Title
Protocol for the prescribing and administration of
Natalizumab in Relapsing Remitting
Multiple Sclerosis (RRMS)
Document Number
Version Number
Name, Date and version number of NA
Previous Document (if applicable)
Staff involved in development
Consultant Neurologists - Dr A Gale
Chief Pharmacist - Mary Evans
Multiple Sclerosis
Advanced Nurse Practitioner - Hüseyin Hüseyin
Deputy Director of Nursing - Janet Graham
Staff with overall responsibility for Consultant Neurologists
dissemination, development
Multiple Sclerosis Advanced Nurse Practitioner
implementation and review
Development period
July 2008
Date approved by Clinical
Guidelines committee
Signed by the Chair Clinical
Guidelines Committee
Date for review
July 2011
Date document was Equality
Impact Assessed:
Target Audience
Key words
Associated Trust Documents
Neurologist, MSSN, Rheumatology team
and Nurses at St Mary’s day unit
Natalizumab-Monoclonal antibody
Multiple sclerosis
 Policy for the Use of Medicines
 Venepuncture policy
 Policy for Consent
 Anaphylaxis Guidance
NO:
Completion by CG Committee:
CG
Protocolforprescribing&administrationof Natalizumab/MEvans/HHuseyin/August 08
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Contents
Document Number .................................................................................................................. 1
Version Number ...................................................................................................................... 1
Staff involved in development ................................................................................................. 1
Introduction ............................................................................................................................. 3
Monograph for Prescribing & Administration of Natalizumab ................................................. 4
Characteristics of staff authorised to prescribe ....................................................................... 4
Characteristics of staff authorised to administer ...................................................................... 4
Clinical condition ...................................................................................................................... 5
Description of treatment .......................................................................................................... 6
Appendix 1 – Checklist For Patients prior to commencing on treatment ................................. 9
Appendix 2- Competency Assessment.................................................................................. 10
Appendix 3 – Pre-Treatment Telephone Checklist ................................................................ 12
Appendix 4- Natalizumab treatment pre-infusion Checklist ................................................... 13
Appendix 5- Infusion and Monitoring Record of Natalizumab treatment 4 weekly. .............. 14
Protocolforprescribing&administrationof Natalizumab/MEvans/HHuseyin/August 08
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Protocol for the prescribing and administration of Natalizumab
Introduction
This document provides guidance on the prescribing and administration of Natalizumab. It
does not cover the preparation of Natalizumab infusions which must take place within the
aseptic suite of the Pharmacy department.
The prescribing of Natalizumab must be in keeping with NICE TA127 Multiple sclerosis Natalizumab: 22 August 2007 guidance. Funding approval for the use of Natalizumab on a
patient specific basis must be obtained from the relevant PCT before therapy is commenced.
Pharmacy will not supply Natalizumab unless authorisation has been obtained. The relevant
medical checklist (Appendix 1) must have been completed before Natalizumab is prescribed
and filed in the patient’s medical notes.
Pharmacy production must be notified at least 3 working days in advance of a patient
requiring Natalizumab infusion. Due to the cost of Natalizumab, Pharmacy production will not
begin preparation of the infusion on the day of treatment until they have been informed that
the patient is fit for the treatment to proceed.
In order to ensure the treatment is administered in a safe, appropriate environment allowing
for the close patient observation required, patients receiving Natalizumab treatment should
ideally be admitted as day cases within the day case unit. Full resuscitation facilities must be
available. These patients will remain under the clinical care of the appropriate Consultant
Neurologist and senior medical cover must be available at all times during the patient’s
treatment episode via Rheumatology team. The infusion will be administered under the
supervision of a Clinical Nurse Specialist or designated, competent, registered nurse.
Where treatment in the day case unit is not possible serious consideration must be given to
the risk/benefit of proceeding on a general ward. If such a situation is unavoidable, treatment
must be scheduled to coincide with the planned availability of a designated, competent
registered nurse and senior medical cover must be available at all times during the patient’s
treatment episode. The patient must be admitted to an acute bed on the appropriate ward
(the day room is not deemed a suitable location for this treatment). The designated,
competent registered nurse will be responsible for ensuring that the patient is closely
observed and monitored in line with the requirements outlined in this protocol. It may be
necessary to review the ward staffing requirements to enable the treatment to proceed
safely. The post infusion follow-up will then be the responsibility of the patient’s Consultant.
