Label: Information for the User

Xyrem 500 mg/ml Oral Solution

Sodium Oxybate

Read this label carefully before taking this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to others who have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

Xyrem contains the active ingredient sodium oxybate. Xyrem acts by consolidating nighttime sleep, although its exact mechanism of action is unknown.

Xyrem is used to treat narcolepsy with cataplexy in adults, adolescents, and children aged 7 years and older.

Narcolepsy is a sleep disorder that may include attacks of sleep during hours when normally awake, as well as cataplexy, sleep paralysis, hallucinations, and insomnia. Cataplexy is the sudden onset of muscle weakness or paralysis without loss of consciousness, in response to a sudden emotional reaction such as anger, fear, joy, laughter, or surprise.

Do not take Xyrem

- if you are allergic to sodium oxybate or any of the other ingredients of this medication (listed in section 6);

- if you have succinic semialdehyde dehydrogenase deficiency (a rare metabolic disorder);

- if you have severe depression;

- if you are receiving treatment with opioid or barbiturate medications.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Xyrem.

- if you have respiratory or pulmonary problems (and especially if you are obese), as Xyrem may cause breathing difficulty;

- if you have or have had depression, suicidal thoughts, anxiety, psychosis (a mental disorder that may involve hallucinations, incoherent speech, or disorganized and agitated behavior) or bipolar disorder;

- if you have heart failure, high blood pressure, liver or kidney problems, your doctor may need to adjust your dose;

- if you have previously consumed drugs or abused medications;

- if you have epilepsy, as Xyrem is not recommended for use in this condition;

- if you have porphyria (a rare metabolic disorder).

If you have any of these problems, inform your doctor before taking Xyrem.

If you experience nocturnal enuresis and incontinence (both urinary and fecal), confusion, hallucinations, sleepwalking episodes, or abnormal thinking while taking Xyrem, you must inform your doctor immediately. Although these effects are rare, they are usually mild to moderate in nature.

In elderly patients, your doctor will closely monitor your progress to check if Xyrem produces the desired effects.

Xyrem has a well-known potential for abuse. Cases of dependence have been reported after illicit use of sodium oxybate.

Your doctor will ask if you have consumed any drugs before starting to take Xyrem and while you are taking this medication.

Children and adolescents

Xyrem can be taken by adolescents and children aged 7 years or older who weigh more than 15 kg.

Xyrem should not be taken by children under 7 years of age or who weigh less than 15 kg.

If you are a child or adolescent, your doctor will monitor your body weight regularly.

While your doctor is adjusting the dose, which may take several weeks, parents/caregivers must carefully monitor the child's breathing for 2 hours after the sodium oxybate intake to evaluate if there are any breathing anomalies; for example, interruptions in breathing during short periods while sleeping, noisy breathing, and a blue color on the lips and face. If breathing anomalies are observed, seek medical assistance and inform your doctor as soon as possible. If any anomalies are observed after the first dose, do not administer the second dose. If no anomalies are observed, the second dose can be administered. The second dose should not be administered before 2.5 hours or after 4 hours after the administration of the first dose.

If you have had or are having unpleasant sensations, especially if you feel very sad or have lost interest in life, it is essential to inform your doctor or caregiver.

Use of Xyrem with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

In particular, Xyrem should not be used with sleep-inducing medications and medications that reduce the activity of the Central Nervous System (the Central Nervous System is the part of the body composed of the brain and spinal cord):

• medications that increase the activity of the central nervous system
• antidepressants
• medications that can be metabolized in a similar way by the body (e.g., valproate, phenytoin, or ethosuximide, which are used to treat epileptic seizures)
• topiramate (used to treat epilepsy)

If you are taking valproate, your daily dose of Xyrem will need to be adjusted (see section 3) as it may cause interactions with valproate.

Xyrem and alcohol

You should not drink alcohol while taking Xyrem, as its effects may be increased.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

There have been very few women who have taken Xyrem during pregnancy, and some of them experienced spontaneous abortions. The risk of taking Xyrem during pregnancy is unknown, so it is not recommended for use in pregnant women or women trying to become pregnant.

Patients taking Xyrem should interrupt breastfeeding, as Xyrem passes into breast milk. Changes in sleep have been observed in infants of mothers exposed to Xyrem.

Driving and operating machinery

Xyrem may affect you if you drive or operate machinery. Do not drive, do not operate heavy machinery, or perform any activity that may be hazardous or require full mental alertness for at least 6 hours after taking Xyrem. When you start taking Xyrem for the first time and until you know if it causes drowsiness the next day, be especially careful when driving, operating heavy machinery, or performing any other activity that may be hazardous or require full mental alertness.

In pediatric patients, doctors, parents, or caregivers are advised that the waiting time for activities requiring full mental alertness, motor coordination, or activities that may have a physical risk may be more than 6 hours, depending on individual sensitivity.

Xyrem contains sodium

This medication contains 182.24 mg of sodium (main component of table salt/for cooking) in each gram. This is equivalent to 9.11% of the maximum daily sodium intake recommended for an adult.

