Xyrem 500 mg/ml oral solution

Patient Information Leaflet

Introduction

Patient Information Leaflet

Xyrem 500 mg/ml oral solution

Sodium oxybate

Read the entire leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

1. What Xyrem is and what it is used for
2. What you need to know before taking Xyrem
3. How to take Xyrem
4. Possible side effects
5. How to store Xyrem
6. Contents of the pack and other information

1. What Xyrem is and what it is used for

Xyrem contains the active substance 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 from 7 years of age.

Narcolepsy is a sleep disorder that may include sudden attacks of sleep during hours when a person is 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, occurring in response to a sudden emotional reaction such as anger, fear, joy, laughter, or surprise.

2. What you need to know before taking Xyrem

Do not take Xyrem

• if you are allergic to sodium oxybate or any of the other ingredients of this medicine (listed in section 6);
• if you have succinic semialdehyde dehydrogenase deficiency (a rare metabolic disorder);
• if you suffer from severe depression;
• if you are receiving treatment with opioid or barbiturate medicines.

Warnings and precautions

Talk to your doctor or pharmacist before starting Xyrem.

• if you have breathing or lung problems (and especially if you are obese), as Xyrem may cause difficulty in breathing;
• 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 (hypertension), or liver or kidney problems, your dose may need to be adjusted;
• if you have previously used drugs or abused medicines;
• if you have epilepsy, as the use of Xyrem is not recommended in this condition;
• if you have porphyria (a rare metabolic disorder).

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

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

In elderly people, your doctor will closely monitor your progress to ensure that Xyrem produces the desired effects.

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

Your doctor will ask you whether you have used any drugs before starting Xyrem and while taking this medicine.

Children and adolescents

Xyrem may be used in adolescents and children aged 7 years and older who weigh more than 15 kg.

Xyrem must not be used in 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 the doctor is adjusting the dose, which may take several weeks, parents/caregivers must carefully monitor the child's breathing during the first 2 hours after taking sodium oxybate to assess for any breathing abnormalities; for example, brief interruptions in breathing during sleep, noisy breathing, or bluish discoloration of the lips and face. If any breathing abnormalities are observed, medical help must be sought and the doctor informed as soon as possible. If abnormalities are observed after the first dose, the second dose must not be administered. If no abnormalities are observed, the second dose may be given. The second dose must not be administered earlier than 2.5 hours or later than 4 hours after the first dose.

If you have had or are experiencing unpleasant feelings, especially if you feel very sad or have lost interest in life, it is important that you inform your doctor or caregiver.

Taking Xyrem with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

In particular, Xyrem must not be used together with medicines that induce sleep and medicines 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):

You should also inform your doctor or pharmacist if you are taking any of the following types of medicines:

• medicines that increase central nervous system activity
• antidepressants
• medicines that may be metabolized similarly by the body (e.g., valproate, phenytoin, or ethosuximide, 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 lead to interactions with valproate.

Taking Xyrem with alcohol

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

Pregnancy and breastfeeding

If you are pregnant, breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Very few women have taken Xyrem during pregnancy, and some of them experienced spontaneous abortions. The risk of taking Xyrem during pregnancy is unknown, so its use is not recommended in pregnant women or women trying to become pregnant.

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

Driving and using machines

Xyrem may affect your ability to drive or use machines. Do not drive, operate heavy machinery, or perform any activity that could be dangerous or require mental alertness for at least 6 hours after taking Xyrem. When you first start taking Xyrem and until you know whether it causes drowsiness the following day, take special care when driving, operating heavy machinery, or performing any other activity that could be dangerous or require full mental alertness.

For pediatric patients, doctors, parents, and caregivers are advised that the waiting time before engaging in activities requiring mental alertness, motor coordination, or activities that may pose a physical risk may exceed 6 hours, depending on individual sensitivity.

Xyrem contains sodium

This medicine contains 182.24 mg of sodium (a main component of table/cooking salt) per gram. This corresponds to 9.11% of the maximum recommended daily sodium intake for an adult.

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

3. How to take Xyrem

Follow exactly the instructions for administering this medicine as given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

It is important that you only use the syringe provided in the pack when preparing doses of Xyrem. The Xyrem syringe has two different measurement scales: one scale may be more suitable 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: taking Xyrem alone

• For adults, the recommended starting 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 each night:

• Take the first dose at bedtime 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 always take Xyrem at a fixed time, 2 or 3 hours after meals.

• Prepare both doses before going to bed.

• Take the doses within 24 hours of their preparation.

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

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

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

Adults: taking Xyrem with valproate

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

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

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

If you are taking valproate together 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 (salt) intake.

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

Instructions for diluting 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 assist you, the Xyrem package contains 1 medicine bottle, a graduated syringe (with two different measurement scales), and two dosing cups with child-resistant safety caps.

Step 1

• Remove the bottle cap by pressing down

and unscrewing counterclockwise (to the left).

• After removing the cap, place the bottle upright

on a table.

• The plastic seal film on the mouth of the bottle

must be removed before first use.

• Keeping the bottle upright, insert the push-in adapter

into the neck of the bottle. This should only be done the first

time the bottle is opened.

The adapter can remain 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 press firmly.

• Holding the bottle and syringe in one hand,

draw up the prescribed dose with the other hand by pulling

the plunger.

NOTE: The medicine will not flow into the syringe

unless you keep the bottle upright.

Figure 2

Step 3

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

Figure 3

Step 4

• Place the caps on the dosing cups

and turn each cap clockwise (to the right) until it clicks

and locks into the child-resistant position

(caution: because the dosing cup cap is reversible, only after hearing the click sound can you be sure the cap is securely closed in child-resistant mode).

• Rinse the syringe with water.

Figure 4

Just before going to sleep:

• Adult patients should place their second dose near their bed.
• Parents or caregivers of adolescents and children aged 7 years and older should not leave the second dose near the child's bed or within the child's reach.
• You may need an alarm clock to ensure you wake up to take your second dose, no sooner than 2.5 hours and no later than 4 hours after your first dose.

Then:

• Remove the cap from the first dosing cup by pressing down on the child-resistant safety cap and turning it counterclockwise (to the left).

• Take the first dose while sitting in bed, cap the cup, and then lie down immediately. In the case of children who sleep 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 2½ to 4 hours later, remove the cap from the second dosing cup. While sitting in bed, take the second dose just before lying down again to continue sleeping. Cap the second cup.

If you think the effect of Xyrem is too strong or too weak, tell your doctor or pharmacist.

If you take more Xyrem than you should

Symptoms of Xyrem overdose may include agitation, confusion, impaired mobility, difficulty breathing, blurred vision, excessive sweating, headache, vomiting, reduced consciousness which may lead to coma and epileptic seizures, excessive thirst, muscle cramps, and weakness. If you take more Xyrem than you should, or take it by accident, seek immediate emergency medical help. You must bring the medicine pack with you, 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 previously described procedure. 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 make up for missed doses.

If you are unsure whether you have taken Xyrem

If in doubt about whether a dose has been administered, do not re-administer the dose to reduce the risk of overdose.

If you stop taking Xyrem

You should continue taking Xyrem for as long as your doctor prescribes it. If treatment is stopped, cataplexy attacks may return and you may experience insomnia, headache, anxiety, dizziness, sleep disturbances, drowsiness, hallucinations, and abnormal thinking.

If you stop treatment with Xyrem for more than 14 days, you must consult your doctor, as you will need to restart treatment with Xyrem at a lower dose.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. These are often mild to moderate in intensity.

Adults: most frequently observed adverse effects in clinical studies (occurring in 10% to 20% of patients):

• dizziness
• nausea
• headache.

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

Children and adolescents: most frequently observed adverse effects in a clinical study:

• bed-wetting (18.3%)
• nausea (12.5%)
• vomiting (8.7%)
• weight loss (8.7%)
• decreased 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 adverse effects, inform your doctor immediately.

The adverse effects in adults and children are the same. If you experience any of these adverse 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, somnolence, nightmares, sleepwalking, bed-wetting, 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)
• awareness of your heartbeat, increased blood pressure, shortness of breath
• vomiting, stomach pain, diarrhoea
• anorexia, decreased appetite, weight loss
• weakness, fatigue, sedation
• sweating
• depression
• muscle cramps, swelling
• joint pain, back pain
• attention disturbance, altered sensation especially to touch, abnormal sensation of touch, abnormal taste
• anxiety, nervousness
• urinary incontinence
• snoring, nasal congestion
• rash
• breast swelling, swelling of 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 behaviour)
• paranoia, abnormal thinking, hallucinations, agitation, suicide attempt
• difficulty falling asleep, restless legs
• memory impairment
• myoclonus (involuntary muscle contractions)
• involuntary defecation
• hypersensitivity

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

• seizure
• decreased depth or rate of breathing, brief cessation of breathing during sleep
• urticaria
• suicidal thoughts, delirium, thoughts of committing violent acts (including harming other people)
• irritability, aggression
• euphoric mood
• panic attack
• mania/bipolar disorder
• dry mouth, dehydration
• facial swelling (angioedema)
• bruxism (teeth grinding and jaw clenching)
• pollakiuria/urinary urgency (increased need to urinate)
• tinnitus (noise in the ears, such as ringing or buzzing)
• sleep-related eating disorder
• increased appetite
• loss of consciousness
• dyskinesia (e.g., abnormal, uncontrolled movements of the limbs)
• dandruff
• increased sex drive
• nocturia (excessive urination at night)
• sensation of suffocation

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Xyrem

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

Do not use this medicine after the expiry date stated on the bottle after (EXP). The expiry date is the last day of the month indicated.

After dilution in the dosing syringes, the preparation must be used within 24 hours.

Once the Xyrem bottle has been opened, any unused content remaining after 90 days from opening should be discarded.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Xyrem

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

Appearance of the product and contents of the container

Xyrem is supplied as a 240 ml amber plastic bottle containing 180 ml of oral solution, closed with a child-resistant cap. The bottle has a plastic seal liner at its mouth, underneath the cap. Each pack contains one bottle, a press-in bottle adapter (PIBA), a graduated plastic 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

Manufacturer

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

Your doctor should have provided you with a Xyrem patient information pack, which includes a leaflet on how to take the medicine, a patient information sheet with Frequently Asked Questions, and a patient alert card.

You can request further information about this medicinal product by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet (MM/YYYY)

Other sources of information

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