Modafinil is a medication that promotes wakefulness and alertness. It's often prescribed to treat conditions like narcolepsy, sleep apnea, and shift work sleep disorder.

It was first approved by the U.S. Food and Drug Administration (FDA) in 1998 under the brand name Provigil, and later under various generic names.

While the exact mechanism of modafinil's action isn't fully understood, it's believed to work by affecting certain neurotransmitters in the brain that play a role in sleep and wakefulness.

Unlike traditional stimulants, modafinil tends to have a more subtle and focused effect on wakefulness without causing the intense highs and lows associated with drugs like amphetamines.

Modafinil (Modiodal) is a brain stimulant drug that is used to treat patients who suffer from fatigue or exhaustion, obstructive sleep apnea, as well as narcolepsy.

Modafinil Uses:

• For People with Odd Work Hours:

  • This medicine helps those who work at strange hours (like nights) and have trouble sleeping. It keeps them more awake.

• For Those with Narcolepsy:

  • This medicine helps people with narcolepsy, a condition where you get very sleepy during the day. It helps you stay awake.

• For Breathing Issues during Sleep:

  • If you have a problem where you stop breathing and start again while sleeping (obstructive sleep apnea), this medicine can help manage it.

• Other Uses (Not Officially Approved):

  • Doctors might use this medicine for things not officially approved.
    • If you're tired because of cancer, it might help.
    • If you have multiple sclerosis and feel very tired, it could be used.
    • It might also be given with antidepressants for people with major depressive disorder to make them work better.

Modafinil Dose in Adults:

Modafinil (Modiodal) Dose in the treatment of Narcolepsy, obstructive sleep apnea (OSA):

• Modafinil is a medication in the form of a pill that helps treat sleep disorders such as narcolepsy and sleep apnea.
• Typically, the initial dose is 200 mg, and it's taken once in the morning.
• In some cases, individuals may be prescribed up to 400 mg, but it's uncertain whether the higher dose is more effective.
• Always follow the dosage recommended by your healthcare provider, and if you have any questions or concerns, it's important to discuss them with your doctor.

Modafinil (Modiodal) Dose in the treatment of Shift work sleep disorder (SWSD):

• For treating Shift Work Sleep Disorder, the usual recommendation is to take a 200 mg Modafinil pill approximately one hour before the start of your work shift.
• This timing is designed to help promote wakefulness and alertness during the work period for individuals who have irregular or nighttime work schedules.
• Always follow the specific instructions provided by your healthcare provider for your individual circumstances.
• If you have any questions or concerns about the timing or dosage, it's best to consult with your doctor.

Modafinil (Modiodal) Dose in the treatment of patients undergoing active therapy, significant cancer-related tiredness, (off-label):

• If you're really tired from cancer treatment (which is not the usual reason for using it), begin with a 100 mg Modafinil pill every day for three days.
• After that, take a 200 mg pill every day while you're getting cancer treatment. Always do this as your doctor tells you to.

Modafinil (Modiodal) Dose in the treatment of the major depressive disorder (antidepressant augmentation) (off-label):

• If you want to use Modafinil to help with depression (even though that's not its main purpose), begin by taking a 100 mg pill every day for 3 to 7 days. After that, take 200 mg every day.

• If necessary, the amount can be changed, up to 400 mg each day. Always follow your doctor's advice on how to take it.

Modafinil (Modiodal) Dose in the treatment of Multiple sclerosis-related fatigues (off-label):

• If you feel tired because of Multiple Sclerosis (even though using Modafinil for this isn't its usual purpose), begin with a 100 mg pill every day.
• If necessary, your doctor might increase it to 200 mg once a day. If you get tired in the afternoon, you can split it: take 100 mg in the morning and 100 mg at noon.
• It doesn't seem to be more helpful if you take more than 200 mg each day. Always follow your doctor's advice on how to take it.

Modafinil Dose in Children:

Modafinil (Modiodal) Dose in the treatment of refractory attention deficit hyperactivity disorder (ADHD):

Important: Modafinil can have serious skin reactions and mental side effects in kids.

Use it only if other treatments haven't worked and the benefits are greater than the risks.

For kids 6 to 13 years old:

• If the child weighs less than 30 kg, they should take a dose of 200 to 340 mg once a day.

• If they weigh more than 30 kg, the recommended dose is 300 to 425 mg once a day.

• Always follow the specific dosing instructions provided by the healthcare provider based on the individual's weight and health condition.

Pregnancy Risk Factor C

• Using Modafinil during pregnancy might not be safe.

