Xyrem 500 mg/ml oral solution

Xyrem works by consolidating night-time sleep, though its exact mechanism of action is unknown.

Xyrem is used to treat narcolepsy with cataplexy in adult patients.

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

Do not take Xyrem

• if you are allergic (hypersensitive) to sodium oxybate or any of the other ingredients of Xyrem
• if you have succinic semialdehyde dehydrogenase deficiency (a rare metabolic disorder)
• if you suffer from major depression
• if you are being treated with opioid or barbiturate medicines

Take special care with Xyrem

• if you have breathing or lung problems (and especially if you are obese), because Xyrem has the potential to cause respiratory depression
• if you have or have previously had depressive illness
• if you have heart failure, hypertension (high blood pressure), liver or kidney problems as your dose may need to be adjusted
• if you are taking other central nervous system depressants or alcohol
• if you have previously had experience with drug abuse
• if you suffer from epilepsy as the use of Xyrem is not recommended in this condition
• if you have porphyria (an uncommon metabolic disorder)

If any of these apply to you, tell your doctor before you take Xyrem.

While you are taking Xyrem, if you experience bed wetting and incontinence (both urine and faeces), confusion, hallucinations, episodes of sleepwalking or abnormal thinking you should tell your doctor straight away. Whilst these effects are uncommon, if they do occur they are usually mild-to-moderate in nature.

If you are elderly, your doctor will monitor your condition carefully to check whether Xyrem is having the desired effects.

Xyrem should not be taken by children and adolescents.

When you discontinue taking Xyrem you need to follow your doctor?s instructions as it may result in side effects e.g. headache, lack of sleep, mood changes and hallucinations.

Xyrem has a well known abuse potential. Cases of dependency have occurred after the illicit use of sodium oxybate.

Your doctor will ask if you have ever abused any drugs before you start taking Xyrem and whilst you are using the medicine

Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

In particular Xyrem should not be taken together with sleep inducing medicines and medicines that reduce central nervous system activity (the central nervous system is the part of the body related to the brain and spinal cord).

Also care should be taken to tell your doctor and pharmacist if your are taking any of the following types of medicines:

• medicines that increase central nervous system activity and antidepressants
• medicines that may be processed in a similar way by the body (eg valporate, phenytoin or ethosuximide)

Taking Xyrem with food and drink
You must not drink alcohol while taking Xyrem, as its effects can be increased.

Xyrem is to be taken at a set time well after a meal (two - three hours) as food decreases the amount of Xyrem that is absorbed by your body.

You need to monitor the amount of salt you take as Xyrem contains sodium (which is found in table salt) which may affect you if you have had high blood pressure, heart or kidney problems in the past. If you take two 2.25 g doses of sodium oxybate each night you will take 0.82 g of sodium, or if you take two 4.5 g doses of sodium oxybate each night you will take in 1.6 g sodium. You may need to moderate your intake of salt.

Pregnancy and breast-feeding

There have been very few women who have taken Xyrem sometime during their pregnancy and a few of them had spontaneous abortions. The risk of taking Xyrem during pregnancy is unknown, and therefore the use of Xyrem in pregnant women or women trying to become pregnant is not recommended. Tell your doctor if you are pregnant or are planning to become pregnant.

It is not known whether Xyrem passes into breast milk. Patients taking Xyrem should stop breast feeding.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
Xyrem will affect you if you drive or operate tools or machines. Do not drive a car, operate heavy machinery, or perform any activity that is dangerous or that requires mental alertness for at least 6

hours after taking Xyrem. When you first start taking Xyrem, until you know whether it makes you sleepy the next day, use extreme care while driving a car, operating heavy machinery or doing anything else that could be dangerous or needs you to be fully mentally alert.

Always take Xyrem exactly as your doctor has told you to. You should check with your doctor or pharmacist if you are not sure.

The usual starting dose is 4.5 g/day, given as two equally divided doses of 2.25 g/dose. Your doctor may gradually increase your dose up to a maximum of 9 g/day given as two equally divided doses of 4.5 g/dose.

Take Xyrem orally two times each night. Take the first dose upon getting into bed and the second dose 2.5 to 4 hours later. You may need to set an alarm clock to make sure you wake up to take the second dose. Food decreases the amount of Xyrem that is absorbed by your body. Therefore, it is best to take Xyrem at set times well after a meal (two-three hours). Prepare both doses before bedtime.

If you stop taking Xyrem for more than 14 consecutive days you should consult your doctor as you should restart taking Xyrem at a reduced dose.

Instructions on how to dilute Xyrem

The following instructions explain how to prepare Xyrem. Please read the instructions carefully and follow them step by step.

To help you, the Xyrem carton contains 1 bottle of medicine, a measuring syringe and two dosing cups with child-resistant caps.

1. Remove the bottle cap by pushing down while turning the cap anticlockwise (to the left). After removing the cap, set the bottle upright on a table-top. There is a plastic covered foil seal on the top of the bottle, which must be removed before using the bottle for the first time. While holding the bottle in its upright position, insert the press-in-bottle-adaptor into the neck of the bottle. This needs only to be done the first time that the bottle is opened. The adaptor can then be left in the bottle for all subsequent uses

2. Next, insert the tip of the measuring syringe into the centre opening of the bottle and press down firmly (See Figure 1).

Figure 1

3. While holding the bottle and syringe with one hand, draw up the prescribed dose with the other hand by pulling on the plunger. NOTE: Medicine will not flow into the syringe unless you keep the bottle in its upright position (See Figure 2).

Figure 2

4. Remove the syringe from the centre opening of the bottle. Empty the medicine from the syringe into one of the dosing cups provided by pushing on the plunger (See Figure 3). Repeat this step for the second dosing cup. Then add about 60 ml of water to each dosing cup (60 ml is about 4 tablespoons).

Figure 3

5. Place the caps provided on the dosing cups and turn each cap clockwise (to the right) until it clicks and locks into its child-resistant position (See Figure 4). Rinse out the syringe with water.

Figure 4

6. Just before going to sleep, place your second dose near your bed. You may need to set an alarm so you wake up to take your second dose no earlier than 2.5 hours and no later than 4 hours after your first dose. Remove the cap from the first dosing cup by pressing down on the child-resistant locking tab and turning the cap anticlockwise (to the left). Drink all of the first dose while sitting in bed, recap the cup, and then lie down right away.

7. When you wake up 2.5 to 4 hours later, remove the cap from the second dosing cup. While sitting in bed, drink all of the second dose right before lying down to continue sleeping. Recap the second cup.

If you have the impression that the effect of Xyrem is too strong or too weak, talk to your doctor or pharmacist.

If you take more Xyrem than you should

Symptoms of Xyrem overdose may include agitation, confusion, impaired movement, impaired breathing, blurred vision, profuse sweating, headache, vomiting, decreased consciousness leading to coma and seizures. If you take more Xyrem than you were told to take, or take it by accident, get emergency medical help right away. You should take the labelled medicine bottle 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 then continue as before. 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 forgotten individual doses.

If you stop taking Xyrem

You should continue to take Xyrem for as long as instructed by your doctor. You may find that your cataplexy attacks return if your medicine is stopped and you may experience insomnia, headache, anxiety, dizziness, sleeping problems, sleepiness, hallucination and abnormal thinking.

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

Like all medicines, Xyrem can have side effects. These are usually mild to moderate. If you experience any of these, tell your doctor straight away.

The frequency of possible side effects listed below is defined using the following convention: very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data)

Very common side effects (affects more than 1 user in 10) include:

Nausea, dizziness, headache

Common side effects (affects 1 to 10 users in 100) include:
Sleeping problems including insomnia, blurred vision, feeling the heart beat, vomiting, stomach pains, diarrhoea, anorexia, decreased appetite, weight loss, weakness, abnormal dreams, tiredness, feeling drunk, sleep paralysis, sleepiness, trembling, confusion/ disorientation, nightmares, sleep walking, bed wetting, sweating, depression, muscle cramps, swelling, fall, joint pain, back pain, cataplexy, balance disorder, disturbance in attention, disturbed sensitivity particularly to touch, abnormal touch sensation, sedation, abnormal taste, anxiety, difficulty in falling asleep in the middle of the night, nervousness, feeling of ?spinning? (vertigo), urinary incontinence, shortness of breath, snoring, congestion of the nose, rash, inflammation of the sinuses, inflammation of nose and throat, increased blood pressure

Uncommon side effects (affects 1 to 10 users in 1,000)include:
Psychosis (a mental disorder that may involve hallucinations, incoherent speech, or disorganized and agitated behaviour), paranoia, abnormal thinking, hallucination, agitation, suicide attempt, difficulty in falling asleep, restless legs, forgetfulness, myoclonus (involuntary contractions of muscles), involuntary passage of faeces, hypersensitivity

Side effects with unknown frequency (cannot be estimated from the available data) include: Convulsion, decreased breathing depth or rate, hives, , suicidal thoughts, short cessation of breathing during sleep.

If any of these affect you severely, tell your doctor.
If you are concerned about any side effect, or if you notice any side effects not mentioned in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Xyrem after the expiry date stated on the bottle (EXP). The expiry date refers to the last day of that month.

Store in the original container.
Do not store Xyrem solutions diluted with water for more than 24 hours.

Once you open a bottle of Xyrem, any contents that you have not used with 40 days of opening should be disposed of.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Xyrem contains

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

What Xyrem looks like and contents of the pack

Xyrem is supplied as an oral solution in a 180 ml amber plastic bottle, which is closed with a childresistant cap. When the bottle is delivered, there is a plastic covered foil seal which is on the top of the bottle, underneath the cap. Each pack contains one bottle, a press-in-bottle-adaptor (PIBA), a plastic measuring syringe and two dosing cups with child-resistant caps.
Xyrem is a clear to slightly opalescent solution.
The amber plastic bottle contains 180 ml of oral solution.
Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder: UCB Pharma Ltd, 208 Bath Road, Slough, Berkshire, SL1 3WE, United Kingdom.
Manufacturer:
Recipharm Limited, Vale of Bardsley, Ashton-under-Lyne, Lancashire, OL7 9RR, United Kingdom. UCB Pharma Ltd, 208 Bath Road, Slough, Berkshire SL1 3WE, United Kingdom

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

You should have received a Xyrem Information Pack from your physician, which includes a booklet all about Xyrem and a video showing you how to take the medicine. If you have not received this, please contact the local representative of the Marketing Authorisation Holder, below.

BelgiëBelgiqueBelgien UCB Pharma SANV TelTél 32 02 559 92 00 LuxembourgLuxemburg UCB Pharma SANV TélTel 32 02 559 92 00

Te. 359 0 2 962 30 49 Magyarország UCB Magyarország Kft. Tel. 36-1 391 0060

eská republika UCB s.r.o. Tel 420 221 773 411 Malta Pharmasud Ltd. Tel 356 21 37 64 36

Danmark UCB Nordic AS Tlf 45 32 46 24 00 Nederland UCB Pharma B.V. Tel. 31 076-573 11 40

Deutschland UCB Pharma GmbH Tel 49 0 2173 48 4848 Norge UCB Nordic AS Tel 45 32 46 24 00

Eesti UCB Pharma Oy Finland Tel 358 10 234 6800 Soome Österreich UCB Pharma GmbH Tel 43 1 291 80 00

UCB .. 30 2109974000 Polska UCB Pharma Sp. z o.o. Tel. 48 0 22 696 99 20

España UCB Pharma, S.A. Tel 34 91 570 34 44 Portugal UCB Pharma Produtos Farmacêuticos, Lda Tel 351 21 302 5300

France UCB Pharma S.A. Tél 33 01 47 29 44 66 România UCB Pharma Romania S.R.L. Tel 40 21 300 29 04

Ireland UCB Pharma Ireland Ltd. Tel 353 01-46 37 395 Slovenija Medis, d.o.o. Tel 386 1 589 69 00

Ísland Vistor hf. Tel 354 535 7000 Slovenská republika UCB s.r.o., organizaná zloka Tel 421 0 2 5920 2020

Italia UCB Pharma S.p.A. Tel 39 02 300 791 SuomiFinland UCB Pharma Oy Finland Puh Tel 358 10 234 6800

Lifepharma Z.A.M. Ltd 357 22 34 74 40 Sverige UCB Nordic AS Tel 46 0 40 29 49 00

Latvija UCB Pharma Oy Finland Tel 358 10 234 6800 Somija United Kingdom UCB Pharma Ltd. Tel 44 01753 534 655

Lietuva
UCB Pharma Oy Finland
Tel: + 358 10 234 6800 (Suomija)

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