This policy should be read in conjunction with the following Trust policies
 Policy for the Use of Medicines
 Venepuncture policy
 Policy for Consent
 Anaphylaxis Guidance
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Monograph for Prescribing & Administration of Natalizumab
Characteristics of staff authorised to prescribe
Qualifications
Consultant Neurologist
required
The prescriber should prescribe within the manufacturers licence
and after obtaining funding from the relevant PCT.
Continued
It is the responsibility of the prescriber to ensure they remain up to
training
date with the research and developments in this area of treatment
Characteristics of staff authorised to administer
Qualifications required
Nurses with the following skills and knowledge may
administer Natalizumab to patients on condition that
there is guaranteed rapid access to a specialist
practitioner (as detailed below) for support if
required.
Level 1 Registered nurse who has undertaken relevant
and current training in the following in line with trust policy
 Administration of intravenous infusions
 Emergency resuscitation and anaphylaxis
procedures
Additional competencies
 Assessed by appropriate Trust designated
assessor as meeting the essential competencies in
Appendix 2
 A minimum of 2 years experience of nursing
patients requiring intravenous therapy
Continued training
Annual update of training is required.
Additional qualifications
required for practitioners
responsible for
assessment and
monitoring of treatment
All practitioners responsible for the assessment and
monitoring of treatment must have clinical experience
within the appropriate disease state and be assessed as
competent by the lead Consultant (e.g. specialist registrar
or clinical nurse specialist). Clinical Nurse specialists
should have completed the relevant diploma course or
have equivalent, recognized experience.
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Clinical condition
Clinical
Natalizumab is licensed for use as single disease modifying therapy in
Condition
highly active relapsing remitting multiple sclerosis for the following
patient groups.
 Patients with rapidly evolving severe relapsing remitting
multiple sclerosis (NICE approved recommendation)
 Patients with high disease activity despite treatment with a full
and adequate course of beta-interferon ( not NICE approved)
Criteria for
inclusion
Criteria for
exclusion
Criteria for
caution (refer
to SPC for
more detailed
information)
Patients who match the above criteria
Patients who do not match NICE criteria must have alternative funding
identified
Patients who have received comprehensive counselling about the risks
and benefits of Natalizumab and have consented to treatment
Women of childbearing age must agree to use adequate contraception
Patients whose baseline full blood screen and observations (BP, pulse,
temperature, RR, O2 sats) are within normal limits
Children and adolescents and patients over the age of 65
Previous sensitivity to Natalizumab or any of the excipients.
Progressive multifocal leukoencephalopathy (PML).
Patients with increased risk of opportunistic infections including
immunocompromised patients
Patients receiving immunosuppressive therapies.
Any patient who has previously developed an opportunistic infection
whilst on Natalizumab
Combination with beta-interferons or Glatiramer Acetate
Known active malignancies, except for patients with cutaneous basal
cell carcinoma
Pregnancy must be excluded and should be avoided for at least 3
months after the last dose of Natalizumab.
Breastfeeding is contra-indicated during treatment and for at least 3
months after treatment.
Patients with a history of chronic infection or a history of recurrent
infections
Patients with Crohn's disease who were immunocompromised or
where significant co-morbidity exists may be at greater risk of
opportunistic infections.
Patients re-exposed to Natalizumab following an initial short exposure
(one or two infusions) and extended period (three months or more)
without treatment are more at risk of infusion related hypersensitivity
reactions.
Pharmacokinetic studies have not been performed on patients with
renal or hepatic disease.
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Description of treatment
Name of
Natalizumab (Tysabri). A recombinant humanised anti-α-4-integrin
medicine
antibody.
Form,
Single-use vial containing Natalizumab 300mg concentrate in 15 ml solution
Strength
for infusion. The infusion will be prepared in the Pharmacy aseptic suite and
presented for administration as a infusion in 100 ml Sodium Chloride 0.9%
containing 2.6 mg/ml Natalizumab. The infusion should be used immediately
or within 8 hours of dilution provided it has been stored at 2oC- 8oC.
POM/P/GSL
POM
Dose/
300mg by intravenous infusion over 1 hour repeated at 4 weekly intervals.
