Download Riluzole for Amyotrophic Lateral Sclerosis (a form of Motor

GMMMG Interface Prescribing
Subgroup
Shared Care Protocol
Shared Care Guideline for
Reference Number
Riluzole for Amyotrophic Lateral Sclerosis (a form of
Motor Neurone Disease)
Version: 1
Replaces: n/a
Author(s)/Originator(s): (please state author name and
department)
MND Team, Salford Royal Foundation Trust
Date approved by Interface Prescribing Group:
08/10/2015
Date approved by Commissioners:
dd/mm/yyyy
Issue date: 19/11/2015
To be read in conjunction
with the following
documents:
Current Summary of Product
characteristics
(http://www.medicines.org.uk)
BNF
Date approved by Greater Manchester
Medicines Management Group:
19/11/2015
Review Date:
19/11/2017
Please complete all sections
1. Name of Drug, Brand
Name, Form and
Strength
2. Licensed Indications
Riluzole 50mg tablets
Riluzole is indicated to extend life or the time to mechanical ventilation for patients with
amyotrophic lateral sclerosis (ALS).
Clinical trials have demonstrated that riluzole extends survival for patients with ALS.
Survival was defined as patients who were alive, not intubated for mechanical ventilation
and tracheotomy-free.
There is no evidence that riluzole exerts a therapeutic effect on motor function, lung
function, fasciculations, muscle strength and motor symptoms. Riluzole has not been
shown to be effective in the late stages of ALS.
Safety and efficacy of riluzole has only been studied in ALS. Therefore, should not be
used in patients with any other form of motor neurone disease.
3. Criteria for shared
Prescribing responsibility will only be transferred when
care
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Version: 1
Date: 19/11/2015
Review: 19/11/2017
Treatment is for a specified indication and duration.
Treatment has been initiated and established by the secondary care specialist.
The patient’s initial reaction to and progress on the drug is satisfactory.
The GP has agreed in writing in each individual case that shared care is
appropriate.
Shared Care Guideline for Riluzole for ALS
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The patient’s general physical, mental and social circumstances are such that
he/she would benefit from shared care arrangements
background
 Unstable disease state
 Patient does not consent to shared care
 Patient does not meet criteria for shared care
Amyotrophic lateral sclerosis (ALS) is a form of Motor Neurone Disease (MND). It is a
progressive and fatal neurodegenerative disorder with a poor prognosis. Patients
experience a gradual loss of muscle function involved in swallowing and breathing. From
onset of symptoms 5 year survival is 5 - 15% and median survival time is about 3 years.
Riluzole is indicated to extend life or the time to mechanical ventilation in patients with
ALS.
6. Contraindications
Riluzole is currently the only drug licensed for treating ALS in the UK. The National
Institute for Health and Care Excellence (NICE) has approved its use for ALS, so it is
available to people who have been diagnosed. In the trials in which Riluzole has shown
some benefit, eligible patients were up to 75 years of age, were in a reasonable state of
general health, had suffered from the disease for no greater than 5 years and had a
forced vital lung capacity of not less than 60% predicted.
Hypersensitivity to the active substance or to any of the excipients.
Hepatic disease or baseline transaminases greater than 3 times the upper limit of
normal.
Patients who are pregnant or breast-feeding.
Children
Riluzole is not recommended for use in patients with impaired renal function, as studies at
repeated doses have not been conducted in this population.
4. Patients excluded
from shared care
5. Therapeutic use &
(please note this does
not replace the SPC or
BNF and should be
read in conjunction
with it).
Caution:
Liver impairment
Riluzole should be prescribed with care in patients with a history of abnormal liver
function, or in patients with slightly elevated serum transaminases (ALT/SGPT;
AST/SGOT up to 3 times the upper limit of the normal range (ULN)), bilirubin and/or
gamma-glutamyl transferase (GGT) levels. Baseline elevations of several liver function
tests (especially elevated bilirubin) should preclude the use of riluzole (see section 4.8).
Because of the risk of hepatitis, serum transaminases, including ALT, should be
measured before and during therapy with riluzole. ALT should be measured every month
during the first 3 months of treatment, every 3 months during the remainder of the first
year, and periodically thereafter. ALT levels should be measured more frequently in
patients who develop elevated ALT levels.
Riluzole should be discontinued if the ALT levels increase to 5 times the ULN. There is no
experience with dose reduction or rechallenge in patients who have developed an
increase of ALT to 5 times ULN. Readministration of riluzole to patients in this situation
cannot be recommended.
Neutropenia:
Patients should be warned to report any febrile illness to their physicians. The report of a
febrile illness should prompt physicians to check white blood cell counts and to
discontinue riluzole in case of neutropenia.
Interstitial lung disease
Cases of interstitial lung disease have been reported in patients treated with riluzole,
some of them were severe. If respiratory symptoms develop such as dry cough and/or
dyspnea, chest radiography should be performed, and in case of findings suggestive of
interstitial lung disease (e.g. bilateral diffuse lung opacities), riluzole should be
discontinued immediately. In the majority of the reported cases, symptoms resolved after
Version: 1
Date: 19/11/2015
Review: 19/11/2017
Shared Care Guideline for Riluzole for ALS
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drug discontinuation and symptomatic treatment.
7. Prescribing in
pregnancy and
lactation
8. Dosage regimen for
continuing care
Use in pregnancy and breastfeeding is contraindicated. Clinical experience in pregnancy
is lacking and it is not known whether riluzole is excreted in breast milk.
Route of administration
Preparations available:
Riluzole 50mg tablets
Oral
Although not strictly necessary, side effects such as nausea are less likely if riluzole is
taken on an empty stomach (if possible, one hour before or two hours after a meal).
It comes in tablet form and should be swallowed whole, but if there are problems
swallowing, the tablets may be crushed and mixed with foods to aid swallowing. Riluzole
should not be dissolved in water as it does not dissolve well.
When crushed, the drug can produce a temporary numbing effect in the mouth. It may be
easier to swallow if crushed and mixed with a soft food product such as a puree, yoghurt,
ice cream or a thick beverage and eaten in the usual way. Once it is crushed riluzole
should be taken immediately due to limited stability problems
Please note: tablets should not be crushed in order to feed through a PEG tube as this
may block the tubing. If swallowing riluzole becomes particularly problematic, please
consult your health care team for advice.
Please prescribe:
Riluzole 50mg twice a day
Is titration required
No
Adjunctive treatment regime:
Not applicable
Conditions requiring dose reduction:
e.g. impaired renal/ liver function
No dose reduction is required
Usual response time :
Riluzole is not a cure, and will not reverse any damage to the motor neurones already
present. After 18 months of treatment, it may increase survival by two to four months on
average. Those taking riluzole will not be aware of any difference in the symptoms of their
ALS, but taking this drug may marginally slow down the progression of the disease.
Duration of treatment:
Treatment will initially be for 12 months, with annual review. Treatment should cease
when patients enter the terminal phase of the disease.
Treatment to be terminated by:
Specialist Consultant or MND specialist nurse
NB. All dose adjustments will be the responsibility of the initiating specialist
care unless directions have been specified in the medical letter to the GP.
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9.Drug Interactions
For a comprehensive
list consult the BNF or
Summary of Product
Characteristics
The following drugs must not be prescribed without consultation with the
specialist:
Not applicable
The following drugs may be prescribed with caution:
No drug interactions are listed for riluzole in the BNF.
10. Adverse drug
reactions
For a comprehensive list
(including rare and very
rare adverse effects), or if
significance of possible
adverse event uncertain,
consult Summary of
Product Characteristics
or BNF
Specialist to detail below the action to be taken upon occurrence of a particular
adverse event as appropriate. Most serious toxicity is seen with long-term use
and may therefore present first to GPs.
Adverse event
System – symptom/sign
Action to be taken Include
whether drug should be stopped prior to
contacting secondary care specialist
By whom
Interstitial lung disease
If respiratory symptoms
develop such as dry cough
and/or dyspnoea, the
patient should be referred to
the consultant neurologist
and chest radiography
should be performed. In
findings suggestive of
interstitial lung disease (e.g.
bilateral diffuse lung
opacities), riluzole should
be discontinued
immediately. In the majority
of the reported cases,
symptoms resolved after
drug discontinuation and
symptomatic treatment.
GP
Elevations in liver function
tests
As per monitoring
GP
Neutropenia
Abdominal symptomsnausea, diarrhoea,
abdominal pain, vomiting
As per monitoring
Symptomatic treatment
GP
Patient/GP
Headache, dizziness, oral
paraesthesia and
somnolence
Symptomatic treatment
Patient/GP
The patient should be advised to report any of the following signs or symptoms to
their GP without delay:
Patients should be made aware that they need to report any febrile illness, fever, sore
throat, bruising or unexpected bleeding, and respiratory symptoms (such as dry cough
and/or dyspnoea.
Other important co morbidities:
Non-applicable
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Any adverse reaction to a black triangle drug or serious reaction to an established
drug should be reported to the MHRA via the “Yellow Card” scheme.
