Package leaflet: Information for the patient

Wakix 4.5 mg film-coated tablets, 18 mg film-coated tablets

pitolisant
This medicinal product is subject to additional monitoring. This will allow for rapid identification of
new safety information. You can help by reporting any side effects you experience while taking this
medicinal product. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before you start taking this medicine, as it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Wakix is and what it is used for
What you need to know before taking Wakix
How to take Wakix
Possible side effects
How to store Wakix
Contents of the pack and other information

1. What Wakix is and what it is used for

Wakix contains the active substance pitolisant. It is a medicine used to treat narcolepsy in adults,
adolescents and children over 6 years of age, with or without cataplexy.
Narcolepsy is a condition causing excessive daytime sleepiness and a tendency to fall asleep suddenly in inappropriate situations (sleep attacks). Cataplexy is characterized by sudden muscle weakness or paralysis without loss of consciousness, triggered by sudden emotional reactions such as anger, fear, joy, laughter or surprise.
The active substance, pitolisant, binds to receptors on brain cells involved in promoting wakefulness. This helps to reduce daytime sleepiness and cataplexy, and to promote alertness.

2. What you should know before taking Wakix

Do not take Wakix

If you are allergic to pitolisant or to any of the other ingredients of this medicine (listed in section 6).
If you have severe liver problems, because pitolisant is usually metabolized in the liver and excessive levels may accumulate in patients with severely impaired liver function.
If you are breastfeeding.

Warnings and precautions
Talk to your doctor before taking Wakix if any of the following situations apply to you:

You have had anxiety or depression with suicidal thoughts.
You have liver or kidney problems, as dose adjustment may be necessary.
You have a gastric ulcer or are taking medicines that may irritate the stomach, such as anti-inflammatory drugs, because gastric reactions have been reported with the use of Wakix.
You are obese or anorexic, as body weight may change (increase or decrease) during treatment with Wakix.
You have heart problems: your doctor will carry out regular checks during treatment with Wakix.
You have severe epilepsy.

If any of the above conditions apply to you, consult your doctor or pharmacist before taking Wakix.
Other issues to discuss with your doctor or pharmacist:
Some people with a history of psychiatric disorders have reported suicidal thoughts while taking this medicine. Inform your doctor immediately if you notice that you are becoming depressed or have suicidal thoughts (see section 4). You may wish to consider asking a family member or close friend to help identify signs of depression or other changes in your behaviour.
Children
Wakix must not be taken by children under 6 years of age.
Other medicines and Wakix
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Wakix can affect how other medicines work, and other medicines can affect how Wakix works. Your doctor may need to adjust the dose.
In particular, caution is recommended when taking Wakix together with certain antidepressants (e.g. imipramine, clomipramine and mirtazapine) and certain medicines used to treat allergic conditions (antihistamines such as maleate pheniramine, chlorpheniramine, diphenhydramine, promethazine, mepyramine, doxylamine).
Tell your doctor or pharmacist if you are taking any of the following medicines: rifampicin (an antibiotic), phenytoin, carbamazepine and phenobarbital (mainly used to control seizures), quinidine, digoxin (used to treat heart rhythm disorders), paroxetine, fluoxetine, venlafaxine, duloxetine (antidepressants), St John’s wort (Hypericum perforatum), a herbal remedy for depression, bupropion (an antidepressant or smoking cessation aid), cinacalcet (for treating parathyroid gland disorders), terbinafine (used to treat fungal infections), metformin, repaglinide (used to treat diabetes), docetaxel, irinotecan (used in cancer treatment), cisapride (used to treat gastric reflux), pimozide (used to treat certain mental disorders), halofantrine (used to treat malaria), efavirenz (an antiviral medicine for HIV treatment), morphine, paracetamol (used to treat pain), dabigatran (used to treat vein problems), warfarin (used to treat heart diseases), probenecid (used to treat gout and gouty arthritis). Pitolisant may be used with modafinil or sodium oxybate.
Wakix may reduce the effectiveness of hormonal contraceptives; therefore, adequate alternative contraceptive methods should be used (see section “Pregnancy”).
Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Pregnancy
Wakix must not be used during pregnancy unless prescribed by your doctor. There is insufficient information available on specific risks associated with the use of Wakix during pregnancy. If you are a woman, you must use contraception during treatment with Wakix and for at least 21 days after stopping treatment. Since Wakix may reduce the effectiveness of hormonal contraceptives, adequate alternative contraceptive methods must be used.
Breastfeeding
Wakix passes into breast milk in animals. Patients taking Wakix must stop breastfeeding.
Driving and using machines
Caution is advised in activities requiring alertness, such as driving vehicles or operating machinery. Consult your doctor if you are unsure whether your condition may negatively affect your ability to drive.