Consult your doctor or pharmacist if you need 2 g of sodium oxybate (Xyrem) or more per day for a prolonged period, especially if you have been recommended a low-sodium diet.

Follow exactly the administration instructions of this medication as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

It is essential to use only the syringe included in the box during the preparation of the Xyrem doses. The Xyrem syringe has two distinct measurement scales: one scale may be more useful for you than the other, depending on the dose prescribed by your doctor. When looking at each scale, you will see which one has the exact mark for your dose.

Adults: Xyrem monotherapy

• For adults, the recommended initial dose is 4.5 g per day, divided into two separate doses of 2.25 g.
• Your doctor may gradually increase your dose up to a maximum of 9 g per day, divided into two separate doses of 4.5 g.
• Take Xyrem orally twice a night:

• Take the first dose when going to bed and the second dose 2½ to 4 hours later. You may need an alarm clock to ensure you wake up to take the second dose.
• Food reduces the amount of Xyrem absorbed by your body. Therefore, it is best to take Xyrem at a set time 2 or 3 hours after meals.
• Prepare both doses before going to bed.
• Take the doses within 24 hours after preparation.

Adolescents and children aged 7 years or older weighing 15 kg or more: Xyrem monotherapy

For children aged 7 years or older weighing 15 kg or more, your doctor will calculate the appropriate dose based on your body weight.

Your doctor will calculate the appropriate dose for you. Do not exceed the dose prescribed.

Adults: Xyrem with valproate

If you are taking valproate along with Xyrem, your doctor will adjust your Xyrem dose.

• For adults, the recommended initial dose of Xyrem when used with valproate is 3.6 g per day, divided into two separate doses of 1.8 g.
• Take the first dose when going to bed and the second dose 2½ to 4 hours later.

Adolescents and children aged 7 years or older weighing 15 kg or more: Xyrem with valproate

If you are taking valproate along with Xyrem, your doctor will adjust your Xyrem dose.

Liver or kidney problems

If you have kidney problems, you should follow dietary recommendations to reduce sodium intake (salt).

If you have liver problems, the initial dose should be reduced to half. Your doctor may gradually increase your dose.

Dilution instructions for Xyrem

The following instructions explain how to prepare Xyrem. Read the instructions carefully and follow them step by step. Do not allow children to prepare Xyrem.

To help you, the Xyrem package contains 1 bottle of medication, a graduated syringe (with two distinct measurement scales), and two dosing cups with child-resistant safety caps.

Step 1

• Remove the cap from the bottle by pressing down and unscrew it counterclockwise (to the left).

and place the bottle upright on a table.

• Remove the plastic seal from the bottle mouth before using it for the first time.

• Hold the bottle upright, insert the pressure adapter into the bottle neck. This should only be done the first time the bottle is opened.

The adapter can be left in the bottle for subsequent uses.

Figure 1

Step 2

• Next, insert the tip of the graduated syringe into the center of the bottle opening and push firmly.

and prepare the prescribed dose by pulling the plunger with the other hand.

NOTE: The medication will not flow into the syringe unless you hold the bottle upright.

Figure 2

Step 3

• Remove the syringe from the center of the bottle opening.
• Empty the medication from the syringe into one of the dosing cups provided by pushing the plunger. Repeat this step for the second dosing cup.
• Add approximately 60 ml of water to each dosing cup (60 ml is approximately 4 tablespoons).

Figure 3

Step 4

• Place the safety caps on the dosing cups and turn each cap clockwise (to the right) until it clicks and locks in the child-resistant position (caution: as the dosing cup cap is reversible, only after hearing the click sound can you be sure that the cap is securely closed for children).

• Clear the syringe with water.

Figure 4

Just before going to bed:

• Adult patients should place their second dose near their bed.
• Parents or caregivers of adolescents and children aged 7 years or older should not leave the second dose near the child's bed or within their reach.
• You may need an alarm clock to ensure you wake up to take your second dose, not before 2.5 hours and not later than 4 hours after your first dose.

Next:

• Remove the cap from the first dosing cup by pressing the child-resistant safety cap and turning it counterclockwise (to the left).
• Drink the first dose while sitting in bed, cap the cup, and then go to bed immediately. For children who sleep for more than 8 hours but less than 12, the first dose may be administered after the child has slept for 1 to 2 hours.

• When you wake up or wake the child between 2½ and 4 hours later, remove the cap from the second dosing cup. Sit in bed and drink the second dose just before going back to sleep. Cap the second cup.

If you consider the effect of Xyrem to be too intense or too weak, inform your doctor or pharmacist.

If you take more Xyrem than you should

The symptoms of Xyrem overdose may include agitation, confusion, altered mobility, difficulty breathing, blurred vision, excessive sweating, headache, vomiting, decreased consciousness that may lead to coma, and seizures. If you take more Xyrem than you should, or take it by accident, seek immediate emergency medical help. You should carry the medication package, even if it is empty.

