Download 1. circumstances when shared care is appropriate

Leflunomide
for active Rheumatoid Arthritis and Psoriatic Arthritis in Adults
Shared Care Guideline: Prescribing Agreement
Section A: To be completed by the hospital consultant initiating the treatment
GP Practice Details:
Name:
Address:
Tel no:
Fax no:
NHS.net e-mail:
Consultant name:
Clinic name:
Contact details:
Address:
Tel no
NHS.net e-mail:
Diagnosis:
Patient Details:
Name:
Address:
DOB:
/
/
Hospital number:
NHS number (10 digits):
Fax no:
Drug name & dose to be prescribed by GP:
Next hospital appointment:
/
/
.
Dear Dr.
,
Your patient was seen on
/
/
and I have started Leflunomide
mg (insert dose) for the
above diagnosis. I am requesting your agreement to sharing the care of this patient from
/
/
in
accordance with the (attached) Shared Care Prescribing Guideline (approval date:
/
/
). Please
take particular note of Section 2 where the areas of responsibilities for the consultant, GP and patient for this
shared care arrangement are detailed.
Patient information has been given outlining potential aims and side effects of this treatment and
* supplied
(* insert any support materials issued such as patient held monitoring book etc where applicable) . The patient has given me
consent to treatment possibly under a shared care prescribing agreement (with your agreement) and has agreed
to comply with instructions and follow up requirements.
.
The following investigations have been performed on
/
/
and are acceptable for shared care.
Please monitor FBC including total and differential WCC and platelets and LFTs every
weeks.
Test
Result
Test
Result
Test
Result
BP:
mmHg
LFTs:
FBC:
Body weight:
AST
Haemoglobin
kg
ALT
WBC
U&E’s:
Sodium (Na)
GGT
Neutrophils
Potassium (K)
Bilirubin
Platelets
Urea (U)
Alk phosp
Creatinine (Cr)
Other relevant information:
Consultant Signature:
………………………………………Date:
/
/
Section B: To be completed by the GP and returned to the hospital consultant as
detailed in Section A above
Please sign and return your agreement to shared care within 14 days of receiving this request
Tick which applies:
I accept sharing care as per shared care prescribing guideline and above instructions
I would like further information. Please contact me on:
I am not willing to undertake shared care for this patient for the following reason:
GP name:
GP signature:
………………………………………………Date:
/
/
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This Page in Intentionally Blank
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working in partnership
SHARED CARE PRESCRIBING GUIDELINE
LEFLUNOMIDE
for Active Rheumatoid Arthritis and Psoriatic Arthritis in Adults
NOTES to the GP
The expectation is that these guidelines should provide sufficient information to enable GPs to be confident to take
clinical and legal responsibility for prescribing this drug.
The questions below will help you confirm this:
 Is the patient’s condition predictable or stable?
 Do you have the relevant knowledge, skills and access to equipment to allow you to monitor treatment as
indicated in this shared care prescribing guideline?
 Have you been provided with relevant clinical details including monitoring data?
If you can answer YES to all these questions (after reading this shared care guideline), then it is appropriate for you
to accept prescribing responsibility.
If the answer is NO to any of these questions, you should not accept prescribing responsibility. You should write to
the consultant within 14 days, outlining your reasons for NOT prescribing. If you do not have the confidence to
prescribe, we suggest you discuss this with your local Trust/specialist service, who will be willing to provide training
and support. If you still lack the confidence to accept clinical responsibility, you still have the right to decline. Your
CCG pharmacist will assist you in making decisions about shared care.
It would not normally be expected that a GP would decline to share prescribing on the basis of cost.
