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Xyrem 500mg/ml oral solution

*
Pharmacy Only: Prescription

  • Company:

    UCB (Pharma) Ireland Limited

  • Status:

    No Recent Update

  • Legal Category:

    Product subject to medical prescription which may not be renewed (A)

  • Active Ingredient(s):

    Sodium Oxybate

    *Additional information is available within the SPC or upon request to the company

Updated on 14 October 2022

File name

ie-pi-xyrem.pdf

Reasons for updating

  • Change to section 3 - how to take/use

Updated on 14 October 2022

File name

ie-pil-xyrem-osl-en.pdf

Reasons for updating

  • Change to section 3 - how to take/use

Updated on 24 September 2021

File name

ie-spc-xyrem-osl-en.pdf

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Type II - CCDS v3.0 Acidosis Update + QRD 10.2

Updated on 07 June 2021

File name

ie-spc-xyrem-osl-en.pdf

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Excipients warning updates (sodium) and PIL editorial change (pictogram 4)

Updated on 07 June 2021

File name

ie-pil-xyrem-osl-en.pdf

Reasons for updating

  • Change to section 2 - excipient warnings
  • Change to section 3 - how to take/use
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Excipients warning updates (sodium) and PIL editorial change (pictogram 4)

Updated on 23 December 2020

File name

ie-pil-xyrem.pdf

Reasons for updating

  • Change to section 1 - what the product is used for
  • Change to section 2 - what you need to know - warnings and precautions
  • Change to section 2 - use in children and adolescents
  • Change to section 2 - interactions with other medicines, food or drink
  • Change to section 2 - driving and using machines
  • Change to section 3 - how to take/use
  • Change to section 4 - possible side effects
  • Change to section 5 - how to store or dispose
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

Xyrem - Paediatric Update - EC Decision 17th Dec 2020

Updated on 23 December 2020

File name

ie-spc-xyrem.pdf

Reasons for updating

  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.3 - Shelf life
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Xyrem - Paediatric Update - EC Decision 17th Dec 2020

Updated on 12 May 2020

File name

IE PIL - Xyrem 500mg-ml OSL (Clean).pdf

Reasons for updating

  • Change to section 4 - possible side effects
  • Change to section 6 - date of revision

Free text change information supplied by the pharmaceutical company

4.       Possible side effects

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

Convulsion, decreased breathing depth or rate, hives, suicidal thoughts, short cessation of breathing during sleep, euphoric mood, dry mouth, swelling face (angioedema), dehydration, panic attack, mania / bipolar disorder, delusion, bruxism (teeth grinding and jaw clenching), pollakiuria / micturition urgency (increase need to urinate), nocturia (excessive urination at night), tinnitus (noise in the ears such as ringing or buzzing) sleep-related eating disorder, loss of consciousness, increased appetite, irritability, aggression, dyskinesia (e.g. abnormal, uncontrolled movements of the limbs) and thoughts of committing violent acts (including harming others), dandruff, and increased sexual desire, and choking sensation

 

6.         Contents of the pack and other information

This leaflet was last revised in April 2020

Updated on 12 May 2020

File name

IE SPC - Xyrem 500mg-ml OSL (Clean).pdf

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.4       Special warnings and precautions for use

Xyrem has the potential to induce respiratory depression

Respiratory and CNS depression

Sodium oxybate also has the potential to induce respiratory depression. Apnoea and respiratory depression have been observed in a fasting healthy subject after a single intake of 4.5 g (twice the recommended starting dose). During post-marketing surveillance, it has been observed that the use of sodium oxybate may predispose the patients to choking sensation during sleep. Patients should be questioned regarding signs of Central Nervous System (CNS) or respiratory depression.

 

4.8       Undesirable effects

Respiratory, thoracic and mediastinal disorders

Common: dyspnoea, snoring, nasal congestion

Not known: respiratory depression, sleep apnoea, choking sensation

 

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu/April 2020

Updated on 22 March 2019

File name

20190305-ie-pil-en-approved-current.pdf

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - manufacturer
  • Change to section 6 - date of revision

Updated on 22 March 2019

File name

20190305-ie-spc-en-approved-current.pdf

Reasons for updating

  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 01 August 2018

File name

Xyrem PIL IE.pdf

Reasons for updating

  • Change to section 6 - marketing authorisation holder
  • Change to section 6 - date of revision

Updated on 01 August 2018

File name

Xyrem 500 mgmL oral solution SPC IE.pdf

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Change to section 7- Marketing authorization holder
Change to section 10- Date of revision of the text

Updated on 06 June 2018

File name

ie-spc-h-593_en.docx

Reasons for updating

  • Change to section 6.5 - Nature and contents of container

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 26 April 2018

File name

PIL Xyrem 20180320.pdf

Reasons for updating

  • Change to section 6 - date of revision

Updated on 27 November 2017

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 27 November 2017

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to Section 4.8 – Undesirable effects - how to report a side effect

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 

Changes were made to the following sections:

Section 4.6: Changes to the breast-feeding statements.

