Modafinil is a racemic compound. The chemical name for modafinil is 2-[ diphenylmethyl sulfinyl]acetamide. Modafinil is a white to off-white, crystalline powder that is practically insoluble in water and cyclohexane. It is sparingly provigil and rash slightly soluble in methanol and acetone, provigil and rash. Consideration should be given to the use of lower doses and close monitoring in geriatric patients [see Use in Specific Populations ]. NDC — Bottles of North Wales, PA 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.
The adverse reaction profile was similar across these studies. Clinical chemistry, hematologyand urinalysis parameters were monitored in the studies. No differences were apparent in alanine aminotransferase ALTaspartate aminotransferase ASTtotal protein, albuminor total bilirubin.
Because these reactions are reported voluntarily from a population of uncertain size, provigil and rash, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Alternative or concomitant methods of contraception are recommended for patients taking steroidal contraceptives e.
Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when used concomitantly with PROVIGIL. Elimination of drugs that are substrates for CYP2C19 e. 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, provigil and rash, 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. Patients should be observed for signs of misuse or abuse e.
The abuse potential of modafinil, and 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 provigil and rash with other scheduled CNS stimulants methylphenidate.
In one placebo-controlled clinical trial, provigil and rash, the effects of modafinil withdrawal were monitored following 9 weeks of modafinil use, provigil and rash. There were no reported withdrawal symptoms with modafinil during 14 days of observation, although sleepiness returned in narcoleptic patients.
Serious rash requiring provigil and rash and discontinuation of treatment has been reported in adults and children in association with the use of modafinil. In clinical trials of modafinil, the incidence provigil and rash rash resulting in discontinuation was approximately 0. Several of the cases were associated with fever and other abnormalities e. The median time to rash that resulted in discontinuation was 13 days. No such cases were observed among pediatric patients who received placebo.
No serious skin rashes have been reported in adult clinical trials 0 per 4, of modafinil. The reporting rate of TEN and SJS associated with modafinil use, which is generally accepted to be an underestimate due to underreporting, exceeds the background incidence rate.
Estimates of the background incidence rate for these serious skin reactions in the general population range between 1 to 2 cases per million-person years. There are no factors that are known to predict the risk of occurrence or the severity of rash associated with modafinil.
Nearly all cases of serious rash associated with modafinil occurred within 1 to 5 weeks after treatment initiation. However, isolated cases have been reported after topamax and coffee treatment e. Accordingly, duration of therapy cannot be relied upon as a means to predict the potential risk heralded by the first appearance of a rash. Although benign rashes also occur with modafinil, it is not possible to reliably predict which rashes will prove to be serious.
Accordingly, modafinil should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug-related. Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring. One serious case of angioedema and one case of hypersensitivity with rash, dysphagiaand bronchospasmwere observed among 1, patients treated with armodafinilthe R enantiomer of modafinil which is the racemic mixture.
No such cases were observed in modafinil clinical trials. However, angioedema has been reported in postmarketing experience with modafinil. Patients should be advised to discontinue therapy and immediately report to their physician any signs or symptoms suggesting angioedema or anaphylaxis e. Multi-organ hypersensitivity reactions, including at least one fatality in postmarketing experience, have occurred in close temporal association median time to detection 13 days: Although there have been a limited number of reports, multi-organ hypersensitivity reactions may result in hospitalization or be life-threatening.
There are no factors that are known to predict the risk of occurrence or the severity of multi-organ hypersensitivity reactions associated with modafinil. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement.
Other associated manifestations included myocarditishepatitisliver function test abnormalities, hematological abnormalities e.
Because multi-organ hypersensitivity is variable in its expression, provigil and rash, other organ system symptoms and signs, not noted here, may occur.
Although there are no case reports to indicate cross-sensitivity with other drugs that produce this syndrome, the experience with drugs associated with multi-organ hypersensitivity would indicate this to be a possibility. Patients with provigil and rash sleepiness, including those taking PROVIGIL modafinilshould be frequently reassessed for their degree of sleepiness and, if appropriate, advised to avoid driving or any other potentially dangerous activity.
Prescribers should also be aware that patients may not acknowledge sleepiness or drowsiness until directly questioned about drowsiness or sleepiness during specific activities. Psychiatric adverse provigil and rash have been reported in patients treated with modafinil. Postmarketing adverse events associated with the use of modafinil have included mania, delusions, hallucinations, suicidal ideation and aggression, some resulting in hospitalization.
Many, but not all, patients had a prior psychiatric history. One healthy male volunteer developed ideas of reference, paranoid delusions, and auditory hallucinations in association with multiple daily mg doses of modafinil and sleep deprivation.
There was no evidence of psychosis 36 hours after drug discontinuation. Such an evaluation usually consists of a complete provigil and rash and physical examination, and it may be supplemented with testing in a laboratory setting. Some patients may have more than one sleep disorder contributing to their excessive sleepiness e. 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 modafinil therapy will not adversely affect their ability to engage in such activities.
Modafinil has not been evaluated in patients with a recent history of myocardial infarction or unstable anginaand such patients should be treated with caution.
In clinical studies of PROVIGIL modafinilsigns 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 vitamin b6 and orthostatic tremor or left ventricular provigil and rash. It is recommended that PROVIGIL modafinil tablets not be used in patients with a history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced the mitral valve prolapse syndrome when previously receiving CNS stimulants.
Such signs may include but are not limited to ischemic ECG changes, chest pain, provigil and rash, or arrhythmia. If new onset of any of these symptoms occurs, consider cardiac evaluation.
However, a retrospective analysis of the use of provigil and rash medication in these studies showed that a greater proportion of patients on PROVIGIL modafinil required new or increased use of antihypertensive medications 2, provigil and rash. The differential use was slightly larger when only studies in OSA were included, with 3, provigil and rash. Monitoring of circulating cyclosporine concentrations and appropriate dosage adjustment for cyclosporine should be considered when these drugs are used concomitantly.
There is inadequate information to determine safety and efficacy of dosing in patients with severe renal impairment, provigil and rash. In elderly patients, elimination of modafinil and its metabolites may be reduced as a consequence of aging. Therefore, consideration should be given to the use of lower doses in this population.
The highest dose studied is 1. There was no evidence of tumorigenesis associated with modafinil administration in these studies. However, since the mouse study used an inadequate high dose that was provigil and rash representative of a maximum tolerated dose, a subsequent carcinogenicity study was conducted in the Tg.
Doses evaluated in the Tg. There was no evidence of tumorigenicity associated with modafinil administration; however, this dermal model may not adequately assess the provigil and rash potential of an orally administered drug.
Modafinil demonstrated no evidence of mutagenic or clastogenic potential in a series of in vitro i. Modafinil was also negative in the unscheduled DNA synthesis assay in rat hepatocytes. In studies conducted in rats and rabbits, developmental toxicity was observed at clinically relevant exposures. The higher no-effect dose for rat embryofetal developmental toxicity was associated with a plasma modafinil exposure approximately 0.
The no-effect dose for rat embryofetal developmental toxicity was associated with a plasma armodafinil exposure AUC approximately one-tenth times the AUC for armodafinil in humans treated with modafinil at the RHD, provigil and rash. No effects on postnatal developmental and neurobehavioral parameters were observed in surviving offspring. There are no adequate and well-controlled studies in pregnant women.
Two cases of intrauterine growth retardation and one case of spontaneous abortion have provigil and rash reported in association with armodafinil and modafinil. Although the pharmacology of sun and antibiotics and armodafinil is not identical to that of the sympathomimetic amines, they do share some pharmacologic properties with this class.
Certain of these drugs have been associated with intrauterine growth retardation and spontaneous abortions. Whether the cases reported are drug-related is unknown.
Modafinil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Healthcare providers are encouraged to register pregnant patients, provigil and rash, or pregnant women may enroll themselves in the registry by calling toll free.
The effect provigil and rash modafinil on labor and delivery in humans has not been systematically investigated. It is not known whether modafinil or its metabolites are excreted in human milk. Safety and effectiveness in pediatric patients, below age 17, have not been established. There were no statistically significant differences favoring modafinil over placebo in prolonging sleep latency as measured by MSLT, or in perceptions of sleepiness as determined by the clinical global impression-clinician scale CGI-C.
Transient leukopenia, which resolved without medical intervention, provigil and rash, was also observed. In the controlled clinical study, 3 of 38 girls, ages 12 or older, treated with modafinil experienced dysmenorrhea compared to 0 of 10 girls who received placebo. Although these studies showed statistically significant differences favoring modafinil over placebo in reducing ADHD symptoms as measured by the ADHD-RS school versionthere were 3 cases of serious rash including one case of possible SJS among patients exposed to modafinil in this program.
Experience in a limited number of patients who were greater than 65 years of age in clinical trials showed an incidence of adverse experiences similar to other age groups. In addition, several intentional acute overdoses occurred; the two largest being mg and mg taken by two subjects participating in foreign depression studies.