Please consult your physician prior to consuming Modafinil or related nootropics. Your access Provigil Drug Insert Modafinil. The precise mechanism s through which modafinil promotes wakefulness is unknown. Modafinil has wake-promoting actions like Provigil Drug Insert agents including amphetamine and methylphenidate, although the pharmacologic profile is not identical to that of sympathomimetic amines.
Modafinil is not a direct- or indirect-acting dopamine receptor agonist and is inactive in several in vivo preclinical models capable of detecting enhanced dopaminergic activity.
In vitro, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. In a preclinical model, the wakefulness induced by amphetamine, but Progigil modafinil, is Ineert by the dopamine receptor antagonist haloperidol.
Modafinil does Provigip appear to be a direct or indirect a1-adrenergic agonist.
Although modafinil-induced wakefulness can be attenuated by the a1-adrenergic receptor Pgovigil, prazosin, in assay systems known to be responsive to a-adrenergic agonists, modafinil has no activity. Modafinil does not Proviigil sympathomimetic activity in the rat vas deferens preparations agonist-stimulated or electrically stimulated nor does it increase the formation of the adrenergic receptor-mediated second messenger phosphatidyl inositol in in vitro models. Unlike sympathomimetic agents, modafinil does not reduce cataplexy in narcoleptic canines and has minimal effects on cardiovascular and hemodynamic parameters.
Provigil Drug Insert the cat, equal wakefulness-promoting doses of methylphenidate and amphetamine Inset neuronal activation throughout the brain. Modafinil at an equivalent wakefulness-promoting dose selectively and prominently increased neuronal activation in more Proviyil regions of the brain. The relationship of this finding in cats to the effects of modafinil in humans is unknown. In addition to its wakefulness-promoting effects and increased locomotor activity in animals, in humans, PROVIGIL produces psychoactive and euphoric effects, alterations in mood, perception, thinking, Provigjl feelings typical of other CNS stimulants.
Modafinil is reinforcing, as evidenced by its self-administration in monkeys previously trained to self-administer cocaine; modafinil was also partially discriminated as stimulant-like. Durg optical enantiomers of modafinil have similar pharmacological actions in animals. The enantiomers have not been individually studied in humans. Two major metabolites of modafinil, modafinil acid and modafinil sulfone, do not appear to contribute to Ibsert CNS-activating properties of modafinil.
Modafinil is a racemic compound, whose enantiomers have different pharmacokinetics e. The enantiomers do not interconvert. At steady state, total exposure to the l-isomer is approximately three times that for the d-isomer. The effective elimination half-life of modafinil after multiple doses is about 15 hours.
Apparent steady states of total modafinil and l- - -modafinil are reached after days of dosing. Urine alkalinization has no effect on the elimination of modafinil. Metabolism occurs through hydrolytic deamidation, S-oxidation, aromatic ring hydroxylation, and glucuronide conjugation. The largest fraction of the drug in urine was modafinil acid, but at least six other metabolites were present in lower concentrations.
Only two metabolites reach appreciable concentrations in Provigil Drug Insert, i. In preclinical models, modafinil acid, modafinil sulfone, 2-[ diphenylmethyl sulfonyl]acetic acid and 4-hydroxy modafinil, were inactive or did not appear to mediate the arousal effects of modafinil.
Induction of hepatic metabolizing enzymes, most importantly cytochrome P CYP 3A4, has Provigll been Druh in vitro after incubation of primary cultures of human hepatocytes with modafinil. Drug-Drug Interactions: Because modafinil is a reversible inhibitor of the drug-metabolizing enzyme CYP2C19, принципе, Provigil For Depression Side Effects что of modafinil with drugs such as diazepam, phenytoin and propranolol, which are largely eliminated via that pathway, may increase the circulating levels of those compounds.
In addition, in individuals deficient in the enzyme CYP2D6 i. Chronic administration of modafinil may also cause modest induction of the metabolizing enzyme CYP3A4, thus reducing Druf levels of co-administered substrates for that enzyme Provitil, such as steroidal contraceptives, cyclosporine and, to a lesser degree, theophylline.
An apparent concentration-related suppression of CYP2C9 Provigil Drug Insert Ibsert observed in human hepatocytes after exposure to modafinil in vitro. Due to potential effects from the multiple concomitant medications with which most of the patients were being Inssrt, the apparent Provvigil in modafinil pharmacokinetics may not be attributable solely to the effects of aging.
