Modafinil

The recommended dose is 200 mg once daily not to exceed 400 mg. It should be administered in the morning for treating narcolepsy or obstructive sleep apnea, and one hour prior to work in those with shift work disorder. It can be taken with or without food. The 400 mg dose may not be more effective than the 200 mg dose.

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Modafinil affects the central nervous system. This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid other dangerous activities until you know how this medication will affect your level of wakefulness.

Avoid drinking alcohol while taking modafinil.

Modafinil may be found in some form under the following brand names:

• Provigil

Tell your doctor if you are pregnant or plan to become pregnant. It is not known if modafinil will harm your unborn baby. Modafinil has not been studied in pregnant women. Modafinil should be used during pregnancy only if clearly needed.

• Store modafinil at room temperature between 68° and 77° F (20° and 25° C).
• Keep modafinil and all medicines out of the reach of children.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Modafinil can cause skin reactions that may be severe enough to need treatment in a hospital. Stop taking this medicine and get emergency medical help if you have:

• skin rash or hives, blisters or peeling;

• mouth sores, trouble swallowing;

• fever, shortness of breath;

• swelling in your legs;

• dark urine, jaundice (yellowing of the skin or eyes); or

• swelling in your face, eyes, lips, tongue, or throat.

Stop using modafinil and call your doctor at once if you have:

• depression, anxiety, suicidal thoughts or actions;

• hallucinations, unusual thoughts or behavior, aggression, being more active or talkative than usual;

• chest pain, trouble breathing, uneven heart beats; or

• the first sign of any skin rash, no matter how minor you think it might be.

Common side effects may include:

• headache, dizziness;

• feeling nervous or anxious;

• back pain;

• nausea, diarrhea, upset stomach;

• sleep problems (insomnia); or

• stuffy nose.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Narcolepsy:

200 mg orally once a day in the morning

Comments:
-In obstructive sleep apnea (OSA), this drug is not a treatment for the underlying obstruction.
-If continuous positive airway pressure (CPAP) is the treatment of choice for excessive sleepiness, a maximal effort to treat with CPAP for an adequate period of time should be made prior to and during treatment with this drug.

Use: Treatment to improve wakefulness in patients with excessive sleepiness associated with narcolepsy and OSA.

Usual Adult Dose for Obstructive Sleep Apnea/Hypopnea Syndrome:

200 mg orally once a day in the morning

Comments:
-In obstructive sleep apnea (OSA), this drug is not a treatment for the underlying obstruction.
-If continuous positive airway pressure (CPAP) is the treatment of choice for excessive sleepiness, a maximal effort to treat with CPAP for an adequate period of time should be made prior to and during treatment with this drug.

Use: Treatment to improve wakefulness in patients with excessive sleepiness associated with narcolepsy and OSA.

Usual Adult Dose for Shift Work Sleep Disorder:

200 mg orally once a day, approximately 1 hour prior to the start of the work shift

Use: Treatment to improve wakefulness in patients with excessive sleepiness associated with shift work disorder.

Administration

Oral Administration

Administer orally once daily without regard to meals.16 19 34 55 (See Food under Pharmacokinetics.)

In patients with narcolepsy or OSAHS, usually administer as a single dose in the morning.1 In patients with SWSD, administer dose approximately 1 hour prior to start of work shift.1 44

In patients with narcolepsy, modafinil also has been administered in 2 divided doses daily, in the morning and at noon†.15 34

Dosage

Adults

200 mg once daily.1 16 34

Dosages up to 400 mg daily have been well tolerated, but may not provide additional clinical benefit beyond 200-mg daily dosage.1 15 16 37

Long-term efficacy (>9 weeks) not systematically established.1 If clinician elects to prescribe for an extended period, periodically reassess long-term usefulness in the individual patient.1

200 mg once daily.1

Dosages up to 400 mg daily have been well tolerated, but may not provide additional clinical benefit beyond 200-mg daily dosage.1

