Pitolisant - About a Newest FDA - Approved Drug for Narcolepsy

Overview

Pitolisant is a pharmaceutical drug that belongs to a class of medications called H3 blockers and is used in the treatment of narcolepsy. This chronic neurological disorder primarily affects the brain’s ability to regulate the sleep-wake cycle. The drug attempts to improve brain functions by helping an individual stay awake during the day, which is achieved by enhancing the activity of histaminergic neurons in the brain. The drug was first approved by the Food and Drug Administration (FDA) in August 2019.

This article extensively briefs about Pitolisant as a useful therapy option for those suffering from narcolepsy. It additionally covers the mechanism of action, available dosage, dosage forms, usage, potential adverse effects, and precautions. Understanding the advantages and factors to be taken into account when using this medicine will help patients and healthcare professionals make well-informed decisions to manage narcolepsy as effectively as possible.

Drug Group

Pitolisant is a pharmaceutical drug that belongs to H3 blockers. These blockers have great potential to treat diverse disease states of the central nervous system. This drug is commonly used to treat excessive daytime sleepiness, which is caused due to narcolepsy. It also additionally treats the episodes of muscle weakness that begin suddenly and last for a shorter duration in cataplexy.

Available Doses and Dosage Forms:

The drug is available in varying doses specific to each country. Some commonly available doses include 4.5 milligrams (mg), nine mg, and 18 mg. The drug is primarily available in the form of tablets. According to each patient's unique condition, the intensity of their symptoms, and how they react to therapy, a particular dose will be recommended. To ensure the safe and effective use of the drug, patients must carefully follow the dose recommendations made by their healthcare professionals.

For Patients:

What Is Narcolepsy?

A neurological disorder that primarily affects the brain to regulate the sleep-wake cycle and is characterized by excessive daytime sleepiness is called narcolepsy. Sometimes, there are uncontrolled bouts of sleep known as sleep attacks. People with this condition find it challenging to stay awake during the day and may experience sudden urges to fall asleep at inappropriate times.

The symptoms of narcolepsy are mentioned below:

• Excessive daytime sleep.

• Sleep paralysis.

• Disrupted nighttime sleep.

• Hallucinations.

How Does Pitolisant Work?

The mechanism of action of the drug is mentioned below:

• Histamine Regulation - The neurotransmitter histamine is important in promoting wakefulness and alertness. The H3 brain receptors act as auto and heteroreceptors that regulate histamine release with other neurotransmitters like dopamine and serotonin.

• H3 Receptor Antagonism - Pitolisant blocks or inhibits the activity of H3 receptors. This increases the release of histamine and promotes neurotransmitters in the brain.

• Increased Wakefulness - By increasing the release of histamine and inhibiting the H3 receptor, it enhances the secretion of other hormones. Thereby it reduces excessive daytime sleep.

What Is the Dosage of Pitolisant?

• Adult Dosage - The starting drug dosage in adults is usually 4.5 mg, once daily in the morning. The dose is gradually increased depending on the response of the individual. The maintenance dosage is between 17.8 mg and 35.6 mg, which is administered in a single dose or divided into two doses.

• Dosage Modifications - The dosage may be modified according to individual factors like the severity of narcolepsy and other medical conditions or medications that are taken by the person. In addition, age-related factors, body weight, and kidney and liver function may also influence the appropriate dosage.

How Effective Is Pitolisant?

The drug is effective in treating excessive daytime sleep in adults with narcolepsy. Various clinical trials have demonstrated the effectiveness of the drug.

How Is Pitolisant Administered?

The drugs are available only in the form of oral formulations. Hence it has to be taken once a day with or without food in the morning. It is better to consume the drug at the same time every day.

What Are the Side Effects of Pitolisant?

A few side effects of the drug are listed below:

• Headache.

• Nausea.

• Loss of appetite.

• Stomach pain.

• Muscle pain.

• Staying asleep.

• Joint pain.

What Are the Things to Inform the Doctor Before Taking Pitolisant?

The following are the most important details to tell the doctor:

• Allergies: Patients should identify all known allergies to foods, drugs, and other substances in detail. This includes any prior negative drug interactions with antispasmodics or similar agents.

• Medical History: Patients must give any relevant information about their health history, including any current or previous problems. If a patient has a history of heart, liver, kidney, or any other pertinent problems, they should specifically let their doctor know.

• Current Medications: Patients should inform the physician about any prescription pharmaceuticals, over-the-counter medicines, dietary supplements, or herbal items they use. Pitolisant and other drugs may interact, which might have adverse effects or lessen their efficacy.

• Breastfeeding and Pregnancy: Patients who are pregnant, want to become pregnant, or are nursing should talk to their doctor about these matters. Pitolisant’s safety during pregnancy and breastfeeding has not been thoroughly proven, and the doctor can weigh the advantages and disadvantages.

• Surgery: Patients should notify their doctor or surgeon about using Pitolisant if they are planning any surgical operations, including dental surgery since this might affect the anesthesia or other drugs used during the procedure.

• Functions of Liver and Kidneys: Patients who suffer from liver or renal dysfunction should inform their doctor about any impairment in these organs. In certain circumstances, dosage modifications may be required.

• Alcohol Use: Patients should be honest with their doctors about their alcohol use since it may interact with Pitolisant and worsen some adverse effects.

• Hypersensitivity: Patients should talk to their doctor if they ever have a hypersensitivity reaction to a medicine.

Dietary Considerations:

• It is advised to take Pitolisant with or without meals. But taking it an hour or so before meals may increase its efficiency in minimizing gastrointestinal spasms and related symptoms.

• While using the side effects of Pitolisant, it is best to refrain from drinking because alcohol may interact with the drug and worsen some adverse effects.

