Download MYCOPHENOLATE MOFETIL for Connective Tissue Disease

Gwent Shared Care Protocol
MYCOPHENOLATE MOFETIL (MMF) 500mg Tablets
for the treatment of connective tissue disease (UNLICENSED USE)
Protocol No. 30
General guidance
PLEASE CHECK http://www.wales.nhs.uk/sites3/page.cfm?orgid=814&pid=38180
FOR THE LATEST VERSION OF THIS PROTOCOL
ABUHB’s Medicines and Therapeutics Committee has agreed this protocol. It outlines the
shared care arrangements for patients initiated on mycophenolate for the treatment of
connective tissue disease and should be read in conjunction with the:
1. Shared Care Agreement Form (see Page 6).
2. Summary of Product Characteristics for mycophenolate mofetil – available at:
http://www.medicines.org.uk/emc/medicine/1680
This Shared Care Protocol does NOT cover use of
1. Mycophenolate capsules, 250mg tablets or oral suspension.
2. Mycophenolate for post transplant immunosuppression.
3. Mycophenolic acid (Myfortic®).
1. Therapeutic use &
Background
information
Mycophenolate mofetil is a pro-drug of mycophenolic acid. It is a suppressor of T and B cell
proliferation and adhesion and inhibits inosine monophosphate dehydrogenase and eventually
blocks the progression to DNA synthesis and proliferation.
It is used ‘off-label’ as a disease modifying drug in connective tissue disease responding to
immunosuppressive therapy when other standard treatments (e.g. azathioprine) have failed
or are not tolerated. Such conditions include; rheumatoid arthritis, systemic lupus
erythematosus and lupus nephritis and inflammatory myopathy such as dermatomyositis and
polymyositis. It is also used in scleroderma, vasculitis and Behçet’s disease.
2. Contra-indications
/ Cautions
Contra-indications:
1. Pregnancy – mycophenolate should not be given to women of childbearing potential who
are not using highly effective contraception. Mycophenolate should not be initiated in
women of child bearing potential without providing a pregnancy test result to rule out
unintended use in pregnancy and it should not be used in pregnancy unless there is no
suitable alternative treatment..
2. Breastfeeding.
3. Live vaccines (e.g. Zostavax®) should be avoided in patients with an impaired immune
response.
4. Known hypersensivity to mycophenolate mofetil (CellCept®) or mycophenolic acid
(Myfortic®).
Cautions:
 Patients with suspected lymphoproliferative disorder or unexplained anaemia, leucopenia
and thrombocytopenia. To reduce the risk of skin malignancies patients should be told to
avoid exposure to strong sunlight and to use a high-factor sunscreen.
 Patients with active gastro-intestinal disease (due to risk of haemorrhage, ulceration and
perforation).
 Localized or systemic infection (e.g. hepatitis B or C).
 Very frail and elderly.
3. Typical dosage
regimen (adults)
Starting dose: 500mg daily for first week, 500mg twice daily for second week and increase
gradually by 500mg each week until the optimal or maximally tolerated dose is reached.
Maximum dose: 3g daily (as 1.5mg twice daily).
Mycophenolate is now available in generic form. To be prescribed as mycophenolate mofetil
500mg tablets and not as a brand e.g. CellCept®.
4. Drug interactions
Check BNF Appendix 1
Aciclovir (not topical
mycophenolate increases plasma concentration of aciclovir, also plasma
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2015 (Update Feb.2016)
Approved by: ABUHB MTC
Page 1 of 6
Review Date: May 2017
before co-prescribing
any other drug.
aciclovir)
Antacids
Colestyramine
Ganciclovir
Iron (oral)
Metronidazole (not
topical metronidazole)
Norfloxacin
Rifampicin
Sevelamer
5. Adverse drug
reactions
All healthcare
professionals have a
responsibility to
patients in
advising/acting on
suspected adverse drug
reactions
concentration of inactive metabolite of mycophenolate increased
Only significant in renal impairment
absorption of mycophenolate reduced – antacids should not be taken at the
same time of day.
