Established Safety and Tolerability Profile in Clinical Studies

  • In clinical studies for narcolepsy, 172 patients were treated with WAKIX® in placebo-controlled trials for up to 8 weeks and in open-label extension trials for up to 5 years
  • In the placebo-controlled clinical studies conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (occurring in ≥5% of patients and at least twice the rate of placebo) with the use of WAKIX were insomnia (6%), nausea (6%), and anxiety (5%)
Adverse Reactions That Occurred in ≥ 2% of WAKIX-Treated Patients and More Frequently Than in Placebo-Treated Patients*
Adverse reactionWAKIX (n=152)Placebo (n=114)
Headache18%15%
Insomnia6%2%
Nausea6%3%
Upper respiratory tract infection5%3%
Musculoskeletal pain5%3%
Anxiety5%1%
Heart rate increased3%0%
Hallucinations3%0%
Irritability3%2%
Abdominal pain3%1%
Sleep disturbance3%2%
Decreased appetite3%0%
Cataplexy2%1%
Dry mouth2%1%
Rash2%1%
  • * In three placebo-controlled clinical studies conducted in patients with narcolepsy with or without cataplexy.
  • Denotes adverse reactions where similar terms were combined.
  • In narcolepsy clinical studies in which WAKIX was directly compared to placebo, the incidence of patients who discontinued because of an adverse event was similar between the WAKIX and placebo groups (3.9 % [n=6/152] vs 3.5% [n=4/114], respectively)
  • No clinically significant changes in mean values for blood pressure were observed in double-blind, placebo-controlled narcolepsy studies1

WAKIX had no clinically important PK interactions with modafinil or sodium oxybate

  • In a clinical pharmacokinetics (PK) study to evaluate the concomitant use of WAKIX with modafinil and sodium oxybate, WAKIX had no effect on the PK of modafinil or sodium oxybate, and these agents had no clinically relevant effect on the PK of WAKIX

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. Data on file. Harmony Biosciences, LLC.