Section 4.8: addition of two new side effects: seborrhoea and increased libido.

Updated on 23 November 2017

File name

PIL_10713_259.pdf

Reasons for updating

  • New PIL for new product

Updated on 23 November 2017

Reasons for updating

  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 4 - possible side effects

Updated on 26 January 2017

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Update of the section 4.4: to add information in the Neuropsychiatric events sub-section.
Update of the section 4.8: To add: increased appetite, homicidal ideation, aggression, irritability, dyskinesia as side effects of 'not known' frequency. 

 

 

Updated on 25 January 2017

Reasons for updating

  • Change to section 4 - possible side effects

Updated on 23 September 2016

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Changes in section 4.8 to add:
dehydration, panic attack , mania / bipolar disorder , delusion , bruxism , pollakiuria / micturition urgency  , tinnitus, sleep-related eating disorder and loss of consciousness as adverse reactions in the not known frequency subsection

Updated on 22 September 2016

Reasons for updating

  • Change to side-effects
  • Change to date of revision

Updated on 15 September 2015

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

The following sections have been updated: 

 

Section 4.2: Changes to be in line with the current QRD template

Section 4.4: Editorial change

Section 4.5: Changes to be in line with the current QRD template

Section 4.8: Changes to be in line with the current QRD template, and to add the following side-effects: dehydration, dry mouth and angioedema

Section 5.2:Changed to be in line with the current QRD template
Section 6.3:Changes to be in line with the current QRD template

Section 6.5:Changes to be in line with the current QRD template

Updated on 14 September 2015

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to storage instructions
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to how the medicine works

Updated on 07 January 2015

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.5 - Nature and contents of container

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Section 4.2 - Minor changes to the wording.
Section 4-4 - Warning added about concomitant use with topiramate.
Section 4.5 - Interaction with topiramate added.
Section 4.6 - Fertility section updated.
Section 4.8 - Information added on clinical trials.
Section 5.2 - Dosing information on hepatic impairment patients updated.
Section 6.5 - Heading updated.

Updated on 22 December 2014

Reasons for updating

  • Change to drug interactions
  • Change to dosage and administration

Updated on 10 September 2014

Reasons for updating

  • Change to warnings or special precautions for use
  • Change of contraindications
  • Change to storage instructions
  • Change to side-effects
  • Change to drug interactions

Updated on 15 August 2014

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 6.4 - Special precautions for storage
  • Change to section 9 - Date of renewal of authorisation

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2 Posology and method of administration

If sodium oxybate and valproate are used concomitantly (see section 4.5), a decrease in sodium oxybate dose by 20% is recommended. The recommended starting dose for sodium oxybate, when used concomitantly with valproate, is 3.6 g per night administered orally in two equal divided doses of approximately 1.8 g. If concomitant use is warranted, patient response and tolerability should be monitored and dose should be adapted accordingly (see section 4.4)

4.4 Special warnings and precautions for use

Respiratory and CNS depression

• Benzodiazepines
Given the possibility of increasing the risk of respiratory depression, the concomitant use of benzodiazepines and sodium oxybate should be avoided.

• Alcohol and CNS depressants
The combined use of alcohol, or any CNS -depressant medicinal product, with sodium oxybate may result in potentiation of the CNS-depressant effects of sodium oxybate as well as increased risk of respiratory depression. Therefore, patients should be warned against the use of alcohol in conjunction with sodium oxybate.

• GHB dehydrogenase inhibitors
Caution is required in patients who are treated concomitantly with valproate or other GHB dehydrogenase inhibitors as pharmacokinetic and pharmacodynamic interactions have been observed when sodium oxybate is co-administered with valproate (see section 4.5). If concomitant use is warranted, dose adjustment is to be considered (see section 4.2). Additionally, patient response and tolerability should be carefully monitored and dose should be adapted accordingly.

4.5 Interaction with other medicinal products and other forms of interaction

Sedative hypnotics
Drug interaction studies in healthy adults with sodium oxybate (single dose of 2.25 g) and lorazepam (single dose of 2 mg) and zolpidem tartrate (single dose of 5 mg) demonstrated no pharmacokinetic interactions.

