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Pitolisant

Medically reviewed by Drugs.com. Last updated on Sep 16, 2020.

Pronunciation

(pi TOL i sant)

Index Terms

  • Pitolisant Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Wakix: 4.45 mg, 17.8 mg

Brand Names: U.S.

  • Wakix

Pharmacologic Category

  • Central Nervous System Stimulant
  • Histamine-3 (H3) Receptor Antagonist/Inverse Agonist

Pharmacology

The mechanism of action of pitolisant is unclear, but may be mediated through its activity as an antagonist/inverse agonist at histamine-3 receptors.

Absorption

~90%

Distribution

Vd: 700 L (5 to 10 L/kg)

Metabolism

Metabolized by CYP2D6 and to a lesser extent by CYP3A4 to inactive metabolites

Excretion

Urine: ~90% (<2% as unchanged drug); feces: 2.3%

Onset of Action

In the treatment of narcolepsy, it may take up to 8 weeks for patients to achieve a clinical response.

Time to Peak

Tmax: 3.5 hours (2 to 5 hours)

Half-Life Elimination

~20 hours (7.5 to 24.2 hours)

Protein Binding

91% to 96%

Special Populations Note

The AUC in CYP2D6 poor metabolizers is 2.4 times higher than in normal metabolizers.

Use: Labeled Indications

Narcolepsy: Treatment of cataplexy or excessive daytime sleepiness in adults with narcolepsy.

Contraindications

Hypersensitivity to pitolisant or any component of the formulation; severe hepatic impairment.

Dosing: Adult

Note: International considerations: Tablet strengths are listed as 4.5 mg and 18 mg in international product labeling, whereas US products are listed as 4.45 mg and 17.8 mg.

Narcolepsy (excessive daytime sleepiness/cataplexy): Oral: Initial: 8.9 mg once daily for 1 week, then increase to 17.8 mg once daily for 1 week; may further increase dose based on response and tolerability during week 3 to a maximum dose of 35.6 mg once daily.

Missed dose: If morning dose is missed, administer the next dose the following morning upon awakening.

Dosage adjustment for known CYP2D6 poor metabolizers: Initial (treatment-naïve): 8.9 mg once daily; may further increase dose based on response and tolerability after 1 week to a maximum dose of 17.8 mg once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Administration

Oral: Administer once daily upon awakening.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Drug Interactions

Ajmaline: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Antihistamines: May diminish the therapeutic effect of Pitolisant. Avoid combination

Cobicistat: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Pitolisant. Monitor therapy

CYP2D6 Inhibitors (Strong): May increase the serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients receiving strong CYP2D6 inhibitors, initiate pitolisant at 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Pitolisant. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Consider therapy modification

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Hormonal Contraceptives: Pitolisant may decrease the serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. Consider therapy modification

Lumefantrine: May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

Mirtazapine: May diminish the therapeutic effect of Pitolisant. Avoid combination

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Tricyclic Antidepressants: May diminish the therapeutic effect of Pitolisant. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Central nervous system: Headache (18%)

1% to 10%:

Cardiovascular: Increased heart rate (3%)

Central nervous system: Insomnia (6%), anxiety (5%), hallucination (3%), irritability (3%), sleep disturbance (3%), cataplexy (2%)

Dermatologic: Skin rash (2%)

Gastrointestinal: Nausea (6%), abdominal pain (3%), decreased appetite (3%), xerostomia (2%)

Neuromuscular & skeletal: Musculoskeletal pain (5%)

Respiratory: Upper respiratory tract infection (5%)

Frequency not defined:

Cardiovascular: Prolonged QT interval on ECG, tachycardia

Central nervous system: Migraine, sleep paralysis, sleep talking

Postmarketing: Abnormal behavior, abnormal dreams, bipolar mood disorder, depressed mood, depression, epilepsy, fatigue, lack of emotion (anhedonia), nightmares, pruritus, sleep disorder, suicidal ideation, suicidal tendencies, weight gain

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular: May prolong the QT interval; avoid use in patients with known QT prolongation or concomitant use with other agents known to prolong the QT interval. Risk may be greater in patients with hepatic or renal impairment. Avoid use in patients with a known history of cardiac arrhythmias or circumstances that may increase the risk of torsades de pointes or sudden death (eg, symptomatic bradycardia, hypokalemia, hypomagnesemia, congenital prolongation of the QT interval).

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; may require dose adjustment. Use is contraindicated in severe hepatic impairment (Child-Pugh class C).

• Renal impairment: Use with caution in patients with renal impairment; dose adjustment required. Use is not recommended in patients with end-stage renal disease (eGFR <15 mL/minute/1.73 m2).

Monitoring Parameters

Renal and hepatic function (at baseline and as clinically indicated)

Reproductive Considerations

Pitolisant may reduce the effectiveness of hormonal contraceptives. Females of reproductive potential should be advised to use an alternative nonhormonal contraceptive method during treatment and for ≥21 days after the last dose of pitolisant.

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Data collection to monitor pregnancy and infant outcomes following exposure to pitolisant is ongoing. Patients exposed to pitolisant during pregnancy are encouraged to enroll in the Pregnancy Registry (1-800-833-7460).

Patient Education

What is this drug used for?

• It is used to treat a lot of sleepiness during the day in patients with narcolepsy.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Trouble sleeping

• Nausea

• Anxiety

• Common cold symptoms

• Muscle pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Fast heartbeat

• Abnormal heartbeat

• Passing out

• Signs of an allergic reaction, like 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; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.