If you forget to take Xyrem

If you forget to take the first dose, take it as soon as you remember and continue with the procedure described above. If you miss the second dose, skip that dose and do not take Xyrem again until the next night. Do not take a double dose to compensate for the missed doses.

If you are unsure whether you have taken Xyrem

In case of doubt about administering a dose, do not re-administer the dose to reduce the risk of overdose

If you interrupt Xyrem treatment

You should continue taking Xyrem as long as your doctor prescribes it. If you interrupt the medication, seizures may recur, and you may experience insomnia, headache, anxiety, dizziness, sleep disorders, somnolence, hallucinations, and abnormal thinking.

If you interrupt Xyrem treatment for more than 14 days, you should consult your doctor as you should start the treatment with Xyrem at a lower dose.

If you have any other questions about using this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them. These are often of mild to moderate intensity.

Adults: most common side effects observed in clinical studies(which occur in 10% to 20% of patients):

• dizziness
• nausea
• headache.

If you experience any of these side effects,inform your doctor immediately.

Children and adolescents: most common side effects observed in a clinical study:

• bedwetting (18.3%)
• nausea (12.5%)
• vomiting (8.7%)
• weight loss (8.7%)
• loss of appetite (6.7%)
• headache (5.8%)
• dizziness (5.8%)
• suicidal thoughts (1%)
• feeling mentally unwell (loss of contact with reality) (1%)

If you experience any of these side effects,inform your doctor immediately.

The side effects in adults and children are the same.If you experience any of these side effects,inform your doctor immediately:

Very common (may affect more than 1 in 10 people):

• nausea

• dizziness
• headache.

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

• sleep problems such as insomnia, abnormal dreams, sleep paralysis, daytime somnolence, nightmares, sleepwalking, excessive daytime sleepiness, difficulty falling asleep in the middle of the night,
• feeling drunk, tremors, confusion or disorientation, blurred vision, balance disorder, falls, sensation of dizziness (vertigo),
• feeling heartbeats, increased blood pressure, shortness of breath
• vomiting, stomach pain, diarrhea
• loss of appetite, decreased appetite, weight loss
• weakness, fatigue, sedation
• sweating
• depression
• muscle cramps, swelling
• joint pain, back pain
• attention disorder, sensitivity disorder especially to touch, abnormal sensation of touch, abnormal taste
• anxiety, nervousness
• urinary incontinence
• snoring, nasal congestion
• hives
• inflammation of the breasts, inflammation of the nose and throat

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

• psychosis (a mental disorder that may include hallucinations, incoherent speech or disorganized and agitated behavior)
• paranoia, abnormal thinking, hallucinations, agitation, suicidal attempt
• difficulty falling asleep, restless legs
• memory loss
• myoclonia (involuntary muscle contractions)
• involuntary bowel movements
• hypersensitivity

Frequency not known (cannot be estimated from available data):

• seizure
• decreased depth or frequency of breathing, brief cessation of breathing during sleep
• urticaria
• suicidal thoughts, delirium, thoughts of committing violent acts (including harming others)
• irritability, aggression
• euphoric mood
• panic attack
• mania/bipolar disorder
• dry mouth, dehydration
• facial swelling (angioedema)
• bruxism (bruxism and clenched jaw)
• polyuria/urgency (increased need to urinate)
• tinnitus (ringing in the ears, such as ringing or buzzing)
• sleep-related eating disorder
• increased appetite
• loss of consciousness
• discinesia (e.g., abnormal and uncontrolled movements of the limbs)
• dandruff
• increased libido
• nocturia (excessive nighttime urination)
• sensation of choking

If you experience any of these side effects,inform your doctor immediately.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the bottle after (CAD). The expiration date is the last day of the month indicated.

After dilution in the dosing vials, the preparation should be used within 24 hours thereafter.

Once the Xyrem bottle is opened, any unused content should be discarded after 90 days of its opening.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Xyrem

Composition of Xyrem

• The active ingredient is sodium oxybate. Each ml contains 500 mg of sodium oxybate.
• The other components are purified water, maleic acid and sodium hydroxide.

Appearance of the product and contents of the container

Xyrem is presented in an amber-colored plastic bottle of 240 ml containing 180 ml of oral solution, closed with a child-resistant cap. The bottle has a plastic sealing film at the mouth of the same, below the cap. Each package contains a bottle, a pressure bottle adapter (PIBA), a plastic graduated syringe and two dosing cups with child-resistant caps.

Xyrem is a clear to slightly opalescent solution.

Marketing Authorization Holder

UCB Pharma S.A., Allée de la Recherche 60, B-1070 Brussels, Belgium

Responsible for manufacturing

UCB Pharma S.A., Chemin du Foriest, B-1420 Braine l'Alleud, Belgium

Your doctor should have given you a package of information about Xyrem, which includes a leaflet on how to take the medication, a patient information leaflet with Frequently Asked Questions and a patient alert card.

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Last review date of this leaflet (MM/YYYY)

Other sources of information

Detailed information about this medication is available on the website of the European Medicines Agency: http://www.ema.europa.eu/