An Overview on Modafinil | Usage, Side Effects, Dosage


Introduction

Modafinil is a pharmaceutical created for treatment in sleep-related disorders, and is associated to enhanced mental function in a sleep deprived state.

Modafinil is a stimulant medicine sold as a 'wakefulness stimulating agent' and is one of the stimulants used in the therapy of narcolepsy. Narcolepsy is instigated by dysfunction of a family of wakefulness-promoting and sleep-suppressing peptides, the orexins, whose neurons are initiated by modafinil. The prexin neuron stimulation is related with psycho activation and euphoria. The preciseprocess of action is vague, though in vitro researches have revealed it to prevent the reuptake of dopamine by binding to the dopamine reuptake pump, and lead to an increase in extracellular dopamine. Modafinil activates glutamatergic circuits while preventing GABA.

Modafinil overview
Modafinil overview

What is Modafinil?

What is modafinil? Modafinil is a waking medicine given to narcolepsy patients, But its medical practice or Pharmacies are growing to improve their attentiveness or to alleviate exhaustion, including healthy individuals. The 'modafinil'term refers to a racemic combination of two isomers, R-modafinil and S-modafinil. The R-isomer by itself is described to as armodafinil.

what is modofine
what is modofine

Modafinil is used to treat extreme sleepiness triggered by narcolepsy, which is a disorder that causes disproportionate daytime sleepiness or shift work sleep disorder or sleepiness during scheduled waking hours and trouble falling asleep or remaining asleep during scheduled sleeping hours in people who work at nighttime or on rotating shifts. Modafinil is also used laterally with breathing devices or furthermedication to avertextreme sleepiness instigated by obstructive sleep apnea/hypopnea syndrome (OSAHS a sleep disorder in which the patient momentarily stops breathing or breathes shallowly several times during sleep and consequently doesnot get adequate restful sleep). Modafinil is in a group of medicinesknown as wakefulness promoting agents. It performs by modifying the quantities of particular natural substances in the section of the brain that regulates sleep and wakefulness.

What are the ingredients in Modafinil?

Modafinil is a white to off-white, crystalline powder that is basically insoluble in water and cyclohexane. It is thinly to somewhat soluble in ethanol and acetone. It has pKa value of 14.88 ± 0.40 and Partition Coefficient [Log P (Octanol/water)] value is 1.18 ± 0.45. Each tablet contains modafinil as the active ingredient.

Moreover, each tablet contains 100 mg of modafinil as the active ingredient.

In addition, each tablet includes the following inactive ingredients:

  • Methylcellulose
  • Croscarmellose sodium
  • Magnesium stearate
  • Silica-colloidal anhydrous

Nevertheless, this drug is gluten-free, lactose-free, sucrose-free, tartrazine-free and free of other azo dyes.

How it works?

Modafinil has been scientifically established as an effective medicine in treating. Narcolepsy is a disabling neurological disorder characterized by lasting and unmanageable daytime sleepiness. Orexin is involved in inducing narcolepsy, which is a family of wakefulness-promoting and sleep-inhibiting peptides. The orexin neurons are establish solely in the lateral hypothalamus and the orexin neurons in the hypothalamic area projects to the entire central nervous system. Orexin neurons may be triggered by modafinil. Hence, modafinil may stimulate wakefulness by its action in the anterior hypothalamus. However, the waking mechanisms of modafinil on orexin neurons yet to be entirely expound.

Modafinil also amplifies cortical serotonin discharge. Amplification of the electro-neurosecretory coupling mechanisms is preferentially concerned in serotonin release by modafinil. Whereas via reuptake process does not link to serotonin release. Modafinil boost histamine release notably in the anterior hypothalamus.

Although it seems that modafinil interacts with multiple molecular targets in the brain, it has been known that modafinil may not be implicated in dopamine discharge in the brain including the nuclear accumbens. Just like other addictive drugs there is considerable evidence that modafinil is sensitive to dopamine signaling in the brain. Modafinil prevent dopamine transporter (DAT) and norepinephrine transporters in a living primate brain. It slows down dopamine reuptake through DAT.

Why is this medication prescribed?

