WAKIX- pitolisant hydrochloride tablet, film coated
Harmony Biosciences, LLC
WAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adult patients with narcolepsy.
The recommended dosage range for WAKIX is 17.8 mg to 35.6 mg administered orally once daily in the morning upon wakening. Titrate dosage as follows:
Week 1: Initiate with a dosage of 8.9 mg (two 4.45 mg tablets) once daily
Week 2: Increase dosage to 17.8 mg (one 17.8 mg tablet) once daily
Week 3: May increase to the maximum recommended dosage of 35.6 mg (two 17.8 mg tablets) once daily
Dose may be adjusted based on tolerability.
If a dose is missed, patients should take the next dose the following day in the morning upon wakening.
It may take up to 8 weeks for some patients to achieve a clinical response.
In patients with moderate hepatic impairment, initiate WAKIX at 8.9 mg once daily and increase after 14 days to a maximum dosage of 17.8 mg once daily [see Warnings and Precautions (5.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
WAKIX is contraindicated in patients with severe hepatic impairment. WAKIX has not been studied in patients with severe hepatic impairment [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
2.3 Dosage Modification and Recommendations in Patients with Renal Impairment and End-Stage Renal Disease
In patients with moderate (eGFR of 30 to 59 mL/minute/1.73 m2) and severe renal impairment (eGFR of 15 to 29 mL/minute/1.73 m2), initiate WAKIX at 8.9 mg once daily and increase after 7 days to a maximum dosage of 17.8 mg once daily [see Warnings and Precautions (5.1), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
WAKIX is not recommended in patients with end-stage renal disease (ESRD) (eGFR of <15 mL/minute/1.73 m2)[see Warnings and Precautions (5.1), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
2.4 Dosage Recommendations for Concomitant Use with Strong CYP2D6 Inhibitors and Strong CYP3A4 Inducers
Coadministration with Strong CYP2D6 Inhibitors
For patients receiving strong CYP2D6 inhibitors, initiate WAKIX at 8.9 mg once daily and increase after 7 days to a maximum dosage of 17.8 mg once daily.
Coadministration with Strong CYP3A4 Inducers
Concomitant use of WAKIX with strong CYP3A4 inducers decreases pitolisant exposure by 50%. Assess for loss of efficacy after initiation of a strong CYP3A4 inducer.
For patients stable on WAKIX 8.9 mg or 17.8 mg once daily, increase the dose of WAKIX to double the original daily dose (i.e., 17.8 mg or 35.6 mg, respectively) over 7 days.
In patients known to be poor CYP2D6 metabolizers, initiate WAKIX at 8.9 mg once daily and titrate to a maximum dose of 17.8 mg once daily after 7 days [see Use in Specific Populations (8.8), Clinical Pharmacology (12.5)].
- WAKIX 4.45 mg tablets: white, round, biconvex film-coated tablet, marked with “S” on one side and plain on the other side. Each tablet contains 5 mg of pitolisant hydrochloride equivalent to 4.45 mg of pitolisant.
- WAKIX 17.8 mg tablets: white, round, biconvex film-coated tablet, marked with “H” on one side and plain on the other side. Each tablet contains 20 mg of pitolisant hydrochloride equivalent to 17.8 mg of pitolisant.
WAKIX is contraindicated in patients with:
- known hypersensitivity to pitolisant or any component of the formulation. Anaphylaxis has been reported in patients treated with WAKIX [see Adverse Reactions (6.2)].
- severe hepatic impairment. WAKIX is extensively metabolized by the liver and there is a significant increase in WAKIX exposure in patients with moderate hepatic impairment [see Use in Specific Populations (8.6)].
WAKIX prolongs the QT interval. The use of WAKIX should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval [see Drug Interactions (7.1)]. WAKIX should also be avoided 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 [see Clinical Pharmacology (12.2)]. The risk of QT prolongation may be greater in patients with hepatic or renal impairment due to higher concentrations of pitolisant. Monitor patients with hepatic or renal impairment for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment [see Dosage and Administration (2.2, 2.3)]. WAKIX is contraindicated in patients with severe hepatic impairment [see Contraindications (4)]. WAKIX is not recommended in patients with end-stage renal disease (ESRD) [see Dosage and Administration (2.3), Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].
The following adverse reactions are discussed in more detail in other sections of the labeling:
- QT Interval Prolongation [see Warnings and Precautions (5.1)]
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the clinical trials 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 trials in which WAKIX was directly compared to placebo, 6 of the 152 patients (3.9%) who received WAKIX and 4 of the 114 patients (3.5%) who received placebo discontinued because of an adverse event.
Most Common Adverse Reactions
In the placebo-controlled clinical trials 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%).
Table 1 presents the adverse reactions that occurred at a rate of ≥2% in patients treated with WAKIX and more frequently than in patients treated with placebo in the placebo-controlled clinical trials in narcolepsy.
* The following terms were combined:
Abdominal pain includes: abdominal discomfort; abdominal pain; abdominal pain upper
Anxiety includes: anxiety; nervousness; stress; stress at work
Hallucinations includes: hallucination; hallucination visual; hypnagogic hallucination
Headache includes: cluster headache; headache; migraine; premenstrual headache; tension headache
Heart rate increased includes: heart rate increased; sinus tachycardia; tachycardia
Insomnia includes: initial insomnia; insomnia; middle insomnia; poor quality sleep
Musculoskeletal pain includes: arthralgia; back pain; carpal tunnel syndrome; limb discomfort; musculoskeletal pain; myalgia; neck pain; osteoarthritis; pain in extremity; sciatica
Rash includes: eczema; erythema migrans; rash; urticaria
Sleep disturbance includes: dyssomnia; sleep disorder; sleep paralysis; sleep talking
Upper respiratory infection includes: pharyngitis; rhinitis; sinusitis; upper respiratory tract infection; upper respiratory tract inflammation; viral upper respiratory tract infection
|Adverse Reaction||WAKIX (n=152) %||Placebo (n=114) %|
|Upper respiratory tract infection*||5||3|
|Heart rate increased*||3||0|
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