Long-term efficacy (>12 weeks) not systematically established.1 If clinician elects to prescribe for an extended period, periodically reassess long-term usefulness in the individual patient.1

200 mg once daily.1

Dosages up to 400 mg daily have been well tolerated, but may not provide additional clinical benefit beyond 200-mg daily dosage.1

Long-term efficacy (>12 weeks) not systematically established.1 If clinician elects to prescribe for an extended period, periodically reassess long-term usefulness in the individual patient.1

Special Populations

Hepatic Impairment

Reduce dosage to 100 mg daily in patients with severe hepatic impairment (with or without cirrhosis).1 (See Hepatic Impairment under Cautions.)

Renal Impairment

Current information inadequate to make specific dosage recommendations in patients with severe renal impairment.1 (See Renal Impairment under Cautions.)

Geriatric Patients

Consider use of lower than usual recommended dosage.1 (See Geriatric Use under Cautions.)

Contraindications

• Known hypersensitivity to modafinil, armodafinil, or any ingredient in the formulation.54 55

Warnings/Precautions

Warnings

Serious skin rash (e.g., Stevens-Johnson syndrome [SJS]) requiring hospitalization and drug discontinuance reported in adult and pediatric patients receiving modafinil.47 48 51 55

Severe rash (e.g., possible SJS, multiorgan hypersensitivity reaction), sometimes associated with fever and other abnormalities (e.g., vomiting, leukopenia), reported in pediatric clinical trials.55 No serious rashes reported in clinical trials in adults.55 Serious or life-threatening rash (e.g., SJS, toxic epidermal necrolysis [TEN], drug rash with eosinophilia and systemic symptoms [DRESS]) reported rarely during postmarketing experience.55 Modafinil is not approved for use in pediatric patients for any indication.47 48 55 (See Pediatric Use under Cautions.)

No known risk factors predict the occurrence or severity of rash.55 Nearly all cases occurred within 1–5 weeks following initiation of therapy, but cases also reported after prolonged (e.g., 3 months) treatment.55

Benign rashes also occur with modafinil; not possible to predict which rashes will become serious.55 Therefore, discontinue drug at first sign of rash unless clearly not drug related.55 (See Advice to Patients.) Rash may become potentially life-threatening or permanently disabling or disfiguring despite drug discontinuance.48 55

In patients with abnormal levels of sleepiness, level of wakefulness may improve with modafinil therapy, but may not return to normal.1 (See Advice to Patients.)

Frequently reassess degree of sleepiness, and, if appropriate, advise patients to avoid driving or other potentially dangerous activity.1 Patients may not acknowledge sleepiness or drowsiness until directly questioned about these symptoms during specific activities.1 (See Advice to Patients.)

Adverse psychiatric effects (e.g., mania, delusions, hallucinations, suicidal ideation, aggression), sometimes resulting in hospitalization, reported in modafinil-treated patients;55 58 59 many, but not all, patients had a psychiatric history.1 59

In controlled clinical trials, psychiatric symptoms that required treatment discontinuance in ≥0.3% of patients and more often for modafinil than for placebo included anxiety, nervousness, insomnia, confusion, agitation, and depression.55

Use with caution in patients with a history of psychosis, depression, or mania.55 59

Some clinicians recommend careful monitoring of patients receiving modafinil or other CNS stimulants for possible psychiatric effects.58 If psychiatric symptoms develop, consider drug discontinuance.55 (See Advice to Patients.)