Frequency/
Duration
Route /
By intravenous infusion over 1 hour infusion using an IMED pump at a rate of
Method
2ml per minute. Do not infuse concomitantly in the same intravenous line as
other agents. Visually inspect to ensure infusion clear of particulate matter or
discolouration prior to use. On completion flush the line with Sodium Chloride
0.9%. Do not remove cannula until post infusion observation period
completed
Dispose of drug and clinical waste in line with Trust procedures
Monitoring
Pre-Treatment Telephone Checklist Appendix 3
Pre-infusion checklist Appendix 4.
Document using, Monitoring checklist Appendix 5. Temperature, pulse,
BP, RR and O2 Saturations must be taken prior to commencing the infusion
and at 30 minute intervals during the infusion. Two further readings at 30
minute intervals following the completion of infusion.
If readings outside normal parameters seek specialist advice.
(Rheumatology Team Registrar)
The cannula site must be observed for signs of extravasations
Observe for signs of acute infusion reactions that might occur during
treatment. If required take action as detailed below.
Any suspected hypersensitivity or infusion reaction must be referred
for medical assessment.
 Patients assessed as experiencing an infusion reaction must
have this recorded in their notes and if any further reactions
occur should be tested for the presence of antibodies
 Patients assessed as experiencing a hypersensitivity reaction
should have treatment discontinued immediately and
permanently
If there has been infusion related reactions the future infusions could be
made with 200mls of Sodium Chloride 0.9% and infused over 2 hours.
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Action to be
taken for
Infusion
reactions
Emergency resuscitation equipment and drugs must be available and
to hand.
Mild fever, chills, pruritus
 Depending on the severity stop the infusion
 Repeat observations
 Continue with infusion if appropriate
 Consider giving prescribed prn medication (paracetamol, ibuprofen)
Chest pain, hypertension, hypotension, dyspnoea, rash, fever > 38.5oC

Stop infusion

Repeat observations

Review with medical team

When symptoms have resolved consider recommencing infusion
.
Severe reaction with anaphylaxis
 Stop infusion
 Alert crash team on 2222 – in meantime
 Lay patient flat and maintain airway
 Administer 0.5ml 1:1000 adrenaline intramuscularly
 Administer O2 and monitor sats, pulse, BP
In the case of any hypersensitivity during the infusion (e.g. urticaria with or
without associated systemic symptoms, anaphylaxis ) the infusion should
be stopped immediately and vascular access maintained for emergency
treatment and fluid support. Seek medical assistance.
Moderate to severe reactions may require symptomatic treatment e.g.
Paracetamol, Hydrocortisone, Chlorphenamine, Adrenaline, iv fluids, oxygen
or bronchodilators.
Future infusions could be made with 200mls of Sodium Chloride 0.9% and
infused over 2 hours.
Adverse
Effects /
Relevant
warnings
Advise to
Patient GP
Advice to
patient
Common adverse effects include; Headache, Dizziness, Vomiting,
Nausea, Arthralgia, Urinary tract infection, Nasopharyngitis. Rigors,
Pyrexia, Fatigue and Urticaria. Hyper-sensitivity, immunogenicity
Uncommon adverse effects; Infections, including PML and opportunistic
infections, hepatic injury
Refer to SPC for comprehensive list of side effects
Use the Yellow card system to report adverse drug reactions to the CSM.
Yellow cards and guidance on its use are available at the back of the BNF.
Once infusion record is completed copy and send/fax it to patient’s GP.
(Appendix 4)
Patient must be given an alert card with all relevant details completed.
Contact numbers must be given
Patient must be given the Natalizumab Patient Information Leaflet
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Follow up
Records
Appropriate patients should be advised not to breastfeed while on
Natalizumab
If their condition deteriorates or any unusual symptoms occur advise the
patient to contact specialist nurse or Consultant. Specifically they must be
advised to contact their Doctor if they believe their MS is getting worse or
they have an infection.
Patients must be advised they will not be able to drive themselves home
Patients should be informed of the date of next infusion.
Patients should be given a telephone contact number for the MS Specialist
Nurse and advised to ring if they have any concerns.
Evaluation of therapeutic response should be made on a 6 month basis.
If no response or progression continues consider stopping the treatment.
Use approved Trust Records -file in patient's notes. Letter to GP .
Specific required records include Patient medical assessment checklist,
patient consent form, prescription chart, treatment monitoring sheet
BNF; Summary of Product Characteristics (http://emc.medicines.org.uk/) ;
Relevant NICE guidance.