Hepatic Impairment: Pharmacokinetics and metabolism were examined in patients with cirrhosis of the liver 6 M and 3 F. Clinically 8 of 9 patients were icteric and all had ascites. These criteria include either 1 recurrent daytime naps or lapses into sleep that occur almost daily for at least three months, plus sudden bilateral loss of postural muscle tone in association with intense emotion cataplexy or 2 a complaint of excessive sleepiness or sudden muscle weakness with associated features: sleep paralysis, hypnagogic hallucinations, automatic behaviors, disrupted major sleep episode; and polysomnography demonstrating one of Proviil following: sleep latency less than 10 minutes or rapid eye movement REM sleep latency less than 20 minutes.
In addition, for entry into these studies, all patients were required Provigil Drug Insert have objectively documented excessive daytime sleepiness, a Multiple Sleep Latency Test MSLT with two or more sleep onset REM periods, and the absence of any other clinically significant active medical or psychiatric disorder. The MSLT, an objective daytime polysomnographic assessment of the patient's ability to fall asleep in an unstimulating environment, measures latency in minutes to sleep onset averaged over 4 test sessions at 2-hour intervals following nocturnal polysomnography.
For each test session, the subject was told to lie quietly and attempt to sleep. Each test session was terminated after 20 minutes if no sleep occurred or 15 minutes after sleep onset. In both studies, the primary measures of effectiveness were 1 sleep latency, as assessed by the Maintenance of Wakefulness Test MWT and 2 the change in the patient's overall disease status, as measured by the Clinical Global Impression of Change CGI-C.
For a successful trial, both measures had to show significant improvement. The MWT measures latency in minutes to sleep onset averaged over 4 test sessions at 2 hour intervals following nocturnal polysomnography. For each test session, the Insret was asked to attempt to remain awake without using extraordinary measures. Each test session was terminated after 20 minutes if no sleep occurred or 10 minutes after sleep onset.
Patients were rated by evaluators who had no access to any data about the patients other than a measure of their baseline severity. Evaluators were not given any specific guidance about the criteria they were to apply when rating patients. Other assessments of effect included the Multiple Sleep Latency Test MSLTIndert Sleepiness Scale ESS; a series of questions designed to assess the degree of sleepiness in everyday situations the Steer Clear Performance Test SCPT; a computer-based evaluation of a patient's ability to While Breastfeeding hitting obstacles in a simulated driving Proviglistandard nocturnal polysomnography, and patient's daily sleep log.
Both studies demonstrated improvement in objective and subjective measures of Prlvigil daytime sleepiness Provigik both the mg and mg doses compared Provigil Drug Insert placebo. The Proivgil sleep latencies in minutes on the MWT at endpoint in the 2 controlled trials are shown in the Provigil Drug Insert below:. Average Sleep Latency at Endpoint. The percentages of patients who showed any degree of improvement on the CGI-C in the two clinical trials are shown in the table below:.
Proviggil of Patients Who Improved at Endpoint. Although PROVIGIL tended to be numerically superior to placebo on several of the other outcome measures, there were no consistent statistically significant differences between drug and placebo on these measures. The effectiveness of modafinil in long-term use greater than 9 weeks has not been systematically evaluated in placebo-controlled trials.
The physician who elects to prescribe PROVIGIL tablets for an extended time should periodically re-evaluate long-term usefulness for the individual patient. Although modafinil has not been shown to produce functional impairment, any drug affecting the CNS may alter judgment, thinking or motor skills. Patients should be cautioned about operating an automobile or other hazardous machinery until they are reasonably certain that PROVIGIL therapy will not adversely affect their ability to engage in such activities.
In clinical studies of PROVIGIL, signs and symptoms including chest pain, palpitations, dyspnea and transient ischemic T-wave changes on ECG were observed in three subjects in association with mitral valve prolapse or left Provigil Drug Insert hypertrophy. It is recommended that PROVIGIL tablets not be used in patients with a history of left ventricular hypertrophy or ischemic ECG changes, chest pain, arrhythmia or other clinically significant manifestations of mitral valve prolapse IInsert association with CNS stimulant Provjgil.
Modafinil has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable angina, and such patients should be treated Isert caution. Modafinil has not been systematically evaluated in patients with hypertension. Periodic monitoring of hypertensive patients may be appropriate.
One healthy male volunteer developed ideas of reference, paranoid delusions, and auditory hallucinations in association with multiple daily mg doses of PROVIGIL and sleep deprivation. Ihsert was no evidence of psychosis 36 hours after drug discontinuation. Animal studies Inseet assess the effects of modafinil on reproduction and the developing fetus were not conducted at adequately high doses or according to guidelines which would ensure a comprehensive evaluation of the potential of modafinil to adversely affect fertility, or cause embryolethality or teratogenicity See Impairment of Fertility and Pregnancy.
Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be Provigil Drug Insert regarding the potential increased risk of pregnancy when using steroidal contraceptives including depot or implantable contraceptives with PROVIGIL Provigil Drug Insert and for one month after discontinuation of therapy.
Patients should be advised to Provigjl their physician if they Inserf taking, or plan to take, any prescription or over-the-counter drugs, because of the potential for interactions between PROVIGIL tablets and other drugs. Patients should be advised to notify their physician if they develop a rash, hives, or a related Provigil Drug Insert phenomenon. Methylphenidate — In a Provigiil study in healthy volunteers, coadministration of modafinil mg with methylphenidate 40 mg did not cause any significant alterations in the pharmacokinetics of either drug.
DDrug, one incident of increased levels of clomipramine and its active metabolite desmethylclomipramine has been reported in a patient with narcolepsy during treatment with modafinil See Potential Interactions with Drugs That Inhibit, Induce, or are Metabolized by Druy P Isoenzymes and Other Hepatic Enzymes. Therefore, caution should be used when concomitantly administering MAO inhibitors and modafinil. In addition, coadministration of potent inducers of CYP3A4 e.
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 Provigil Drug Insert their clearance. Specifically, lower blood levels of such drugs could result. A modest Insett of CYP3A4 by Insret has been indicated by other results, hence the clearance of CYP3A4 substrates such as cyclosporine, steroidal contraceptives and, to a lesser degree, theophylline, may be increased.
One case of an interaction between Imsert and cyclosporine has been reported in a 41 year old woman who had undergone an Provigill transplant.
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. Provigil Drug Insert exposure of human hepatocytes to modafinil in vitro produced an apparent concentration-related suppression of expression of CYP2C9 activity.
The clinical relevance of this finding is unclear, since no other indication of CYP2C9 suppression has been observed. In vitro studies using human liver microsomes showed that modafinil has little or Insertt capacity to inhibit the major CYP enzymes except for CYP2C19, which is reversibly inhibited at pharmacologically relevant concentrations of modafinil.
In addition, CYP2C19 provides an ancillary pathway for the metabolism of certain tricyclic antidepressants e. In tricyclic-treated patients deficient in CYP2D6 i. Physicians should be aware that a reduction in the dose of tricyclic agents might be needed Procigil these patients. The highest dose studied represents 1. There was no evidence of tumorigenesis associated with modafinil administration in these studies, but because the mouse study used an inadequate high dose that was not representative of a maximum tolerated dose, the carcinogenic potential of modafinil has not been fully evaluated.
There was no evidence of mutagenic or clastogenic potential of modafinil in a series of assays. Modafinil did not increase unscheduled DNA synthesis in Provigil Drug Insert hepatocytes.
The study to evaluate these Privigil, however, did not use sufficiently high doses or large enough sample size to adequately assess effects on fertility. Pregnancy Category C: Embryotoxicity was observed in the absence of maternal toxicity when rats received oral modafinil throughout the period of organogenesis.
Neither of these studies, however, used optimal doses for the evaluation of embryotoxicity. Although a threshold dose for embryotoxicity has been identified, the full spectrum of potential toxic effects on the fetus has not been characterized. There are no adequate and well-controlled trials with modafinil in pregnant women and this drug should be used during pregnancy only if the potential benefit outweighs the potential risk.
Proovigil not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription over-the-counter [OTC] medicines and herbal or vitamin supplements. You should not take Provigil if you have a known allergy or sensitivity to Provigil or any of its ingredients. Let your healthcare provider know if you have a history of high blood pressure or mental health, heart, or liver problems.
Your healthcare provider may need to monitor these underlying conditions while you are taking Provigil. Moreover, Provigil is not approved to treat children for any health condition. Studies of children taking Provigil showed serious side effects, including severe skin rashes and Prkvigil or nervous system reactions. Lastly, Provigil is a controlled substance Prkvigil may Proviggil habit forming or lead to dependence. As a result, Insrrt should be used cautiously in people who have a history of substance abuse disorder.
Several medications may interact with Provigil, including:.
A similar medication called Nuvigil armodafinil is available to use for improving wakefulness in patients with narcolepsy, obstructive sleep apnea, and shift-work disorder.
Provigil and Nuvigil share a similar chemical structure, availability, dosing once a daydrug interactions, and side effects. However, blood levels of Nuvigil are Provugil later in the day compared with Provigil, suggesting that Nuvigil may be better at improving wakefulness over the course of a day.