Sensitivity Reactions

Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm) reported with armodafinil.55 Angioedema also reported during postmarketing experience with modafinil.55

Immediately discontinue therapy if any signs or symptoms of angioedema or anaphylaxis (e.g., swelling of face, eyes, lips, tongue, or larynx; difficulty swallowing or breathing; hoarseness) develop.55

Multiorgan hypersensitivity reactions, including at least 1 fatality, reported with modafinil.55

Reactions detected a median of 13 days (range: 4–33 days) after initiation of modafinil.55 Clinical presentation was variable but typically included fever and rash associated with other organ system involvement (e.g., myocarditis, hepatitis, liver function test abnormalities, hematologic abnormalities [e.g., eosinophilia, leukopenia, thrombocytopenia], pruritus, asthenia).55

No risk factors known to predict occurrence or severity.55

If a multi-organ hypersensitivity reaction is suspected, discontinue therapy.55 Cross-sensitivity with other drugs that produce this syndrome not yet reported but is possible.55

General Precautions

Use only in patients who have had a complete evaluation (e.g., complete history, physical examination, testing in a laboratory setting [polysomnography]) of excessive sleepiness and in whom a diagnosis of narcolepsy, OSAHS, and/or SWSD has been made in accordance with International Classification of Sleep Disorders (ICSD) or DSM diagnostic criteria.55

Consider that >1 sleep disorder may contribute to excessive sleepiness in some patients (e.g., OSAHS and SWSD concurrently in the same patient).55

Although modafinil has not been shown to cause functional impairment, altered judgment, thinking, or motor skills is possible with any drug affecting the CNS.55 (See Advice to Patients.)

In OSAHS, modafinil is indicated as an adjunct to standard treatment(s) for the underlying obstruction.55 If CPAP is the treatment of choice, make a maximal effort to treat with CPAP for an adequate period of time prior to initiating modafinil therapy.55 If modafinil is used adjunctively with CPAP, encourage and periodically assess CPAP compliance.55 (See Advice to Patients.)

Adverse cardiovascular effects (e.g., chest pain, palpitations, dyspnea, transient ischemic T-wave changes on ECG) reported in several modafinil-treated patients in association with mitral valve prolapse or left ventricular hypertrophy.55

Not recommended in patients with history of left ventricular hypertrophy or in patients with mitral valve prolapse who have experienced mitral valve prolapse syndrome (e.g., ischemic ECG changes, chest pain, arrhythmia) with previous CNS stimulant use.55 If new onset of any of these symptoms of mitral valve prolapse syndrome occurs during modafinil therapy, consider cardiac evaluation.55

Use with caution in patients with recent history of MI or unstable angina.55

A greater proportion of modafinil-treated patients required new or increased use of antihypertensive medication compared with those receiving placebo in a retrospective analysis (2.4 and 0.7%, respectively).55 Increased monitoring of BP may be appropriate during therapy.55

Modafinil is subject to control as a schedule IV (C-IV) drug.1 34 35

Produces psychoactive and euphoric effects, and alterations in mood, perception, thinking, and feelings similar to those observed with other CNS stimulants (e.g., amphetamines, methylphenidate), but current evidence indicates risk of abuse or misuse is lower with modafinil than with schedule II CNS stimulants (e.g., amphetamine, methylphenidate).1 34 35 (See Actions.)

Monitor patients closely during treatment for possible signs of misuse or abuse (e.g., incrementation of doses, drug-seeking behavior), particularly in those with history of drug or stimulant abuse (e.g., amphetamine, cocaine, methylphenidate).1

Possible reduced efficacy of hormonal contraceptives during and for 1 month after discontinuance of therapy.1 Alternative or concomitant nonhormonal contraceptive methods recommended during these periods.1 (See Specific Drugs under Interactions and see Advice to Patients.)

Possible reduced blood cyclosporine concentrations when given concurrently with modafinil.55 (See Specific Drugs under Interactions.)

Specific Populations

Category C.1

Provigil Pregnancy Registry (for clinicians or patients) at 866-404-4106, or .55

Not known whether modafinil or its metabolites are distributed into milk.1 Caution if used in nursing women.1

Modafinil is not approved for use in pediatric patients for any indication, including attention deficit hyperactivity disorder (ADHD).47 48 55 Safety and efficacy not established in children <17 years of age.55

Serious skin rashes (e.g., erythema multiforme, Stevens-Johnson syndrome) associated with use of modafinil in pediatric patients.55 (See Serious Dermatologic Reactions under Cautions.)