Resources used in compiling protocol
NICE Guidance, TA127 Multiple sclerosis - Natalizumab: guidance 22 August 2007
SPC for Natalizumab, May 2008
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Patient addressograph here
The Luton and Dunstable Hospital NHS Foundation Trust
Appendix 1 – Checklist For Patients prior to commencing on treatment
Department of Neurology Medical checklist
CHECKLIST FOR PATIENTS WITH Relapsing Remitting Multiple Sclerosis
COMMENCING NATALIZUMAB
(to be completed by doctor initiating therapy)
Yes
No
Initials
1. Patient has a diagnosis of Relapsing remitting Multiple
Sclerosis and meets criteria for NICE guidelines.
2. Patient not under 18years or over the age of 65
3. Patient not experienced previous sensitivity to
Natalizumab or any of the excipients.
4. Patient has no increased risk of opportunistic infections
and not immunocompromised
5. Patient not currently receiving immunosuppressive
therapies.
6. Patient not on beta-interferons or Glatiramer Acetate
7. Excluded active malignancies, except for patients with
cutaneous basal cell carcinoma
8. Pregnancy has been excluded
9. Patient has been advised that pregnancy should be
avoided for at least 3 months after the last dose of
Natalizumab.
10. Patient is not breastfeeding
11. Patient has been advised breastfeeding is contraindicated during treatment and for at least 3 months
after treatment.
12. Patient has been advised:
To inform MS Nurse or the Neurology consultant if
neurological symptoms develop.
13. Patient has completed Consent form 3 in line with
Trust’s Consent Policy
Treatment should not commence If any NO responses.
Name Of Neurologist:……………………………
Signature of Neurologist initiating therapy ……………………………….Date……..………
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Appendix 2- Competency Assessment
ASSESSMENT FOR THE ADMINISTRATION OF NATALIZUMAB
PRACTITIONER………………………………
ASSESSOR……………………………
POSITION………………………………
DATE…………………………………...
Proficient
HOLISTIC CARE
The nurse is able to assess, plan and manage the holistic care of the patient requiring
Natalizumab, acknowledging patient preference and individuality
Welcomes the patient and demonstrate a caring approach sensitive to the patient’s
needs
Demonstrate awareness of the rationale for pre-medications
Discuss the immediate, short and long term side effects
Review medical history and note any allergies, contraindications or adverse experience
Support pre-printed information with verbal explanation
Respect each patient as unique, supporting independence and autonomy
Verify the patient has consented to treatment and the consent process is understood
Thoroughly check prior to administration: drug, dose, diluents, storage, expiry date,
time of administration, relevant results, prescriber’s signature
Ensure correct identification of patient
Utilise knowledge to demonstrate empathy and understanding
Use discretion in the disclosure of information always acting in a professional manner
and within the boundaries of the profession
SAFE PRACTICE
The nurse demonstrates correct handling of Natalizumab to ensure the safety of
patients, carers, staff and the environment
Prepare equipment and environment to reduce the risk of contamination
Apply protective measures for the well-being of patients, colleagues and self
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Requires
further training
Assessor’s
signature
Proficient
Requires
further training
Assessor’s
signature
Dispose of waste products and equipment correctly, according to policy
Demonstrate knowledge of procedures for dealing with spillage
Report any incidents accurately and knowledgably following local procedures
MANAGEMENT OF COMPLICATIONS AND ADVERSE REACTIONS
The nurse demonstrates appropriate prevention strategies and evaluation of
interventions in the effective management of side effects of treatment.
Identify infusion related side effects of Natalizumab
Communicate effectively to patients and carers possible side effects without causing
anxiety
Provide accurate and detailed documentation of side effects
Recognise uncommon side effects
Demonstrate ability to detect and manage hypersensitivity and anaphylaxis reactions
ACCOUNTABILITY
The nurse demonstrates knowledge of professional and legal responsibilities in relation
to administration of biotherapies
Demonstrate knowledge of professional and legal accountability and responsibility in
relation to administration of Natalizumab
Apply ethical principles to practice
Demonstrates knowledge of procedures for dealing with drug error / clinical incidents
Comments/extra training needs identified:
…………………………………………………………………………………………………………………………………………………………
…………………………………………………………………………………………………………………………………………………………
Practitioner………………………………
Assessor………………………………….