The patient’s best interests are always paramount
Date Prepared: January 2014
Review date: January 2017
Approved by:
SWL Medicines Commissioning Group, Jan 2014
This shared care prescribing guideline has been signed off by the following individuals on behalf of
their respective organisations:
Participating CCGs
Participating Hospital Trusts
Croydon CCG
Croydon University Hospitals
Janice Steele, Deputy Chief Pharmacist
Louise Coughlan, Chief Pharmacist on behalf of
on behalf of Croydon Prescribing Committee
Croydon Prescribing Committee
Kingston CCG
Epsom and St. Helier University Hospitals
Seema Buckley, Chief Pharmacist
Anne Davies, Chief Pharmacist
Dr Jonathan Edwards, Medicines Management GP
Dr Sanjeev Patel, DTC Chair
Merton CCG
St. George’s Healthcare
Sedina Agama, Acting Chief Pharmacist
Chris Evans, Chief Pharmacist
Dr Vasa Gnanapragam, GP
Emma Baker, Professor of Clinical Pharmacology
Richmond CCG
Kingston Hospital
Emma Richmond, Chief Pharmacist
Derek Cock, Chief Pharmacist
Harriet Bradley, Medical Director
Sutton CCG
Sarah Taylor, Acting Chief Pharmacist
Dr Simon Elliott, Dr Roshni Scott, Prescribing Lead GPs
Wandsworth CCG
Nick Bevan, Chief Pharmacist
Dr Rod Ewen, Chair CEMMaG
Date prepared:
Date approved:
Review date:
January 2014
January 2014
January 2017
3
SHARED CARE PRESCRIBING GUIDELINE
Leflunomide
1.
CIRCUMSTANCES WHEN SHARED CARE IS APPROPRIATE
 Prescribing responsibility will only be transferred when the consultant and the GP are in agreement
that the patient’s condition is stable or predictable.
 Patients will only be referred to the GP once the GP has agreed in each individual case and the
hospital will continue to provide prescriptions until successful transfer of responsibilities as outlined
below.
 The hospital specialist will supervise treatment with leflunomide including prescribing for 6
months and if stable shared care will be requested.
2.
AREAS OF RESPONSIBILITY
Consultant:
Pre-treatment checks:
 Assess patient suitability for treatment with leflunomide including risk/benefit, drug interactions, contraindications, co-morbidities.
 Conduct baseline monitoring of FBC, LFTs including ALT, U&Es, blood pressure and body weight.
 Exclude pregnancy in women of childbearing potential prior to initiation of leflunomide.
Patient education:
 Discuss benefits vs risks with patient.
 Educate patient about all aspects of treatment including potential adverse effects and monitoring requirements.
 Provide Arthritis Research Campaign (ARC) patient information sheet on Leflunomide.
 Issue / explain shared care monitoring card.
Starting treatment:
 Prescribe leflunomide for at least 6 months.
 Monitor tolerance and follow up to ensure efficacy during first 6 months of treatment.
Continuation of treatment:
 Liaise with GP suggesting that shared care is agreed for the patient after 6 months. The hospital will provide
prescriptions until shared care has been agreed.
 Review patient at agreed intervals.
 Monitor efficacy and update GP of patient’s progress after each clinic visit
 Provide advice on dose adjustment if necessary and liaise with GP if repeat prescribing should stop.
 Evaluate and follow up adverse effects reported by patient or GP.
 Monitor for drug interactions.
 Identify non-compliance with drug safety monitoring.
GP:











Notify the consultant in writing whether or not the GP is agreeable to share care within 14 days (using “Shared
Care Guideline: Prescribing Agreement” if available).
Continue prescribing maintenance dose of leflunomide as recommended by consultant rheumatologist.
Monitor patient’s overall health status and well-being.
Monitor FBC, LFTs and blood pressure every 4 or 8 weeks as directed by Consultant and monitoring
requirements listed on, page 8.
Report any adverse reactions to the consultant rheumatologist.
Discuss with rheumatologist before initiating washout procedure and/or reducing or stopping leflunomide.
Monitor for drug interactions, see page 8.
Monitor for compliance with drug safety monitoring. Report non-compliance to consultant rheumatologist.
Liaise with consultant rheumatologist if signs/symptoms of disease progression occur.
If pregnancy occurs discuss urgently with supervising rheumatologist and refer back to hospital. GP may initiate
washout to avoid delay.
If patient wishes to become pregnant, refer back to hospital (shared care is no longer appropriate in such
cases).
Patient:




Comply with drug safety monitoring schedule.
Report adverse effects and inform GP/Consultant if wishing to become pregnant (if applicable).
Show shared care monitoring card to healthcare professionals.
Limit alcohol intake well within national limits (4-8 units per week).
Date prepared:
Date approved:
Review date:
January 2014
January 2014
January 2017
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SHARED CARE PRESCRIBING GUIDELINE
3.