11.Baseline
investigations
12. Ongoing
monitoring
requirements to be
undertaken by GP
List of investigations / monitoring undertaken by secondary care
The Consultant will arrange for LFTs and FBC to be done at baseline.
The Neurologist will review the patient every 3 months, advise the patient, carers and GP,
enquire as to whether FBC and LFT testing are due and supervise other treatments that
may be needed (physiotherapy, occupational therapy, speech therapy, dietary advice,
gastrostomy, respiratory support).
Yes
Is monitoring required?
Monitoring
Frequency
Results
Action
By whom
Serum transaminases
including ALT
Monthly for 3
months, 3monthly for 12
months then
annually
thereafter.
Discuss with
Consultant
Treatment
should be
stopped if the
ALT rises to
five times the
upper limit of
normal.
Discontinue
riluzole in case
of neutropenia.
GP
Full Blood
Counts
13. Pharmaceutical
Monthly during
Discuss with
the first 3
Consultant
months in view
of the rare
reported cases
of neutro-penia
This medicinal product does not require any special storage conditions.
GP
aspects
14. Responsibilities
of initiating specialist
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Version: 1
Date: 19/11/2015
Review: 19/11/2017
Confirm the diagnosis, if necessary by repeating the examination and tests such
as neurophysiology.
Check LFTs and FBCs before commencement of treatment
Give the MND Association Riluzole information sheet to the patient and/or their
carers stressing the importance of regular blood test monitoring, the need to
report symptoms suggesting neutropenia e.g. fever, sore throat etc, bruising or
unexpected bleeding
Arrange follow up in the MND clinic at SRFT (typically three monthly)
Initiate treatment and prescribe until the patient is stable (usually 3 months
supply)
Monitor patient’s initial reaction to and progress on the drug.
During the first three months of therapy the patient is seen twice by MND clinic,
once by the specialist nurse 2 weeks after starting riluzole and then by the
neurologist after 3 months.
Ensure that the patient has an adequate supply of medication until GP supply can
be arranged.
Patients will be considered suitable for transfer to GP prescribing ONLY when
they meet the criteria listed in section 3 above.
The consultant team will write formally to the GP to request shared care using the
Shared Care Agreement Form (Appendix 2) which must be fully completed.
Failure to supply all the required information will result in the refusal of the request
until all information has been supplied.
Patients will only be transferred to the GP once the GP has agreed via signing
copies of the Shared Care Agreement Form (Appendix 2).
Continue to monitor and supervise the patient according to this protocol, while the
patient remains on this drug, and agree to review the patient promptly if contacted
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15. Responsibilities
of the GP
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Version: 1
Date: 19/11/2015
Review: 19/11/2017
by the GP
Provide GP with diagnosis, relevant clinical information and baseline results,
treatment to date and treatment plan, duration of treatment before consultant
review.
Provide GP with details of outpatient consultations, ideally within 14 days of
seeing the patient or inform GP if the patient does not attend appointment.
Provide GP with advice on when to stop this drug.
Act upon communication from the GP in a timely manner.
Provide patient with relevant drug information to enable Informed consent to
therapy.
Provide patient with relevant drug information to enable understanding of potential
side effects and appropriate action.
Provide patient with relevant drug information to enable understanding of the role
of monitoring.
Provide patient with monitoring booklet where appropriate.
Be available to provide patient specific advice and support to GPs as necessary.
Provide ongoing monitoring
Monitor the FBC and LFTs in collaboration with the specialist at monthly intervals
for the first 3 months, then every 3 months during the remainder of the first year
and annually thereafter.
Monitor clinically for symptoms of liver dysfunction (jaundice, pain, bruising,
bleeding) or bone marrow suppression (fever, sore throat, bruising bleeding) or
respiratory symptoms.
To formally reply to the request for shared care from the specialist within 14 days.
Continue treatment as directed by the specialist and prescribe Riluzole 50mg bd.
Act upon communication from the specialist in a timely manner.
Ensure no drug interactions with concomitant medicines.
To monitor and prescribe in collaboration with the specialist according to this
protocol.
Symptoms or results are appropriately actioned, recorded and communicated to
secondary care when necessary.
Formally reply to the consultant’s request to shared care within 14 days of receipt,
using the shared care agreement forms (Appendix 2). NB the GP should only
agree to the transfer of prescribing if all details of the form have been completed.
If the GP does not feel it is appropriate to take on the prescribing then the
prescribing responsibilities will remain with the specialist. The GP should indicate
the reason for declining.
Enter a READ code (e.g. 8BM5.00) on to the patient record to highlight the
existence of shared care for the patient.