• Some may discover that particular meals or drinks may worsen their stomach issues. To uncover potential dietary components that might influence symptom management, keeping a food diary and recording any triggers can be beneficial.

• Maintaining a balanced, healthy diet of fiber, fruits, and vegetables can improve gastrointestinal health. Still, it is essential to talk with a doctor about specific dietary needs, especially if the patient has underlying digestive problems or dietary restrictions.

Missed Dose:

If a dose of Pitolisant is forgotten, the patient should take it as soon as they remember. However, if it is almost time for the next scheduled dose, they should skip the missed dose and resume their regular dosing schedule. Taking a double dose to compensate for the missed one should be avoided.

Overdose:

In the event of an overdose, which can lead to severe side effects, individuals should promptly seek immediate medical attention or contact a poison control center. Overdose symptoms may include a pronounced dry mouth, rapid or irregular heartbeat, fever, confusion, hallucinations, and difficulty swallowing or speaking.

Storage and Disposal:

• Pitolisant must be stored at room temperature, away from moisture and direct sunlight. Keep the medication out of reach of children and pets.

• Do not use Pitolisant after the expiration date stated on the packaging.

• If there are unused or expired medications, individuals should follow proper disposal guidelines as instructed by local regulations or a healthcare professional.

• They should avoid flushing them down the toilet or pouring them into drains unless specifically directed to do so.

For Doctors:

Indication:

Pitolisant treats irregular sleep-wake cycles caused by narcolepsy and its symptoms. It is categorized as an H3 blocker that works to calm brain activity and helps to release other neurotransmitters by increasing the release of histamine.

Dose:

The medical professional decides the dosage to be administered based on the patient's condition, the intensity of their symptoms, and how they react to the therapy. The first dose for adults is often 4.5 grams (g) administered orally once daily.

What Are the Pharmacological Aspects of Pitolisant?

1. Mechanism:

Pitolisant is an H3 receptor blocker that enhances the secretion of histamine to regulate the sleep cycle and prevents narcolepsy. This helps an individual to stay awake during the day without feeling drowsy.

2. Pharmacokinetics:

• Pitolisant is given orally in tablet form, and the gastrointestinal tract readily absorbs it.

• The drug is metabolized in the liver through hepatic metabolism, which results in active metabolites that support the medication's pharmacological effects.

• Pitolisant has a variable elimination half-life, although it lasts between ten to 12 hours, indicating it takes this long for half of the medication to leave the body.

• A tiny amount of the medicine is removed from the feces, but most of it is excreted in the urine.

• The dose regimen and interval are influenced by the pharmacokinetic features of Pitolisant, ensuring optimal levels of the medicine for symptom alleviation while preventing excessive drug buildup.

3. Toxicity

• Pitolisant is typically well tolerated when administered at therapeutic levels to treat narcolepsy.

• The most commonly reported clinical side effects include headache, nausea, vomiting, stomach pain, and staying asleep. As the body becomes used to the medicine, these adverse effects are often brief, moderate, and improve with time.

• Some people may develop more severe clinical side effects, including allergic reactions, difficulties urinating, and an elevated heart rate. Patients should seek quick medical assistance if these significant adverse effects manifest.

4. Drug Interactions:

• Pitolisant enhances the effects of CNS (central nervous system) effects like benzodiazepines, opioids, and antihistamines. So their combination may cause more drowsiness.

• Pitolisant is metabolized by CYP3A4, which may affect the metabolism of the drugs and may cause adverse effects.

• Pitolisant, when administered with monoamine oxidase, is known to increase serotonin syndrome, which can be a life-threatening condition.

• Pitolisant prolongs the QT interval when used with antidepressants.

• Pitolisant tends to reduce the effectiveness of birth control pills. So alternative contraceptive methods are recommended.

5. Clinical Studies:The drug has undergone various clinical studies to assess its effectiveness in treating excessive sleep during the daytime. An important study about the drug is mentioned below:

• The Phase III trial of the drug in assessing the efficacy and safety in 131 adults was conducted. The trial found the drug had significantly reduced daytime sleep compared to placebo, demonstrating a sustained improvement. Hence it was safe to use in adults with narcolepsy.

What Are the Contraindications?

Pitolisant contraindications include:

• Individuals with a history of allergy or hypersensitivity should avoid using this drug.

• The drug is metabolized in the liver, so individuals with severe liver impairment should avoid using the medication.

• The use of this drug with monoamine oxidase inhibitors is contraindicated due to the risks like hallucinations and rapid heart rate.

• Pregnant and breastfeeding should avoid this drug, as there are no well-established reports about their caution.

Considerations for Dosing:

• Patients who are elderly or have certain medical issues could need lower initial dosages, and the dosage can be changed as necessary.

• Pitolisant is typically not advised for use in children unless expressly prescribed; hence, a pediatric physician should establish the dosage and administration for pediatric patients.

• Pitolisant should be taken exactly as the doctor suggests, and the recommended dosage should not be increased.

• Even if symptoms improve, patients should keep taking Pitolisant for the entire period the doctor recommends.

• It is not advisable to stop taking the drug suddenly without first talking to a doctor because it might cause withdrawal symptoms to recur.

• Any other prescription drugs, dietary supplements, or herbal items must be disclosed to the healthcare professional since they may interact with Pitolisant.

Specific Considerations:

• Patients should abstain from drinking alcohol while taking Pitolisant since the drug's adverse effects may be exacerbated by alcohol.

• Older patients may be more vulnerable to Pitolisant's side effects and interactions with other drugs. There may need to be dose modifications or close monitoring.

• To reduce the danger of potential drug interactions, adhere to the healthcare provider's recommendations.

• Any odd symptoms or side effects that occur while taking should be Pitolisant reported immediately to the patient's healthcare practitioner for further analysis.