work.
Provigil is a stimulant drug marketed as a 'wakefulness promoting agent' and is one of the stimulants used in the treatment of narcolepsy. Narcolepsy is caused by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are activated by Provigil. The prexin neuron activation is associated with psychoactivation and euphoria. The exact mechanism of action is unclear, although in vitro studies have shown it to inhibit the reuptake of dopamine by binding to the dopamine reuptake pump, and lead to an increase in extracellular dopamine. Provigil activates glutamatergic circuits while inhibiting GABA.
Dosage in Narcolepsy and Obstructive Sleep Apnea (OSA)
The recommended dosage of Provigil tablets for patients with narcolepsy or OSA is 200 mg taken orally once a day as a single dose in the morning.
Doses up to 400 mg/day, given as a single dose, have been well tolerated, but there is no consistent evidence that this dose confers additional benefit beyond that of the 200 mg/day dose.
Dosage in Shift Work Disorder (SWD)
The recommended dosage of Provigil tablets for patients with SWD is 200 mg taken orally once a day as a single dose approximately 1 hour prior to the start of their work shift.
Dosage Modifications in Patients with Severe Hepatic Impairment
In patients with severe hepatic impairment, the dosage of Provigil tablets should be reduced to one-half of that recommended for patients with normal hepatic function.
Use in Geriatric Patients
Consideration should be given to the use of lower doses and close monitoring in geriatric patients.
CNS Active Drugs
Methylphenidate - In a single-dose study in healthy volunteers, coadministration of Provigil (200 mg) with methylphenidate (40 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with methylphenidate.
Dextroamphetamine - In a single dose study in healthy volunteers, simultaneous administration of Provigil (200 mg) with dextroamphetamine (10 mg) did not cause any significant alterations in the pharmacokinetics of either drug. However, the absorption of PROVIGIL may be delayed by approximately one hour when coadministered with dextroamphetamine.
Clomipramine - The coadministration of a single dose of clomipramine (50 mg) on the first of three days of treatment with Provigil (200 mg/day) in healthy volunteers did not show an effect on the pharmacokinetics of either drug. However, one incident of increased levels of clomipramine and its active metabolite desmethylclomipramine has been reported in a patient with narcolepsy during treatment with Provigil.
Triazolam - In the drug interaction study between PROVIGIL and ethinyl estradiol (EE2), on the same days as those for the plasma sampling for EE2 pharmacokinetics, a single dose of triazolam (0.125 mg) was also administered. Mean Cmax and AUC0-∞ of triazolam were decreased by 42% and 59%, respectively, and its elimination half-life was decreased by approximately an hour after the Provigil treatment.
Monoamine Oxidase (MAO) Inhibitors - Interaction studies with monoamine oxidase inhibitors have not been performed. Therefore, caution should be used when concomitantly administering MAO inhibitors and Provigil.
Warfarin - There were no significant changes in the pharmacokinetic profiles of R- and S- warfarin in healthy subjects given a single dose of racemic warfarin (5 mg) following chronic administration of Provigil (200 mg/day for 7 days) followed by 400 mg/day for 27 days) relative to the profiles in subjects given placebo. However, more frequent monitoring of prothrombin times/INR is advisable whenever PROVIGIL is coadministered with warfarin.
Ethinyl Estradiol - Administration of Provigil to female volunteers once daily at 200 mg/day for 7 days followed by 400 mg/day for 21 days resulted in a mean 11% decrease in Cmax and 18% decrease in AUC0-24 of ethinyl estradiol (EE2; 0.035 mg; administered orally with norgestimate). There was no apparent change in the elimination rate of ethinyl estradiol.
Cyclosporine - One case of an interaction between Provigil and cyclosporine, a substrate of CYP3A4, has been reported in a 41 year old woman who had undergone an organ transplant. After one month of administration of 200 mg/day of Provigil, cyclosporine blood levels were decreased by 50%. The interaction was postulated to be due to the increased metabolism of cyclosporine, since no other factor expected to affect the disposition of the drug had changed. Dosage adjustment for cyclosporine may be needed.
Potential Interactions with Drugs That Inhibit, Induce, or are Metabolized by Cytochrome P-450 Isoenzymes and Other Hepatic Enzymes
In in vitro studies using primary human hepatocyte cultures, Provigil was shown to slightly induce CYP1A2, CYP2B6 and CYP3A4 in a concentration-dependent manner. Although induction results based on in vitro experiments are not necessarily predictive of response in vivo, caution needs to be exercised when PROVIGIL is coadministered with drugs that depend on these three enzymes for their clearance. Specifically, lower blood levels of such drugs could result.
The exposure of human hepatocytes to Provigil in vitro produced an apparent concentration-related suppression of expression of CYP2C9 activity suggesting that there is a potential for a metabolic interaction between Provigil and the substrates of this enzyme (e.g., S-warfarin and phenytoin). In a subsequent clinical study in healthy volunteers, chronic Provigil treatment did not show a significant effect on the single-dose pharmacokinetics of warfarin when compared to placebo.
In vitro studies using human liver microsomes showed that Provigil reversibly inhibited CYP2C19 at pharmacologically relevant concentrations of Provigil. CYP2C19 is also reversibly inhibited, with similar potency, by a circulating metabolite, Provigil sulfone. Although the maximum plasma concentrations of Provigil sulfone are much lower than those of parent Provigil, the combined effect of both compounds could produce sustained partial inhibition of the enzyme. Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, phenytoin (also via CYP2C9) or S-mephenytoin may have prolonged elimination upon coadministration with PROVIGIL and may require dosage reduction and monitoring for toxicity.
