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SHARED CARE GUIDELINE Sodium Oxybate (Xyrem )
Sodium Oxybate (Xyrem®)
SCG: For the treatment of narcoleptic patients with cataplexy
(Adopted by the CCG until review and further notice)
This guideline provides information relating to Sodium Oxybate and outlines the
responsibilities of the general practitioner and the Respiratory Support and Sleep Centre at
Papworth Hospital NHS Foundation Trust in the prescribing of this medicine.
AREAS OF RESPONSIBILITY FOR THE SHARING OF CARE
Introduction:
Narcolepsy occurs in 1 in 2500 subjects and is a chronic, debilitating, neurological disease
characterised by excessive daytime sleepiness, cataplexy (sudden loss of muscle tone), sleep
paralysis, hypnagogic hallucinations and fragmented nocturnal sleep. Cataplexy affects
approximately 75% of people with narcolepsy and is triggered by emotional stimuli such as
anger, excitement or laughter.
The severity ranges from dropping of the jaw or the head, to buckling of the legs. During an
episode, speech can be slurred and eyesight impaired, but hearing and awareness remain
undisturbed. Episodes can last a few seconds or for several minutes. Up until now, the only
licensed therapy for cataplexy in the UK has been the tricyclic antidepressant clomipramine,
which is licensed as adjunctive treatment. Other antidepressants such as imipramine and
SSRIs are used, but are unlicensed for this indication.
Sodium Oxybate (Xyrem®) is now licensed for the treatment of cataplexy in adult patients with
narcolepsy. At Papworth Hospital NHS Foundation Trust, Sodium Oxybate will be reserved for
those patients who fail on clomipramine (the only other licensed treatment), and other antidepressants. It will only be used in patients who are resistant to other medication and in
whom cataplexy is at least moderately severe. The recommendation to start treatment will be
made by Consultant only and the Consultant will be personally responsible for the decision to
initiate Sodium Oxybate treatment.
Sodium Oxybate is a central nervous system depressant whose precise mechanism of action
is unique and differs from all other agents used in narcolepsy and probably involves systems
other than central GABAergic systems.
Sodium Oxybate use is associated with dose-related improvements in the symptoms of
narcolepsy and reduction in the numbers of attacks of cataplexy. No withdrawal effects have
been seen with Sodium Oxybate at therapeutic doses and trials demonstrated that after
stabilisation on Sodium Oxybate therapy, acute withdrawal led to a gradual increase in the
number of cataplexy attacks.
Policies / GUID – Shared Care –Sodium Oxybate
/ May 2006
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SHARED CARE GUIDELINE Sodium Oxybate (Xyrem )
RESPONSIBILITIES and ROLES
Specialist Responsibilities (Respiratory Support and Sleep Centre (RSSC)):
The patients will be assessed by one of the consultants (Dr Shneerson, Dr Smith or Dr
Quinnell) and the hospital will undertake to:
1.
2.
3.
4.
5.
6.
7.
8.
Ensure that an agreement to accept prescribing responsibility has been obtained from
the general practitioner before treatment is initiated, stabilised and before the patient is
informed.
Provide information to the patient regarding the medicine
Provide an initial eight week supply of Sodium Oxybate
Recommend an initial dose and how this may be altered according to the response to
treatment
Communicate this information to the general practitioner
Be available for advice to the general practitioner
Review the patient’s progress on treatment
Answer patient enquiries on any aspect of this therapy.
General Practitioner’s responsibilities:
1.
2.
3.
Continue to prescribe Sodium Oxybate after treatment has been initiated and titrated to
an optimal dose (once patient is stabilised) by the Respiratory Support and Sleep
Centre
Monitor the patient’s progress
Communicate any adverse events or other problems with the medicine to the
supervising consultant at Papworth Hospital
Patient’s role:
1.
2.
3.
4.
Report any adverse effects to their Consultant or G.P. whilst taking Sodium Oxybate
Share any concerns they have in relation to treatment with Sodium Oxybate
Report to the Consultant or G.P. if they do not have a clear understanding of their
treatment
Obtain their prescription from the same dedicated pharmacy of their own choice
BACK-UP ADVICE AND SUPPORT
•
Papworth Hospital Main Switchboard 01480 830541
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Respiratory Support and Sleep Centre 01480 364260 (direct line)
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Secretary to Dr Shneerson 01480 364165 (direct line)
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Secretary to Dr Smith 01480 364164 (direct line)
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Secretary to Dr Quinnell 01480 364174 (direct line)
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Pharmacy Medicines Information Service 01480 364179 (direct line)
•
Pharmacy Medicines Helpline (answerphone) 01480 364739
Policies / GUID – Shared Care –Sodium Oxybate
/ May 2006
®
SHARED CARE GUIDELINE Sodium Oxybate (Xyrem )
SUPPORTING INFORMATION
Indications and Usage:
Sodium Oxybate (Xyrem®) is indicated for the treatment of cataplexy in patients with
narcolepsy.