Tramadol
A drug interaction study in healthy adults with sodium oxybate (single dose of 2.25 g) and tramadol (single dose of 100 mg) demonstrated no pharmacokinetic/pharmacodynamic interaction.

Modafinil
A drug interaction study in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate (single dose of 4.5 g) and modafinil (single dose of 200 mg).

Omeprazole
The co-administration of omeprazole has no clinically significant effect on the pharmacokinetics of sodium oxybate. The dose of sodium oxybate therefore does not require adjustment when given concomitantly with proton pump inhibitors.

Ibuprofen
Drug interaction studies in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate and ibuprofen.

Diclofenac
Drug interaction studies in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate and diclofenac. Co-administration of sodium oxybate and diclofenac in healthy volunteers reduced the attention deficit caused by the administration of Xyrem alone as measured by psychometric tests.

GHB dehydrogenase inhibitors
Since sodium oxybate is metabolised by GHB dehydrogenase there is a potential risk of an interaction with medicinal products that stimulate or inhibit this enzyme (e.g. valproate, phenytoin or ethosuximide) (see section 4.4).

The co-administration of sodium oxybate (6 g per day) with valproate (1250 mg per day) resulted in an increase in systemic exposure to sodium oxybate by approximately 25% and no significant change in Cmax. No effect on the pharmacokinetics of valproate was observed. The resulting pharmacodynamic effects, including increased impairment in cognitive function and sleepiness, were greater with co-administration than those observed with either drug alone. If concomitant use is warranted, patient response and tolerability should be monitored and dose adjustments made if required (see section 4.2).


4.8 Undesirable effects


Psychiatric disorders:
Not known (cannot be estimated from the available data): suicidal ideation, euphoric mood


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.
For storage conditions after first opening of the medicinal product, see section 6.3
For storage conditions after dilution of the medicinal product, see section 6.3.



7. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

Date for first authorisation: 13 October 2005
Date of latest renewal: 18 October 2010

Updated on 17 August 2012

Reasons for updating

  • Change to packaging

Updated on 06 July 2011

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to information about pregnancy or lactation

Updated on 18 May 2011

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2     Posology and method of administration

Due to the well known potential of abuse of sodium oxybate, physicians should evaluate patients for a history of or susceptibility to drug abuse prior to commencing treatment. During treatment, patients should be monitored for the risk of diversion, misuse and abuse of sodium oxybate (see section 4.4).

 

Discontinuation of Xyrem

 If the patient stops taking the medicinal product for more than 14 consecutive days, titration should be restarted from the lowest dose.

 4.3     Contraindications

 Hypersensitivity to the active substance or to any of the excipients.


Patients with major depression

 

Patients with succinic semialdehyde dehydrogenase deficiency.

 

Patients being treated with opioids or barbiturates.

 

4.4     Special warnings and precautions for use

Respiratory depression

Sodium oxybate also has the potential to induce respiratory depression. Apnoea and respiratory depression have been observed in a fasting healthy subject after a single intake of 4.5 g (twice the recommended starting dose). Patients should be questioned regarding signs of Central Nervous System (CNS) or respiratory depression.  Special caution should be observed in patients with an underlying respiratory disorder. Because of the higher risk of sleep apnoea, patients with a BMI ≥40 kg/m2 should be monitored closely when taking sodium oxybate.

 

Abuse potential and dependence

Sodium oxybate, which is as the sodium salt of GHB, is a CNS depressant active substance with well known abuse potential. Prior to treatment physicians should evaluate patients for a history of or susceptibility to drug abuse. Patients should be routinely monitored and in the case of suspected abuse, treatment with sodium oxybate should be discontinued.

 

Neuropsychiatric events

Patients may become confused while being treated with sodium oxybate. If this occurs, they should be evaluated fully, and appropriate intervention considered on an individual basis. Other neuropsychiatric events include anxiety, psychosis, paranoia, hallucinations, and agitation. The emergence of thought disorders and/or behavioural abnormalities when patients are treated with sodium oxybate requires careful and immediate evaluation.

 

The emergence of depression when patients are treated with sodium oxybate requires careful and immediate evaluation. Patients with a previous history of a depressive illness and/or suicide attempt should be monitored especially carefully for the emergence of depressive symptoms while taking sodium oxybate. Major depression is contraindicated for use with Xyrem (section 4.3).

 

 

Sodium oxybate should not be used in combination with sedative hypnotics or other CNS depressants.