COMMUNICATION AND SUPPORT
Hospital contacts:
Out of hours contacts & procedures:
(the referral letter will indicate named consultant)
St Helier Hospital
Dr Oliver Duke
Dr Sanjeev Patel
CNS Rheumatology Josephine Walmsley
CNS Rheumatology Preeja Kugathasan
Fax: 020 8296 3643
Epsom General Hospital
Dr Helen Linklater / Dr. Pamela Leventis
CNS Rheumatology Preeja Kugathasan
Tel: 01372 735120;
Fax: 01372 735141
St George’s Hospital
Dr Patrick Kiely (PK)
Dr Virinderjit Sandhu (VS)
Dr Katie Moss (KM)
Dr Nidhi Sofat
Dr A. Kaul
Duty Rheumatology SpR
Nurse Specialists
Margaret Sibley 020 8666 6812
Francesca Leone 020 8666 6807
Dida Cankov 020 8666 6801
Croydon University Hospital
Tel: 020 401 3000
Dr Natalie Horwood:: Ext 3010
Dr Rosh Sathanathan: Ext 3010
Dr Sarah Levy: Ext 3010
Ruth Britten CNS Rheumatology: Ext 3010
Medicines Information: Ext 3059
020 8296 2473
020 8296 2473
020 8296 2473
020 8296 2473
On-Call Medical SpR
via St Helier Hospital switchboard
020 8296 2000
On-Call Medical SpR
via Epsom Hospital switchboard
01372 735 735
020 8725 2109
020 8725 1418
020 8725 1419
020 8725 1419
020 8725 3596
020 8672 1255
Duty Medical SpR
via St George’s Hospital switchboard
020 8672 1255
Medical Registrar on call via switchboard
020 8401 3000
On-Call Medical SpR
via Kingston Hospital Switchboard
Tel: 0208 546 7711
Kingston Hospital
Dr Shahid Jawed Tel:0208 934 2089
Dr Hugh Jones Fax No. 0208 934 3287
Dr Jane Foley – Queen Mary’s Hospital
Tel 0208 487 6897 or 6898 Fax No. 0208 487 6916
CNS Rheumatology Kate Hunt
0208 934 2089 (or at Queen Mary’s on Tel 0208 487 6898)
Specialist support/resources available to GP including patient information:
See www.arc.org.uk
For patient information on leflunomide see:
http://www.arthritisresearchuk.org/arthritis_information/arthritis_drugs__medication/leflunomide.aspx
4.
CLINICAL INFORMATION
Indication(s):
Treatment of adult patients with active rheumatoid arthritis or psoriatic
arthritis either alone or in combination with methotrexate.
Place in Therapy:
For treatment of active rheumatoid arthritis or psoriatic arthritis.
Therapeutic summary:
Leflunomide is an isoxazole derivative. The active metabolite inhibits
the enzyme dihydroorotate dehydrogenase. This results in inhibition
of pyrimidine synthesis and arrests activated autoimmune
lymphocytes which decreases the autoimmune response.
Date prepared:
Date approved:
Review date:
January 2014
January 2014
January 2017
5
SHARED CARE PRESCRIBING GUIDELINE
Dose & route of administration:
Duration of treatment:
Summary of adverse effects:
RA - Maintenance dose: 10 – 20mg once a day (if used as
monotherapy)
10mg once a day if used in combination with another DMARD like
methotrexate.
Psoriatic arthritis – Maintenance dose: 20mg once a day.
Long term provided treatment effective and without adverse effect.
