Download Gwent Shared Care Protocol

Shared Care Agreement Form – Accredited
CONSULTANT REQUEST
DENOSUMAB 60mg (Prolia®)
To: Dr.
Your patient:
NHS No. (10 digit):
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 ABUHB’s MTC.
I agree to the responsibilities set out in the protocol SCP No. 27 (copy attached and at:
http://www.wales.nhs.uk/sites3/page.cfm?orgid=814&pid=38180).
Your practice is accredited to provide pre-assessment and administration of denosumab 60mg (Prolia®) as a Local
Enhanced Service. I am therefore requesting your agreement to share the care of this patient. The preliminary tests
set out in the Protocol (Section 7) have been carried out.
First 60mg dose administered on (date):
Baseline renal function:
Baseline hydroxyvitamin D (25OHD) level:
(Normal/abnormal)
Baseline bone profile
(Normal/abnormal)
(serum calcium, alk phos, phosphate, albumin)
 Next review with this department: (add date)
OR
 Routine review in hospital is not required. However, the medical staff of the department are available to
give you advice. If the patient continues on denosumab 60mg for 5 years, please notify this department so that
review can be arranged.
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: January 2014 (updated Jan. 2016 & March 2017)
Approved by: ABUHB MTC
Page 1 of 6
Review Date: January 2018
Gwent Shared Care Protocol
DENOSUMAB 60mg (Prolia®)
for the treatment of osteoporosis in postmenopausal women and in men at
increased risk of fractures
Protocol No. 27
General guidance
1. Licensed
indication
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 endorsed this protocol in 2014. It outlines
shared care arrangements for.
This Protocol should be read in conjunction with:
 The Shared Care Agreement Form (see Page 1).
 The Summary of Product Characteristics for Prolia® see:
http://www.medicines.org.uk/emc/medicine/23127
 NICE TA204 (October 2010) http://guidance.nice.org.uk/TA204 – Osteoporotic fractures.
Note: This Protocol does NOT cover the prescribing and administration of denosumab:
 60mg (Prolia®) in patients with an eGFR <30 or for any patients subsequently developing
eGFRs <30. In such cases Secondary Care will retain the responsibility for the prescribing
and administration of denosumab.
 60mg (Prolia®) for the treatment of bone loss associated with hormone ablation in men
with prostate cancer at increased risk of fractures (NICE is unable to recommend this use).
 120mg (▼XGEVA®) for the prevention of skeletal related events (pathological fracture,
radiation to bone, spinal cord compression or surgery to bone) in adults with bone
metastases from solid tumours.
Treatment of osteoporosis in postmenopausal women and in men at increased risk of
fractures.
In 2014 denosumab (Prolia®) was granted a license extension for treatment of osteoporosis in
men at increased risk of fracture and in March 2017 a One Wales Interim Commissioning
decision recommended that denosumab be made available within NHS Wales for this
indication (see: https://openrepository.awttc.org/app/serve/resource/trpp2722).
In Gwent denosumab is considered a third line option after failure of two oral
bisphosphonates in patients unsuitable for zoledronic acid or fourth line after failure of
zoledronic acid (or the development of severe renal impairment during treatment – this
cohort to remain specialist managed).
2. Background
information
Denosumab (Prolia®) has been prescribed for the treatment of osteoporosis/bone loss for this
individual.
Denosumab is a human monoclonal antibody (IgG2) that decreases bone resorption in cortical
and trabecular bone.
When denosumab (Prolia®) is used for the prevention of osteoporotic fractures in
postmenopausal women, it should be prescribed in accordance with the recommendations in
NICE TA204 (www.nice.org.uk/TA204) i.e. when the following conditions are met:
 Primary prevention of osteoporotic fragility fractures in postmenopausal women at
increased risk of fractures: who are unable to comply with the special instructions for
administering alendronate and either risedronate or etidronate, or have an intolerance
of, or a contra-indication to, those treatments and who comply with particular
combinations of bone mineral density measurement, age, and independent risk factors
for fracture, as indicated in NICE TA204.
 Secondary prevention of osteoporotic fragility fractures only in postmenopausal women
at increased risk of fractures: who are unable to comply with the special instructions for
administering alendronate and either risedronate or etidronate, or have an intolerance
of, or a contra-indication to, those treatments.