absorption of mycophenolate reduced – take at least 1 hour before or 4–6
hours after colestyramine
mycophenolate possibly increases plasma concentration of ganciclovir, also
plasma concentration of inactive metabolite of mycophenolate possibly
increased
absorption of mycophenolate reduced
bioavailability of mycophenolate possibly reduced
bioavailability of mycophenolate possibly reduced
plasma concentration of active metabolite of mycophenolate reduced
plasma concentration of mycophenolate possibly reduced
Clinical condition
(reported frequency)
Diarrhoea, nausea, vomiting, abdominal cramps and
dyspepsia.
(Very Common >10%)
Abnormal bruising with or without sore throat - may indicate
bone marrow failure.
(Severe neutropenia occurs in 0.5% patients receiving
mycophenolate in the full dose).
Recurrent infections associated with
hypogammaglobulinaemia
(frequency not known)
Development of persistent respiratory symptoms, such as
cough and dyspnoea
(frequency not known)
Skin malignancies.
(Common ≥1/100 to <1/10)
Hepatitis, jaundice, hyperbilirubinaemia and raised LFTs
(Common ≥1/100 to <1/10)
Note LFTs are not a monitoring requirement for
mycophenolate and the frequency of these reactions was
from patients treated with mycophenolate in renal, cardiac
and hepatic clinical trials when used in combination with
ciclosporin and corticosteroids.
Action
Discuss with specialist if severe or
persistant
STOP the drug. Check FBC
immediately and also discuss with
specialist team.
Discuss with specialist – serum
immunoglobulin levels should be
measured.
Discuss with specialist
patients should be told to avoid
exposure to strong sunlight and to
use a high-factor sunscreen
Discuss with specialist if there is a
particular concern
Discuss with specialist
Patients should be particularly warned to report any signs or symptoms of bone marrow
suppression e.g. infection or unexplained bruising or bleeding.
All serious adverse events should be reported to MHRA.
6. Baseline
investigations
To be undertaken by specialist centre:
7. Monitoring
Ongoing Monitoring by GP:
FBC, LFTs, U&Es and chest x-ray (within last 6 months)
Pregnancy test if appropriate – see contraindications in Section 2 of this protocol.
Monitoring
FBC weekly until dose stable for
4 weeks then fortnightly for 2
months
Result
WBC < 3.5 x 109/L
Neutrophils < 1.7x109/L
Action
Stop drug and discuss with
specialist
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2015 (Update Feb.2016)
Approved by: ABUHB MTC
Page 2 of 6
Review Date: May 2017
then monthly thereafter
Platelets < 150x109/L
Abnormal bruising with or without sore throat
Check FBC immediately and
withhold drug until results are
available. Discuss with specialist
Please note that in addition to absolute values for haematological indices, a rapid fall or
consistent downward trend in any values should prompt caution and extra vigilance.
8. Specialist centre
contact
information
If stopping the medication or needing advice please contact:
01873 732046 (Rheumatology Helpline)
In an emergency a Rheumatology Clinical Nurse can be bleeped via the Nevill Hall Hospital
Switchboard on the number 432.
Further information on use and monitoring of DMARDs
Rheumatology - Frequently Asked Questions for Health Professionals
http://howis.wales.nhs.uk/sitesplus/866/page/57539
Vaccination advice for patients with Autoimmune Inflammatory Rheumatic Disease is available
for ABUHB Rheumatology at: http://howis.wales.nhs.uk/sitesplus/866/page/57540
9. Criteria for shared
care
All Wales criteria for Shared Care can be found at:
http://www.awmsg.org/docs/awmsg/medman/Criteria%20for%20Shared%20Care.pdf
GMC guidance on Shared Care (2013) states:
Decisions about who should take responsibility for continuing care or treatment
after initial diagnosis or assessment should be based on the patient’s best
interests, rather than on convenience or the cost of the medicine and associated
monitoring or follow-up.