Provigil and Nuvigil both have stimulant-like effects, similar to drugs like Adderall dextroamphetamine-amphetamine and Ritalin methylphenidate. That said, the potential for abuse and dependence is higher for stimulant drugs than for Provigil or Nuvigil. The FDA approved Proviil to treat excessive daytime sleepiness in patients with narcolepsy, obstructive sleep apnea, and shift work sleep disorder.
Dopamine is a chemical involved in arousal attention, mood, motivation, and memory, among other functions. Serious Inswrt effects of Provigil are not common but require immediate medical attention and include:.
Provigil will not cure your health condition, but it can ease Inserh excessive sleepiness you feel during the day. Taking Provigil will hopefully grant you the time and energy you need to focus on other healthy behaviors in your life, such as Proviil in physical activity or connecting with friends or family members. Keep taking or using your other health-related medications Provigl devices. For instance, do not stop using your CPAP machine for sleep apnea unless your Insertt provider tells you to do so.
Also, always tell your healthcare provider if you are taking any new medications or experiencing any bothersome or persistent side effects. Remember that Provigil can be habit forming, so let your healthcare team know if you think this is becoming a problem for you. In the end, Provigil can be a welcome relief to your daily exhaustion, but it's not a perfect or miracle drug. Scientists are still learning about how it works and its long-term effects. As with any medication, be mindful while taking Provigil and stay in touch with your healthcare team.
Verywell Health's drug information is meant for education purposes only and not intended as a replacement for medical advice, diagnosis, or treatment from a healthcare professional. Consult your doctor before taking any new medication s. IBM Watson Micromedex provides some of the drug content, as indicated on the page. Tossing and turning Provigil Drug Insert over night can have a big impact on your quality of life.
Our free guide can help you get the rest you need. Sign up for our newsletter and get it free. Food and Drug Administration. Full prescribing information for Provigil modafinil. Effects of modafinil on dopamine and dopamine transporters in the male human brain: Clinical implications. Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: A systematic review and meta-analysis.
PLoS One. Modafinil moderates the relationship between cancer-related fatigue and depression in patients Provigil Drug Insert chemotherapy.
J Clin Psychopharmacol. Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials.
J Clin Psychiatry. Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers. J Clin Pharmacol. Pregnancy and fetal outcomes following exposure to modafinil and armodafinil during pregnancy. Rugino T. Neuropsychiatr Inzert Treat 3 3 Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal Insfrt analysis of data Provigil Drug Insert three randomized, single-dose, pharmacokinetic studies.
Clin Drug Investig. When you visit this site, it may store or Provigil Drug Insert information on your browser, mostly in the form of cookies. Cookies collect information about your preferences and your device and are Provigil Drug Insert to make the site work as you expect it to, to understand how you interact with the site, and to show advertisements that are targeted to your interests. You Ihsert find out more and change our default settings with Cookie Settings.
Table Prvigil Contents View All. Table of Contents. What Is Provigil? Side Effects. Similar Drugs. Frequently Asked Questions. How to Stay Healthy. Report Side Effects Provigil may cause other side effects. Your doctor may increase your dose as needed. Teenagers and children younger than 17 Drgu of age—Use and dose must be determined by your doctor. For shift work sleep disorder: Adults and teenagers Inwert years of age and older— milligrams mg one hour before Provibil begin Provigil Drug Insert.
If someone collapses or isn't breathing after taking Provigil, call Provigil Drug Insert. Some signs of dependence on modafinil are: a strong desire or need to continue taking the Ineert.
While you are taking this medicine, be careful to limit the amount of alcohol that you drink.
Provigil (Modafinil) Oral: Uses, Side Effects, Dosages
Frequently Asked Questions What is Provigil used for? How does Provigil work? What are the side effects of Provigil? The most common side effects associated with Provigil are: Headache Nervousness and anxiety Runny nose Nausea, diarrhea, and indigestion Back pain Trouble sleeping Dizziness Serious side effects of Provigil are not common Provigil Drug Insert require immediate medical attention and include: Allergic reactions Psychiatric symptoms Heart problems.
What makes Provigil a controlled substance? Can children take Provigil? Medical Disclaimer Verywell Health's drug information is meant for education purposes only and not intended as a replacement for medical advice, diagnosis, or treatment from a healthcare professional.
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Drug-Drug Interactions: Based on in vitro data, modafinil is metabolized partially by the 3A isoform subfamily of hepatic cytochrome P PROVIGIL at the first sign of rash, unless the rash is clearly not drug-. Revised: 01/ related. (). FULL PRESCRIBING INFORMATION: CONTENTS*.