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:

• Shift work sleep disorder:

  • This drug is effective in the therapy of narcolepsy related drowsiness.

• Narcolepsy:

  • Helps in the management of narcolepsy-related sleepiness.

• Obstructive sleep apnea:

  • Helps in the management of obstructive sleep apnea (OSA)

• Off Label Use of Modafinil in Adults:

  • Malignancy-related lethargy/fatigue
  • Multiple sclerosis-related lethargy/fatigue
  • Major depressive disorder (antidepressant augmentation)

Modafinil Dose in Adults:

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

• As a starting dose, give 200 mg orally in the morning on a daily basis.
• Note: a dose of 400 mg is tolerated once per day

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

• 60 minutes before the beginning of the shift, give a single dose of  200 mg orally

Off-label uses:

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

• On the 5th day of the second cycle of chemotherapy, start with 100 mg per day for the next 3 days, followed by a 200 mg dose per day only once for the entirety of the active treatment

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

• Raise the dose up to 400 mg per day if the patient can tolerate it.
• For three to seven days, start off with a dose of 100 mg per day only once, then raise the dose to 200 mg per day.

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

• Greater daily doses (above 200 mg) do not provide any further benefits.
• Oral: If the patient feels post-noon weariness, increase the dosage to 200 mg once daily as tolerated after starting with 100 mg once daily (ie, morning and noon).

Modafinil Dose in Children:

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

Note: Modafinil should only be used as an emergency treatment option because there have been reports of serious skin-related side effects and psychiatric problems in children. However, the advantages exceed the dangers.

• Children aged 6 years or above and teenagers aged 13 years or above:

  • Patient weight <30 kg:
    • Once per day, give a dose of 200 to 340 mg orally.
  • Patient weight >30 kg:
    • Once per day, give a dose of 300 to 425 mg orally.

Pregnancy Risk Factor C

• Modafinil pregnancy use is not known to have any significant effects.
• Initial data from the Nuvigil/Provigil pregnant registry suggest teratogenicity, especially for cardiac anomalies.
• Modafinil has been shown to increase the risk of spontaneous abortions and intrauterine growth restriction.
• Within one week of modafinil initiation, assess your pregnancy status. 
• Modafinil therapy may result in decreased effectiveness of steroidal contraceptives, including implantable and depot contraceptives.
• Alternate methods of effective contraception should also be considered during and after the discontinuation of modafinil.
• Patients who have taken modafinil while pregnant should be monitored for any adverse effects.

Use while breastfeeding

• Breast milk contains armodafinil which is the active metabolite modafinil.
• After long-term modafinil of 250mg daily, breast milk samples were taken in 24 hours by a woman who had given birth 19 days before.
• Peak armodafinil concentrations occurred two hours after the maternal dose. They decreased over the dosing period. She did not breastfeed her infant.
• Breastfeeding should be done with caution, as active metabolites are secreted and safety is not known.

Dose in Kidney Disease:

There is no need for any modification in the dose.

Dose in Liver disease:

• Mild to moderate hepatic impairment:

  • There is no need for any modification in the dose.

• Severe hepatic illness:

  • Patients with the hepatic disease must be given half of the suggested dose.

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):

Hypersensitivity to modafinil or armodafinil has been reported.

Labeling in Canada: Further contraindications not mentioned in the US labeling

• Females who might become pregnant by a male partner
• Patients with severe anxiety or in agitated states;

Warnings and precautions

• CNS effects

  • Caution is advised when engaging in activities that could pose risks, such as diving, high-roof activities, or driving.

• Dermatologic effects (severe).

  • There have been cases of potentially fatal severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.
  • Post-marketing cases were also discovered in adults, despite the fact that clinical trials had initially documented cases in children.
  • Within the first five weeks of therapy, the majority of cases happen. However, after repeated use, uncommon situations may occur (eg 3 months).
  • You must stop using the drug immediately after you notice a rash.
  • FDA has withdrawn modafinil from pediatrics with ADHD.

• Hypersensitivity reactions

  • Rarely, there have been fatal allergic reactions to modafinil.
  • Patients with organ-system dysfunction can have fever and rash, which may vary depending on their clinical picture.
  • These symptoms should be reported to the doctor immediately. Treatment discontinuation is recommended.

• Cardiovascular disease

  • Cardiovascular disease is a serious problem. Regular vital monitoring is recommended.
  • This drug should not be used by anyone who has left ventricular hypertrophy, mitral valve prolapse syndrome, or a history of the condition.
  • Patients with irregular chest pains or heart damage should have a higher heart rate and blood pressure measurement.

• Hepatic impairment

  • Patients with hepatic disease should be careful.
  • Patients with severe hepatic impairment should reduce their dosage.

• Psychiatric disorders

  • Patients who have previously had mania, depression, or psychosis should exercise caution.
  • If you experience psychiatric symptoms, it is worth considering quitting therapy.

• Renal impairment

  • Patients with impaired renal function should exercise caution.

• Seizure disorder

  • The usage of stimulants like modafinil in people with ADHD or seizure disorders is not well understood.
  • Patients with ADHD have a higher risk of seizure activity than the general population.
  • However, a retrospective analysis using data from drug claims showed that patients who used stimulant medication had a lower risk.
  • Some stimulant manufacturers recommend that you stop taking the medication if you experience seizures.

• Sleep disorders

  • Use only when necessary: Some patients may not respond to the treatment. 
  • Modafinil can be used to manage excessive sleepiness in patients with obstructive sleeping apnea.
  • Modafinil cannot treat underlying obstructions. 
  • Modafinil is not recommended for patients with persistent positive airway pressure (CPAP).
  • Patients who are unable to tolerate CPAP should make every effort to get CPAP treatment for their excessive sleepiness.

• Tourette syndrome/tics

  • Patients with tic disorders such as Tourette syndrome should take precautions.
  • Stimulants can cause Tourette syndrome and motor and phonic tics.
  • Before you start the therapy, make sure to check for Tourette syndrome and tics.

Monitoring parameters:

• Assess levels of wakefulness. 
• Patients with unstable angina or recent MI need to have vital monitoring. 
• A minimum of one week must be spent assessing a female of reproductive age for pregnancy before treatment can begin.
• You should monitor for any skin reactions.

How to administer Modafinil (Modiodal)?

• To treat shift work sleep disturbance, the drug should be taken around an hour before to the start of the shift.
• Narcolepsy and obstructive sleep apnea/hypopnea syndrome to be managed by administering once-daily dosing in the morning.

Mechanism of action of Modafinil (Modiodal):

• It is unknown what the exact mechanism might be. 
• The brain does not produce dopamine unless it blocks dopamine transporters. 
• EEG studies can be used to increase high-frequency alpha waves and decrease delta waves.
• These findings suggest an improvement in mental alertness (James 2011, 2011). 
• Research also shows an increase in the activity of serotonin receptors as well as a decrease in GABA transmission.
• Due to the fact that modafinil is a racemic molecule with either a 10% S-isomer or a 90% R-isomer at a constant state, it has a variety of pharmacokinetics.

Half-life elimination:

• Effective half-life: 15 hours

Metabolism:

• Hepatic; multiple pathways including CYP3A4

Excretion:

• Urine (80% as metabolites, <10% as unchanged drug);
• feces (1%)

Time to peak, serum:

• 2 to 4 hours;
• Maybe delayed ~1 hour with food.

Protein binding:

• ~60%, primarily to albumin

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: