Xyrem 500 mg/ml oral solution – patient leaflet, side effects, dosage

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• 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 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

Children and adolescents

Xyrem can be taken by adolescents and children from 7 years of age when they are over 15 kg in weight.

Xyrem cannot be taken by children below 7 years of age or below 15 kg in weight.

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

Whilst the doctor is adjusting the dose which may take a number of weeks, parent/caregivers should carefully monitor the child’s breath during the first 2 hours after sodium oxybate intake to assess if there is any abnormality in breathing, for example stoppage of breathing for short periods while sleeping, noisy breathing and bluish colour of the lips and face. If abnormality in breathing is observed medical support should be sought and the doctor should be informed as soon as possible. If any abnormality is noted after the first dose, the second dose should not be administered. If no abnormality is noted the second dose can be administered. The second dose should not be given earlier than 2.5 hours or later than 4 hours after the first dose.

If you have had or are having upsetting feelings particularly if you are feeling very sad or have lost interest in life it is important that you tell the doctor or caregiver.

Other medicines and Xyrem

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

⁷ GB 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 tell 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 processed in a similar way by the body (e.g., valproate, phenytoin or ethosuximide which are used for the treatment of fits)
• topiramate (used for treatment of 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. Xyrem with alcohol

You must not drink alcohol while taking Xyrem, as its effects can be increased. Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. 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.

8 Patients taking Xyrem should not breast feed since it is known that Xyrem passes into breast milk. Changes in sleep patterns have been observed in breastfed infants from exposed mothers.

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. For paediatric patients, physicians, parents or caregivers are advised that the waiting time for performing activities that require mental alertness, motor co-ordination or any activities that may have a physical risk may have to be longer than 6 hours, depending on individual sensitivity.

Xyrem contains sodium

This medicine contains 182.24 mg sodium (main component of cooking/table salt) in each gram. This is equivalent to 9.11% of the recommended maximum daily dietary intake of sodium for an adult. Talk to your doctor or pharmacist if you need 2 g of sodium oxybate (Xyrem) or more daily for a prolonged period, especially if you have been advised to follow a low salt (sodium) diet.

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• Prepare both doses before bedtime.
• Take doses within 24 hours after preparation.

Adolescents and children aged 7 years and over who weigh 15 kg or more

• taking Xyrem on its own

For those aged 7 years and over who weigh 15 kg or more, a doctor will work out the right dose based on your body weight.

Your doctor will work out the right dose for you. Do not exceed the dose prescribed for you.

Adults - taking Xyrem with Valproate

If you are taking valproate together with Xyrem, the dose of Xyrem will be adapted by your doctor.

• For adults the recommended starting dose for Xyrem, when used together with Valproate, is 3.6 g each day, given as two separate doses of 1.8 g.
• Take the first dose when getting into bed and the second dose 2½ to 4 hours later.

Adolescents and children aged 7 years and older who weigh 15 kg or more

• taking Xyrem with Valproate

If you are taking Valproate together with Xyrem, the dose of Xyrem will be adapted by your doctor.

¹¹ GB Kidney or liver problems

• If you have kidney problems, you should consider a dietary recommendation to reduce sodium (salt) intake. If you have liver problems, the starting dose should be halved. Your doctor may gradually increase your 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. Do not allow children to prepare Xyrem.

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

Step 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.

  1

  Figure 1

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• 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

Step 2.

• Next, insert the tip of the measuring syringe into the

  centre opening of the bottle and press down firmly.

• 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.

  Figure 2 2

  3

  Figure 3

¹³ GB Step 3.

• 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.

  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).

Step 4.

• 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 (Caution: as the dosing cup cap is reversible, only after the clicking noise is heard it is ensured that the cap is closed in the child-resistant manner).
• Rinse out the syringe with water.

• Just before going to sleep:

  • Adult patients should place the second dose near their bed.

  • The parent or caregiver of adolescents and children aged 7 years and over should not leave the second dose near the child’s bed or within easy reach of the child.

    Figure 4

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• You may need to set an alarm so you wake up to take your second dose no earlier than 2½ 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 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. For children who sleep longer than 8 hours but less than 12 hours, the first dose may be given after the child has been sleeping for 1 to 2 hours.
• When you wake up or wake up the child 2 ½ 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, excessive thirst, muscle cramps and weakness. 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.

16 Adults – most common side effects observed in clinical studies (occurring in 10% to 20% of patients):

• dizziness
• nausea
• headache.

If you experience any of these side effects, tell your doctor straight away.

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

• bed wetting (18.3%)
• nausea (12.5%)
• vomiting (8.7%)
• weight decrease (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 side effects, tell your doctor straight away.

¹⁷ GB The side effects in adults and children are the same. If you experience any of the side effects listed below, tell your doctor straight away:

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

• nausea
• dizziness
• headache

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

• sleeping problems including insomnia, abnormal dreams, sleep paralysis, sleepiness, nightmares, sleep walking, bed wetting, excessive daytime sleepiness, difficulty in falling asleep in the middle of the night
• feeling drunk, trembling, confusion/ disorientation, blurred vision, balance disorder, fall, feeling of "spinning" (vertigo),
• feeling the heart beat, increased blood pressure, shortness of breath
• vomiting, stomach pains, diarrhoea
• anorexia, decreased appetite, weight loss
• weakness, tiredness, sedation
• sweating
• depression
• muscle cramps, swelling
• joint pain, back pain

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• disturbance in attention, disturbed sensitivity particularly to touch, abnormal touch sensation, abnormal taste
• anxiety, nervousness
• urinary incontinence
• snoring, congestion of the nose
• rash
• inflammation of the sinuses,
• inflammation of nose and throat

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

• 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

Not known (cannot be estimated from the available data):

• convulsion
• decreased breathing depth or rate, short cessation of breathing during sleep
• hives

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• suicidal thoughts, delusion, thoughts of committing violent acts (including harming others)
• irritability, aggression
• euphoric mood
• panic attack
• mania / bipolar disorder
• dry mouth, dehydration
• swelling face (angioedema)
• bruxism (teeth grinding and jaw clenching)
• pollakiuria / micturition urgency (increase 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 sexual desire
• nocturia (excessive urination at night)
• choking sensation

If you experience any of the side effects listed above, tell your doctor straight away.

CIB72663H 1000014238

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