Sodium Oxybate (Xyrem®) is the sodium salt of gamma hydroxybutyrate (GHB) a CNS
depressant active substance with well known abuse potential. Patients will be evaluated for a
history of drug abuse potential and monitored closely. GHB is a Schedule 4 (part 1 CD Benz)
Controlled Drug in the UK.
Dosage and Administration:
Sodium Oxybate (Xyrem®) is required to be taken at bedtime while in bed and again 2.5 to 4
hours later. The recommended starting dose is 4.5g/day divided in two equal doses of 2.25g.
The starting dosage can then be increased to a maximum of 9g/day in increments of 1.5g/day
(0.75g per dose). Two weeks are recommended between dosage increases to evaluate
clinical response and minimize adverse effects. The efficacy and safety at doses higher than
9g/day has not been investigated, and doses greater than 9g/day ordinarily should not be
administered.
Both doses of Sodium Oxybate should be prepared prior to bedtime. Each dose must be
diluted with 60mls of water in the child resistant dosing cups provided prior to ingestion.
Patients will probably need to set an alarm to awaken for the second dose. After ingesting
each dose patients should then lie down and remain in bed.
Absorption is delayed and decreased by a high fat meal and the patient should be told to eat
several hours before going to sleep and taking the first dose of sodium Oxybate. Patients
should try to minimise variability in the timing of dosing in relation to meals.
Dose in hepatic and renal impairment:
Sodium Oxybate is metabolised in the liver to inactive metabolites and clearance is almost
entirely by biotransformation to carbon dioxide, which is then eliminated by expiration. The
doses should be halved in patients with compromised liver function and dose increments
monitored closely. As less than 5% is excreted via the kidney no dosage adjustment should be
necessary in patients with renal impairment.
Sodium Intake:
Daily sodium intake in patients taking Sodium Oxybate ranges from 0.5g (for a 3g dose) to
1.6g (for a 9g dose). This should be considered in patients with heart failure, hypertension or
compromised renal function.
Policies / GUID – Shared Care –Sodium Oxybate
/ May 2006
®
SHARED CARE GUIDELINE Sodium Oxybate (Xyrem )
Special Populations:
The pharmacokinetics of Sodium Oxybate has not been studied in patients under the age of
18 years or over 65 years.
Pregnancy and Breast Feeding:
Not advised in pregnancy or breast feeding.
Contraindications:
Sodium Oxybate is contra-indicated in patients being treated with sedative hypnotic agents,
opioids and barbiturates.
The combined use of alcohol with Sodium Oxybate may result in potentiation of the central
nervous system-depressant effects of Sodium Oxybate and alcohol. Therefore, patients
should be warned strongly against the use of any alcoholic beverages in conjunction with
Sodium Oxybate. Sodium Oxybate should not be used in combination with sedative or other
CNS depressants.
Sodium Oxybate is contra-indicated in patients with succinic semialdehyde dehydrogenase
deficiency. This rare disorder is an inborn error of metabolism variably characterised by
mental retardation, hypotonia, and ataxia.
Side Effects:
The most commonly reported adverse drug reaction is headache, affecting approximately 25%
of patients. Other reported adverse effects in clinical trials include nausea 21%, dizziness
17%, pain 16%, somnolence 13%, pharyngitis 11%, infection 10%, viral infection 10%, flu
syndrome 9%, accidental injury 9%, diarrhoea 8%, rhinitis 8%, asthenia 8%, sinusitis 7%,
nervousness 7%, back pain 7%, confusion 7%, sleepwalking 7%, depression 6%, dyspepsia
6%, abdominal pain 6%, abnormal dreams 6%, insomnia 6%
For full details of potential adverse effects refer to the Summary of Product Characteristics for
Sodium Oxybate (Xyrem®)
Monitoring:
Laboratory tests are not required to monitor patient response to Sodium Oxybate
administration.
Drug Interactions:
No pharmacokinetic interactions have been demonstrated with drugs commonly used in
patients with narcolepsy. Sodium Oxybate should not be used in combination with sedative
hypnotics or other CNS depressants.
Policies / GUID – Shared Care –Sodium Oxybate
/ May 2006
®
SHARED CARE GUIDELINE Sodium Oxybate (Xyrem )
Cost:
Papworth Hospital will fund the initial prescription for Sodium Oxybate (Xyrem®) for up to a
maximum of 8 weeks, but responsibility for ongoing supplies of the medicine will rest with the
general practitioner or Primary Care Trust.
The unit price for Sodium Oxybate Oral Solution 500mg/ml (Xyrem) is £360 per 180ml
bottle.
Cost per annum: 4.5g/day £6,570, 6g/day £8,760 and 9g/day £13,140 inclusive of V.A.T.
References:
Xyrem® (Sodium Oxybate) SPC UCP Pharma Ltd 13th Feb 2006.
These guidelines were produced by Netta Tyler, Pharmacist 2006
Policies / GUID – Shared Care –Sodium Oxybate
/ May 2006