• Limited studies suggest it could raise the risk of birth defects, particularly heart problems, and may also increase the chances of miscarriage and slow fetal growth.

• If you're considering starting Modafinil, it's important to check if you're pregnant within a week before beginning the medication.

• Additionally, be aware that Modafinil might reduce the effectiveness of certain birth control methods like injections, implants, and pills.

• If you're taking Modafinil, think about using a different form of birth control and continue using it for at least a month after you stop taking the medication.

• Always discuss these concerns with your healthcare provider to ensure the best course of action for your specific situation.

Use while breastfeeding

• Armodafinil, derived from Modafinil, can be present in breast milk.
• According to one study, a woman taking Modafinil had the highest levels of Armodafinil in her breast milk about 2 hours after taking the medication.
• During this time, she chose not to breastfeed her baby.
• Therefore, if a mother is taking Modafinil and plans to breastfeed, it's important for her to exercise caution and consult with her healthcare provider to make informed decisions about the safety of breastfeeding while on the medication.

Modafinil Dose in Kidney Disease:

The current dosage does not require any adjustments.

Modafinil Dose in Liver disease:

• If you have mild to moderate liver problems, there isn't a specific guideline from the maker on how much to adjust the dose.

• However, if you have severe liver problems, it's advised to take only half of the usual recommended dose.

• Always consult with your healthcare provider for personalized advice based on your specific health condition.

Common Side Effects of Modafinil (Modiodal):

• Gastrointestinal:
  • Decreased appetite
  • Abdominal pain
• Central nervous system:
  • Headache

Less Common Side Effects of Modafinil (Modiodal):

• Endocrine & Metabolic:
  • Weight Loss
  • Increased Thirst
• Cardiovascular:
  • Palpitations
  • Tachycardia
  • Chest Pain
  • Hypertension
  • Vasodilation
  • Edema
• Gastrointestinal:
  • Constipation
  • Dysgeusia
  • Diarrhea
  • Dyspepsia
  • Xerostomia
  • Anorexia
  • Flatulence
  • Oral Mucosa Ulcer
• Central Nervous System:
  • Dizziness
  • Insomnia
  • Depression
  • Nervousness
  • Anxiety
  • Confusion
  • Emotional Lability
  • Chills
  • Vertigo
  • Hypertonia
  • Drowsiness
  • Paresthesia
  • Agitation
• Dermatologic:
  • Diaphoresis
• Neuromuscular & Skeletal:
  • Back Pain
  • Dyskinesia
  • Hyperkinesia
  • Tremor
• Genitourinary:
  • Urine Abnormality
• Hematologic & Oncologic:
  • Eosinophilia
• Respiratory:
  • Rhinitis
  • Pharyngitis
  • Asthma
  • Epistaxis
• Hepatic:
  • Hepatic Insufficiency
• Ophthalmic:
  • Visual Disturbance

Frequency of side effects not defined:

• Hepatic:
  • Increased Serum Alkaline Phosphatase
• Endocrine & Metabolic:
  • Increased Gamma-Glutamyl Transferase

Contraindications to Modafinil (Modiodal):

Do not take Modafinil if:

1. You are allergic to Modafinil, Armodafinil, or any of the components in the pill.

Additionally, in Canada, avoid taking it if:

1. You are highly anxious or agitated.
2. You are pregnant.
3. There is a possibility that you might become pregnant.

Always follow the guidance of your healthcare provider and inform them of any allergies or specific conditions you may have before taking Modafinil.

Warnings and precautions

CNS effects

• Modafinil could impact your thinking and reactions.

• Be cautious if you need to engage in activities that require alertness, such as driving or operating heavy machinery.

• Always prioritize safety and understand how the medicine might affect you before undertaking such activities.

Dermatologic effects (severe).

• Modafinil has the potential to cause severe skin reactions, including dangerous rashes.

• These rashes can occur in both children and adults.

• While most of these rashes appear within the first 5 weeks of taking the medicine, some may even show up after using it for an extended period, like 3 months.

• If you observe any rash while taking Modafinil, it's important to stop taking the medication and promptly consult with a doctor, unless you are certain the rash is not related to the medicine.

• Due to these risks, the FDA decided not to approve Modafinil for use in children with ADHD.

• Always prioritize your safety and seek medical attention if you experience any concerning reactions.

Hypersensitivity reactions

• Modafinil has been associated with very rare but serious allergic reactions that can affect multiple organs and, in extreme cases, may be fatal.