Undertake more frequent tests if there is evidence of clinical deterioration,
abnormal results, or other risk factors. Contact consultant team for advice on
monitoring in these circumstances if required.
Check all monitoring results prior to issuing a repeat prescription to ensure it is
safe to do so.
Monitor the patient’s general wellbeing.
Inform the consultant immediately if a patient has become pregnant or is planning
to become pregnant for treatment options to be considered
Seek urgent advice from secondary care if:
 Toxicity is suspected
 Non-compliance is suspected
 The GP feels a dose change is required
 There is marked deterioration in the patient’s condition
 The GP feels the patient is not benefiting from the treatment
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16. Responsibilities
of the patient
17.Additional
Responsibilities
e.g. Failure of patient to
attend for monitoring,
Intolerance of drugs,
Monitoring
parameters
outside
acceptable
range, Treatment failure,
Communication failure
The shared care agreement will cease to exist, and prescribing responsibility will
return to secondary care, where:
 The clinical situation deteriorates such that the shared care criterion of stability
is not achieved.
 The clinical situation requires a major change in therapy.
 The patient is a risk to self or others
 GP feels it to be in the best stated clinical interest of the patient for prescribing
responsibility to transfer back to the Consultant. The Consultant will accept
such a transfer within a timeframe appropriate to the clinical circumstances.
There must be discussion between the consultant team and GP on this matter
and agreement from the consultant team to take back full prescribing
responsibility for the treatment of the patient. The consultant team should be
given 14 days’ notice in which to take back prescribing responsibilities from
primary care.
 To take medication as directed by the prescriber, or to contact the GP if not taking
medication
 To attend hospital and GP clinic appointments.
 Failure to attend will result in medication being stopped (on specialist advice).
 To report adverse effects to their Specialist or GP e.g. febrile illness, respiratory
symptoms.
List any special
Action required
By whom
Date
considerations
[insert]
18. Supporting
[insert]
[insert]
[insert]
documentation
The SCG must be accompanied by a patient information leaflet. (Available from
http://www.medicines.org.uk/emc OR http://www.mhra.gov.uk/spc-pil/)
19. Patient monitoring
MND Association Riluzole information sheet: http://www.mndassociation.org/wpcontent/uploads/2015/07/5A-Riluzole.pdf
Non-applicable
booklet
(may not be applicable
for all drugs)
20. Shared care
agreement form
Attached below
21. Contact details
See Appendix 1
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Appendix 1 – Local Contact Details
Lead author contact
information
Name: [insert text here]
Email: [insert text here]
Contact number: [insert text here]
Organisation: [insert text here]
Commissioner contact
information
Name: [insert text here]
Email: [insert text here]
Contact number: [insert text here]
Organisation: [insert text here]
Secondary care contact
information
If stopping medication or needing advice please contact:
Dr [insert text here]
Contact number: [insert text here]
Fax:[insert text here]
Hospital: [insert text here]
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Shared Care Agreement Form
Specialist request
*IMPORTANT: ACTION NEEDED
Dear Dr
[insert Doctors name here]
Patient name: [insert Patients name here]
Date of birth: [insert date of birth]
NHS Number: [insert NHS Number]
Diagnosis:
[insert diagnosis here]
This patient is suitable for treatment with [insert drug name] for the treatment of
[insert indication]
This drug has been accepted for Shared Care according to the enclosed protocol
(as agreed by Trust / CCG / GMMMG). I am therefore requesting your agreement
to share the care of this patient.
The patient has been fully counselled on the medication.
Treatment was started on [insert date started] [insert dose].
If you are in agreement, please undertake monitoring and treatment from [insert
date]
NB: date must be at least 1 month from initiation of treatment.
Baseline tests:
[insert information]
Next review with this department:
[insert date]
You will be sent a written summary within 14 days. The medical staff of the
department are available at all times to give you advice. The patient will not be
discharged from out-patient follow-up while taking [insert text here].
Please use the reply slip overleaf and return it as soon as possible.
Thank you.
Yours
[insert Specialist name]
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Shared Care Agreement Form
GP Response
Dear Dr [insert Doctors name]
Patient
[insert Patients name]
NHS Number [insert NHS Number]
Identifier
[insert patient date of birth/address]
I have received your request for shared care of this patient who has been
advised to start [insert text here]
A
I am willing to undertake shared care for this patient as set out in the
protocol
B
I wish to discuss this request with you
C
I am unable to undertake shared care of this patient.
