Wakix 4.45mg Tablets
It is used to treat severe sleepiness during the day in patients with narcolepsy.It is used to treat sudden loss of muscle tone (cataplexy) in patients with narcolepsy.
Drug Class
Wakefulness-promoting agent
Pharmacologic Class
Histamine-3 (H3) receptor antagonist/inverse agonist
Pregnancy Category
Not available
FDA Approved
Aug 2019
DEA Schedule
Not Controlled
Overview
What is this medicine?
Wakix is a medication used to help people with narcolepsy or idiopathic hypersomnia stay awake during the day. It works by increasing the activity of a natural chemical in your brain called histamine, which helps promote wakefulness.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your dose in the morning, as soon as you wake up.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry location, avoiding storage in a bathroom. Ensure that all medications are stored in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose, skip it and resume your normal dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your dose in the morning, as soon as you wake up.
Storing and Disposing of Your Medication
Keep your medication at room temperature in a dry location, avoiding storage in a bathroom. Ensure that all medications are stored in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose, skip it and resume your normal dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Take Wakix exactly as prescribed, usually once daily in the morning upon waking.
- Do not take a double dose if you miss a dose. Skip the missed dose and take your next dose at the regular time.
- Avoid alcohol and other medicines that can make you drowsy, as Wakix can increase these effects.
- Be aware that Wakix may reduce the effectiveness of hormonal birth control. Discuss alternative or additional birth control methods with your doctor.
- Inform your doctor about all other medications you are taking, including over-the-counter drugs, vitamins, and herbal supplements, especially those that affect heart rhythm or are metabolized by the liver.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 4.45 mg orally once daily, titrate weekly based on tolerability and efficacy. May increase to 8.9 mg, then 17.8 mg, then maximum 35.6 mg once daily.
Dose Range:
4.45 - 35.6 mg
Condition-Specific Dosing:
Narcolepsy:
Initial 4.45 mg, titrate to 8.9 mg, 17.8 mg, or 35.6 mg once daily.
Idiopathic Hypersomnia:
Initial 4.45 mg, titrate to 8.9 mg, 17.8 mg, or 35.6 mg once daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed (CrCl 60-89 mL/min)
Moderate:
Maximum dose 17.8 mg once daily (CrCl 30-59 mL/min)
Severe:
Avoid use (CrCl < 30 mL/min)
Dialysis:
Avoid use
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A)
Moderate:
Maximum dose 17.8 mg once daily (Child-Pugh B)
Severe:
Avoid use (Child-Pugh C)
Pharmacology
Mechanism of Action
Pitolisant is a selective histamine-3 (H3) receptor antagonist/inverse agonist. By blocking H3 autoreceptors, it increases the synthesis and release of histamine from histaminergic neurons in the brain, leading to increased wakefulness. It also modulates the activity of other neurotransmitter systems, including acetylcholine, norepinephrine, and dopamine, through indirect mechanisms.
Pharmacokinetics
Absorption:
Bioavailability:
Not available
Tmax:
3.5 hours
FoodEffect:
Food does not affect absorption.
Distribution:
Vd:
Not available
ProteinBinding:
82-92%
CnssPenetration:
Yes
Elimination:
HalfLife:
20 hours
Clearance:
Not available
ExcretionRoute:
Primarily renal (90%), some fecal (3%)
Unchanged:
Not available
Pharmacodynamics
OnsetOfAction:
Not precisely defined, clinical effects observed within weeks of titration.
PeakEffect:
Not precisely defined, steady state reached after approximately 7 days.