3. How to take Wakix

Take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Adults
Treatment is usually started at a dose of 9 mg once daily and gradually increased to the most appropriate dose over a period of three weeks. At any time, your doctor may increase or decrease the dose depending on how the medicine affects you and how well you tolerate it.
It may take several days before you feel the benefit of the medicine, while maximum benefit is usually felt after a few weeks.
Do not change the dose of Wakix on your own. Any change in dosage must be prescribed and monitored by your doctor.
For a dose of 4.5 mg, take one 4.5 mg tablet.
For a dose of 9 mg, take two 4.5 mg tablets.
For a dose of 18 mg, take one 18 mg tablet.
For a dose of 36 mg, take two 18 mg tablets.

Adolescents and children over 6 years of age
Treatment is usually started at a dose of 4.5 mg once daily and gradually increased to the most appropriate dose over a period of three to four weeks (see above).
If your body weight is less than 40 kg, you should not take more than 18 mg per day.

Take Wakix once daily by mouth in the morning with breakfast.
Do not take a dose of Wakix in the afternoon, as you may have difficulty sleeping.

If you take more Wakix than you should
If you take too many Wakix tablets, go immediately to the nearest emergency room or contact your doctor or pharmacist right away. You may experience headache, stomach ache, a feeling of discomfort or irritability. You may also have difficulty sleeping. Bring this leaflet and any remaining tablets with you.

If you forget to take Wakix
If you forget to take your dose, take the next dose at your usual time. Do not take a double dose to make up for the missed tablet.

If you stop taking Wakix
You should continue taking Wakix for the duration prescribed by your doctor. Do not stop taking Wakix suddenly on your own.

If you have any questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this one can cause side effects, although not everyone experiences them. If any side effects occur, contact your doctor.

Common side effects (may affect up to 1 in 10 people):

difficulty sleeping, feeling anxious, feeling irritable, feeling depressed, sleep problems
headaches, sensation of dizziness ("spinning sensation"), loss of balance, tremor
feeling unwell, vomiting, indigestion
tiredness (fatigue)

Uncommon side effects (may affect up to 1 in 100 people):

sweating
decreased or increased appetite
oedema
feeling of nervous tension, nervousness, seeing or hearing things that are not really there
mood swings
abnormal dreams
tension
difficulty falling asleep at the beginning of the night, during the night, or towards the end of the night, difficulty staying asleep, excessive sleep, drowsiness
state of indifference with lack of emotions
nightmares
feeling restless and unable to stay still
panic reaction
suicidal thoughts
altered or increased sexual interest
sudden and transient episode of muscle weakness, uncontrollable muscle spasms, or movement of a leg
altered attention
migraine
epilepsy
weakness
movement disorder, slowed body movement
sensation of tingling, itching, pricking, or burning of the skin
sudden and unpredictable episodes of mobility and immobility
feeling of instability
reduced visual acuity, abnormal eyelid contraction or tic
hearing a sound when no external sound is present
abnormal heartbeat, slow or fast heart rate, increase or decrease in blood pressure, hot flushes
yawning
dry mouth
diarrhoea, abdominal pain, discomfort or pain in the abdomen, constipation, heartburn, stomach ache and stomach discomfort, gastritis, excessive acidity in the gastrointestinal tract
itching, unusually red skin colouring of the face, nose and cheeks, excessive sweating
joint pain, back pain, muscle stiffness, muscle weakness, pain in muscles and bones, pain in fingers of hands and feet
urinary disorders
irregular uterine bleeding
loss of strength or extreme tiredness, chest pain, malaise, oedema
weight gain, weight loss, abnormal electrocardiogram (ECG) findings, abnormal laboratory liver function tests.

Rare side effects (may affect up to 1 in 1,000 people):

loss of appetite, increased appetite
abnormal behaviour, confusion, depressed mood, excitability, feelings of emotional or mental discomfort, sensation during sleep of seeing or hearing things that are not really there
loss of consciousness, tension headache, memory difficulties, poor quality of sleep
abdominal discomfort, difficulty or pain when swallowing, flatulence, inflammation of the digestive tract
skin infection, excessive sensitivity to sunlight
neck pain, chest pain
spontaneous abortion
pain, night sweats, feeling of oppression
elevated blood levels of the enzyme creatine phosphokinase, abnormal general physical condition, changes in electrocardiogram (ECG) results

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you help provide more information on the safety of this medicine.

5. How to store Wakix

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp." The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Wakix Contains
The active substance is pitolisant.
Wakix 4.5 mg tablet
Each tablet contains pitolisant hydrochloride, equivalent to 4.45 mg of pitolisant.
Wakix 18 mg tablet
Each tablet contains pitolisant hydrochloride, equivalent to 17.8 mg of pitolisant.
The other ingredients are microcrystalline cellulose, crospovidone Type A, talc, magnesium stearate, anhydrous colloidal silicon dioxide, poly(vinyl alcohol), titanium dioxide (E171), and polyethylene glycol 3350.