Limited experience indicates that the incidence of adverse effects in patients >65 years of age is similar to that in younger patients.55

Elimination of modafinil and its metabolites may be reduced; consider reduced dosage.55 (See Geriatric Patients under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Reduce dosage in patients with severe hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Use with caution in patients with severe renal impairment.1 (See Renal Impairment under Dosageand Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Headache, 1 15 16 17 23 24 25 27 nausea,1 15 16 17 nervousness,1 15 16 rhinitis,1 diarrhea,1 back pain,1 anxiety,1 insomnia,1 25 dizziness,1 dyspepsia.1

• Modafinil, a nonamphetamine wakefulness-promoting agent, is a 50:50 racemic mixture of the R- and S-enantiomers; exhibits pharmacologic properties similar to those of armodafinil.54 55

• Promotes vigilance and wakefulness.1 2 3 4 6 8 10 26 27 28 30 32 34 37 38 39 40 41 42 44 Exact mechanism of action unknown,1 but may alter metabolic activity and increase neuronal activity in areas of the brain that control sleep/wakefulness and the biologic clock.1 9 10 11 16

• Inhibits release of GABA2 4 5 6 14 and increases release of glutamate from the cerebral cortex,12 hippocampus,10 12 nucleus accumbens,6 12 medial preoptic area,5 6 12 and posterior hypothalamus in animals.5 12

• Does not appear to act as a direct- or indirect-acting dopamine-receptor or α1-adrenergic agonist1 2 10 13 16 or as a sympathomimetic agent; 1 may stimulate central α1-adrenergic activity8 15 32 33 but has no important peripheral adrenergic activity.1 2 8 32 Blocked dopamine transporters and increased dopamine concentrations in the human brain (including the nucleus accumbens); drugs with such activity generally have abuse potential.57

• At usual pharmacologic concentrations, does not bind to certain receptors that regulate sleep and wakefulness (e.g., norepinephrine, serotonin, dopamine, GABA, adenosine, histamine H3, melatonin, benzodiazepine).1

• Does not inhibit MAO-B or phosphodiesterases 2-5; does not alter plasma melatonin or cortisol hormone profiles.7 55

• Reinforcing properties in animals; produces psychoactive, euphoric, and subjective effects typical of classic CNS stimulants (e.g., amphetamines, methylphenidate) in humans.35 55

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For modafinil, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to modafinil or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of modafinil in children younger than 17 years of age. Safety and efficacy have not been established.

Geriatric

Although appropriate studies on the relationship of age to the effects of modafinil have not been performed in the geriatric population, geriatric-specific problems are not expected to limit the usefulness of modafinil in the elderly. However, elderly patients may have a slower removal of modafinil from the body, which may require an adjustment in the dose for patients receiving modafinil.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking modafinil, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using modafinil with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Axitinib
• Bosutinib
• Citalopram
• Clarithromycin
• Cobimetinib
• Daclatasvir
• Darunavir
• Deflazacort
• Desogestrel
• Dienogest
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Drospirenone
• Elbasvir
• Enzalutamide
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Gestodene
• Grazoprevir
• Ifosfamide
• Levonorgestrel
• Mestranol
• Nifedipine
• Norethindrone
• Norgestimate
• Norgestrel
• Olaparib
• Piperaquine
• Simeprevir
• Sonidegib
• Tacrolimus
• Tolvaptan
• Velpatasvir
• Venetoclax

Using modafinil with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Clomipramine
• Cyclosporine
• Ospemifene
• Triazolam

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of modafinil. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, history of or
• Drug abuse or dependence, history of—Dependence may be more likely to develop.

• Angina (severe chest pain), unstable or
• Heart attack, recent or
• Heart disease—Use with caution. It is not known how modafinil will affect these conditions.

• Depression, history of or
• Hypertension (high blood pressure) or
• Mania, history of or
• Psychosis (mental illness), history of—Use with caution. May make these conditions worse.

