Download Denosumab Shared Care Guideline - airedale

PHARMACY DEPARTMENT
DOCUMENT
Denosumab (PROLIA® ▼)subcutaneous injection Rheumatology
Shared Care Guideline
Title:
FILENAME
PHA_Medicines management_Shared Care
Guidelines_Denosumab Shared Care Guideline
VERSION №
3
DATE OF ISSUE
4/02/2011
REVIEW INTERVAL
2 Years
AUTHORISED BY
Drug and Therapeutics Committee
AUTHOR
Dr Shabina Sultan – Consultant Rheumatologist
Dr Cornelle Parker – Consultant Endocrinologist
Linda Stewart – Pharmacist
Linda Sigsworth – Rheumatology Nurse Specialist
EMAIL ADDRESS OF AUTHOR
[email protected]
COPY №
1
LOCATION OF COPIES
1. SHAREPOINT
2. PHARMACY NETWORK
ASSOCIATED WORKING INSTRUCTIONS
N/A
LOCATION OF WORKING INSTRUCTIONS
N/A
TO BE VIEWED
TRUST WIDE
X
PHARMACY ONLY
DOCUMENT REVIEW HISTORY
REVIEW DATE
REVIEWED BY
CHANGES
4.2.13
Linda Stewart
30/9/2013
Linda Stewart – Pharmacist
Review date extended. Sent to consultants for
consultation
Consultant now recommends that the GP start the
treatment rather than initiating it.
Dr Sultan – Consultant Rheumatologist
Drug and Therapeutics Committee
20/11/2014
Linda Stewart – Pharmacist
Dr Sultan – Consultant Rheumatologist
Additional cautionary information added regarding
osteonecrosis of the jaw and hypocalcaemia.
Area Prescribing Committee
30/9/2015
Linda Stewart – Pharmacist
Dr Sultan – Consultant Rheumatologist
Area Prescribing Committee
17/12/2015
Linda Stewart – Pharmacist
Dr Sultan – Consultant Rheumatologist
Additional cautionary information added regarding
osteonecrosis of the jaw and the provision of patient
reminder cards as per Drug Safety Update July 2015
Denosumab patient safety reminder card
added as an appendix.
Area Prescribing Committee
4/3/2016
Linda Stewart – Pharmacist
Dr Sultan – Consultant Rheumatologist
Drug and Therapeutics Committee
Information on osteonecrosis of the external
auditory canal added from MHRA drug safety
update December 2015
17/12/2017
NB: ONLY SHAREPOINT VERSION OR NUMBERED COPIES IN STATED LOCATIONS ARE VALID FOR OPERATIONAL
USE
Denosumab (PROLIA® ▼)subcutaneous injection
Rheumatology Shared Care Guideline
GENERAL
STATEMENTS


Denosumab is suitable for patients with established osteoporosis for both
primary and secondary fracture prevention who either cannot tolerate oral
medication such as bisphosphonates or strontium ranelate (i.e. GI sideeffects or rash), have renal impairment precluding the use of other drugs
(eGFR < 35ml/min) or are non-compliant (usually impaired mentation) or
unable to travel to hospital because of poor mobility). See also NICE
guidance on Denosumab.
Although denosumab is ideally suited for use in primary care it is a second
line drug after oral medication (bisphosphonates and/or strontium).

Its use should be recommended by a secondary care physician
experienced in the use of this drug with appropriate guidance on monitoring
and duration of use. The treatment can then be started in primary care.

The primary care physician should inform the secondary care physician if
there are any problems with the use of denosumab (i.e. side effects
precluding further use, further fractures after 2-3 years) so that further
appropriate treatment can be recommended.
The full summary of product characteristics (SPC) should be read before prescribing.
PHARMACOLOGICAL Denosumab is the first in a new class of drug to treat osteoporosis. It is a
human monoclonal antibody (IgG2) BUT it does not act as an
SUMMARY
immunosuppressive agent. It inhibits osteoclast formation, function and
survival, thereby decreasing bone resorption in cortical and trabecular bone.
INDICATIONS FOR
THERAPY
Licensed indication
Treatment of osteoporosis in postmenopausal women and in men at increased risk
of fractures. Denosumab significantly reduces the risk of vertebral, non vertebral and
hip fractures.
[It is also important to note that Denosumab is licensed for bone loss associated with
hormone ablation in men with prostate cancer at increased risk of fractures.]
CONTRAINDICATIONS



o
Hypocalcaemia (see section 4.4 of SPC).
Low Vitamin D - ensure patient is vitamin D replete. Even insufficient patients
may require a stat dose of high dose vitamin D3 (100,000units) to ensure
vitamin D >50
Hypersensitivity to the active substance or to any of the excipients.
The needle sheath contains latex so denosumab is contra-indicated in
latex allergy
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Denosumab (PROLIA® ▼)subcutaneous injection
Rheumatology Shared Care Guideline
CAUTIONS
Osteonecrosis of the jaw (ONJ) has been reported rarely in clinical studies in patients
receiving denosumab at a dose of 60 mg 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.
Denosumab 60mg (osteoporosis indication) check for ONJ risk factors before starting
denosumab 60mg. A dental examination and appropriate preventive dentistry are now
recommended for patient with risk factors. While on treatment, these patients should avoid
invasive dental procedures if possible. If dental extraction is required then refer to
maxillofacial surgery. Avoid interruption in therapy. Where retreatment is recommended it
should be commenced within +/- 10 days of the six month date to prevent elevated bone
turnover.
Before prescribing denosumab:
 Give patients the patient reminder card for their medicine
 Explain the risk of osteonecrosis of the jaw and advise on the 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 if they need
dental treatment or 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)
o do not prescribe denosumab to patients with unhealed lesions from dental or
oral surgery
The MHRA Drug Safety Update ‘Denosumab (Xgeva, Prolia; intravenous bisphosphonates:
osteonecrosis of the jaw – further measures to minimise the risk’ shows the content of the
patients reminder cards.
For patients who develop ONJ while on denosumab therapy, dental surgery may exacerbate
the condition. If ONJ occurs during treatment with Denosumab, use clinical judgment and
guide the management plan of each patient based on individual benefit/risk evaluation.
Osteonecrosis of the external auditory canal
o
o
o
o
The possibility of osteonecrosis of the external auditory canal should be
considered in patients receiving bisphosphonates who present with ear
symptoms, including chronic ear infections, or in patients with suspected
cholesteatoma
Possible risk factors include steroid use and chemotherapy, with or without
local risk factors such as infection or trauma
Patients should be advised to report any ear pain, discharge from the ear, or
an ear infection during bisphosphonate treatment
Report any cases of osteonecrosis of the external auditory canal suspected
to be associated with bisphosphonates or any other medicines, including
denosumab, on a Yellow Card
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Denosumab (PROLIA® ▼)subcutaneous injection
Rheumatology Shared Care Guideline
CAUTIONS
CONTINUED
Atypical Fracture - During denosumab treatment patients should be advised to report new
or unusual thigh, hip, or groin pain. Patients presenting with such symptoms should be
evaluated for an incomplete femoral fracture.
Atypical femoral fractures may occur with little or no trauma in the subtrochanteric and
diaphyseal regions of the femur. The contralateral femur should be examined in denosumabtreated patients who have sustained a femoral shaft fracture, as atypical femoral fractures
are often bilateral
Discontinuation of denosumab treatment should be considered if an atypical femur fracture is
suspected – refer urgently to orthopaedics
These events occurred rarely (in ≥ 1/10,000 to < 10/10,000 patients), based on 8,928
subjects being exposed to denosumab 60 mg in bone loss studies.
POTENTIAL DRUG
INTERACTIONS
INITIAL SCREENING
STORAGE AND
PRESCRIBING
Nil known
Hypocalcaemia must be corrected by adequate intake of calcium and vitamin D
before initiating therapy. Patients with severe renal impairment (creatinine clearance
< 30 ml/min) or receiving dialysis are at greater risk of developing hypocalcaemia.
Clinical monitoring of calcium levels is recommended for patients predisposed to
hypocalcaemia. These patients may require alfacalcidol; liaise with endocrinology or
renal team re dose of calcitriol
Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the pre-filled syringe in the
outer carton in order to protect from light. Do not shake excessively.
Shelf life is 30 months. Denosumab 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.
The recommended dose of Denosumab is 60 mg administered as a single
subcutaneous injection once every 6 months into the thigh, abdomen or back of arm.
Patients must be adequately supplemented with calcium and vitamin D (see section
4.4 of SPC).
MONITORING
Denosumab 60mg (osteoporosis indication)
o Check calcium levels:
o before each dose
o within two weeks after initial dose in patients with risk factors for
hypocalcaemia (e.g. severe renal impairment, creatinine clearance
<30ml/min)
o if suspected symptoms of hypocalcaemia occur