• Symptoms can vary, but they often include fever and a rash along with problems in specific organs.

• It's not possible to predict who might experience these reactions.

• If you notice any unusual symptoms or start feeling unwell while taking Modafinil, it's crucial to stop the medication and seek medical help immediately.

• Your safety is paramount, and prompt medical attention is essential in such cases.

Cardiovascular disease

• If you have heart issues, use caution with Modafinil.

• It has the potential to increase blood pressure and heart rate, requiring more frequent monitoring of these vital signs.

• It's advisable to avoid using Modafinil if you've experienced specific heart problems, such as thickened heart muscles or issues with a heart valve, especially if these were caused by similar medicines in the past.

• If you've had recent heart attacks or chest pain, close monitoring is recommended.

• Always consult with your healthcare provider to determine the suitability and safety of using Modafinil based on your individual health circumstances.

Hepatic impairment

• If you have liver problems, exercise caution when using Modafinil. Individuals with severe liver issues should take a lower dose of the medication.
• It's essential to discuss your liver health with your healthcare provider, who can provide guidance on the appropriate dosage based on your specific condition.
• Always follow your healthcare provider's recommendations to ensure the safe and effective use of Modafinil.

Psychiatric disorders

• If you've experienced mental health issues such as psychosis, depression, or mania, exercise caution with Modafinil.

• The medication has the potential to cause or worsen these conditions.

• Be vigilant for signs of aggressive behavior, hallucinations (seeing or hearing things that aren't there), extreme mood changes, or thoughts of self-harm.

• If you notice any of these symptoms or if your mental health condition worsens while taking Modafinil, it's crucial to seek immediate medical attention

• . Always communicate openly with your healthcare provider about your mental health history and any changes in your condition while using Modafinil.

Renal impairment

• If you have kidney problems, it's important to exercise caution when taking Modafinil.

• Kidney function can impact how the body processes medications, and your healthcare provider may need to adjust the dosage based on your specific kidney condition.

• Always communicate openly with your healthcare provider about any kidney issues you may have, and follow their guidance to ensure the safe and effective use of Modafinil.

• Regular monitoring and adjustments may be necessary to manage the medication appropriately in individuals with kidney problems.

Seizure disorder

• If you have both seizures and ADHD, there's limited information on how Modafinil might affect you.

• People with ADHD generally have a slightly higher risk of seizures compared to others, but some studies suggest that stimulant medications, including those for ADHD, may potentially reduce the risk of seizures.

• However, it's important to note that there isn't conclusive evidence, and different individuals may react differently.

• Some drug companies recommend stopping their medication if a seizure occurs.

• If you have concerns or experience seizures while taking Modafinil, it's crucial to consult with your healthcare provider promptly for guidance on how to proceed.

• They can provide personalized advice based on your medical history and condition.

Sleep disorders

• If you're using Modafinil for sleep-related issues, it's important to regularly assess how sleepy you feel.

• While Modafinil can be effective in reducing sleepiness, some individuals may not completely eliminate feelings of tiredness.

• If you have sleep apnea, it's crucial to understand that Modafinil addresses sleepiness but does not fix the underlying breathing problem.

• If your doctor suggests using a CPAP machine, it's recommended to try that before turning to Modafinil to see if it helps alleviate your sleepiness more effectively.

• Always follow your healthcare provider's advice and keep them informed about your experiences and any ongoing sleep issues.

Tourette syndrome/tics

• If you have Tourette syndrome or another condition involving tics, it's important to exercise caution with Modafinil.

• Limited evidence suggests that some stimulants may potentially worsen tics.

• Before starting Modafinil, it's advisable to check for signs of tics or Tourette syndrome.

• If you have concerns or notice any changes in your condition while using Modafinil, promptly consult with your healthcare provider.

• They can provide guidance based on your individual health circumstances and help monitor for any adverse effects on tics or related conditions.

Monitoring parameters:

Sleepiness:

• It's important to regularly assess and be aware of how sleepy you feel.
• Monitoring your level of sleepiness can help you stay mindful of the effectiveness of any sleep-related treatments or medications, such as Modafinil.
• If you notice persistent sleepiness or any changes in your condition, it's advisable to discuss these observations with your healthcare provider.
• Open communication with your doctor allows for adjustments to your treatment plan, ensuring it best meets your needs and addresses any ongoing concerns.

Heart and Blood Pressure:

• It's crucial to monitor your blood pressure and heart rate regularly, especially if you're taking medications like Modafinil.