Tricyclic antidepressants - CYP2C19 also provides an ancillary pathway for the metabolism of certain tricyclic antidepressants (e.g., clomipramine and desipramine) that are primarily metabolized by CYP2D6. In tricyclic-treated patients deficient in CYP2D6 (i.e., those who are poor metabolizers of debrisoquine; 7-10% of the Caucasian population; similar or lower in other populations), the amount of metabolism by CYP2C19 may be substantially increased. PROVIGIL may cause elevation of the levels of the tricyclics in this subset of patients. Physicians should be aware that a reduction in the dose of tricyclic agents might be needed in these patients.
In addition, due to the partial involvement of CYP3A4 in the metabolic elimination of Provigil, coadministration of potent inducers of CYP3A4 (e.g., carbamazepine, phenobarbital, rifampin) or inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole) could alter the plasma levels of Provigil.
Provigil side effects
The following serious adverse reactions are described elsewhere in the labeling:
- Serious Rash, including Stevens-Johnson Syndrome
- Angioedema and Anaphylaxis Reactions
- Multi-organ Hypersensitivity Reactions
- Persistent Sleepiness
- Psychiatric Symptoms
- Effects on Ability to Drive and Use Machinery
- Cardiovascular Events
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.
Provigil tablets have 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 Provigil tablets 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 Provigil tablets-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
* Adverse Reactions that occurred in ≥1% of Provigil tablets-treated patients (either 200, 300, or 400mg 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 Provigil tablets 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 Provigil tablets 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 Provigil tablets than placebo patients were headache (2%), nausea, anxiety, dizziness, insomnia, chest pain, and nervousness (each <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 Provigil tablets, 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 Provigil tablets in the placebo- controlled clinical trials. No differences were apparent in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, or total bilirubin.
The following adverse reactions have been identified during post approval use of Provigil tablets. 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.
Psychiatric disorders: psychomotor hyperactivity
Provigil tablets are contraindicated in patients with known hypersensitivity to Provigil or arModafinil or its inactive ingredients.
Active ingredient matches for Provigil:
Modafinil in Belgium, Ireland, Israel, Italy, Malta, South Africa, South Korea, Taiwan, United Kingdom, United States.
Chorionic gonadotrophin in India.
Human chorionic gonadotrophin in India.
- DailyMed. "MODAFINIL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailymed/se... (accessed September 17, 2018).
- DrugBank. "modafinil". http://www.drugbank.ca/drugs/DB00745 (accessed September 17, 2018).
- PubChem. "modafinil". https://pubchem.ncbi.nlm.nih.gov/compoun... (accessed September 17, 2018).
- MeSH. "Wakefulness-Promoting Agents". https://www.ncbi.nlm.nih.gov/mesh/680646... (accessed September 17, 2018).
- Wikipedia. "modafinil: Link to the compound information in Wikipedia.". https://en.wikipedia.org/wiki/Modafinil (accessed September 17, 2018).
- HSDB. "MODAFINIL". https://toxnet.nlm.nih.gov/cgi-bin/sis/s... (accessed September 17, 2018).
- KEGG. "Cytochrome P450 interactions". http://www.genome.jp/kegg-bin/get_htext?... (accessed September 17, 2018).
- Human Metabolome Database (HMDB). "Modafinil: The Human Metabolome Database (HMDB) is a freely available electronic database containing detailed information about small molecule metabolites found in the human body.". http://www.hmdb.ca/metabolites/HMDB00148... (accessed September 17, 2018).
- PubMed Health. "Provigil: This section provide the link out information of drugs collectetd in PubMed Health. ". http://www.ncbi.nlm.nih.gov/pubmedhealth... (accessed September 17, 2018).
- EPA DSStox. "Modafinil: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/dsstox... (accessed September 17, 2018).
- DTP/NCI. "modafinil: The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents.". https://dtp.cancer.gov/dtpstandard/servl... (accessed September 17, 2018).
- European Chemicals Agency - ECHA. "2-[(Diphenylmethyl)sulfinyl]acetamide: The information provided here is aggregated from the "Notified classification and labelling" from ECHA's C&L Inventory. ". https://echa.europa.eu/information-on-ch... (accessed September 17, 2018).
- LiverTox. "Armodafinil: LIVERTOX provides up-to-date, accurate, and easily accessed information on the diagnosis, cause, frequency, patterns, and management of liver injury attributable to prescription and nonprescription medications, herbals and dietary supplements. ". https://livertox.nlm.nih.gov//ModafinilA... (accessed September 17, 2018).
- Springer Nature. "modafinil: Literature references related to scientific contents from Springer Nature journals and books. ". https://pubchem.ncbi.nlm.nih.gov/substan... (accessed September 17, 2018).
- FDA Orange Book. "MODAFINIL: The publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book), identifies drug products approved on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (the Act).". https://www.fda.gov/Drugs/InformationOnD... (accessed September 17, 2018).
ReviewsThe results of a survey conducted on ndrugs.com for Provigil are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Provigil. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.
1 consumer reported usefulWas the Provigil drug useful in terms of decreasing the symptom or the disease?
According to the reports released by ndrugs.com website users, the below mentioned percentages of users say the drug is useful / not useful to them in decreasing their symptoms/disease. The usefulness of the drug depends on many factors, like severity of the disease, perception of symptom, or disease by the patient, brand name used [matters only to a certain extent], other associated conditions of the patient. If the drug is not effective or useful in your case, you need to meet the doctor to get re-evaluated about your symptoms/disease, and he will prescribe an alternative drug.
Information checked by Dr. Sachin Kumar, MD Pharmacology