DurationOfAction:
24 hours (once daily dosing)
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help Immediately
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Hallucinations (seeing or hearing things that are not there)
Abnormal heartbeat (prolonged QT interval), which can cause:
+ Fast heartbeat
+ Irregular heartbeat
+ Fainting (passing out)
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help:
Headache
Trouble sleeping
Upset stomach
Anxiety
Signs of a common cold
* Pain in the back, joints, muscles, neck, arms, or legs
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, contact your doctor for medical advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical attention right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Hallucinations (seeing or hearing things that are not there)
Abnormal heartbeat (prolonged QT interval), which can cause:
+ Fast heartbeat
+ Irregular heartbeat
+ Fainting (passing out)
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms, contact your doctor or seek medical help:
Headache
Trouble sleeping
Upset stomach
Anxiety
Signs of a common cold
* Pain in the back, joints, muscles, neck, arms, or legs
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, contact your doctor for medical advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- New or worsening heart palpitations, dizziness, or fainting (may indicate QTc prolongation)
- Severe headache
- Severe insomnia or anxiety
- Signs of an allergic reaction (e.g., rash, itching, swelling, severe dizziness, trouble breathing)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
Existing health conditions, including:
+ Kidney disease or liver disease
+ Low levels of magnesium or potassium in your blood
+ A slow heartbeat
+ A history of abnormal heart rhythms, such as a prolonged QT interval on an electrocardiogram (ECG)
If you are taking any medications that can cause abnormal heart rhythms, including a prolonged QT interval. There are many drugs that can have this effect, so ask your doctor or pharmacist if you are unsure.
If you are currently taking any of the following medications:
+ Clomipramine
+ Diphenhydramine
+ Imipramine
+ Mirtazapine
+ Pheniramine
+ Promethazine
This list is not exhaustive, and it is crucial to inform your doctor and pharmacist about all the medications you are taking, including:
Prescription and over-the-counter (OTC) medications
Natural products
* Vitamins
Your doctor needs to be aware of all your medications and health conditions to ensure it is safe for you to take this medication. Do not start, stop, or change the dose of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
Existing health conditions, including:
+ Kidney disease or liver disease
+ Low levels of magnesium or potassium in your blood
+ A slow heartbeat
+ A history of abnormal heart rhythms, such as a prolonged QT interval on an electrocardiogram (ECG)
If you are taking any medications that can cause abnormal heart rhythms, including a prolonged QT interval. There are many drugs that can have this effect, so ask your doctor or pharmacist if you are unsure.
If you are currently taking any of the following medications:
+ Clomipramine
+ Diphenhydramine
+ Imipramine
+ Mirtazapine
+ Pheniramine
+ Promethazine
This list is not exhaustive, and it is crucial to inform your doctor and pharmacist about all the medications you are taking, including:
Prescription and over-the-counter (OTC) medications
Natural products
* Vitamins
Your doctor needs to be aware of all your medications and health conditions to ensure it is safe for you to take this medication. Do not start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. The full effect of this drug may not be apparent until up to 8 weeks after starting treatment.
If you are using birth control pills or other hormone-based birth control methods, they may be less effective in preventing pregnancy while taking this medication. To minimize the risk of unplanned pregnancy, use an additional form of birth control, such as a condom, during treatment with this drug and for 3 weeks after discontinuing it.
If you are pregnant, planning to become pregnant, or are breast-feeding, notify your doctor immediately. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
If you are using birth control pills or other hormone-based birth control methods, they may be less effective in preventing pregnancy while taking this medication. To minimize the risk of unplanned pregnancy, use an additional form of birth control, such as a condom, during treatment with this drug and for 3 weeks after discontinuing it.
If you are pregnant, planning to become pregnant, or are breast-feeding, notify your doctor immediately. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
Overdose Information
Overdose Symptoms:
- Insomnia
- Headache
- Nausea
- Abdominal pain
- Vomiting
- Dizziness
- Irritability
- QTc prolongation (potential)
What to Do:
Seek immediate medical attention or call Poison Control at 1-800-222-1222. Treatment is symptomatic and supportive. Consider ECG monitoring due to potential for QTc prolongation.