• Left ventricular hypertrophy (heart disease), history of or
• Mitral valve prolapse (heart disease) after receiving CNS stimulants—Use is not recommended in patients with these conditions.

• Liver disease, severe—Use with caution. You may require a dose adjustment. Talk with your doctor if you have concerns about this.

Your doctor should check your progress at regular visits to make sure that modafinil is working properly. Your blood pressure may need to be checked more often while taking modafinil.

It is important to tell your doctor if you become pregnant. Your doctor may want you to join a pregnancy registry for patients taking modafinil.

Serious skin reactions can occur with modafinil. Stop using modafinil and check with your doctor right away if you have blistering, peeling, or loosening of the skin; red skin lesions; severe acne or skin rash; sores or ulcers on the skin; or fever or chills while you are using modafinil.

modafinil may cause you to have a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Stop taking modafinil and call your doctor right away if you have a skin rash; itching; hives; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth while you are using modafinil.

modafinil may cause serious allergic reactions affecting multiple body organs (e.g., heart, liver, or blood cells). Stop using modafinil and check with your doctor right away if you have the following symptoms: chest pain or discomfort, fever and chills, dark urine, headache, rash, stomach pain, unusual tiredness, unusual bleeding or bruising, or yellow eyes or skin.

If you think modafinil is not working properly after you have taken it for a few weeks, do not increase the dose. Instead, check with your doctor.

If you are using a medicine for birth control (such as birth control pills, implants, shots, patches, vaginal rings, or an IUD), it may not work properly while you are taking modafinil. To keep from getting pregnant, use another form of birth control while you are using modafinil and for one month after your last dose. Other forms of birth control include condoms, diaphragms, or contraceptive foams or jellies.

Modafinil may cause some people to feel dizzy, drowsy, have trouble thinking or controlling movements, or trouble seeing clearly. Make sure you know how you react to modafinil before you drive, use machines, or do other jobs that require you to be alert, well-coordinated, or able to think or see well.

Stop using modafinil and check with your doctor right away if you have the following symptoms while taking the medicine: aggressive behavior, anxiety, depression, hallucinations, mania, thoughts of suicide, or other mental problems.

If you have been taking modafinil for a long time or in large doses and you think you may have become mentally or physically dependent on it, check with your doctor. Some signs of dependence on modafinil are:

• a strong desire or need to continue taking the medicine.
• a need to increase the dose to receive the effects of the medicine.
• withdrawal side effects when you stop taking the medicine.

While you are taking modafinil, be careful to limit the amount of alcohol that you drink.

If you have been taking modafinil in large doses or for a long time, do not stop taking it without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely.

Do 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.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Modafinil tablets 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, Modafinil tablets 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 Modafinil tablets for excessive sleepiness. 

Carcinogenesis, Mutagenesis,Impairment of Fertility

Carcinogenesis  

Carcinogenicity studies were conducted in which Modafinil (a mixture of R-and S-Modafinil) was administered in the diet to mice for 78 weeks and to rats for 104 weeks at doses of 6, 30, and 60 mg/kg/day. The highest doses studied were associated with plasma Modafinil exposures (AUC) less than that in humans at the recommended human dose (RHD) of Modafinil (200 mg/day). There was no evidence of tumorigenesis associated with Modafinil administration in these studies. However, the mouse study was inadequate because the high dose was not a maximum tolerated dose (MTD). In a mouse carcinogenicity study in which arModafinil (the R-enantiomer of Modafinil) was administered at oral doses of up to 300 mg/kg/day in males and 100 mg/kg/day in females for approximately 2 years, no tumorigenic effects were observed. The highest doses studied, which were considered MTDs, were associated with plasma arModafinil exposures less than (females) or 2 times (males) that in humans at the RHD of Modafinil.

