denosumab Flashcards
what is it and how does it work
Denosumab is a human monoclonal antibody that inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption
MHRA - atypical femoral fractures
Atypical femoral fractures have been reported rarely in patients receiving denosumab for the long-term treatment (2.5 or more years) of postmenopausal osteoporosis.
Patients should be advised to report any new or unusual thigh, hip, or groin pain during treatment with denosumab.
Discontinuation of denosumab in patients suspected to have an atypical femoral fracture should be considered after an assessment of the benefits and risks of continued treatment.
what electrolyte disturbance is it predicted to cause and what does the risk increase with
and when does it usually happen
Denosumab is associated with a risk of hypocalcaemia. This risk increases with the degree of renal impairment. Hypocalcaemia usually occurs in the first weeks of denosumab treatment, but it can also occur later in treatment.
MHRA - osteonecrosis of the jaw
how common is it
what are the risk factors for it
known and common side-effect in patients receiving denosumab 120 mg for cancer.
Risk factors include smoking, old age, poor oral hygiene, invasive dental procedures (including tooth extractions, dental implants, oral surgery), comorbidity (including dental disease, anaemia, coagulopathy, infection), advanced cancer, previous treatment with bisphosphonates, and concomitant treatments (including chemotherapy, anti-angiogenic biologics, corticosteroids, and radiotherapy to head and neck)
what do patients need to be given (hint for osteonecrosis of jaw)
patient reminder card
the following precautions are now recommended to reduce the risk of osteonecrosis of the jaw:
Denosumab 120 mg (cancer indication)
A dental examination and appropriate preventative dentistry before starting treatment are now recommended for all patients
Do not start denosumab in patients with a dental or jaw condition requiring surgery, or in patients who have unhealed lesions from dental or oral surgery
Denosumab 60 mg (osteoporosis indication)
Check for ONJ risk factors before starting treatment. A dental examination and appropriate preventative dentistry are now recommended for patients with risk factors
Plasma-calcium concentration monitoring is recommended for denosumab 120 mg (cancer indication):
before the first dose
within two weeks after the initial dose
if suspected symptoms of hypocalcaemia occur
consider monitoring more frequently in patients with risk factors for hypocalcaemia (e.g. severe renal impairment, creatinine clearance less than 30 mL/minute)
Plasma-calcium concentration monitoring is recommended for denosumab 60 mg (osteoporosis indication):
before each dose
within two weeks after the initial dose in patients with risk factors for hypocalcaemia (e.g. severe renal impairment, creatinine clearance less than 30 mL/minute)
if suspected symptoms of hypocalcaemia occur
All patients should be advised to report symptoms of hypocalcaemia to their doctor
(e.g. muscle spasms, twitches, cramps, numbness or tingling in the fingers, toes, or around the mouth).
patient comes in to the pharmacy concerned because she has numbness in the hands and feet and a lot of cramps. she wants to buy a painkiller.
her PMR is as followed
ramipril 10mg
denosumab
refer to Gp as these are signs of hypocalaemia ((e.g. muscle spasms, twitches, cramps, numbness or tingling in the fingers, toes, or around the mouth).
MHRA osteonecrosis of the ear canal
Osteonecrosis of the external auditory canal has been reported with denosumab and this should be considered in patients who present with ear symptoms including chronic ear infections or in those with suspected cholesteatoma. Possible risk factors include steroid use and chemotherapy, with or without local risk factors such as infection or trauma. The MHRA recommends advising patients to report any ear pain, discharge from the ear, or an ear infection during denosumab treatment.
MHRA - genosumab for giant cell tumour of bone: risk of clinically significant hypercalcaemia following discontinuation
Cases of clinically significant hypercalcaemia (rebound hypercalcaemia) have been reported up to 9 months after discontinuation of denosumab treatment for giant cell tumour of bone. The MHRA recommends that prescribers should monitor patients for signs and symptoms of hypercalcaemia after discontinuation, consider periodic assessment of serum calcium, re-evaluate the patient’s calcium and vitamin D supplementation requirements, and advise patients to report symptoms of hypercalcaemia.
Denosumab is not recommended in patients with growing skeletons.
mhra - Denosumab 60 mg (Prolia®): increased risk of multiple vertebral fractures after stopping or delaying ongoing treatment
Cases of multiple vertebral fractures have been reported in patients within 18 months of discontinuation or interruption of ongoing denosumab 60 mg treatment for osteoporosis. The MHRA advises healthcare professionals not to discontinue denosumab without a specialist review, and to evaluate patients’ individual risk and benefit factors before initiating treatment, particularly in those at increased risk of vertebral fractures (such as patients with previous vertebral fracture). Healthcare professionals should re-evaluate the need for continued treatment periodically based on expected benefits and potential risks of treatment on an individual basis, particularly after 5 or more years of use.
MHRA - why should prolia (60mg) not be used in under 18s
due to the risk of serious hypercalcaemia
contraindications for denosumab
Hypocalcaemia