(See summary of product characteristics (SPC) for full list)
Adverse effect
Frequency
Hypertension
Mild -common
Severe- rare
Respiratory, thoracic and mediastinal
disorders- Interstitial lung disease
(including interstitial pneumonitis), which
may be fatal)
GI disorders
- Diarrhoea, nausea, vomiting, abdominal
pain
Rare
Common
- Oral mucosal disorders -Aphthous
stomatitis, mouth ulceration
Common
- Taste disturbances
- Pancreatitis
Nervous system disorders
- Headache
Uncommon
Very rare
- Paraesthesia, dizziness
- Peripheral neuropathy
Skin reactions/hair loss
- Increased hair loss
Common
Very rare
- Eczema, dry skin
- Rash (incl maculopapular rash), pruritus
Common
Common
- Urticaria
- Severe anaphylactic, anaphylactoid
reactions, vasculitis (incl cutaneous
necrotizing vasculitis)
- Stevens-Johnson syndrome, toxic
epidermal necrolysis, erythema multiforme
Uncommon
Very rare
Date prepared:
Date approved:
Review date:
January 2014
January 2014
January 2017
Common
Common
Very rare
Very common: ≥ 1/10
Common:≥1/100, <1/10)
Uncommon:≥1/1000, <1/100
Rare:≥1/10,000, <1/1000
Very rare: <1/10,000
Management by GPs
If BP > 140/90 treat in line with NICE guidance. If
BP remains uncontrolled discuss with consultant
and consider referral back to consultant for dose
adjustment / wash-out or change in treatment.
Contact hospital urgently if cough plus dyspnoea
presents. If increasing shortness of breath occurs
stop leflunomide and refer back to hospital for
washout
Give symptomatic treatment (eg anti emetic,
antidiarrhoeal) or refer back to hospital for dose
reduction. If severe or persistent stop and consider
wash-out.
Discuss with consultant in all cases. Stop treatment
until extent of reaction clear. If Stevens Johnson
syndrome refer immediately to hospital. If reaction
confined to mouth then symptomatic relief or dose
reduction, with or without partial wash-out.
Discuss with consultant.
Refer to hospital.
If headache is severe refer back to hospital to
consider dose reduction and if headaches persist
stop and consider washout.
Discuss with supervising consultant.
Discuss with consultant.
Alopecia is reversible with dose reduction or
discontinuation. Contact consultant for advice with a
view to consider dosage reduction. If severe refer
back to consultant to consider stopping treatment
and washout.
Treat symptomatically.
If mild continue leflunomide and monitor. If
moderate or severe discuss with consultant with a
view to consider symptomatic treatment (eg anti
histamine) or dose reduction, with or without partial
wash-out.
Discuss with supervising consultant.
Requires immediate assessment in hospital.
As soon as skin and/or mucosal reactions observed
which raise suspicion of such severe reactions,
discontinue leflunomide, contact consultant
immediately and refer back to hospital for washout.
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SHARED CARE PRESCRIBING GUIDELINE
Summary of adverse effects cont’d:
(See summary of product characteristics (SPC) for full list)
Adverse effect
Liver reactions
- Raised liver parameters
 Transaminases (mainly ALT)
 Gamma-GT, alkaline phosphatase,
bilirubin
- Hepatitis, jaundice/cholestasis
- Hepatic failure, acute hepatic necrosis
(may be fatal)
Frequency
Infections
Severe - rare
Haematological reactions
(manifested as abnormal bruising or severe
sore throat)
- Anaemia
Uncommon
- Leucopenia(leucocytes>2G/l)
- Leucopenia(leucocytes<2G/L)
- Mild thrombocytopenia
(platelets <100G/l)
- Pancytopenia, eosinophilia
- Agranulocytosis, vasculitis
Common
Less often
Rare
Very rare
Common
Rare
Uncommon
Rare
Very rare
Management by GPs
If < 2 fold rise in AST, ALT (from upper limit of
normal reference range –ULN)
 Monitor LFTs every 2 weeks and expect values
to normalise spontaneously.
If between 2 and 3 times rise in AST, ALT (from
upper limit normal reference range-ULN)
 Recheck LFTs within 72 hours. If still 2 to 3
times ULN, reduce dosage and recheck LFTs
every 2 weeks. If still 2 to 3 times ULN then
stop Leflunomide.
If > 3 fold rise in AST, ALT (from upper limit of
normal reference range –ULN)
 Recheck LFTs within 72 hours. If still > 3 times
ULN, contact consultant, stop leflunomide and
consider washout.
In event of severe, uncontrolled infection refer to
hospital. Susceptibility to infections increased,
particularly opportunistic infections.
Infections may be more severe and require early
and vigorous treatment.
Patients with tuberculin reactivity must be carefully
monitored because of risk of tuberculosis
reactivation.
Check FBC immediately and withhold drug(s) until
results known.
Check haematinics and replace appropriately.