Modafinil is used to manage extreme sleepiness caused by narcolepsy, a disorder that causes too much daytime sleepiness or shift work sleep disorder or sleepiness for the duration of scheduled waking hours and difficulty falling asleep or remaining asleep during scheduled sleeping hours in people who work at night or on rotating shifts. Modafinil is in a group of medicine described as wakefulness promoting agents. It works by altering the quantity of specific normal substances in the region of the brain that manages sleep and wakefulness. Modafinil is also used along with breathing devices or other medication to avoid excessive sleepiness caused by disruptive sleep apnea/hypopnea syndrome (OSAHS; a sleep disorder in which the patient momentarily stops breathing or breathes shallowly numerous times during sleep and consequently does not get adequate restful sleep..

Modafinil has wake-promoting actions but a pharmacological profile that is different from sympathomimetic amines, which boost wakefulness by other mechanisms. Modafinil does not bind to mainly of the potentially related receptors for sleep/wake regulation, as well as those for noradrenaline, serotonin, dopamine, GABA, adenosine, histamine-3 and benzodiazepines.

Although modafinil stimulate wakefulness can be attenuated by the α1-adrenergic receptor antagonist prazosin, modafinil has no activity in assay systems recognized to be responsive to the α-adrenergic agonists.

What Is The Most Important Information I Should Know About Modafinil?

Modafinil must only be used in individuals who have had a entire assessment of their extreme sleepiness, and in whom a diagnosis of either narcolepsy, OSAHS, and/or SWSD has been made in accordance with ICSD or DSM diagnostic criteria. This kind of evaluation typically involves of testing in a laboratory setting and a complete history and physical examination. Some individuals might involve more than one sleep disorder causing to their disproportionate sleepiness such as OSAHS and SWSD concurrent in the same individual.

Medication with modafinil should be initiated and supervised by physicians with appropriate experience in the treatment of sleep disorders who have access to sleep laboratory diagnostic facilities. That is the only and must be of how to get modafinil.

Narcolepsy

The modafinil dosage is 200 to 400 mg/day, given as a single dose in the morning, or as two divided doses, in the morning and at noon. Tablets should be swallowed whole.

Dosage of 400 mg/day has been well tolerated, but there are no statistically important facts that this dose grants extra advantage further than that of the 200 mg dose.

For patients who need more than 200 mg/day, the dosage should be increased, to a maximum of 400 mg/day, in increments of 100 mg as required and tolerated.

Obstructive Sleep Apnoea/Hypopnoea Syndrome

Modafinil is suggestive of as an addition to continuous positive airway pressure (CPAP) in OSAHS. A maximal attempt to treat with CPAP for an ample period of time must be made prior to starting modafinil. If modafinil is used adjunctively with CPAP, the encouragement of and periodic assessment of CPAP compliance is necessary.

The dosage of modafinil is 200 to 400 mg/day, given as a single dose in the morning, or as two divided doses, in the morning and at noon. Tablets should be swallowed whole.

Dosage of 400 mg/day has been well tolerated, but there is no statistically significant proof that this dosage grants additional advantage further than that of the 200 mg dose.

For patients who need more than 200 mg/day, the dosage should be increased, to a maximum of 400 mg/day, in increments of 100 mg as required and tolerated.

Moderate to Severe Chronic Shift Work Sleep Disorder

The suggested every day dose is 200mg. Modafinil should be taken as a single dose roughly 1 hour prior to the start of the work shift. Tablets should be swallowed whole.

Dosing in Special Populations

In patients with extreme hepatic impairment, the dosage of modafinil must be decreased to one-half of that advised for individual with normal hepatic function.

There is insufficient data to establish safety and effectiveness of modafinil dosing in individuals with severe renal impairment. Removal of modafinil and its metabolites may be lessening as a result of aging in elderly patients. Consequently, consideration must be given to the use of lesser doses in this people.

Before I take Modafinil?

Before Take Modafinil
Before Take Modafinil

Before taking modafinil pill, here are special safety measures I should follow?