 The first dose should be administered by the specialist team. Thereafter, prescribing and
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: January 2014 (updated Jan. 2016 & March 2017)
Approved by: ABUHB MTC
Page 2 of 6
Review Date: January 2018
administration can be undertaken in primary care in accordance with the shared care
agreement.
3. Contraindications
& cautions
Contraindications:
1. Hypocalcaemia.
2. Hypersensitivity to the active substance or to any of the excipients of denosumab
(Prolia®)
Cautions:
Hypocalcaemia – (note contraindication) must be corrected by adequate intake of
calcium and vitamin D before initiating therapy. Patients with severe renal
impairment (eGFR <30) or receiving dialysis are at greater risk of developing
hypocalcaemia. Clinical monitoring of calcium levels is recommended for patients
predisposed to hypocalcaemia.
Skin Infections – Patients receiving denosumab may develop cellulitis leading to
hospitalisation. Patients should be advised to seek prompt medical attention if
they develop signs or symptoms of cellulitis.
Osteonecrosis of the jaw (ONJ) – Although most cases have been in cancer patients;
ONJ has been reported rarely in clinical studies in patients receiving 60mg of
denosumab every 6 months for osteoporosis. Known risk factors for ONJ include
a diagnosis of cancer with bone lesions, concomitant therapies (e.g.,
chemotherapy, antiangiogenic biologics, corticosteroids, radiotherapy to head
and neck), poor oral hygiene, dental extractions, and co-morbid disorders (e.g.,
pre-existing dental disease, anaemia, coagulopathy, infection) and previous
treatment with bisphosphonates.
Atypical femoral fractures – have been reported in patients receiving 60mg of
denosumab and they may occur with little or no trauma in the subtrochanteric
and diaphyseal regions of the femur. Specific radiographic findings characterize
these events. Atypical femoral fractures have also been reported in patients with
certain comorbid conditions (e.g. vitamin D deficiency, rheumatoid arthiritis,
hypophosphatasia) and with use of certain medicines (e.g. bisphosphonates,
glucocorticoids, PPIs). Similar fractures reported in association with
bisphosphonates are often bilateral; therefore the contralateral femur should be
examined in denosumab-treated patients who have sustained a femoral shaft
fracture.
4. Dosage regimen
POSTMENOPAUSAL WOMEN AND MEN AT INCREASED RISK OF FRACTURES: 60mg every 6 months by
subcutaneous injection into the thigh, abdomen or upper arm.
Note. No dose adjustment is required in the elderly or patients with renal impairment.
DURATION OF TREATMENT: review therapy by specialist team after 5 years.
5. Drug Interactions
Patients being treated with denosumab (Prolia®) should not be treated concomitantly with
other denosumab-containing medicinal products (for prevention of skeletal-related events in
adults with bone metastases from solid tumours).
6. Adverse drug
reactions
Common (≥1/100 to <1/10) adverse effects listed in the denosumab SmPC include urinary
tract infection, upper respiratory tract infection, sciatica, cataracts, eczema, rash, constipation
and cataracts.
The only very commonly (≥1/10) associated adverse effect in the SmPC is pain in extremity.
All serious adverse
events should be
reported to
MHRA/CHM using
the Yellow Card.
Adverse event
Cellulitis
Atypical femoral fractures
(i.e. new or unusual thigh,
hip, or groin pain)
ONJ
Good oral hygiene practices
Frequency
Uncommon
≥1/1,000 to <1/100
Rare ≥1/10,000 to
<1/1,000
Rare ≥1/10,000 to
<1/1,000
Management
Standard clinical management
Evaluate for an incomplete femoral fracture
and if fracture confirmed consider stopping
drug and discuss
If ONJ occurs during treatment with use
clinical judgment and guide the management
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: January 2014 (updated Jan. 2016 & March 2017)
Approved by: ABUHB MTC
Page 3 of 6
Review Date: January 2018
should be maintained during
treatment.
plan of each patient based on individual
benefit/risk evaluation. Note dental surgery
may exacerbate the condition.
7. Baseline
investigations
To be undertaken by specialist in secondary care:
Ensure calcium and vitamin D replete (vitamin D deficiency and hypocalcaemia must be
corrected before initiation of therapy)
i. Renal function, bone profile (serum calcium, alkaline phosphatase, phosphate, albumin)
and serum vitamin D.
ii. A dental examination with appropriate preventive dentistry should be considered in
patients with concomitant risk factors. While on treatment, these patients should avoid
invasive dental procedures if possible.
8. Ongoing
monitoring &
administration
To be undertaken by GP following administration of the first dose of denosumab:
(a) Blood monitoring
Prior to each denosumab injection:
Renal profile
vitamin D and bone profile (serum
calcium, alkaline phosphatase,
phosphate, albumin).
Do not administer denosumab if patient has hypocalcaemia or
low vitamin D levels; refer to initiating consultant for advice.
In patients with calcium or vitamin D deficiency at first
injection, administration of the second dose of denosumab
(at 6 months) is also the responsibility of initiating consultant.
(b) Clinical monitoring
Assess for adverse effects prior to
each injection (see cautions in
Section 3)
If denosumab is considered for patients with eGFR < 30,
administration should remain in the hospital setting.
Do not administer denosumab if eGFR < 30; refer to specialist
clinic for advice.
Irrespective of who administered the injection: if a patient
becomes acutely unwell such that renal function may be
impaired, clinicians should consider the risk of hypocalcaemia
and the need to check calcium/renal function.
During denosumab treatment, patients presenting with new
or unusual thigh, hip or groin pain should be evaluated for an
incomplete femoral fracture. Delay administration of
denosumab while the patient is evaluated.
9. Pharmaceutical
aspects
Denosumab (Prolia®) is a fridge item so store between 2 and 8°C. Do not freeze.
Keep the pre-filled syringe in the outer carton in order to protect from light.
Do not shake excessively.
Denosumab (Prolia®) may be stored at room temperature (up to 25°C) for up to 30 days in the
original container. Once removed from the refrigerator, it must be used within this 30-day
period.
10. Specialist contact
details
If stopping the medication or needing advice please contact
Rheumatology Helpline: 01633 656251
In an emergency a Clinical Nurse can be bleeped via the Nevill Hall Hospital
Switchboard on the number 432.
Rheumatology Intranet homepage:
http://howis.wales.nhs.uk/sitesplus/866/page/55676
Care of the elderly:
Dr Inder Singh (secretary): 01443 802212 (YYF)
Dr Muhammad Usman: 01873 732770 (NHH)
Dr Amit Sah: 01633 234387 (RGH)
11. 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.
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: January 2014 (updated Jan. 2016 & March 2017)
Approved by: ABUHB MTC
Page 4 of 6
Review Date: January 2018
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.
12. Responsibilities of
Specialists
(Secondary Care)
i.
13. Responsibilities of
patients
i. To attend hospital and GP clinic appointments.
ii. To maintain an adequate intake of calcium and vitamin D.
iii. To maintain good dental health and report any dental problems or invasive dental
procedures/extractions to the GP prior to the administration of 60mg denosumab.
iv. Whilst on treatment, to report the development of new or unusual thigh, hip, or groin
pain or episodes of cellulitis to their specialist, GP or practice nurse.
14. Responsibilities of
Primary Care
i.
See also Local
Enhanced Service
Specification
To provide a patient information leaflet indicating the risks and benefits associated with
denosumab 60mg.
ii. To advise the patient on potential side effects and the action to be taken should they
occur; particularly the risk and signs of atypical femoral fractures (new or unusual thigh,
hip, or groin pain) and the need for good oral hygiene (questioning about dental health or
a basic dental examination should be undertaken). Patients should be specifically advised
to:
a. seek prompt medical attention if they develop signs or symptoms of cellulitis
and
b. maintain good oral hygiene, receive routine dental check-ups, and
immediately report any oral symptoms such as dental mobility, pain, or
swelling to a doctor and dentist.
iii. To undertake baseline monitoring of calcium and vitamin D (as detailed in Section 7),
correcting levels as required. Patient’s ability to tolerate calcium supplements should be
established before the first dose of denosumab is administered. Adequate intake of
calcium and vitamin D is important in all patients receiving 60mg denosumab.
iv. To confirm patient’s understanding and consent to treatment.
v. Initiate treatment by administering the first dose of denosumab.
In patients with calcium or vitamin D deficiency at first injection, administration of the
second dose of denosumab (at 6 months) is also the responsibility of initiating consultant.
vi. To retain the responsibility for prescribing and administering 60mg denosumab in
patients with an eGFR <30 (or for any patients subsequently developing eGFRs <30).
vii. To send the GP a Shared Care Agreement Form – Accredited (Page 1) requesting them to
provide continued monitoring and 6 monthly administration of denosumab.
viii. Further administration of denosumab should not be undertaken if an atypical femur
fracture is suspected, while the patient is evaluated.
ix. Monitor patient’s initial reaction to the drug.
x. Continue to monitor and supervise the patient according to this protocol, while the
patient remains on this drug.
xi. To advise GP on when to stop denosumab (see 14 v. below).
ii.
iii.
iv.
v.
vi.
15. Responsibilities of
all prescribers
To monitor (Section 8), prescribe and administer denosumab (Prolia®) every 6 months
following initial dose from specialist according to this protocol.
To ensure that the monitoring and dosage record is kept up to date. Prescribing records
should demonstrate that denosumab has been administered within the last 6 months.
To ensure that symptoms or results are appropriately actioned, recorded and
communicated to secondary care when necessary.
To refer any patient subsequently developing an eGFR <30 back to the specialist in
Secondary Care (for continued administration of denosumab 60mg).
To notify specialist once patient has received a total of 10 doses (5 years treatment) of
denosumab so that a review can be arranged.
To reinforce advice on importance of maintaining good oral hygiene and to report
immediately if they have any problems with their mouth or teeth during treatment.
Any suspected serious adverse reaction to an established drug should be reported to MHRA
via the “yellow card scheme.” http://yellowcard.mhra.gov.uk/
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: January 2014 (updated Jan. 2016 & March 2017)
Approved by: ABUHB MTC
Page 5 of 6
Review Date: January 2018
16. Supporting
documentation /
information
BNF Section 6.6.2 Bisphosphonates and other drugs affecting bone metabolism
Patient information leaflet for Prolia:
http://www.medicines.org.uk/emc/medicine/23128/XPIL/Prolia/
MHRA advice:
Drug Safety Update (Oct 2012): Denosumab: fatal cases of severe symptomatic
hypocalcaemia, and risk of hypocalcaemia at any time during treatment – monitoring
recommended.
Drug Safety Update (Feb. 2013): Denosumab 60 mg (Prolia®): rare cases of atypical femoral
fracture with long-term use.
Drug Safety Update (Sept. 2014): Denosumab: minimising the risk of osteonecrosis of the jaw;
monitoring for hypocalcaemia—updated recommendations.
Drug Safety Update (July 2015): Denosumab (Xgeva▼, Prolia); intravenous bisphosphonates:
osteonecrosis of the jaw—further measures to minimise risk.
Osteonecrosis of the jaw
The following precautions are now recommended to reduce the risk of ONJ:
Before prescribing denosumab:
 give patients the patient reminder card for their medicine
 explain the risk of osteonecrosis of the jaw and advise patients on precautions
to take—advise patients to:
o tell their doctor if they have any problems with their mouth or teeth
before starting treatment; if they wear dentures they should make sure
their dentures fit properly before starting treatment
o maintain good oral hygiene and get routine dental check-ups during
treatment
o tell their doctor and dentist that they are receiving denosumab or an
intravenous bisphosphonate if they need dental treatment or dental
surgery
o tell their doctor and dentist immediately if they have any problems
with their mouth or teeth during treatment (e.g. loose teeth, pain,
swelling, non-healing sores or discharge)
 do not prescribe denosumab 120 mg (cancer indication) to patients with
unhealed lesions from dental or oral surgery
Hypocalcaemia
Calcium levels should now be monitored as follows:
Denosumab 60 mg (osteoporosis indication)
 Check calcium levels:
 before each dose
 within two weeks after the initial dose in patients with risk factors for
hypocalcaemia (e.g. severe renal impairment, creatinine clearance <30
ml/min)
 if suspected symptoms of hypocalcaemia occur.
Tell all patients to report symptoms of hypocalcaemia to their doctor (eg, muscle
spasms, twitches, or cramps; numbness or tingling in the fingers, toes, or around the
mouth).
This Shared Care Protocol should be read in conjunction with the Summary of Product Characteristics
Status: APPROVED
Issue Date: January 2014 (updated Jan. 2016 & March 2017)
Approved by: ABUHB MTC
Page 6 of 6
Review Date: January 2018