Tell patients to report symptoms of hypocalcaemia to their doctor (e.g. muscle
spasm, twitches, or cramps: numbness or tingling in the fingers, toes or around the
mouth.
Suggest annual checks of vitamin D to ensure compliance.
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Denosumab (PROLIA® ▼)subcutaneous injection
Rheumatology Shared Care Guideline
ADVERSE EVENTS
Patients receiving Denosumab may develop skin infections (predominantly cellulitis)
leading to hospitalisation (see section 4.8 of SPC). Patients should be advised to
seek prompt medical attention if they develop signs or symptoms of cellulitis.
Common undesirable effects observed with an incidence of 1-10% were: urinary
tract infection, upper respiratory tract infection, cataract, constipation, sciatica, rash,
pain in extremity. In prostate cancer patients receiving androgen deprivation therapy,
cataracts and diverticulitis were reported more frequently in the Denosumab patients
compared to placebo. No imbalances of either adverse event were observed in
postmenopausal women with osteoporosis.
The needle cover of the pre-filled syringe contains dry natural rubber (a derivative of
latex), which may cause allergic reactions.
Please refer to section 4.8 of the SPC for more information.
RESPONSIBILITY OF
THE SPECIALIST
RECOMMENDING
TREATMENT
Summary
 Assess for the suitability of treatment and duration of therapy.
If
recommendation for treatment is made by e-consultation then it is the
responsibility of the primary care physician to provide the drug information
leaflet (appended to the end of this guidance).
 Supply GP with summary of out-patient review, as well as the instructions
provided to the patient
 Report any adverse events to the Committee on Safety of Medicines (CSM) at
the Medicines and Health Care Regulatory Agency (MHRA).
 Establish process for GP to seek advice or support as needed.
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Denosumab (PROLIA® ▼)subcutaneous injection
Rheumatology Shared Care Guideline
RESPONSIBILITY OF
Summary
OTHER
PRESCRIBERS
 As with bisphosphonates, assess the patient to ensure she has good oral
hygiene and use clinical judgement to determine if a dental examination is
required prior to initiating therapy (see section 4.4 of product SPC if needed)
 Ensure practice system is set-up to recall patient after six month interval.
 Ensure account is set up to order denosumab and determine if it will come
direct to the practice (preferred scenario, as this is more straightforward for
the patient) or if the patient will need to collect their prescription from the
pharmacy. If it is the latter, ensure a reminder letter is set up to be sent to
patient with the relevant instructions.
 Prescribe and administer denosumab at six-monthly intervals. It is important
that where re-treatment is recommended this is commenced within +/10 days of the six month date to prevent elevated bone turnover.
 Note: a protocol on how to administer the injection is available from the
pharmaceutical companies if required and is appended to the end of the
guidance.
 The primary care physician should inform the secondary care physician if
there are any problems with the use of denosumab (i.e. side effects
precluding further use, further fractures after 2-3 years) so that further
appropriate treatment can be recommended.
 Report any adverse events to the Committee on Safety of Medicines (CSM) at
the Medicines and Health Care Regulatory Agency (MHRA).
 There is currently data for the use of denosumab for up to 8 years but a review
of the need for ongoing therapy should be made after 5 years. A DEXA scan
may be required.
PATIENT
RESPONSIBILITY

All patients must 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.

Patients must report symptoms of hypocalcaemia to their doctor (e.g.
muscle spasm, twitches, or cramps: numbness or tingling in the
fingers, toes or around the mouth.
CONTACTS
A patient information leaflet has been issued to your patient. If any problems
occur please contact relevant specialist:
Consultant Endocrinologist:
01535 294388
For Rheumatology Patients ONLY:
Consultant Rheumatologists secretary:
Rheumatology Nurse Specialist:
Rheumatology Helpline:
Pharmacy (for all patients):
01535 292067
01535 292084
01535 292084
01535 293503
Access to shared care guidelines is available via the internet at Airedale NHS
Trust at: http://www.airedale-trustformulary.nhs.uk/default.asp
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Rheumatology Shared Care Guideline
Appendix 1 Denosumab Patient Information Leaflet for treatment of post-menopausal
osteoporosis
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Rheumatology Shared Care Guideline
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Rheumatology Shared Care Guideline
Appendix 2: Support Documents for Healthcare Professionals (Available from
Amgen & GlaxoSmithKline)
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Rheumatology Shared Care Guideline
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