Instructions for Pitolisant-wakix

1. Name: Pitolisant tablets, Pitolisant, Wakix

2. Indications:

Pitolisant tablets (Pitolisant) are indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy.

3. Usage and dosage:

1. Recommended dosage: The recommended dosage range of tilolixen tablets is 17.8mg to 35.6mg, which should be taken orally once every morning after waking up. Start taking 8.9 mg once daily (two 4.45 mg tablets) in the first week; increase the dose to 17.8 mg once daily (one 17.8 mg tablet) in the second week; and increase to the maximum recommended dose of 35.6 mg once daily (two 17.8 mg tablets) in the third week. Dosage may be adjusted based on tolerance. If a dose is missed, the patient should take the next dose upon waking the next morning. Some patients may take up to 8 weeks to achieve clinical response.

2. Dosage adjustment:

（1) Patients with hepatic impairment: For patients with moderate hepatic impairment, the initial dose of tilolixen tablets is 8.9 mg once a day, and is increased to the maximum dose of 17.8 mg once a day after 14 days. Tilolixen tablets are contraindicated in patients with severe hepatic impairment.

(2) Patients with renal impairment and end-stage renal disease: For patients with moderate (eGFR 30-59mL/min/1.73m2) or severe (eGFR 15-29mL/min/1.73m2) renal impairment, the starting dose of tilolixen tablets is 8.9 mg once a day, and after 7 days, increase to the maximum dose of 17.8 mg once a day. Tilolixen tablets are not recommended for patients with end-stage renal disease (ESRD) (eGFR <15mL/min/1.73m2).

4. Adverse reactions:

The most common side effects of Tilolixen tablets in adults are insomnia (difficulty sleeping), headache, nausea, anxiety, irritability, dizziness, depression, tremor, sleep disturbance, fatigue, vomiting, vertigo (spinning sensation) and indigestion (heartburn). Serious but rare side effects are abnormal weight loss and spontaneous abortion. Symptoms of tilolixan overdose may include headache, insomnia, irritability, nausea, and abdominal pain.

5. Storage:

Tilorisen tablets will be stored in20°C to 25°C (68°F to 77°F); tolerances allowed between 15°C to 30°C (59°F to 86°F).

6. Taboo:

1. Tilolisant tablets are contraindicated in people with known allergies to pitolisant or any ingredients in the formula. Anaphylaxis has been reported in patients receiving tilolixen tablets.

2. Pitolisant tablets are extensively metabolized by the liver, and the exposure to pitolisant in patients with moderate liver damage is significantly increased. Therefore, tilolixen tablets are contraindicated in patients with severe hepatic impairment.

7. Mechanism of action:

Ingredients in Pitolisant TabletsThe mechanism of action of Pitolisant in excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy is unclear. However, its efficacy may be mediated through its activity as an antagonist/inverse agonist at the histamine-3 (H3) receptor.