Sedative hypnotics

Drug interaction studies in healthy adults with sodium oxybate (single dose of 2.25 g) and lorazepam (an anxiolytic [benzodiazepine]; single dose of 2 mg) and zolpidem tartrate (a hypnotic [non-benzodiazepine]; single dose of 5 mg) demonstrated no pharmacokinetic interactions. Increased sleepiness was observed after concomitant administration of sodium oxybate (2.25 g) and lorazepam (2 mg). The pharmacodynamic interaction with zolpidem has not been assessed. When higher doses up to 9 g/d of sodium oxybate are combined with higher doses of hypnotics (within the recommended dose range) pharmacodynamic interactions associated with symptoms of CNS depression and/or respiratory depression cannot be excluded (see section 4.3).


Tramadol

A drug interaction study in healthy adults with sodium oxybate (single dose of 2.25 g) and tramadol (a central acting opioid; single dose of 100 mg) demonstrated no pharmacokinetic/pharmacodynamic interaction. When higher doses up to 9 g/d of sodium oxybate are combined with higher doses of opioids (within the recommended dose range) pharmacodynamic interactions associated with symptoms of CNS depression and/or respiratory depression cannot be excluded (see sections 4.3).


Antidepressants

Drug interaction studies in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate (single dose of 2.25 g) and the antidepressants protriptyline hydrochloride (single dose of 10 mg) and duloxetine (60 mg at steady state). No additional effect on sleepiness was observed when comparing single doses of sodium oxybate alone (2.25 g) and sodium oxybate (2.25 g) in combination with duloxetine (60 mg at steady state). Antidepressants have been used in the treatment of cataplexy. A possible additive effect of antidepressants and sodium oxybate cannot be excluded. The rate of adverse events has increased when sodium oxybate is co-administered with tricyclic antidepressants.


Modafinil

A drug interaction study in healthy adults demonstrated no pharmacokinetic interactions between sodium oxybate (single dose of 4.5 g) and modafinil (a stimulant; single dose of 200 mg). Sodium oxybate has been administered concomitantly with CNS stimulant agents in approximately 80% of patients in clinical studies in narcolepsy. Whether this affected respiration during the night is unknown.

 

 

4.6     Fertility, pregnancy and lactation

 

Pregnancy

Animal studies have shown no evidence of teratogenicity but embryolethality was seen in both rat and rabbit studies (see section 5.3).

Data from a limited number of pregnant women exposed in the first trimester indicate a possible increased risk of spontaneous abortions. To date no other relevant epidemiological data are available. Limited data from pregnant patients during second and third trimester indicate no malformative nor foeto/neonatal toxicity of sodium oxybate.

 

Sodium oxybate is not recommended during pregnancy.

 

Breastfeeding

It is not known whether sodium oxybate and/or its metabolites are excreted into breast milk. Breastfeeding is not recommended during treatment with sodium oxybate.

 
4.8     Undesirable effects

 

Immune system disorders:

Uncommon : hypersensitivity

 

Metabolism and nutrition disorders:

Common: anorexia, decreased appetite

 

Psychiatric disorders:

Common: depression, cataplexy, anxiety, abnormal dreams, confusional state, disorientation, nightmares, sleepwalking, sleep disorder, insomnia, middle insomnia, nervousness

Uncommon: suicide attempt, psychosis, paranoia, hallucination, abnormal thinking, agitation, initial insomnia

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


Nervous system disorders:

Very common: dizziness, headache

Common: sleep paralysis, somnolence, tremor, balance disorder, disturbance in attention, hypoaesthesia, paraesthesia, sedation, dysgeusia

Uncommon:  myoclonus, amnesia, restless legs syndrome

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


Ear and labyrinth disorders:

Common: vertigo


Eye disorders:

Common: blurred vision


Cardiac disorders:

Common: palpitations


Vascular disorders:

Common: hypertension


Respiratory, thoracic and mediastinal disorders:

Common: dyspnoea, snoring, nasal congestion

Not known (cannot be estimated from the available data): respiratory depression, sleep apnoea

 

Gastrointestinal disorders:

Very common: nausea (the frequency of nausea is higher in women than men)

Common: vomiting, diarrhoea, abdominal pain upper,

Uncommon: faecal incontinence


Skin and subcutaneous tissue disorders:

Common: hyperhidrosis, rash

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


Musculoskeletal, connective tissue and bone disorders:

Common: arthralgia, muscle, spasms, back pain


Renal and urinary disorders:

Common: enuresis nocturna, urinary incontinence


General disorders and administration site conditions:

Common: asthenia, fatigue, feeling drunk, oedema peripheral


Infections and infestations:

Common: nasopharyngitis, sinusitis


Investigations:

Common: blood pressure increased, weight decreased

 

 5.2     Pharmacokinetic properties

 

Sodium oxybate is rapidly and almost completely absorbed after oral administration; absorption is delayed and decreased by a high fat meal.  It is eliminated mainly by metabolism with a half-life of 0.5 to 1 hour.  Pharmacokinetics are nonlinear with the area under the plasma concentration curve (AUC) versus time curve increasing 3.8-fold as dose is doubled from 4.5 g to 9 g. The pharmacokinetics are not altered with repeat dosing.

