Narcolepsy is Characterized by Unstable Wakefulness1,2

All patients with narcolepsy have chronic, daily, excessive daytime sleepiness (EDS).3

  • The inability to stay awake and alert throughout the day3
  • Daily periods of an irrepressible need for sleep3
  • Unintended lapses into drowsiness or sleep3
  • More likely to occur in sedentary, boring, and monotonous situations3
  • May also occur in unexpected situations3

Loss of hypocretin neurons in patients with narcolepsy leads to reduced activation of histamine and other wake-promoting neurons, ultimately causing EDS3,4

  • May lead to periodic activation of non-REM sleep-promoting neurons and REM sleep-promoting neurons, further exacerbating EDS2,5,6

Histamine is important for promoting wakefulness7-9

  • In the brain, hypocretin and histamine neurons both originate only in the hypothalamus and play complementary roles1,7-9
  • Histamine promotes wakefulness by activating the cortex and activating other wake-promoting neurons9
    • Histamine also directly and indirectly inhibits non-REM sleep-promoting neurons and REM sleep-promoting neurons7-9

Ongoing or unrecognized symptoms can have significant impact6,10,11

  • In a national survey of 200 people living with narcolepsy*12:
88%
(n=176)
  • Indicated their symptoms were not completely or mostly under control13
86%
(n=173)
  • Reported changing their lives because of the disorder13
94%
(n=188)
  • Agreed new treatment options are needed13

* The Know Narcolepsy® Survey was a 3-part survey of 1654 US adults including those with narcolepsy (n=200), the general public (n=1203), and physicians (n=251) currently in clinical practice who have treated patients with narcolepsy in the last 2 years. Surveys of people with narcolepsy and the general public were conducted online in March and April 2018, and physicians were surveyed in August 2018. Versta Research conducted the survey on behalf of Harmony Biosciences, LLC.12 The Narcolepsy Network collaborated on the patient survey. Eighty-four percent (n=169) of respondents with narcolepsy were taking medications for their narcolepsy.13

INDICATIONS AND USAGE & IMPORTANT SAFETY INFORMATION

  • WAKIX® (pitolisant) is indicated for the treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy.

IMPORTANT SAFETY INFORMATION

Contraindications

  • WAKIX is contraindicated in patients with severe hepatic impairment.

Warnings and Precautions

  • WAKIX prolongs the QT interval; avoid use of WAKIX in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval. Avoid use in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval.
  • The risk of QT prolongation may be greater in patients with hepatic or renal impairment due to higher concentrations of pitolisant; monitor these patients for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment (see full prescribing information). WAKIX is not recommended in patients with end-stage renal disease (ESRD).

Adverse Reactions

  • In the placebo-controlled clinical trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (≥5% and twice placebo) for WAKIX were insomnia (6%), nausea (6%), and anxiety (5%). Other adverse reactions that occurred at ≥2% and more frequently than in patients treated with placebo included headache, upper respiratory infection, musculoskeletal pain, heart rate increased, hallucinations, irritability, abdominal pain, sleep disturbance, decreased appetite, cataplexy, dry mouth, and rash.

Drug Interactions

  • Concomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold. Reduce the dose of WAKIX by half.
  • Concomitant use of WAKIX with strong CYP3A4 inducers decreases exposure of pitolisant by 50%. Dosage adjustments may be required (see full prescribing information).
  • H receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of WAKIX. Patients should avoid centrally acting H receptor antagonists.
  • WAKIX is a borderline/weak inducer of CYP3A4. Therefore, reduced effectiveness of sensitive CYP3A4 substrates may occur when used concomitantly with WAKIX. The effectiveness of hormonal contraceptives may be reduced when used with WAKIX and effectiveness may be reduced for 21 days after discontinuation of therapy.

Use in Specific Populations

  • WAKIX may reduce the effectiveness of hormonal contraceptives. Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with WAKIX and for at least 21 days after discontinuing treatment.
  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to WAKIX during pregnancy. Patients should be encouraged to enroll in the WAKIX pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call 1-800-833-7460.
  • The safety and effectiveness of WAKIX have not been established in patients less than 18 years of age.
  • WAKIX is extensively metabolized by the liver. WAKIX is contraindicated in patients with severe hepatic impairment. Dosage adjustment is required in patients with moderate hepatic impairment.
  • WAKIX is not recommended in patients with end-stage renal disease. Dosage adjustment of WAKIX is recommended in patients with moderate or severe renal impairment.
  • Dosage reduction is recommended in patients known to be poor CYP2D6 metabolizers; these patients have higher concentrations of WAKIX than normal CYP2D6 metabolizers.

Please see the Full Prescribing Information for WAKIX.

To report suspected adverse reactions, contact Harmony Biosciences, LLC at 1-800-833-7460 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References:

  1. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
  2. Saper CB, Fuller PM, Pedersen NP, Lu J, Scammell TE. Sleep state switching. Neuron. 2010;68(6):1023-1042.
  3. American Academy of Sleep Medicine. International Classification of Sleep Disorders. 3rd ed. 2014.
  4. Scammell TE, Narcolepsy. N Engl J Med. 2015;373(27):2654-2662.
  5. Kumar S, Sagili H. Etiopathogenesis and neurobiology of narcolepsy: a review. J Clin Diagn Res. 2014;8(2):190-195.
  6. Overeem S, Reading P, Bassetti CL. Narcolepsy. Sleep Med Clin. 2012:7(2012):263-2817.
  7. Scammell TE, Jackson AC, Franks NP, Wisden W, Dauvilliers Y. Histamine: neural circuits and new medications. Sleep. 2019;42(1). doi: 10.1093/sleep/zsy183.
  8. Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
  9. Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiol Rev. 2008;88(3):1183-1241.
  10. Ahmed I, Thorpy M. Clinical features, diagnosis and treatment of narcolepsy. Clin Chest Med. 2010;31(2):371-381.
  11. Maski K, Steinhart E, Williams D, et al. Listening to the patient voice in narcolepsy: diagnostic delay, disease burden, and treatment efficacy. J Clin Sleep Med. 2017;13(3):419-425.
  12. Data on file. Harmony Biosciences, LLC.
  13. Data on file. Harmony Biosciences, LLC.