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Pitolisant: Drug information

Pitolisant: Drug information
(For additional information see "Pitolisant: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Wakix
Brand Names: Canada
  • Wakix
Pharmacologic Category
  • Central Nervous System Stimulant;
  • Histamine-3 (H3) Receptor Antagonist/Inverse Agonist
Dosing: Adult

Note: Dosage form considerations: Dosing below is based on pitolisant base. In the United States, tablet strengths are listed as 4.45 mg and 17.8 mg (pitolisant base); whereas, international products may be listed as 4.5 mg and 18 mg (approximate pitolisant base amount), and Canadian products are listed as 5 mg and 20 mg (pitolisant hydrochloride).

Narcolepsy

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-naive): 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: Kidney Impairment: Adult

eGFR ≥60 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling.

eGFR 15 to <60 mL/minute/1.73 m2: Initial: 8.9 mg once daily for 1 week, then increase to a maximum dose of 17.8 mg once daily.

eGFR <15 mL/minute/1.73 m2 (end-stage renal disease): Use is not recommended.

Dosing: Hepatic Impairment: Adult

Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate hepatic impairment (Child-Pugh class B): Initial: 8.9 mg once daily for 2 weeks, then increase to a maximum dose of 17.8 mg once daily.

Severe hepatic impairment (Child-Pugh class C): Use is contraindicated; has not been studied.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

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

Tablet, Oral:

Wakix: 4.45 mg, 17.8 mg

Generic Equivalent Available: US

No

Dosage Forms: Canada

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

Tablet, Oral, as hydrochloride:

Wakix: 5 mg, 20 mg

Administration: Adult

Oral: Administer once daily upon awakening. The Canadian product monograph recommends administration with food and not to chew, crush, or divide the tablets.

Use: Labeled Indications

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

Medication Safety Issues
Sound-alike/look-alike issues:

Pitolisant may be confused with Pitocin

Wakix may be confused with Lasix

International issues:

Pitolisant may be confused with Pitogin brand name for oxytocin [Indonesia].

Wakix: Brand name for pitolisant [US] may be confused with Walix brand name for oxaprozin [Italy] or Warix brand name for podofilox [Switzerland].

Adverse Reactions

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

>10%: Nervous system: Headache (18%)

1% to 10%:

Cardiovascular: Increased heart rate (3%)

Dermatologic: Skin rash (2%)

Gastrointestinal: Abdominal pain (3%), decreased appetite (3%), nausea (6%), xerostomia (2%)

Nervous system: Anxiety (5%), cataplexy (2%), hallucination (3%), insomnia (6%), irritability (3%), sleep disturbance (3%)

Neuromuscular & skeletal: Musculoskeletal pain (5%)

Respiratory: Upper respiratory tract infection (5%)

Frequency not defined:

Cardiovascular: Prolonged QT interval on ECG, tachycardia

Nervous system: Migraine, sleep paralysis, sleep talking

Postmarketing:

Dermatologic: Pruritus

Endocrine & metabolic: Weight gain

Hypersensitivity: Anaphylaxis, hypersensitivity reaction

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

Contraindications

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

Canadian labeling: Additional contraindications (not in the US labeling): Breastfeeding.

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).

Metabolism/Transport Effects

Substrate of CYP2D6 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

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

CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Pitolisant. Risk C: 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. Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Pitolisant may decrease the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: 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. Risk D: Consider therapy modification

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

Mirtazapine: May diminish the therapeutic effect of Pitolisant. Risk X: 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). Risk C: Monitor therapy

Promethazine: May diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination

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. Risk C: Monitor therapy

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

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).

Breastfeeding Considerations

It is not known if pitolisant is present in breast milk

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

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

Mechanism of Action

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

Pharmacokinetics

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

Absorption: ~90%

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

Protein binding: 91% to 96%

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

Half-life elimination: ~20 hours (7.5 to 24.2 hours)

Time to peak: Tmax: 3.5 hours (2 to 5 hours)

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

Pricing: US

Tablets (Wakix Oral)

4.45 mg (per each): $136.10

17.8 mg (per each): $272.20

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Wakix (AT, BE, CZ, DE, DK, EE, FI, FR, GB, HR, HU, IE, LT, LU, LV, NL, NO, PL, RO, SE, SK)


For country code abbreviations (show table)
  1. Wakix (pitolisant) [prescribing information]. Plymouth Meeting, PA: Harmony Biosciences LLC; March 2021.
  2. Wakix (pitolisant) [product monograph]. Quebec, Canada: Paladin Labs Inc; August 2021.
Topic 122332 Version 52.0