 

Absorption: Sodium oxybate is absorbed rapidly following oral administration with an absolute bioavailability of about 88 %.  The average peak plasma concentrations (1st and 2nd peak) following administration of a 9 g daily dose divided into two equivalent doses given four hours apart were 78 and 142 mg/ml, respectively.  The average time to peak plasma concentration (Tmax) ranged from 0.5 to 2 hours in eight pharmacokinetic studies.  Following oral administration, the plasma levels of sodium oxybate increase more than proportionally with increasing dose.  Single doses greater than 4.5 g have not been studied.  Administration of sodium oxybate immediately after a high fat meal resulted in delayed absorption (average Tmax increased from 0.75 hr to 2.0 hr) and a reduction in peak plasma level (Cmax) by a mean of 58% and of systemic exposure (AUC) by 37%.

 

Special populations:

 

Elderly patients:. In a limited number of patients greater than the age of 65 years the pharmacokinetics of sodium oxybate was not different compared to patients younger than 65 years of age.

 

 

5.3     Preclinical safety data

 

 

Drug discrimination studies show that GHB produces a unique discriminative stimulus that in some respects is similar to that of alcohol, morphine and certain GABA-mimetic medicinal products. Self-administration studies in rats, mice and monkeys have produced conflicting results, whereas tolerance to GHB as well as cross-tolerance to alcohol and baclofen has been clearly demonstrated in rodents.

Updated on 16 November 2010

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 6.4 - Special precautions for storage

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

Due to renewal the following sections have been moved within the section or reworded: 4.2, 4.3, 4.4, 4.5, 4.8, 5.1

4.6     Fertility, Ppregnancy and lactation

 

Fertility

There is no clinical data available on the effect of sodium oxybate on fertility. No effect on fertility parameters in the rat were observed (see section 5.3)

6.4     Special precautions for storage

 

 

This medicinal product does not require any special storage conditions.

For storage conditions of the diluted medicinal product see section 6.3.

Updated on 19 April 2010

Reasons for updating

  • Change to MA holder contact details

Updated on 07 August 2008

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

4.2       Posology and method of administration

 

The recommended starting dose is 4.5 g/day sodium oxybate (9ml Xyrem) divided into two equal doses of 2.25 g/dose (4.45ml/dose). The dose should be titrated to effect based on efficacy and tolerability (see Section 4.4) up to a maximum of 9 g/day divided into two equal doses of 4.5g/dose (9ml/dose) by adjusting up or down in dose increments of 1.5 g/day (i.e. 0.75 g/dose or 1.5ml dose). A minimum of one to two weeks is recommended between dosage increments. The dose of 9g/day should not be exceeded due to the possible occurrence of severe symptoms at doses of 18 g/day or above (see section 4.4).

 

 

4.4          Special warnings and special precautions for use

 

Sodium intake

Patients taking sodium oxybate will have an additional daily intake of sodium that ranges from 0.8275g (for a 4.5g/day (9ml) Xyrem dose) to 1.6g (for a 9g/day  (18ml) Xyrem dose). A dietary recommendation to reduce sodium intake should be carefully considered in the management of patients with heart failure, hypertension or compromised renal function. (see section 4.2).

Updated on 10 July 2008

Reasons for updating

  • Change of manufacturer

Updated on 16 November 2007

Reasons for updating

  • Addition of marketing authorisation holder

Updated on 14 November 2007

Reasons for updating

  • Change of special precautions for disposal

Updated on 28 August 2007

Reasons for updating

  • Correction of spelling/typing errors

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 18 July 2007

Reasons for updating

  • Change to improve clarity and readability

Updated on 06 March 2007

Reasons for updating

  • Change to section 4.1 - Therapeutic indications

Legal category:Product subject to medical prescription which may not be renewed (A)

Free text change information supplied by the pharmaceutical company

 4.1 Treatment of narcolepsy with cataplexy in adult patients.

Updated on 22 August 2006

Reasons for updating

  • Change to date of revision

Updated on 17 February 2006

Reasons for updating

  • New SPC for new product

Legal category:Product subject to medical prescription which may not be renewed (A)

Updated on 17 February 2006

Reasons for updating

  • New PIL for new product