Description of the Appearance of Wakix and Contents of the Pack
Wakix 4.5 mg is available as a film-coated tablet, white, round and biconvex, 3.7 mm in diameter, marked with the number "5" on one side.
Wakix 18 mg is available as a film-coated tablet, white, round and biconvex, 7.5 mm in diameter, marked with the number "20" on one side.
Wakix is available in bottles containing 30 or 90 tablets.
Wakix 4.5 mg: Available in a pack containing 1 bottle with 30 tablets.
Wakix 18 mg: Available in a pack containing 1 bottle with 30 tablets, or a pack containing 1 bottle with 90 tablets, or a multiple pack containing 90 tablets (3 bottles of 30 tablets each).
Not all pack sizes may be marketed.

Marketing Authorization Holder
Bioprojet Pharma
9, rue Rameau
75002 Paris
France

Manufacturer
Wakix 18 mg
Inpharmasci
ZI N°2 de Prouvy-Rouvignies
1 rue Nungesser
59121 Prouvy
France

Wakix 4.5 mg
Patheon
40 Boulevard de Champaret
38300 Bourgoin-Jallieu
France

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Bioprojet Benelux UAB Norameda
0032(0)78050202 +370 5 2306499
[email protected] [email protected]

България Luxembourg/Luxemburg
GTS Solution Bioprojet Benelux
+40 21 528 02 92 0032(0)78050202
[email protected] [email protected]

Česká republika Magyarország
BIOXA Therapeutics (Czech) s.r.o. UAB Norameda
+420 606 501 778 +370 5 2306499
[email protected] [email protected]

Danmark Malta
Zambon Sweden, filial of Zambon Nederland Bioprojet Pharma
B.V. 0033 (0)1 47 03 66 33
+46 (0)10 33 50 800 [email protected]

Deutschland Nederland
Bioprojet Deutschland GmbH Bioprojet Benelux N.V.
030/3465 5460-0 088 34 34 100
[email protected] [email protected]

Eesti Norge
UAB Norameda Eesti filiaal Zambon Sweden, filial of Zambon Nederland
+372 514 2118 B.V.
[email protected] +46 (0)10 33 50 800
[email protected]

Ελλάδα Österreich
Bioprojet Pharma Bioprojet Deutschland GmbH
0033 (0)1 47 03 66 33 030/3465 5460-0
[email protected] [email protected]

España Polska
Bioprojet Pharma Norameda Polska Sp. z o.o.
0033 (0)1 47 03 66 33 +48 504 278 778
[email protected] [email protected]

France Portugal
Bioprojet Pharma Ferrer Portugal, S.A
0033 (0)1 47 03 66 33 00351 214 449 600
[email protected] [email protected]

Hrvatska România
Lenis farmacevtika d.o.o. GTS Solution
+386 1 23 50 700 +40 21 528 02 92
[email protected] [email protected]

Ireland Slovenija
Bioprojet Pharma Lenis farmacevtika d.o.o.
0033 (0)1 47 03 66 33 +386 1 23 50 700
[email protected] [email protected]

Ísland Slovenská republika
Bioprojet Pharma BIOXA Therapeutics s.r.o.
0033 (0)1 47 03 66 33 +421 907 927 010
[email protected] [email protected]

Italia Suomi/Finland
Bioprojet Italia srl Zambon Sweden, filial of Zambon Nederland
0039 02 84254830 B.V.
[email protected] +46 (0)10 33 50 800
[email protected]

Κύπρος Sverige
Bioprojet Pharma Zambon Sweden, filial of Zambon Nederland
0033 (0)1 47 03 66 33 B.V.
[email protected] +46 (0)10 33 50 800
[email protected]

Latvija United Kingdom (Northern Ireland)
Norameda pārstāvniecība Bioprojet Pharma
+371 29272107 0033 (0)1 47 03 66 33
[email protected] [email protected]

Additional Sources of Information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.
This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION(S)

Scientific Conclusions
Taking into account the assessment by the Pharmacovigilance Risk Assessment Committee (PRAC) of the final report of the imposed non-interventional post-authorisation safety study (PASS) for the above-mentioned medicinal product(s), the scientific conclusions of the Committee for Medicinal Products for Human Use (CHMP) are as follows:
The Marketing Authorisation Holder (MAH) has fulfilled the obligation to submit the final results of a non-interventional post-authorisation safety study:
A 5-year, multicentre, observational PASS study designed to document the use of Wakix in the treatment of narcolepsy with and without cataplexy and to collect information on its long-term safety in routine clinical practice.
The study provided data on the long-term use and safety of pitolisant under real-world conditions. The final data do not indicate any new or unexpected safety findings related to pitolisant.
Therefore, in light of the available data from the final PASS study report, the PRAC considered justified modifications to the terms of the marketing authorisation.
The CHMP agrees with the scientific conclusions drawn by the PRAC.

Reasons for the Variation of the Terms of the Marketing Authorisation(s)
Based on the scientific conclusions regarding the results of the study for the above-mentioned medicinal product(s), the CHMP considers that the benefit-risk balance of this/these medicinal product(s) remains unchanged, subject to the proposed changes to the product information.
The CHMP considers that the terms of the marketing authorisation(s) for the above-mentioned medicinal product(s) should be varied.