What is modafinil

Modafinil is a medication that promotes wakefulness (a class of medications called wakefulness promoting agent). Modafinil works by changing the amounts of certain natural substances in the area of the brain that controls sleep and wakefulness. But the exact way modafinil promotes “wakefulness” is not fully understood. Modafinil is used to treat excessive sleepiness caused by narcolepsy (a condition that causes excessive daytime sleepiness), or shift work sleep disorder to stay awake during the day (sleepiness during scheduled waking hours and difficulty falling asleep or staying asleep during scheduled sleeping hours in people who work at night or on rotating shifts). Modafinil is also used along with breathing devices or other treatments to prevent excessive sleepiness caused by obstructive sleep apnea/hypopnea syndrome (OSAHS; a sleep disorder in which the patient briefly stops breathing or breathes shallowly many times during sleep and therefore doesn’t get enough restful sleep). Modafinil does not cure these conditions and will only work as long as you continue to take it. Modafinil may also be used for purposes not listed in this medication guide; ask your doctor or pharmacist for more information.

Modafinil is available only with your doctor’s prescription.

You must NOT take Modafinil if you:

• are allergic to modafinil or any of the other ingredients listed at the end of this leaflet. Signs of allergic reaction may include a skin rash, itching, shortness of breath or swelling of the face, lips or tongue
• are pregnant, or likely to become pregnant.

Do not take Modafinil if the packaging is torn or shows signs of tampering or the tablets do not look quite right.

Do not take Modafinil if the expiry date on the pack has passed.

If you are not sure about whether you should start taking Modafinil, you should contact your doctor.

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

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

Serious skin reactions can occur with this medicine. Stop using this medicine 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 this medicine.

This medicine 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 this medicine 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 this medicine.

This medicine may cause serious allergic reactions affecting multiple body organs (e.g., heart, liver, or blood cells). Stop using this medicine 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 this medicine 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 this medicine 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 this medicine 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 this medicine 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 ¹:

• 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 this medicine, be careful to limit the amount of alcohol that you drink.

If you have been taking this medicine 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.

How should modafinil be used?

Modafinil comes as a tablet to take by mouth. It is usually taken once a day with or without food. If you are taking modafinil to treat narcolepsy or obstructive sleep apnea/hypopnea syndrome, you will probably take it in the morning. If you are taking modafinil to treat shift work sleep disorder, you will probably take it 1 hour before the beginning of your work shift. Take modafinil at the same time every day. Do not change the time of day that you take modafinil without talking to your doctor. Talk to your doctor if your work shift does not begin at the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take modafinil exactly as directed.

Modafinil may be habit-forming. Do not take a larger dose, take it more often, or take it for a longer period of time than prescribed by your doctor.

Modafinil may decrease your sleepiness, but it will not cure your sleep disorder. Continue to take modafinil even if you feel well-rested. Do not stop taking modafinil without talking to your doctor.

Modafinil should not be used in place of getting enough sleep. Follow your doctor’s advice about good sleep habits. Continue to use any breathing devices or other treatments that your doctor has prescribed to treat your condition, especially if you have obstructive sleep apnea/hypopnea syndrome.