Avoid taking this drug if you have or have had any of the following medical situations:
  • Inform your doctor and pharmacist if you are allergic to modafinil, armodafinil (Nuvigil), or whichever other medicine.
  • Inform your doctor and pharmacist what medicine and nonprescription medications, vitamins, nutritional supplements, and herbal products you are using. Be certain to declare whichever 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); particular medications for seizures such as carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin); monoamine oxidase (MAO) inhibitors, as well as 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). Several other medicines may also interact with modafinil, so be sure to inform your doctor concerning all the medicine you are using, even the medicines not appearing on the list. Your doctor may require altering the dosage of your medicine or observe you cautiously for side effects of modafinil.
  • Inform your doctor if you consume or have ever drunk large amounts of alcohol, use or have ever used street drugs, or have overused prescription medications, especially stimulants. Further inform 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 illness.
  • Be informed that modafinil may reduce the efficiency of hormonal contraceptives (birth control pills, patches, rings, implants, injections, and intrauterine devices). Use a different form of birth control while taking modafinil and for 1 month after you stop taking it. Discuss with your doctor about types of birth control that will work for you throughout and after your medication with modafinil.
  • Inform your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking modafinil, consult your doctor.
  • Inform the doctor or dentist that you are taking modafinil if you are having surgery, including dental surgery.
  • Avoid driving a car or operate machinery until you know how this medication affects you. Be informed that modafinil may affect your judgment or thinking and may not totally relieve the sleepiness caused by your disorder. If you avoided driving and other dangerous activities because of your sleep disorder, avoid to start performing these activities again without talking to your doctor even if you feel more alert.
  • Avoid drinking modafinil and alcohol together.

How Should I Take Modafinil?

Modafinil comes as a tablet and to be orally or by mouth. It is typically taken once a day with or without food. You will most likely take it in the morning if you are taking modafinil to treat narcolepsy or OSAHS. You will most likely take it 1 hour before the beginning of your work shift if you are taking modafinil to treat shift work sleep disorder. Take modafinil at the same time daily. Do not alter the time of day that you take modafinil without discussing to your doctor. Speak to your doctor if your work shift does not start at the same time every day. Follow the instructions on your medicine label cautiously, and ask your doctor or pharmacist to clarify any part you do not comprehend. Take modafinil precisely as instructed.

Modafinil may be habit-forming. Avoid taking larger dose, or taking it more often, or taking it for a longer duration of time than advised by your doctor. Modafinil may reduce your sleepiness, but it will not heal your sleep disorder. Maintain to take modafinil even if you feel well-rested. Do not stop taking modafinil without consulting to your doctor.

Modafinil must not be used in place of getting enough sleep. Follow your doctor's counsel about good sleep practice. Continue to use any breathing devices or other medications that your doctor has prescribe to treat your condition, particularly if you have OSAHS.

What Happens If I Miss A Dose?

If you overlook to take it and if it is almost time to take your next dosage, skip the missed dose and take your next dose at the usual time. Or else, take it as soon as you recall and then go back to taking your medicine as you would usually.

Do not take a double dose to make up for missed doses. This may enhance the possibility of you experiencing side effects.

If you have difficulty remembering to take your medication, ask your pharmacist for some hints to assist you keep in mind.

Taking too much may cause overdose. Immediately telephone your doctor or the Poisons Information Centre for recommendation if you think that you or anyone else may have taken too much of this drug. Otherwise, go to the Accident and Emergency department at your nearest hospital. Other noted high dose effects in clinical studies have involved anxiety, irritability, aggressiveness, confusion, nervousness, tremor, palpitations, sleep disturbances, nausea, diarrhea and decreased prothrombin time.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Death can occur with modafinil overdose taken solely or in mixture with additional drugs. The unpleasant incidents witnessed were limited, anticipated and non-life threatening, and the patients recuperated fully by the following day.

What Happens If I Overdose?

Most often associated indications of modafinil overdose, taken solely or mixture with additional drugshave involved: insomnia; central nervous system symptoms such as restlessness, disorientation,confusion, excitation and hallucination; digestive changes such as nausea and diarrhea; andcardiovascular shifts such as tachycardia, bradycardia, hypertension and chest pain. Other noted high dose effects in clinical studies have involved anxiety, irritability, aggressiveness, confusion, nervousness, tremor, palpitations, sleep disturbances, nausea, diarrhea and decreased prothrombin time.

Death can occur with modafinil overdose taken solely or in mixture with additional drugs. A small few of individuals must each taken modafinil at doses of 1000 mg/day (2.5 times the maximum suggested daily dosage of 400 mg) or more. The unpleasant incidents witnessed were limited, anticipated and non-life threatening, and the patients recuperated fully by the following day.

Induced emesis or gastric lavage should be regarded. Hospitalization and supervision ofpsychomotor condition; cardiovascular observing or surveillance until the patient's symptoms havesettled are advised. Supervision of overdosage is mainly indicative, as no certain antidote to the toxic effects of modafinil overdose has been discovered. Overdoses ought to be handled empirically, with encouraging care, involving cardiovascular checking.