Shared care requires the agreement of all parties, including the patient. Effective
communication and continuing liaison between all parties to a shared care
agreement are essential.
10. Responsibilities of
initiating
consultant
i.
ii.
iii.
iv.
v.
To consider initiating mycophenolate 500mg tablets, where azathioprine is contraindicated
or not tolerated.
To undertake the baseline clinical investigations (see Section 6).
To provide a patient information leaflet indicating the risks and benefits associated with
mycophenolate, and to discuss these with the patient or carer. The importance of regular
monthly blood monitoring should be made clear to the patient/carer.
The advice to the patient/carer should cover:
a. The potential side effects and the action to be taken should they occur
(particularly in relation to reporting any infection, unexplained
bruising/bleeding or persistent cough or breathlessness).
b. The possible effect of mycophenolate on live vaccines – this is available at:
http://howis.wales.nhs.uk/sitesplus/866/page/57540
(Note
NHS
net
connection required).
c. The need for women (and female partners of male patients treated with
mycophenolate) to use highly effective contraception during treatment and for
90 days after the last dose. Men (including those who have had a vasectomy)
should use condoms during treatment and for 90 days after stopping
treatment. Record in GP referral letter that contraceptive advice has been
given.
d. That mycophenolate is being prescribed outside the manufacturer’s product
licence (off-label).
To confirm patient/carer understanding and consent to treatment. Informed consent for
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2015 (Update Feb.2016)
Approved by: ABUHB MTC
Page 3 of 6
Review Date: May 2017
‘off-label’ use should be obtained and documented. See the GMC's Good practice in
prescribing and managing medicines and devices1 for further information. This consent
should be communicated to the GP on the Shared Care Agreement Form (see Page 5).
vi. To write the first prescription for 6 weeks of mycophenolate 500mg tablets and to inform
the patient/carer of the dose titration regime and target maintenance dose (usually 1g
twice daily) – this information should be communicated to the GP on the Shared Care
Agreement Form (see Page 6).
vii. To fax the Shared Care Agreement Form (see Page 6) to the GP once the 4th blood test has
been reviewed.
viii. To provide the patient with FOUR blood sample request forms for the initial monitoring at
1, 2, 3 and 4 weeks post initiation (see detail in Section 7 above). These should allow the
patient the option to return to hospital or to attend their GP surgery for the blood samples
to be taken. The blood forms should specify that the results should go back to Secondary
Care, with copies to the GP surgery.
FOLLOWING ANY SUBSEQUENT DECISION TO FURTHER INCREASE THE DOSE (FROM THE
INITIAL TARGET DOSE) TO PROVIDE:
a. ONE BLOOD SAMPLE REQUEST FORM FOR A WEEK TWO TEST FOLLOWING THE
DOSE INCREASE.
b. A FUTHER 4 WEEK PRESCRIPTION FOR MYCOPHENOLATE.
ix. To keep GP fully informed of any dose adjustments and non attendance following
subsequent specialist appointments.
11. Responsibilities of
Primary Care
i.
To prescribe mycophenolate 500mg tablets (generically) from week 6 and monitor the
patient in accordance with the schedule above (see Section 7).
ii. To inform specialist of any non attendance for ongoing blood tests. Patients should be
informed of the consequences to their safety (and that their mycophenolate may be
stopped) if they fail to attend for blood tests.
iii. To administer annual flu vaccination. Vaccination advice for patients with Autoimmune
Inflammatory Rheumatic Disease is available for ABUHB Rheumatology at:
http://howis.wales.nhs.uk/sitesplus/866/page/57540
iv. Whenever practicable, to reaffirm with the patient the importance of reporting any
infection unexplained bruising/bleeding or persistent cough or breathlessness).
12. Responsibilities of
patients/carer
 To attend hospital and GP practice blood test/monitoring appointments.
 Significant failure to attend (which affects patient safety) will result in medication being
stopped.
 To report adverse effects to their specialist or GP (particularly any infection, unexplained
bruising/bleeding or persistent cough or breathlessness).
13. Responsibilities of
all prescribers
Any suspected serious adverse reaction to an established drug should be reported to MHRA
via the “yellow card scheme.” http://yellowcard.mhra.gov.uk/
14. Responsibilities of
pharmacists
 Whenever practicable, to reaffirm with the patient the importance of reporting any
infection, unexplained bruising/bleeding or persistent cough or breathlessness).
15. Supporting
documentation /
information
Patient information leaflet at:
http://beta.medicines.org.uk/emc/PIL.4075.19.pdf/Cellcept%20500mg%20Tablets.pdf
or at:
http://xpil.medicines.org.uk/viewpil.aspx?docid=4075
2008 BSR/BHPR guideline for disease-modifying anti-rheumatic drug (DMARD) therapy
http://www.rheumatology.org.uk/includes/documents/cm_docs/2009/d/diseasemodifying
_antirheumatic_drug_dmard_therapy.pdf
2015 Mycophenolate mofetil (CellCept) and mycophenolic acid: risk of
hypogammaglobulinaemia and risk of bronchiectasis:
1
http://www.gmc-uk.org/guidance/ethical_guidance/14316.asp
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2015 (Update Feb.2016)
Approved by: ABUHB MTC
Page 4 of 6
Review Date: May 2017
https://www.gov.uk/drug-safety-update/mycophenolate-mofetil-cellcept-andmycophenolic-acid-risk-of-hypogammaglobulinaemia-and-risk-of-bronchiectasis
2015 Mycophenolate mofetil, mycophenolic acid: new pregnancy-prevention advice for
women and men:
https://www.gov.uk/drug-safety-update/mycophenolate-mofetil-mycophenolic-acid-newpregnancy-prevention-advice-for-women-and-men
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2015 (Update Feb.2016)
Approved by: ABUHB MTC
Page 5 of 6
Review Date: May 2017
Shared Care Agreement Form – Accredited
CONSULTANT REQUEST
To: Dr.
Your patient:
NHS No. (10digit):
was seen on:
with a diagnosis of:
I recommend that the following drug is continued:
This drug has been accepted as suitable for shared care by the ABUHB’s MTC.
I agree to the responsibilities set out in the protocol SCP No. 30 (copy attached and also at:
http://www.wales.nhs.uk/sites3/page.cfm?orgid=814&pid=38180)
Your practice is accredited to provide near patient testing for DMARDs as a National Enhanced Service. I am therefore
requesting your agreement to share the care of this patient. The preliminary tests set out in the protocol have been
carried out. I am currently prescribing the stabilising treatment.
Treatment START DATE (agreed with GP practice):
The initial dose regime will be:
Patient consented to ‘off-label’ use confirmed:
Yes

The baseline tests are:
If you undertake treatment I will reassess the patient in ____ weeks. You will be sent a written summary within 14
days. I will accept referral for reassessment at your request.
The medical staff of the department are available at all times to give you advice.
Consultant Name:
Signature:
Department:
Hospital:
Date:
Contact Telephone Nos:
NOTE FOR GENERAL PRACTITIONER
AS THE PRACTICE IS ACCREDITED TO UNDERTAKE NEAR PATIENT TESTING, IT WILL BE ASSUMED THAT THE
PRACTICE WILL WISH TO ACCEPT REFERRALS FOR SHARED CARE.
IF FOR ANY REASON THIS IS NOT THE CASE, PLEASE CONTACT THE CONSULTANT URGENTLY SO THAT
ARRANGEMENTS CAN BE MADE TO UNDERTAKE THE NECESSARY MONITORING FOLLOWING INITIATION OF THE
DRUG.
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: May 2015 (Update Feb.2016)
Approved by: ABUHB MTC
Page 6 of 6
Review Date: May 2017