Before taking modafinil – precautions

• tell your doctor and pharmacist if you are allergic to modafinil, armodafinil (Nuvigil), or any other medications.
• tell your doctor you have heart problems, including, for example, angina (chest pain), previous heart attack, enlarged heart
• tell your doctor you have an abnormal/irregular heart rhythm
• tell your doctor you have high blood pressure or your high blood pressure is controlled by medication
• tell your doctor you have kidney or liver problems
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin); certain antidepressants such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); certain antifungals such as itraconazole (Sporanox) and ketoconazole (Nizoral); cyclosporine (Neoral, Sandimmune); diazepam (Valium); certain medications for seizures such as carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin); monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate); propranolol (Inderal); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); rifampin (Rifadin, Rimactane); and triazolam (Halcion). Many other medications may also interact with modafinil, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you drink or have ever drunk large amounts of alcohol, use or have ever used street drugs, or have overused prescription medications, especially stimulants. Also tell your doctor if you have ever had chest pain, an irregular heartbeat, or other heart problems after taking a stimulant, and if you have or have ever had high blood pressure; a heart attack; chest pain; a mental illness such as depression, mania (frenzied, abnormally excited mood), or psychosis (difficulty thinking clearly, communicating, understanding reality, and behaving appropriately); or heart, liver, or kidney disease.
• you should know that modafinil may decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, implants, injections, and intrauterine devices). Use another form of birth control while taking modafinil and for 1 month after you stop taking it. Talk to your doctor about types of birth control that will work for you during and after your treatment with modafinil.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking modafinil, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking modafinil.
• you should know that modafinil may affect your judgment or thinking and may not completely relieve the sleepiness caused by your disorder. Do not drive a car or operate machinery until you know how this medication affects you. If you avoided driving and other dangerous activities because of your sleep disorder, do not start performing these activities again without talking to your doctor even if you feel more alert.
• be aware that you should avoid drinking alcohol while taking modafinil.

Talk to your doctor about eating grapefruit or drinking grapefruit juice while you are taking this medication.

Things you must do

• If you become pregnant while you are taking Modafinil, stop taking it and tell your doctor immediately.
• If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking Modafinil.
• Tell your doctor if you believe that Modafinil is not helping your condition. Your doctor may need to change the dose.

Things you must NOT do

• Do not give Modafinil to anyone else, even if they have the same symptoms as you.

Things to be careful of

Modafinil may reduce the effectiveness of oral contraceptives. If you are using these forms of contraceptives while taking Modafinil (and for 1 month after you stop treatment with Modafinil) you should either use: an alternative birth control method or another effective birth control method together with your current contraceptive.

Do not drive or operate machinery until you know how Modafinil affects you.

Serious Rash, including Stevens Johnson syndrome

Serious rash requiring hospitalization and discontinuation of treatment has been reported in association with the use of Modafinil.

In clinical trials of Modafinil, the incidence of rash resulting in discontinuation was approximately 0.8% (13 per 1,585) in pediatric patients (age < 17-years); these rashes included 1 case of possible Stevens Johnson syndrome and 1 case of apparent multi-organ hypersensitivity reaction. Several of the cases were associated with fever and other abnormalities (e.g., vomiting, leukopenia). The median time to rash that resulted in discontinuation was 13-days. No such cases were observed among 380 pediatric patients who received placebo. Modafinil is not approved for use in pediatric patients for any indication.

Rare cases of serious or life-threatening rash, including Stevens Johnson syndrome, Toxic Epidermal Necrolysis and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported in adults and children in worldwide postmarketing experience. The reporting rate of Toxic Epidermal Necrolysis and Stevens Johnson syndrome 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-week to 5-weeks after treatment initiation. However, isolated cases have been reported after prolonged treatment (e.g., 3-months). 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 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.

Angioedema and Anaphylaxis Reactions

Angioedema and hypersensitivity (with rash, dysphagia, and bronchospasm), were observed in patients treated with armodafinil, the 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.g., swelling of face, eyes, lips, tongue or larynx; difficulty in swallowing or breathing; hoarseness).

Multi-organ Hypersensitivity Reactions

Multi-organ hypersensitivity reactions, including at least one fatality in postmarketing experience, have occurred in close temporal association (median time to detection 13-days: range 4 to 33) to the initiation of Modafinil.

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. 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 myocarditis, hepatitis, liver function test abnormalities, hematological abnormalities (e.g., eosinophilia, leukopenia, thrombocytopenia), pruritus, and asthenia. Because multi-organ hypersensitivity is variable in its expression, other organ system symptoms and signs, not noted here, may occur.

If a multi-organ hypersensitivity reaction is suspected, Modafinil should be discontinued. 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.