Side Effects Of Modafinil?

side effects of modafinil
side effects of modafinil

Modafinil containing medicinal products can cause modafinil side effects like any other medicines, although not everyone gets them.

Discontinue taking this medicine and tell your doctor immediately if:

  • You have unexpected trouble breathing or wheeziness or your face, mouth or throat begins to swell.
  • You observe a skin rash or itching (particularly if it affects your whole body). Severe rashes may cause blistering or peeling of the skin, ulcers in your mouth, eyes, nose or genitals. You may also have a high temperature (fever) and irregular blood test results.
  • You feel any modification in your mental health and wellbeing. The signs may include:
    • mood swings or abnormal thinking,
    • aggression or hostility,
    • forgetfulness or confusion,
    • feeling of tremendous happiness,
    • over-excitement or hyperactivity,
    • anxiety or nervousness,
    • depression, suicidal thoughts or behaviour,
    • agitation or psychosis (a loss of contact with reality which may include delusions or
    • sensing things that are not real), feeling detached or numb, or personality disorder.

Other side effects comprise the following:

Very common side effects (affecting more than 1 in 10 people):

  • Headache.

Common side effects (affecting fewer than 1 in 10 people):

  • Dizziness.
  • Sleepiness, extreme tiredness or difficulty sleeping (insomnia).
  • Awareness of your heart beat, which may be faster than normal.
  • Chest pain
  • Flushing.
  • Dry mouth.
  • Loss of appetite, feeling sick, stomach pain, indigestion, diarrhoea or constipation.
  • Weakness.
  • Numbness or tingling of the hands or feet (‘pins and needles’).
  • Blurred vision.
  • Abnormal blood test results showing how your liver is working (increased liver enzymes).

Uncommon side effects (affecting fewer than 1 in 100 people):

  • Back pain, neck pain, muscle pain, muscle weakness, leg cramps, joint pain, twitching or tremor.
  • Vertigo (spinning sensation).
  • trouble moving muscles smoothly or other movement problems, muscle tension, coordination problems.
  • Hayfever symptoms including itchy/runny nose or watery eyes.
  • Increased cough, asthma or shortness of breath.
  • Skin rash, acne or itchy skin.
  • Sweating.
  • Changes in blood pressure (high or low), abnormal heart trace (ECG), and uneven or unusually slow heart beat.
  • trouble swallowing, swollen tongue or mouth ulcers.
  • Excess wind, reflux (bringing back fluid from the stomach), increased appetite, weight changes, thirst or taste alteration.
  • Being sick (vomiting)
  • Migraine.
  • Speech problems.
  • Diabetes with increased blood sugar.
  • High blood cholesterol.
  • Swollen hands and feet.
  • Disrupted sleep or abnormal dreams,
  • Loss of sex drive.
  • Nose bleed, sore throat or inflamed nasal passages (sinusitis).
  • Abnormal vision or dry eyes.
  • Abnormal urine or more frequent urination.
  • Abnormal periods.
  • Abnormal blood test results showing that the information of your white blood cells have changed.

Please inform your doctor, pharmacist or nurse if any of these side effects become bothersome or you experience whichever side effects not listed.

Warnings

Do not take Modafinil containing medicinal products if you:

  • Are allergic (hypersensitive) to modafinil, or to whichever of the other ingredients of these tablets.
  • Have an irregular heartbeat.
  • Have uncontrolled, moderate to severe high blood pressure (hypertension).

Be cautious with Modafinil comprise medicinal products if you:

  • Have any heart problems or high blood pressure. Your doctor will require to check these frequently while you are taking Modafinil containing medicinal products.
  • Have ever had depression, low mood, anxiety, psychosis (loss of contact with reality) or mania (over-excitement or feeling of extreme happiness) or bipolar disorder because Modafinil containing medicinal products may make your condition worse.
  • Have kidney or liver illness (because you will need to take a lower dose).
  • Have had alcohol or drug troubles in the past.

Children should not take this medicine of aged less than 18 years.

Other things to discuss to your doctor or pharmacist about:

  • A few individuals have reported having suicidal or aggressive feelings or behavior while taking this medicine. Inform your doctor immediately if you observe that you are becoming depressed, feel aggressive or unfriendly towards other people or have suicidal thoughts or other changes in your behavior. You may want to think asking a family member or close friend to help you look out for indications of depression or further changes in your behavior.
  • This drug has the potential for you to become reliant (dependent) on it after long-term use. Your doctor will check frequently if you need to take it for a long time that it is still the best medicine for you.

Taking other medicines

Modafinil comprising medicinal products and particular other medicines are able to affect each other and your doctor may need to change the dosage that you are taking. It is particularly significant if you are taking any of the following medicines as well as Modafinil containing medicinal products:

  • Hormonal contraceptives (including the contraceptive pill, implants, intrauterine devices (IUDs) and patches). You will need to consider other birth control methods while taking Modafinil containing medicinal products, and for two months after stopping treatment, because Modafinil containing medicinal products lessen their efficiency.
  • Omeprazole (for acid reflux, indigestion or ulcers).
  • Antiviral medicines to treat HIV infection (protease inhibitors e.g. indinavir or ritonavir).
  • Ciclosporin (used to avoid organ transplant rejection, or for arthritis or psoriasis).
  • Drug for epilepsy such as carbamazepine, phenobarbital or phenytoin.
  • Drug for depression such as amitriptyline, citalopram or fluoxetine) or anxiety like diazepam.
  • Drug for thinning the blood (e.g. warfarin). Your doctor will supervise your blood clotting times during medication.
  • Calcium channel blockers or beta-blockers for high blood pressure or heart problems such as amlodipine, verapamil or propranalol.
  • Statin drug for lowering cholesterol (e.g. atorvastatin or simvastatin).
  • Pregnancy and breast-feeding

Precautions

  • Serious Skin Rash, including Stevens - Johnson syndrome
  • Serious rash requiring hospitalization and discontinuation of treatment has been reported in adults and children in association with the use of modafinil.
  • Modafinil is not approved for use in pediatric patients for any indication.

In clinical trials of modafinil, the occurrence of rash ensuing in discontinuation was just about 0.8% (13 per 1,585) in pediatric patients (age <17 years); these rashes included 1 case of potential Stevens - Johnson syndrome (SJS) and 1 case of apparent multiorgan hypersensitivity reaction. A number of the cases were connected with fever and other abnormalities such as vomiting, leukopenia. The median time to rash that resulted in discontinuation was 13 days. No such cases were noticed among 380 pediatric patients who received placebo. No serious skin rashes have been reported in adult clinical trials (0 per 4,264) of modafinil.

Rare cases of serious or life-threatening rash, including SJS, Toxic Epidermal Necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been accounted in adults and children in worldwide post-marketing experience. The reporting rate of TEN and SJS linked with modafinil use, which is normally acknowledged to be undervalued due to underreporting, surpass the background occurrence rate. Estimates of the background occurrence rate for these serious skin reactions in the common population range between 1 to 2 cases per million-person years.

The risk may boost with higher doses although little is known about factors that can predict the risk of incidence or the severity of rash linked with modafinil. Almost all cases of grave rash linked with modafinil happened within 1 to 5 weeks after medication begins.

Even though benign rashes also happen with modafinil, it is not likely to dependably foresee which rashes will confirm to be severe. Modafinil must typically be discontinued at the first indication of rash, except the rash is evidently not drug-related. Discontinuation of treatment may not stop a rash from becoming life-threatening or permanently disabling or disfiguring.

Drug interactions

Modafinil prescription can boost its own metabolism via induction of CYP3A4/5 activity but the effect is moderate and not likely to have substantialscientificresults.