Discuss with consultant.
If WBC < 3.5 x109/l, neutrophils <2.0x109/l or
platelets < 150x109/l stop leflunomide and any
concomitant myelosuppressive medication and
contact consultant immediately. Refer back to
hospital.
Monitor carefully. If >10% weight loss with no other
cause identified discuss with consultant with a view
to consider dose reduction. Refer back if stopping
treatment/washout required.
Neoplasms, benign, malignant and unspecified (including cysts and polyps)
Increased risk of malignancy, particularly lymphoproliferative disorders is increased with use of some
immunosuppressive agents.
Metabolism and nutrient disorders:
Common
- CPK increased
Uncommon
Discuss with consultant.
- Hypokalaemia, hyperlipidaemia,
hypophosphataemia
Rare
- LDH increased
Unknown
- Hypouricemia
Miscellaneous
Uncommon
Seek advice from consultant if needed.
- Anxiety
Common
- Tenosynovitis
Uncommon
- Tendon rupture
Not known
- Renal failure
Common
- Asthenia
Not known
-Marginal (reversible) decreases in sperm
concentration, total sperm count and rapid
progressive motility.
Weight loss (usually insignificant) /
anorexia
Date prepared:
Date approved:
Review date:
January 2014
January 2014
January 2017
Common
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SHARED CARE PRESCRIBING GUIDELINE
Monitoring Requirements:
Clinically relevant drug interactions:
Practical issues:
Key references:
Original Author(s)
Update Author(s)
Date prepared:
Date approved:
Review date:
January 2014
January 2014
January 2017
Monitoring conducted by the hospital:
Pre-treatment assessment
 Baseline FBC, LFTs including ALT, U&Es, blood pressure and
body weight.
 Pregnancy test prior to initiation of leflunomide if appropriate.
Monitoring treatment†
 FBC including total and differential white cell count, LFTs every 4
weeks for first 6 months then every 8 weeks thereafter. The
frequency should be increased to monthly where combination
therapy with another immunosuppressant or hepatotoxic drug is
used.
Monitoring conducted by GP :
 FBC including total and differential white cell count, LFTs every 8
weeks or if used in combination with another immunosuppressant
or hepatotoxic drug every 4 weeks.
 Monitor for side effects and act accordingly (see under side
effects).
 Check blood pressure and weight at the time of blood testing.
 Increased risk of toxicity with other haematotoxic drugs.
 Increased risk of toxicity with other hepatotoxic drugs.
 Alcohol should be avoided due to the risk of additive hepatotoxic
effects.
 Should ONLY be used /initiated in combination with other
DMARDs under consultant supervision.
 Warfarin – metabolism may be inhibited by leflunomide with
increased anticoagulant effect–check INR 7 days after initiation of
leflunomide and 7 days after any dose change of warfarin. Ask
patient to report any evidence of severe bruising which may
indicate high INR.
 Phenytoin – metabolism may be inhibited with increased
phenytoin levels. Take phenytoin levels 14 days after initiation of
leflunomide.
 Tolbutamide – metabolism may be inhibited with enhanced
hypoglycaemic effect. Increase blood glucose monitoring for a
few days following introduction of leflunomide then revert to
normal frequency of monitoring.
 Cholestyramine – effect of leflunomide significantly decreased.
Avoid unless drug elimination required.
 Vaccines – avoid concomitant use of leflunomide with live
vaccines.
Full washout procedure – Cholestyramine 8g TDS or Activated
charcoal 50g QDS for 11 days.
Partial washout procedure – Cholestyramine 8g TDS for 1 – 3 days
 British Society of Rheumatology Guidelines. Rheumatology 2008
 Summary of Product Characteristics, Arava®,
www.emc.medicines.org.uk accessed 14/11/2013 (last updated
08/01/2013)
†The guidance and monitoring requirements included in this
document derived from the BSR guidelines may deviate from
those included in the SPC
Dr. Patrick Kiely, Consultant Rheumatologist, St. George’s Hospital
Dr. Sanjeev Patel, Consultant Rheumatologist, Epsom and St. Helier
Hospital
Brigitte van der Zanden, Chief Pharmacist Sutton and Merton PCT
Christopher Haigh, Commissioning Support Pharmacist, South
London CSU
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