Persistent Sleepiness

Patients with abnormal levels of sleepiness who take Modafinil should be advised that their level of wakefulness may not return to normal. Patients with excessive sleepiness, including those taking Modafinil, should 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 Symptoms

Psychiatric adverse reactions have been reported in patients treated with Modafinil.

In the adult Modafinil controlled trials, psychiatric symptoms resulting in treatment discontinuation (at a frequency ≥ 0.3%) and reported more often in patients treated with Modafinil compared to those treated with placebo were anxiety (1%), nervousness (1%), insomnia (< 1%), confusion (< 1%), agitation (< 1%), and depression (< 1%).

Postmarketing adverse reactions 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 600 mg doses of Modafinil (three times the recommended dose) and sleep deprivation. There was no evidence of psychosis 36-hours after drug discontinuation.

Caution should be exercised when Modafinil is given to patients with a history of psychosis, depression, or mania. Consideration should be given to the possible emergence or exacerbation of psychiatric symptoms in patients treated with Modafinil. If psychiatric symptoms develop in association with Modafinil administration, consider discontinuing Modafinil.

Effects on Ability to Drive and Use Machinery

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 automobile or other hazardous machinery until it is reasonably certain that Modafinil therapy will not adversely affect their ability to engage in such activities.

Cardiovascular Events

In Modafinil clinical studies, cardiovascular adverse reactions, including chest pain, palpitations, dyspnea, and transient ischemic T-wave changes on ECG occurred in three subjects in association with mitral valve prolapse or left ventricular hypertrophy. 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). Modafinil is not recommended 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. Findings suggestive of mitral valve prolapse syndrome include but are not limited to ischemic ECG changes, chest pain, or arrhythmia. If new onset of any of these findings occurs, consider cardiac evaluation. Consider increased monitoring in patients with a recent history of myocardial infarction or unstable angina.

Blood pressure monitoring in short term (≤ 3-months) controlled trials showed no clinically significant changes in mean systolic and diastolic blood pressure in patients receiving Modafinil as compared to placebo. However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on Modafinil required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). The differential use was slightly larger when only studies in OSA were included, with 3.4% of patients on Modafinil and 1.1% of patients on placebo requiring such alterations in the use of antihypertensive medication. Increased monitoring of heart rate and blood pressure may be appropriate in patients on Modafinil. Caution should be exercised when prescribing Modafinil to patients with known cardiovascular disease.

Pregnancy

Pregnancy Category C (all trimesters): Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breastfeeding

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.

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 this medicine from the body, which may require an adjustment in the dose for patients receiving modafinil.

‘Smart drug’ modafinil may not make you smarter

It is claimed one in five students have taken the ‘smart’ drug Modafinil to boost their ability to study and improve their chances of exam success. But a new randomized controlled trial ² into the effects of Modafinil has shown that healthy students could find their performance impaired by the drug. Researchers gave 64 healthy volunteers either modafinil 200mg or a placebo and asked them to complete a spoken language test. Contrary to the media headline, the people who took modafinil had slowed responses, and were no more accurate than the placebo. The randomized controlled trial that aimed to determine the effects of modafinil (a licensed treatment for narcolepsy) on the performance of healthy people in the Hayling Sentence Completion Test. The Hayling test involves listening to sentences with a missing word and providing either the missing word or a word unrelated to the sentence. The Hayling test consisted of 30 sentences, each missing the last word, which were constructed to strongly constrain what the missing word should be. In the first section, people were asked to listen to sentences, and were asked to provide, as quickly as possible, a word that correctly and sensibly completed the sentence. Participants were then asked to complete sentences, as quickly as possible, with words unrelated to the meaning of the sentences in every way. Both responses and reaction times were recorded, and the performance of people who were randomized to modafinil compared to those randomized to placebo. The researchers performed this experiment because it has been suggested that modafinil might improve task performance, while slowing it – a phenomenon that has been referred to as “delay-dependent cognitive enhancement”. Modafinil is reportedly used off-label (outside of its licensed indication) by some healthy people, notably students, as a “smart drug” to try to enhance cognitive performance. One student website’s survey estimates that 20% of students may have taken modafinil, with almost half buying it online and many taking it daily.