My reasons for not accepting are:
(Please complete this section)
GP signature
Date
GP address/practice stamp
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Shared Care Guideline Summary:
RILUZOLE for the treatment of AMYOTROPHIC LATERAL
SCLEROSIS (a form of Motor Neurone Disease)
Drug
Indication
Overview
Specialist’s
Responsibilities
Riluzole 50mg tablets
Amyotrophic lateral sclerosis (ALS) - a form of Motor Neurone Disease (MND)
Amyotrophic lateral sclerosis (ALS) is a form of Motor Neurone Disease (MND). It is a
progressive and fatal neurodegenerative disorder with a poor prognosis. Patients experience
a gradual loss of muscle function involved in swallowing and breathing. From onset of
symptoms 5 year survival is 5 - 15% and median survival time is about 3 years. Riluzole is
indicated to extend life or the time to mechanical ventilation in patients with ALS.
Riluzole is currently the only drug licensed for treating ALS in the UK. The National Institute
for Health and Care Excellence (NICE) has approved its use for ALS, so it is available to
people who have been diagnosed. In the trials in which Riluzole has shown some benefit,
eligible patients were up to 75 years of age, were in a reasonable state of general health,
had suffered from the disease for no greater than 5 years and had a forced vital lung
capacity of not less than 60% predicted.
Initial investigations: Assessment of the patient and diagnosis of ALS. Assess suitability of
patient for treatment. Discuss benefits and side-effects of treatment with the patient. The
Consultant will arrange for LFTs and FBC to be done at baseline.
Initial regimen: Riluzole 50mg twice a day
Clinical monitoring: The Neurologist will review the patient every 3 months, advise the
patient, carers and GP, enquire as to whether FBC and LFT testing are due and supervise
other treatments that may be needed (physiotherapy, occupational therapy, speech therapy,
dietary advice, gastrostomy, respiratory support).
Safety monitoring: Monitoring for response and adverse drug reactions (ADRs) during
initiation period. Evaluating ADRs raised by the GP and evaluating any concerns arising
from reviews undertaken by GP
Prescribing details: Hospital initiated. Transferred to GP once stabilised after the first 3
months of therapy. To stop the drug or provide GP with advice on when to stop this drug.
Documentation: Patients will only be transferred to the GP once the GP has agreed via
signing copies of the Shared Care Agreement Form
Provide GP with diagnosis, relevant clinical information, treatment plan, duration of
treatment within 14 days of seeing the patient or inform GP if the patient does not attend
appointment
GP’s
Responsibilities
Maintenance prescription: Prescribe riluzole in accordance with the specialist’s
recommendations. Max dose is 50mg twice a day.
Clinical monitoring: To report to and seek advice from the specialist on any aspect of
patient care which is of concern to the GP and may affect treatment.
Safety monitoring:
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As advised by the specialist
Serum
Monthly for 3 months, 3-monthly
transaminases
for 12 months then annually
thereafter.
Full Blood Counts
Monthly during the first 3 months in
view of the rare reported cases of
neutropenia
Treatment should be
stopped if the ALT rises to
five times the upper limit of
normal.
Discontinue riluzole in case
of neutropenia.
Duration of treatment: Stop treatment on advice of specialist.
Re-referral criteria: Seek urgent advice from secondary care if:
 Toxicity is suspected e.g. respiratory symptoms
 The patient becomes pregnant
 Non-compliance is suspected
 The GP feels a dose change is required
 There is marked deterioration in the patient’s condition
 The GP feels the patient is not benefiting from the treatment
Documentation: Formally reply to the consultant’s request to shared care within 14 days of
receipt, using the shared care agreement forms
Adverse Events
Adverse events
Interstitial lung disease
Elevations in liver function tests
Neutropenia
Abdominal symptoms- nausea, diarrhoea,
abdominal pain, vomiting
Headache, dizziness, oral paraesthesia
and somnolence
Action
If respiratory symptoms develop such as
dry cough and/or dyspnoea, the patient
should be referred to the consultant
neurologist and chest radiography should
be performed. In findings suggestive of
interstitial lung disease (e.g. bilateral
diffuse lung opacities), riluzole should be
discontinued immediately. In the majority of
the reported cases, symptoms resolved
after drug discontinuation and symptomatic
treatment.
As per monitoring
As per monitoring
Symptomatic treatment
Contraindications
Cautions
Drug
Interactions
Other
Information
Please refer to the BNF and/or SPC for information
Contact Details
Name: [insert text here]
Address: [insert text here]
Telephone: [insert text here]
Symptomatic treatment
Patients should be made aware that they need to report any febrile illness, fever, sore
throat, bruising or unexpected bleeding, and respiratory symptoms (such as dry cough
and/or dyspnoea.
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Check with internet that this printed copy of the latest issue
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