Mutagenesis  

Modafinil was negative in a series of in vitro (i.e., bacterial reverse mutation, mouse lymphoma tk, chromosomal aberration in human lymphocytes, cell transformation in BALB/3T3 mouse embryo cells) or in vivo (mouse bone marrow micronucleus) assays.

Impairment of Fertility  

Oral administration of Modafinil (doses of up to 480 mg/kg/day) to male and female rats prior to and throughout mating, and continuing in females through day 7 of gestation produced an increase in the time to mate at the highest dose; no effects were observed on other fertility or reproductive parameters. The no-effect dose of 240 mg/kg/day was associated with a plasma Modafinil AUC less than that in humans at the RHD of Modafinil. 

Product Name: Modafinil Tablets USP 100 mg
Each tablet contains Modafinil USP 100 mg
62332-385-30

In patients with cirrhosis of the liver, clearance is decreased ~60% and steady-state concentrations are doubled.

Concerns related to adverse effects:

• CNS effects: May impair the ability to engage in potentially hazardous activities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Dermatologic effects (severe): Serious and life-threatening rashes, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS) have been reported. Although initially reported in children during clinical trials, postmarketing cases have occurred in both children and adults. Most cases have occurred within the first 5 weeks of therapy; however, rare cases have occurred after long-term use (eg, 3 months). No risk factors have been identified to predict occurrence or severity. Patients should be advised to discontinue at first sign of rash (unless the rash is clearly not drug-related). As a result of these serious dermatologic adverse events, approval for the use of modafinil in children for ADHD was denied by the FDA.

• Hypersensitivity reactions: Rare cases of multiorgan hypersensitivity reactions (with fatality) in association with modafinil use; lone cases of angioedema and anaphylactoid reactions with armodafinil have been reported (angioedema has been noted in postmarketing reports with modafinil). Signs and symptoms are diverse, reflecting the involvement of specific organs; patients typically present with fever and rash associated with organ-system dysfunction. No risk factors have been identified to predict occurrence or severity of multiorgan hypersensitivity reactions. Patients should be advised to report any signs and symptoms related to these effects; discontinuation of therapy is recommended.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease; increased blood pressure and heart rate monitoring may be required. Use is not recommended in patients with a history of left ventricular hypertrophy or patients with mitral valve prolapse who have developed mitral valve prolapse syndrome with previous CNS stimulant use. Increased monitoring should be considered in patients with a recent history of myocardial infarction or unstable angina.

• Hepatic impairment: Use with caution in patients with hepatic impairment. Dosage reduction is recommended in patients with severe hepatic impairment.

• Psychiatric disorders: Use with caution in patients with a history of psychosis, depression, or mania. Use may result in emergence of or exacerbation of psychiatric symptoms. Observe for symptoms of aggression, hallucinations, mania, delusions, or suicidal ideation. Consider discontinuing therapy if psychiatric symptoms develop.

• Renal impairment: Use with caution in patients with renal impairment.

• Sleep disorders: Appropriate use: The degree of sleepiness should be reassessed frequently; some patients may not return to a normal level of wakefulness. In obstructive sleep apnea, modafinil is indicated as treatment for excessive sleepiness and not 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 modafinil for excessive sleepiness.

• Tourette syndrome: Use with caution in patients with Tourette syndrome; limited evidence suggests stimulants may exacerbate tics and Tourette syndrome (AACAP [Murphy 2013]; Pringsheim 2012; Rossner 2011).

Special populations:

• Pediatric: Modafinil is not FDA-approved for use in pediatrics for any indication. Serious skin reactions and psychiatric events have been observed in pediatric patients treated with modafinil. The serious nature of these adverse effects resulted in the FDA’s Pediatric Advisory Committee unanimously recommending that a specific warning against the use of modafinil in children be added to the manufacturer’s labeling.

Other warnings/precautions:

• Ethanol use: Instruct patients to avoid concomitant ethanol consumption.

Commonly reported side effects of modafinil include: headache and nausea. Other side effects include: anorexia and xerostomia. See below for a comprehensive list of adverse effects.