The results of that research ² showed people who took modafinil took significantly longer to provide a word. There was no difference in the number of errors made on the test between people who received modafinil and people received placebo, showing that modafinil did not improve accuracy. This study has cast doubt upon these supposed effects. In this randomized controlled trial ², modafinil slowed responses while having no effect on the accuracy of performance on the Hayling Sentence Completion Test. This study has only assessed the one-off use of this drug in a relatively small sample of people. The study has not looked at safety outcomes, and scientists don’t know what adverse effects there might be for healthy individuals regularly taking this drug solely for the purpose of trying to enhance cognitive performance.

Modafinil Drug Interactions

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
• Clozapine
• Cobimetinib
• Daclatasvir
• Darunavir
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Elbasvir
• Enzalutamide
• Fentanyl
• Grazoprevir
• Hydrocodone
• Ifosfamide
• Nifedipine
• Olaparib
• Piperaquine
• Simeprevir
• Sofosbuvir
• 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
• Desogestrel
• Dienogest
• Drospirenone
• Estradiol Cypionate
• Estradiol Valerate
• Ethinyl Estradiol
• Ethynodiol Diacetate
• Etonogestrel
• Levonorgestrel
• Mestranol
• Norelgestromin
• Norethindrone
• Norgestimate
• Norgestrel
• Ospemifene
• Triazolam

Other Interactions

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 this medicine. 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.

What is modafinil used for

Modafinil is used to improve wakefulness in people with excessive daytime sleepiness associated with the medical condition known as narcolepsy or with obstructive sleep apnea/hypopnea syndrome (OSAHS), or shift work sleep disorder (SWSD).

In narcolepsy, there is a sudden and irresistible tendency to fall asleep during normal waking hours. This happens at unpredictable times, even when it is inappropriate or may be unsafe to do so. Modafinil decreases this unwanted excessive daytime sleepiness.

With obstructive sleep apnea/hypopnea syndrome, daytime sleepiness may occur due to an interrupted night time sleep. Modafinil only treats the symptom of sleepiness and does not treat the cause of obstructive sleep apnea/hypopnea syndrome. Whilst taking Modafinil you should continue with treatments intended to help manage your underlying medical condition, such as Continuous Positive Airway Pressure, unless your doctor tells you otherwise.

If you have been diagnosed with moderate to severe chronic Shift Work Sleep Disorder (SWSD) and non-drug therapies have been unsuitable or unsuccessful, Modafinil may be prescribed to keep you awake during your work shift.

Precisely how Modafinil works is not known, but it is known that it acts on the central nervous system (the brain). It differs from other stimulant medicines that promote wakefulness. Modafinil increases wakefulness.

Your doctor may have prescribed Modafinil for another reason. Ask your doctor if you have any questions about why Modafinil has been prescribed for you.

Modafinil dosage

The dose of modafinil will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of modafinil. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of modafinil that you take depends on the strength of the modafinil. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take modafinil depend on the medical problem for which you are using the modafinil.

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.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

• Mild to moderate hepatic impairment: There are no dosage adjustments provided in the manufacturer product information.
• Severe hepatic impairment: Dose should be reduced by half.

Dialysis

Data not available

When and how should you take modafinil

Take modafinil only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming.

Modafinil comes with a Medication Guide. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Modafinil does not take the place of getting enough sleep. It should not be used for occasional sleepiness that has not been diagnosed as narcolepsy, sleep apnea, or shift work sleep problems. Ask your doctor for advice about good sleep habits.

If you have sleep apnea and use a continuous positive airway pressure (CPAP) machine at night, continue using this machine with modafinil.

Take modafinil at the same time each day. Do not change the time of day you take modafinil without talking first with your doctor.

You may take modafinil with or without food.