Drug Interactions
Major Interactions
- Strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine, bupropion)
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's Wort)
- Drugs that prolong the QT interval (e.g., Class IA and Class III antiarrhythmics, some antipsychotics, some antidepressants, some antibiotics)
Moderate Interactions
- Moderate CYP2D6 inhibitors
- Moderate CYP3A4 inducers
- Moderate CYP3A4 inhibitors (e.g., erythromycin, diltiazem, verapamil, grapefruit juice)
- Hormonal contraceptives
Monitoring
Baseline Monitoring
Electrocardiogram (ECG)
Rationale: To assess for baseline QTc interval and identify patients at increased risk for QTc prolongation.
Timing: Prior to initiation of therapy
Liver function tests (LFTs)
Rationale: To assess hepatic function, as dose adjustments are needed in hepatic impairment.
Timing: Prior to initiation of therapy
Renal function tests (e.g., CrCl)
Rationale: To assess renal function, as dose adjustments are needed in renal impairment.
Timing: Prior to initiation of therapy
Routine Monitoring
Electrocardiogram (ECG)
Frequency: Periodically, especially in patients with cardiac disease or other risk factors for QTc prolongation, or when co-administered with other QTc-prolonging drugs.
Target: QTc < 450 ms (males), < 470 ms (females)
Action Threshold: Discontinue if QTc > 500 ms or if QTc increases by > 60 ms from baseline.
Efficacy (e.g., Epworth Sleepiness Scale)
Frequency: During dose titration and periodically thereafter
Target: Improvement in excessive daytime sleepiness
Action Threshold: Lack of efficacy or intolerable side effects may warrant dose adjustment or discontinuation.
Adverse effects (e.g., insomnia, anxiety, headache, nausea)
Frequency: Regularly, especially during dose titration
Target: Tolerable side effect profile
Action Threshold: Persistent or severe adverse effects may warrant dose reduction or discontinuation.
Symptom Monitoring
- Excessive daytime sleepiness (improvement)
- Insomnia
- Anxiety
- Headache
- Nausea
- Upper respiratory tract infection symptoms
- Palpitations, dizziness, syncope (signs of QTc prolongation)
- Signs of hypersensitivity reactions
Special Patient Groups
Pregnancy
Wakix may cause fetal harm. Based on animal studies, it is embryotoxic and fetotoxic. Advise females of reproductive potential to use effective contraception during treatment and for at least 21 days after the last dose.
Trimester-Specific Risks:
First Trimester:
Potential for embryotoxicity and fetotoxicity based on animal data.
Second Trimester:
Potential for fetotoxicity based on animal data.
Third Trimester:
Potential for fetotoxicity based on animal data.
Lactation
It is unknown if pitolisant is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, advise women not to breastfeed during treatment with Wakix and for at least 21 days after the last dose.
Infant Risk:
Potential for serious adverse reactions (e.g., CNS effects, cardiac effects) in breastfed infants. Risk is unknown but considered moderate to high.
Pediatric Use
Safety and effectiveness in pediatric patients (under 18 years of age) have not been established.
Geriatric Use
No specific dose adjustment is required based on age alone. However, consider age-related decreases in renal and hepatic function, and increased susceptibility to adverse effects. Start at the lower end of the dosing range and titrate carefully.
Clinical Information
Clinical Pearls
- Wakix is the first and only FDA-approved treatment for narcolepsy that is not a controlled substance.
- It is also approved for idiopathic hypersomnia, making it a unique option for this condition.
- Dose titration is crucial and should be done weekly based on patient response and tolerability.
- Patients should be advised about the potential for QTc prolongation, especially if they have pre-existing cardiac conditions or are on other QTc-prolonging medications.
- Counsel patients on the potential for reduced efficacy of hormonal contraceptives and advise on alternative birth control methods.
- Avoid concomitant use with strong CYP2D6 inhibitors, strong CYP3A4 inducers, and drugs known to prolong the QT interval.
Alternative Therapies
- Modafinil
- Armodafinil
- Sodium oxybate
- Solriamfetol
- Methylphenidate
- Amphetamines
Cost & Coverage
Average Cost:
Highly variable, typically several thousand USD per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.