  • Anticonvulsants: Co-administration of powerful inducers of CYP activity, such as carbamazepine andphenobarbital, mightlessen the plasma levels of modafinil. Because of a probablehindrance of CYP2C19by modafinil and suppression of CYP2C9 the clearance of phenytoin can bereduced whenmodafinil is taken concomitantly. Patients should be supervised for indications of phenytoin toxicity,and recurringamounts of phenytoin plasma levels might be suitable upon beginning ortermination of medication with modafinil.
  • Steroidal contraceptives: The efficiency of steroidal contraceptives may be compromisedbecauseof the induction of CYP3A4/5 by modafinil. Alternative or concomitant approaches of contraception areadvised for patients handled with modafinil. Sufficient contraception will involve continuation ofthese practices for two months after stopping modafinil.
  • Antidepressants: Some tricyclic antidepressants and selective serotonin reuptake inhibitors aregenerallymetabolized by CYP2D6. In patients lacking in CYP2D6 (roughly 10% of a Caucasianpopulation) a typically ancillary metabolic pathway including CYP2C19 becomes more essential. Asmodafinil may hamper CYP2C19, reducedosages of antidepressants may be necessary in such patients.
  • Anticoagulants: Because ofpotential suppression of CYP2C9 by modafinil the clearance of warfarin maybe reduced when modafinil is taken concomitantly. Prothrombin times should be observedfrequently during the first 2 months of modafinil use and after adjustments in modafinil dose.
  • Other pharmaceutical products: Substances that are mostlyremoved via CYP2C19 metabolism, such asdiazepam, propranolol and omeprazole may have decreased clearance upon co-administration ofmodafinil and may thereforeneeddosedecrease. Furthermore, in vitro induction of CYP1A2, CYP2B6and CYP3A4/5 activities has been noticed in human hepatocytes, which were it to happen in vivo,could decline the blood levels of medicinesmetabolized by these enzymes, in that wayperhapsdiminishingtheir medicinalefficiency. Findings from clinical interaction researchesadvise that the major effectsmay be on substrates of CYP3A4/5 that go through important presystemic removal, specifically viaCYP3A enzymes in the gastrointestinal tract. Examples contain ciclosporin, HIV-protease inhibitors,buspirone, triazolam, midazolam and most of the calcium channel blockers and statins. In a case report,7a 50% drop in ciclosporinconcentration was detected in a patient getting ciclosporin in whom simultaneous modafinil prescription was started.

What other drugs will affect Modafinil?

CNS Active Drugs
  • Methylphenidate – absorption of modafinil may be delayed by almost one hour when co-administered with methylphenidate.
  • Clomipramine – coadministration of a single dose of clomipramine (50 mg) on the first three daysof treatment with modafinil (200 mg/day) in healthy volunteers did not show an effect on the pharmacokinetics of either drug.
  • Triazolam – healthy, female volunteers receiving long-term treatment with ethinyl estradiol,the co-administration of two single doses of 0.125 mg of triazolam (one taken before and theother at the end of medication) with modafinil (200 mg for seven days, followed by 400 mg for 21 days)showed that, for triazolam, the Cmax and AUC0-∞ were lessened by 59% and 42% respectively, and theremoval rate was improved by almost 50%. Consequently, dosemodification of triazolam maybe required when co-administered with modafinil.
  • Monoamine Oxidase (MAO) Inhibitors – caution should be employed when concomitantly administering MAO inhibitorsand modafinil. No interaction studies with monoamine oxidase inhibitors have been performed.
    Potential Interactions with Drugs That Inhibit, Induce, or are Metabolised by Cytochrome P-450Isoenzymes and Other Hepatic Enzymes.
  • Diazepam, Phenytoin, Propranolol, Tricyclic Antidepressants, Selective Serotonin Reuptake Inhibitors Since modafinil pill is a reversible inhibitor of the drug-metabolising enzyme CYP2C19, coadministration of modafinil with drugs such as diazepam, phenytoin, and propranolol, which are mostlyremoved via that pathway, may enhance the circulating levels of those compounds. In addition, inindividuals deficient in the enzyme CYP2D6, the levels of CYP2D6 substrates such as tricyclic antidepressants and selective serotonin reuptake inhibitors, which have ancillary routes of removalthrough CYP2C19, may beincreased by co-administration of modafinil. Dose modifications may beneeded for patients being treated with these and relatedmedicines.
  • Steroidal Contraceptives, Cyclosporin, Theophylline – Chronic administration of modafinil also causesmodest induction of the metabolizing enzyme CYP3A4, consequentlydropping the levels of co-administeredsubstrates for that enzyme system, such as steroidal contraceptives,cyclosporin and to a smaller degree,theophylline. Dose modifications may be needed for patients being treated with these and relatedmedications.
  • Inducers or Inhibitors of CYP3A4 – Co-administration of strong inducers of CYP3A4 (e.g.,carbamazepine, phenobarbital, rifampicin) or inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole)could modify the levels of modafinil because to the partial participation of that enzyme in the metabolicremoval of the compound (see Patients (Women) Using Contraception).
  • Warfarin, Phenytoin – The exposure of human hepatocytes to modafinil in vitro generated an obviousconcentration-related suppression of expression of CYP2C9 activity. The clinical significance of thisdiscovery is uncertain, since no furthersign of CYP2C9 suppression has been detected.

However,monitoring of prothrombin times is recommended as a precaution for the first several months of coadministration of modafinil and warfarin, a CYP2C9 substrate, andsubsequentlyeach time modafinil dosingis altered.