For oral dosage form (tablets):

• For narcolepsy or obstructive sleep apnea/hypopnea syndrome:
  • Adults and teenagers 17 years of age and older—200 milligrams (mg) once a day, in the morning or split the dose in half taking one (100 mg) in the morning and one (100 mg) at midday. For narcolepsy or obstructive sleep apnea/hypopnea syndrome, do not take your Modafinil tablets later than midday, or you may have trouble sleeping at night. Your doctor may increase your dose as needed.
  • Teenagers and children younger than 17 years of age—Use and dose must be determined by your doctor.
• For shift work sleep disorder:
  • Adults and teenagers 17 years of age and older—200 milligrams (mg) one hour before you begin working. For shift work sleep disorder, you should take your Modafinil tablets as a single dose 1 hour prior to commencing your shift work.
  • Teenagers and children younger than 17 years of age—Use and dose must be determined by your doctor.

Swallow the tablets whole with a little water.

NOTE: Your doctor may start your treatment with less than two tablets a day.

If you need more than two tablets per day, your doctor should increase the dose stepwise, one additional tablet at a time, depending on how you respond to the treatment. The highest dose is four tablets per day.

If you are currently on another treatment for narcolepsy, your doctor will advise you how best to withdraw from that treatment and begin taking Modafinil. Other stimulants used for narcolepsy may cause a “high” feeling. Be aware therefore that you may feel different as you withdraw from other stimulants.

Modafinil only treats the symptom of sleepiness. Other treatments intended to help manage your underlying medical condition should still be used regularly, unless your doctor tells you otherwise. You should commence or continue disease-modifying interventions (for example, Continuous Positive Airway Pressure).

What should I do if I forget a dose?

You should skip the missed dose. Wait until the next time you are supposed to take modafinil, and then take your normal dose. If you take modafinil too late in your waking day, you may find it harder to go to sleep. Do not take a double dose to make up for a missed one.

If you miss a dose of modafinil and you remember it before 12:00 noon the same day, take the missed dose as soon as possible.

How long does modafinil last?

Modafinil is a 1:1 racemic compound, whose enantiomers have different pharmacokinetics (e.g., the half-life of R-Modafinil is approximately three times that of S-Modafinil in adult humans). The enantiomers do not interconvert. At steady state, total exposure to R-Modafinil is approximately three times that for S-Modafinil. The trough concentration (Cmin,ss) of circulating Modafinil after once daily dosing consists of 90% of R-Modafinil and 10% of S-Modafinil. The effective elimination half-life of Modafinil after multiple doses is about 15-hours. The enantiomers of Modafinil exhibit linear kinetics upon multiple dosing of 200 mg/day to 600 mg/day once daily in healthy volunteers. Apparent steady states of total Modafinil and R-Modafinil are reached after 2-days to 4-days of dosing.

Absorption

Modafinil is readily absorbed after oral administration, with peak plasma concentrations occurring at 2-hours to 4-hours. The bioavailability of Modafinil tablets is approximately equal to that of an aqueous suspension. The absolute oral bioavailability was not determined due to the aqueous insolubility (< 1 mg/mL) of Modafinil, which precluded intravenous administration. Food has no effect on overall Modafinil bioavailability; however, time to reach peak concentration (tmax) may be delayed by approximately one hour if taken with food.

Distribution

Modafinil has an apparent volume of distribution of approximately 0.9 L/kg. In human plasma, in vitro, Modafinil is moderately bound to plasma protein (approximately 60%), mainly to albumin. The potential for interactions of Modafinil with highly protein-bound drugs is considered to be minimal.

Metabolism and Elimination

The major route of elimination is metabolism (approximately 90%), primarily by the liver, with subsequent renal elimination of the metabolites. Urine alkalinization has no effect on the elimination of Modafinil.

Metabolism occurs through hydrolytic deamidation, S-oxidation, aromatic ring hydroxylation, and glucuronide conjugation. Less than 10% of an administered dose is excreted as the parent compound. In a clinical study using radiolabeled Modafinil, a total of 81% of the administered radioactivity was recovered in 11-days post-dose, predominantly in the urine (80% vs. 1% in the feces). 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 plasma, i.e., Modafinil acid and Modafinil sulfone. 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.

In adults, decreases in trough levels of Modafinil have sometimes been observed after multiple weeks of dosing, suggesting auto-induction, but the magnitude of the decreases and the inconsistency of their occurrence suggest that their clinical significance is minimal. Significant accumulation of Modafinil sulfone has been observed after multiple doses due to its long elimination half-life of 40-hours. Auto-induction of metabolizing enzymes, most importantly cytochrome P-450 CYP3A4, has also been observed in vitro after incubation of primary cultures of human hepatocytes with Modafinil and in vivo after extended administration of Modafinil at 400 mg/day.

Specific Populations

Age

A slight decrease (approximately 20%) in the oral clearance (CL/F) of Modafinil was observed in a single dose study at 200 mg in 12 subjects with a mean age of 63-years (range 53-years to 72-years), but the change was considered not likely to be clinically significant. In a multiple dose study (300 mg/day) in 12 patients with a mean age of 82-years (range 67-years to 87-years), the mean levels of Modafinil in plasma were approximately two times those historically obtained in matched younger subjects. Due to potential effects from the multiple concomitant medications with which most of the patients were being treated, the apparent difference in Modafinil pharmacokinetics may not be attributable solely to the effects of aging. However, the results suggest that the clearance of Modafinil may be reduced in the elderly.

Modafinil side effects

Modafinil may cause you to have a serious rash.

Stop Modafinil and call your doctor right away or get emergency treatment if you have a skin rash, hives, sores in your mouth, or your skin blisters and peels, or if you have any sudden wheeziness, difficulty in breathing, swelling, rash or itching (especially affecting the whole body).

Modafinil may cause the following side effects in some people. In clinical studies, these side effects also occurred in people who received non-active (sugar) tablets.

Modafinil may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• headache
• dizziness
• difficulty falling asleep or staying asleep
• drowsiness
• nausea
• diarrhea
• constipation
• gas
• heartburn
• loss of appetite
• unusual tastes
• dry mouth
• excessive thirst
• nosebleed
• flushing
• sweating
• tight muscles or difficulty moving
• back pain
• confusion
• uncontrollable shaking of a part of your body
• burning, tingling, or numbness of the skin
• difficulty seeing or eye pain

Some side effects can be serious. If you experience any of these symptoms, stop taking modafinil and call your doctor immediately:

• rash
• blisters
• peeling skin
• mouth sores
• hives
• itching
• hoarseness
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• chest pain
• fast, pounding, or irregular heartbeat
• frenzied, abnormally excited mood
• hallucinating (seeing things or hearing voices that do not exist)
• anxiety
• depression
• thinking about killing or harming yourself

Modafinil may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything that makes you feel unwell. Do not be alarmed by this list of possible side effects. You may not experience any of them.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/Safety/MedWatch/default.htm)

Modafinil overdose

In case of modafinil overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call your local emergency services number.

Symptoms of modafinil overdose may include:

• difficulty falling asleep or staying asleep
• agitation
• restlessness
• confusion
• hallucinations (seeing things or hearing voices that do not exist)
• nervousness
• uncontrollable shaking of a part of the body
• fast, slow, or pounding heartbeat
• chest pain
• nausea
• diarrhea

1. Dependence on supratherapeutic doses of modafinil: a case report. The Primary Care Companion for CNS Disorders. 2012;14(5):PCC.11l01333. doi:10.4088/PCC.11l01333 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583757/[↩]
2. Modafinil Increases the Latency of Response in the Hayling Sentence Completion Test in Healthy Volunteers: A Randomised Controlled Trial. PLOS One Published: November 12, 2014 https://doi.org/10.1371/journal.pone.0110639[↩][↩][↩]