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Date…………………………
Patient addressograph here
The Luton and Dunstable Hospital NHS Foundation Trust
Appendix 3 – Pre-Treatment Telephone Checklist
For Patients With Relapsing Remitting Multiple Sclerosis COMMENCING
NATALIZUMAB
(to be completed by Clinical Nurse Specialist 3 days prior to infusion)
Infusion No:…..
Yes No
Initials
Does the patient have a current infection?
(e.g.cold, cough, dental abscess, UTI) Clear MSU?
Is the patient pregnant or breastfeeding?
Are recent blood tests within normal limits?
(FBC, LFTs, U&Es, ESR)
Has the patient been given verbal and written information
on Natalizumab?
Does the patient know when to arrive at St Mary’s Day Unit
and what will happen during the day?
Has the patients Natalizumab, and prn medications been
prescribed?
Has the patient’s inpatient prescription chart been taken to
Pharmacy production?
Signature of clinical nurse specialist:……………………………………
Date ……..…………………………………
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Patient addressograph here
The Luton and Dunstable Hospital NHS Foundation Trust
Appendix 4- Natalizumab treatment pre-infusion Checklist
Date:..................................
Pre infusion checklist:
Normal blood tests
Clear MSU
Signed medical checklist in notes
Drug chart completed for
Natalizumab, and pre-infusion prn
medicines* administered if required
Baseline pre-infusion observations
within normal parameters
Patient is wearing a hospital name
band
*
Ibuprofen 400mg (if there is no contra-indication) Chlorphenamine 4mg oral
Paracetamol 1g oral
Comments
....................................................................................................................................................
....................................................................................................................................................
....................................................................................................................................................
....................................................
Post infusion Follow-up: (please complete as appropriate).
Date of next treatment (if known): Date:….. /…… /……
Copy of infusion record sent to GP:
TBA
Date………………
Patient given blood forms (FBC, LFT’s, U+E’s, ESR/CRP) for next check: YES /NO
Signature………………………..
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Patient Name:………………..
TLuton and Dunstable Hospital NHS Foundation
Trust
Appendix 5- Infusion and Monitoring Record of
Natalizumab treatment 4 weekly.
MS Status
Dob:……………………………
Hospital No:……………………
Patient Addressograph
Since last infusion Has there been significant change in
Walking
YES / NO
Mental Function
YES / NO
Balance/ Coordination
YES / NO
Vision
YES / NO
Has there been any infection in the last four weeks/ ongoing infection
YES / NO
If yes to the above contact Consultant Neurologist.
If new neurological signs refer to care pathway.
Date of First Dose:
Date and Dose Number:
Time infusion made up
Time infusion started
Batch Number
Expiry Date
Given By
Pre-Infusion
Urine (MSU)
Vital Signs
Pre - Infusion
Bloods
Post – Infusion
Time:
Temp:
Pulse:
Resp:
B/P
O2 Saturations
Date and Time of Next Infusion:
Complete and Fax Discharge summary to GP.
Any queries contact MS Specialist Nurse on Bleep 355 Ext:- 8276 Mob:- 077680448762
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Audit Tool for Prescribing and Administering Natalizumub
1. Patient Hospital Number
2. Date of Prescription
3. Date of Administration
4. Did the patient match the inclusion criteria?
Yes
No
5. Was drug prescribed by consultant Neurologist ?
Yes
No
6. Was the prescription correct?
Yes
No
7. Is the patient infection free?
Yes
No
8. Was the monitoring accurate and documented?
Yes
No
Tem/pulse/BP/Sats prior to commencement of infusion
Yes
No
Tem/pulse/BP/Sats 30 min intervals during the of infusion
Yes
No
Tem/pulse/BP/Sats 30 min intervals for 1 hour post
Yes
No
9. Did the patient have an adverse reaction?
Yes
No
10. If yes to 9 was the correct procedure followed?
Yes
No
11. Was the patient given an alert card?
Yes
No
12. Was the patient given information leaflet
Yes
No
Telephone checklist(appendix 3)
Yes
No
Checklist for patients prior to commencement of infusion
Yes
No
Yes
No
Yes
No
Yes
No
IV infusion to be given over 1 hour , 2ml per minute
infusion during the of infusion
13. Were the following forms completed and signed
(appendix 4)
infusion and monitoring record (Appendix 5)
14. Was the nurse administering the drug designated as
competent?
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