• If you've experienced recent heart issues or chest pain, it's even more important to check these vital signs more frequently.

• Regular monitoring helps ensure that any potential effects of the medication on your cardiovascular system are promptly identified, allowing for timely intervention if needed.

• Always follow your healthcare provider's recommendations for monitoring your blood pressure and heart rate based on your individual health circumstances.

• If you observe any unusual changes, consult with your doctor promptly.

Pregnancy:

• If there is a possibility that you could become pregnant, it's advisable to confirm that you are not pregnant about a week before starting the medicine.

• This precaution helps ensure that you are aware of your pregnancy status before beginning any medication, allowing you and your healthcare provider to make informed decisions about the safety of the treatment plan.

• Always discuss family planning and potential pregnancy with your healthcare provider before initiating any new medication.

Skin Reactions:

• Be vigilant for any signs of severe skin issues.

• If you notice unusual or concerning changes in your skin, such as rashes, blistering, or other serious reactions, it's crucial to seek immediate medical attention.

• Monitoring your skin health is important while taking medications like Modafinil, as severe skin issues can sometimes be associated with certain medications.

• Always report any adverse reactions or changes in your skin condition to your healthcare provider promptly.

Mental Health:

• Be attentive to signs of increased agitation, anxiety, or depression while taking Modafinil.
• Changes in mood or mental well-being should be closely monitored.
• If you experience any significant shifts in your emotional state, it's essential to discuss these changes with your healthcare provider.
• Open communication allows your healthcare team to assess and address any potential side effects or concerns associated with the medication, ensuring your well-being throughout the course of treatment.

How to administer Modafinil (Modiodal)?

• Narcolepsy & Sleep Apnea:

  • Take Modafinil in the morning.

  • This is often recommended to maximize its effectiveness in promoting wakefulness during the daytime.

  • Following the prescribed timing helps align the medication's benefits with your daily routine and supports better management of sleep-related issues.

  • Always adhere to the specific instructions provided by your healthcare provider regarding the timing and dosage of Modafinil.

  • If you have any questions or concerns, consult with your doctor for personalized guidance.

• Shift Work Sleep Disorder:
  • If you are using Modafinil to manage shift work sleep disorder, it is often recommended to take the medication about 1 hour before starting your work shift.
  • This timing is designed to help optimize its effectiveness in promoting wakefulness and alertness during your work hours.
  • Always follow the specific dosing instructions provided by your healthcare provider and consult with them if you have any questions or concerns about the timing of your medication.

Mechanism of action of Modafinil (Modiodal):

• Dopamine Increase:

  • Modafinil works by increasing dopamine levels in the brain.

  • It does this by blocking dopamine transporters, which are proteins responsible for removing dopamine from the synapses (gaps between nerve cells).

  • By blocking these transporters, Modafinil allows dopamine to remain in the synapses for a longer time, leading to increased levels of dopamine.

  • Dopamine is a neurotransmitter associated with alertness, focus, and wakefulness, which explains Modafinil's stimulant-like effects on the central nervous system.

• Different from Amphetamines:
  • Unlike amphetamines, Modafinil has a different mechanism of action and affects dopamine receptors to a lesser extent.
  • While amphetamines increase the release of dopamine and other neurotransmitters and also bind to dopamine receptors, Modafinil primarily works by blocking the reuptake of dopamine.
  • It inhibits the reabsorption of dopamine by nerve cells, leading to increased concentrations of dopamine in the synapses between nerve cells.
  • The overall effect is heightened wakefulness and alertness without the pronounced impact on dopamine receptors that is characteristic of amphetamines.
• Brain Waves Change:

  • Modafinil has been associated with changes in brain wave patterns that may contribute to its wakefulness-promoting effects.

  • It has been reported to increase high-frequency alpha waves, which are associated with a state of relaxed alertness and focus.

  • Additionally, Modafinil has been observed to decrease delta and theta waves, which are linked to deeper stages of sleep and relaxation.

  • The modulation of these brain wave patterns aligns with the overall goal of promoting wakefulness and reducing feelings of sleepiness.

  • However, the exact mechanisms through which Modafinil influences these brain waves are complex and not fully understood.

  • Individual responses to Modafinil can vary, and more research is needed to fully elucidate its impact on brain activity.

• Serotonin and GABA:

  • Modafinil does influence neurotransmitters in the brain, including serotonin and GABA:

  • Serotonin (5-HT):

  • Modafinil has been reported to increase serotonin turnover, meaning it enhances the synthesis and release of serotonin.

  • It also boosts the activity of serotonin receptors (5-HT receptors), contributing to its effects on mood and wakefulness.

  • GABA (Gamma-Aminobutyric Acid):

  • While Modafinil's exact impact on GABA is not fully understood, it's known to have complex effects on neurotransmitter systems, and GABAergic transmission may be influenced.

  • Alpha-Adrenergic System:

  • Modafinil appears to require a functioning alpha-adrenergic system for optimal effectiveness.

  • The alpha-adrenergic system involves neurotransmitters like norepinephrine, and Modafinil's wakefulness-promoting effects may be linked to its interaction with this system.

  • It's important to note that the precise mechanisms of Modafinil's actions are still a subject of ongoing research, and individual responses can vary.

  • Always follow your healthcare provider's guidance regarding the use of Modafinil and discuss any potential interactions with other medications or health conditions.

• Racemic Compound:

  • Modafinil is a racemic compound, meaning it contains two mirror-image isomers: the R-isomer and the S-isomer.

  • In the case of Modafinil, it's typically composed of 90% R-modafinil and 10% S-modafinil.

  • These isomers can have slightly different pharmacokinetic properties, including how they are absorbed, distributed, metabolized, and eliminated in the body.

  • While both isomers contribute to the overall effects of Modafinil, the R-isomer is thought to be primarily responsible for its wakefulness-promoting effects.

  • Understanding the different properties of the isomers helps in studying how Modafinil interacts with the body and how its effects are achieved.

Distribution:

• The volume of distribution for Modafinil is 0.9 liters per kilogram of body weight.

• This means that, on average, the drug is distributed in the body in a way that suggests it stays somewhat limited to the bloodstream and doesn't spread extensively into tissues.

• This information helps us understand how the drug moves in the body and can affect how it is dosed.

Binding to Proteins:

• Approximately 60% of Modafinil binds to proteins in the blood, with albumin being the main protein involved in this binding.
• This means that a significant portion of the drug is attached to proteins and not freely circulating in the bloodstream.
• Protein binding can affect the distribution, metabolism, and elimination of a drug, and it also plays a role in determining the drug's overall effectiveness and duration of action.

How it's Processed (Metabolism):

• Modafinil is primarily metabolized in the liver, where it undergoes various pathways, including one known as CYP3A4.
• This enzyme, CYP3A4, plays a role in breaking down Modafinil into its metabolites, which are then further processed and eventually eliminated from the body.
• Understanding the specific metabolic pathways of a drug is important for predicting how it will be processed in the body and for evaluating potential interactions with other medications that may be metabolized through the same pathways.

Half-life:

• The elimination half-life of Modafinil is approximately 15 hours.
• This means that it takes about 15 hours for half of the drug to be cleared from the body.
• The half-life is a measure of how long it takes for the concentration of a drug in the bloodstream to reduce by half.
• Understanding the half-life is important for determining dosing intervals and estimating how long the effects of the drug may last.

Peak Time in Blood:

• Modafinil typically reaches its peak concentration in the bloodstream 2 to 4 hours after being taken.
• If taken with food, the time to reach peak concentration may be extended by about an hour.
• This is why healthcare providers may advise taking Modafinil on an empty stomach to optimize its absorption and onset of action.
• The interaction with food can affect the rate and extent of absorption, potentially influencing the drug's effectiveness.
• Always follow your healthcare provider's instructions regarding the administration of Modafinil, including whether it should be taken with or without food.

How it Leaves the Body (Excretion):

• Approximately 80% of Modafinil is eliminated from the body through urine, but less than 10% of it is excreted in its original unchanged form.
• The majority of the drug undergoes metabolism in the body, forming various metabolites.
• A small portion (about 1%) is eliminated in feces.
• This information provides insights into how the body processes and eliminates Modafinil, which is important for understanding its pharmacokinetics and potential interactions with other medications or substances.

International Brand Names of Modafinil:

• Provigil
• Mar-Modafinil
• TEVA-Modafinil
• Activigil
• Alertex
• Aspendos
• Carim
• Forcilin
• Intensit
• Mentix
• Modafin
• APO-Modafinil
• Auro-Modafinil
• Modalert
• Modanil
• Modasomil
• Modavigil
• Modfil
• Modiodal
• Movigil
• Nopral
• Prosentio
• Provake
• Provigil
• Resotyl
• Alertec
• BIO-Modafinil
• Stavigile
• Vigia
• Vigicer
• Vigil
• Zalox

Modafinil Brand Names in Pakistan: