Dosing & Uses
Dosage Forms & Strengths
injectable solution
- Prolia: 60mg/mL (1mL prefilled syringe or vial)
- Xgeva: 70mg/mL (120mg/1.7mL vial)
Osteoporosis
Prolia only
Indicated for postmenopausal women with osteoporosis at high risk for fracture (defined as history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy)
Indicated for treatment to increase bone mass in men with osteoporosis at high risk for fracture
60 mg SC q6months
Aromatase Inhibitor Induced Bone Loss
Prolia only
Indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer
60 mg SC q6months
Androgen Deprivation Induced Bone Loss
Prolia only
Indicated as a treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer
60 mg SC q6months
Glucocorticoid Induced Osteoporosis
Prolia only
Indicated for glucocorticoid-induced osteoporosis in men and women at high risk of fracture who are either initiating or continuing systemic glucocorticoids equivalent to ≥7.5 mg/day of prednisone and are expected to remain on glucocorticoids for at least 6 months
60 mg SC q6months
Skeletal-Related Events
Xgeva only
Prevention of skeletal-related events (SREs; eg, bone fractures and pain) in patients with multiple myeloma and in patients with bone metastases from solid tumors
120 mg SC q4Weeks
Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia
Giant Cell Tumor
Xgeva only
Treatment of adults and skeletally mature adolescents with giant cell tumor of bone in whom surgical resection is impossible or is likely to result in severe morbidity
120 mg SC q4Weeks
Give 2 additional 120 mg doses during the first month of therapy on Days 8 and 15
Hypercalcemia of Malignancy
Xgeva only
Indicated for treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy
120 mg SC q4Weeks
Give 2 additional 120 mg doses during the first month of therapy on Days 8 and 15
Dosage Modifications
Hepatic impairment: Safety and efficacy not evaluated
Renal impairment
- Mild-to-severe: No dosage adjustment necessary
- Severe (CrCl < 30 mL/min) or receiving dialysis: In clinical trial, patients were at greater risk of developing hypocalcemia (see Cautions)
Dosing Considerations
Prolia
- Patients receiving Prolia should not receive Xgeva (see Cautions)
- All patients should receive calcium 1000 mg/day and at least 400 IU vitamin D daily
Dosage Forms & Strengths
solution for injection
- Xgeva: 70mg/mL (120mg/1.7mL vial)
Giant Cell Tumor
Xgeva only
Treatment of skeletally mature adolescents with giant cell tumor of bone in whom surgical resection is impossible or is likely to result in severe morbidity
Skeletal maturity is defined by at least 1 mature long bone (eg, closed epiphyseal growth plate of the humerus)
<13 years or <45kg: Safety and efficacy not established
13-17 years (≥45kg): 120 mg SC q4Weeks; give 2 additional 120 mg doses during the first month of therapy on Days 8 and 15
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (3)
- influenza virus vaccine quadrivalent, adjuvanted
denosumab decreases effects of influenza virus vaccine quadrivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.
- influenza virus vaccine trivalent, adjuvanted
denosumab decreases effects of influenza virus vaccine trivalent, adjuvanted by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Immunosuppressive drugs may reduce the immune response to influenza vaccine.
- palifermin
palifermin increases toxicity of denosumab by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
Monitor Closely (109)
- abatacept
abatacept, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- adalimumab
adalimumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- alefacept
alefacept, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems.
- alemtuzumab
alemtuzumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- anakinra
anakinra, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- azacitidine
azacitidine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- azathioprine
azathioprine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- basiliximab
basiliximab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- beclomethasone, inhaled
denosumab increases toxicity of beclomethasone, inhaled by immunosuppressive effects; risk of infection. Use Caution/Monitor.
- belatacept
belatacept and denosumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor.
- belimumab
belimumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- betamethasone
betamethasone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- budesonide
budesonide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- busulfan
busulfan, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- cabazitaxel
cabazitaxel, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- canakinumab
canakinumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- capecitabine
capecitabine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- carboplatin
carboplatin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- carmustine
carmustine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- certolizumab pegol
certolizumab pegol, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- chlorambucil
chlorambucil, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- cholera vaccine
denosumab decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.
- cisplatin
cisplatin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- cladribine
cladribine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- cortisone
cortisone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- cyclophosphamide
cyclophosphamide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- cyclosporine
cyclosporine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- cytarabine
cytarabine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- dacarbazine
dacarbazine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- dactinomycin
dactinomycin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- daunorubicin
daunorubicin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- dengue vaccine
denosumab decreases effects of dengue vaccine by immunosuppressive effects; risk of infection. Use Caution/Monitor. Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine.
- dexamethasone
dexamethasone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- docetaxel
docetaxel, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- doxorubicin
doxorubicin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- doxorubicin liposomal
doxorubicin liposomal, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- efgartigimod alfa
efgartigimod alfa will decrease the level or effect of denosumab by receptor binding competition. Use Caution/Monitor. Coadministration of efgartigimod with medications that bind to the human neonatal Fc receptor may lower systemic exposures and effectiveness of such medications. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies.
- epirubicin
epirubicin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- etanercept
etanercept, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- etoposide
etoposide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- everolimus
everolimus, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- fingolimod
fingolimod, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- floxuridine
floxuridine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- fludarabine
fludarabine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- fludrocortisone
fludrocortisone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- fluorouracil
fluorouracil, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- gemcitabine
gemcitabine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- glatiramer
glatiramer, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- golimumab
golimumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- hydrocortisone
hydrocortisone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- hydroxychloroquine sulfate
hydroxychloroquine sulfate, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- hydroxyurea
hydroxyurea, denosumab. Other (see comment). Use Caution/Monitor. Comment: Combination therapy may lead to increased risk of infection.
- ibritumomab tiuxetan
ibritumomab tiuxetan, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- idarubicin
idarubicin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- ifosfamide
ifosfamide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
ifosfamide, denosumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. - imatinib
imatinib, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- infliximab
infliximab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- irinotecan
irinotecan, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- irinotecan liposomal
irinotecan liposomal, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- leflunomide
leflunomide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- lenalidomide
lenalidomide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- lomustine
lomustine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- mechlorethamine
mechlorethamine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
mechlorethamine, denosumab. immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections. - melphalan
melphalan, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
melphalan, denosumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections. - meningococcal group B vaccine
denosumab decreases effects of meningococcal group B vaccine by pharmacodynamic antagonism. Use Caution/Monitor. Individuals with altered immunocompetence may have reduced immune responses to the vaccine.
- mercaptopurine
mercaptopurine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- methotrexate
methotrexate, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- methylprednisolone
methylprednisolone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- mitomycin
mitomycin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- mitoxantrone
mitoxantrone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- muromonab CD3
muromonab CD3, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- mycophenolate
mycophenolate, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- natalizumab
natalizumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- nelarabine
nelarabine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- ofatumumab
ofatumumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- ofatumumab SC
ofatumumab SC, denosumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.
- olaparib
denosumab and olaparib both increase pharmacodynamic synergism. Use Caution/Monitor. Coadministration with other other myelosuppressive anticancer agents, including DNA damaging agents, may potentiate and prolongate the myelosuppressive toxicity.
- oxaliplatin
oxaliplatin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- paclitaxel
paclitaxel, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- paclitaxel protein bound
paclitaxel protein bound, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- pazopanib
pazopanib, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- pemetrexed
pemetrexed, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- pentostatin
pentostatin, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- ponesimod
ponesimod and denosumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- pralatrexate
pralatrexate, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- prednisolone
prednisolone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- prednisone
prednisone, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- procarbazine
procarbazine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
procarbazine, denosumab. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections. - rilonacept
rilonacept, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- rituximab
rituximab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- rituximab-hyaluronidase
rituximab-hyaluronidase, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- siponimod
siponimod and denosumab both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- sirolimus
sirolimus, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- sorafenib
sorafenib, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- sunitinib
sunitinib, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- tacrolimus
tacrolimus, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- temozolomide
temozolomide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- temsirolimus
temsirolimus, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- teniposide
teniposide, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- thiotepa
thiotepa, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- tocilizumab
tocilizumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- topotecan
topotecan, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- trastuzumab deruxtecan
trastuzumab deruxtecan, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- ustekinumab
ustekinumab, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- vinblastine
vinblastine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- vincristine
vincristine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- vincristine liposomal
vincristine liposomal, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
- vinorelbine
vinorelbine, denosumab. Other (see comment). Use Caution/Monitor. Comment: Caution should be taken in patients on concomitant immunosuppressants or with impaired immune systems because of increased risk for serious infections.
Minor (0)
Adverse Effects
>10% (Prolia)
Back pain (34.7%)
Extremity pain (11.7%)
>10% (Xgeva)
Fatigue/asthenia (45%)
Hypophosphatemia (32%)
Nausea (31%)
Dyspnea (21%)
Diarrhea (20%)
Hypocalcemia (18%)
Cough (15%)
Headache (13%)
1-10% (Prolia)
Musculoskeletal pain (7.6%)
Cystitis (5.9%)
Vertigo (5%)
Upper respiratory tract infection (4.9%)
Peripheral edema (4.9%)
Sciatica (4.6%)
Pneumonia (3.9%)
Bone pain (3.7%)
Upper abdominal pain (3.3%)
Anemia (3.3%)
Insomnia (3.2%)
Myalgia (2.9%)
Angina pectoris (2.6%)
Rash (2.5%)
Pharyngitis (2.3%)
Asthenia (2.3%)
Flatulence (2.2%)
Pruritus (2.2%)
Spinal osteoarthritis (2.1%)
Gastroesophageal reflux disease (2.1%)
Atrial fibrillation (2%)
Herpes zoster (2%)
<1%
Serious infection of abdomen resulting in hospitalization (0.9%)
Serious infection of urinary tract resulting in hospitalization (0.7%)
Serious infection resulting in death (0.2%)
Pancreatitis (0.2%)
Serious infection of ear resulting in hospitalization (0.1%)
Postmarketing Reports
Prolia
- Drug-related hypersensitivity reactions: Anaphylaxis, rash, urticaria, facial swelling, and erythema
- Severe symptomatic hypocalcemia
- Musculoskeletal pain, including severe cases
- Parathyroid Hormone (PTH): Marked elevation in serum PTH in patients with severe renal impairment (CrCl <30 mL/min) or receiving dialysis
- Multiple vertebral fractures following discontinuation of Prolia
- Alopecia
- Vasculitis (eg, ANCA positive vasculitis, leukocytoclastic vasculitis)
- Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
Xgeva
- Hypocalcemia: Severe symptomatic hypocalcemia, including fatal cases
- Hypercalcemia following treatment discontinuation in patients with giant cell tumor of bone and in patients with growing skeletons
- Hypersensitivity, including anaphylactic reactions
- Musculoskeletal pain, including severe musculoskeletal pain
- Positive rechallenge has been reported
- Lichenoid drug eruptions (e.g., lichen planus-like reactions)
- Atypical subtrochanteric and diaphyseal fracture
Warnings
Contraindications
Hypersensitivity
Hypocalcemia
Pregnancy (Prolia only)
Cautions
Denosumab is available as 2 distinct brands (Prolia and Xgeva) that have different dosage strengths for their respective indications; do not use concurrently
Serious infections (including cellulitis) and dermatologic reactions (eg, dermatitis, rashes, eczema) have been reported; advise patients to seek prompt medical attention if they develop signs or symptoms of infection, including cellulitis; consider discontinuing therapy if severe symptoms develop
Hypersensitivity (including anaphylaxis) has been reported; symptoms have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and urticaria
Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported; discontinue use if severe symptoms develop
Atypical femoral fracture reported; risk increased with longer duration of treatment; events have occurred during and after treatment discontinued; evaluate patients with thigh or groin pain to rule out a femoral fracture
Following discontinuation of denosumab, fracture risk increases, including risk of multiple vertebral fractures
Pediatric use is not recommended; drug may impair bone growth in children with open growth plates and may inhibit eruption of dentition
Thearpy results in significant suppression of bone turnover; cessation of therapy results in increased bone turnover above pretreatment values 9 months after last dose; bone turnover then returns to pretreatment values 24 months after last dose
Significant suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry; long-term consequences of the degree of suppression of bone remodeling observed may contribute to adverse outcomes such as osteonecrosis of the jaw, atypical fractures, and delayed fracture healing
Osteonecrosis of the Jaw
- Bone turnover suppression may increase risk for osteonecrosis of jaw; perform an oral examination prior to initiating therapy; osteonecrosis of the jaw (ONJ), can occur spontaneously and is generally associated with tooth extraction and/or local infection with delayed healing; known risk factors include invasive dental procedures (eg, tooth extraction, dental implants, bone surgery), diagnosis of cancer, concomitant therapies (eg, chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and comorbid disorders; risk of ONJ may increase with duration of therapy
- Good oral hygiene practices should be maintained during treatment; concomitant administration of drugs associated with ONJ may increase risk of developing ONJ; risk of ONJ may increase with duration of exposure to treatment; for patients requiring invasive dental procedures, clinical judgment of treating physician and/or oral surgeon should guide management plan of each patient based on individual benefit-risk assessment
- Patients who are suspected of having or who develop ONJ while on therapy should receive care by a dentist or an oral surgeon; in these patients, extensive dental surgery to treat ONJ may exacerbate condition; consider discontinuing therapy based on individual benefit-risk assessment
Xgeva only
- Clinically significant hypercalcemia requiring hospitalization and complicated by acute renal injury reported in patients with giant cell tumor of bone and patients with growing skeletons; hypercalcemia reported within first year after treatment discontinuation; after treatment is discontinued, monitor for signs and symptoms of hypercalcemia, assess serum calcium periodically, reevaluate patient’s calcium and vitamin D supplementation requirements and manage patients as clinically appropriate
- Based on data from animal studies and its mechanism of action, Xgeva can cause fetal harm when administered to a pregnant woman (see Pregnancy)
Prolia only
- Patients on concomitant immunosuppressant agents or with impaired immune systems may be at increased risk for serious infections; consider benefit-risk profile in such patients before treating with Prolia; in patients who develop serious infections while on therapy, prescribers should assess need for continued therapy
- Atypical low energy or low trauma fractures of the shaft reported in patients receiving therapy; these fractures can occur anywhere in femoral shaft from just below lesser trochanter to above supracondylar flare and are transverse or short oblique in orientation without evidence of comminution; causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with antiresorptive agents
- In postmarketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported; time to onset of symptoms varied from one day to several months after starting Prolia; consider discontinuing use if severe symptoms develop
- In a large clinical trial which included women with postmenopausal osteoporosis, epidermal and dermal adverse events (eg, dermatitis, eczema, and rashes); most of these events were not specific to the injection
Hypocalcemia
- Hypocalcemia may occur; monitor calcium levels during therapy, especially in the first weeks of initiating therapy, and adequately supplement all patients with calcium and vitamin D
- Hypocalcemia may be exacerbated by therapy with Prolia; correct pre-existing hypocalcemia prior to initiating therapy; in patients predisposed to hypocalcemia and disturbances of mineral metabolism (e.g. history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment [CrCl <30 mL/min] or receiving dialysis), clinical monitor calcium and mineral levels (phosphorus and magnesium) within 14 days of injection; in some postmarketing cases, hypocalcemia persisted for weeks or months and required frequent monitoring and IV and/or oral calcium replacement, with or without vitamin D
- Hypocalcemia is a significant risk in patients with severe renal impairment [CrCl <30 mL/min] or receiving dialysis; dose adjustment not necessary when administered at 60 mg every 6 months; once monthly dosing not evaluated in patients with renal impairment; these patients may also develop marked elevations of serum parathyroid hormone (PTH)
- Concomitant use of calcimimetic drugs may worsen hypocalcemia risk and serum calcium should be closely monitored; Instruct all patients with severe renal impairment, including those receiving dialysis, about symptoms of hypocalcemia and importance of maintaining calcium levels with adequate calcium and vitamin D supplementation
Pregnancy & Lactation
Pregnancy
Prolia: Contraindicated
Xgeva
- Based on findings in animals and its mechanism of action, denosumab can cause fetal harm when administered to a pregnant woman
- In utero exposure in cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 50-fold higher than the recommended human dose based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality, and absent lymph nodes, abnormal bone growth, and decreased neonatal growth
- Present at low concentrations (~2% of serum exposure) in seminal fluid of male subjects receiving therapy; following vaginal intercourse, maximum amount of denosumab delivered to a female partner would result in exposures ~11,000 times lower than the prescribed 60 mg subcutaneous dose; male condom use not necessary as it is unlikely that a female partner or fetus would be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid
Pregnancy testing
- Prolia and Xgeva
- Verify pregnancy status of females of reproductive potential prior to initiating treatment
Contraception
- Prolia and Xgeva
- Females: Advise females of reproductive potential to use effective contraception during therapy, and for at least 5 months after the last dose of denosumab
- Males: Denosumab was present at low concentrations (~2% of serum exposure) in the seminal fluid of male subjects; condom use would not be necessary as it is unlikely that a female partner or fetus would be exposed to pharmacologically relevant concentrations of denosumab via seminal fluid
Lactation
There is no information regarding presence of denosumab in human milk, effects on breastfed infant, or effects on milk production;
Detected in maternal milk of cynomolgus monkeys up to 1 month after last dose (≤0.5% milk: serum ratio) and maternal mammary gland development was normal, with no impaired lactation; however, pregnant RANKL knockout mice showed altered maturation of maternal mammary gland, leading to impaired lactation
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Monoclonal antibody that specifically targets RANKL; binds to RANKL and inhibits its binding to RANK receptor, thereby preventing osteoclast formation; this results in decreased bone resorption and increases bone mass in osteoporosis; in solid tumors with bony metastases, RANKL inhibition decreases tumor-induced bone destruction and SREs
Absorption
Prolia
- Peak serum time: 10 days
- Peak plasma concentration: 6.75 mcg/mL
- AUC: 316 mcg•day/mL
Xgeva
- Bioavailability: 62%
- Steady was achieved by 6 months with multiple SC doses of 120 mg q4Weeks
Elimination
Duration: Markers of bone resorption return to baseline within 12 months of discontinuing therapy
Half-life: 25.4 days (Prolia); 28 days (Xgeva)
Administration
SC Preparation
Visually inspect for particulate matter and discoloration prior to administration
Solution should appear clear, colorless-to-pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles
Do not use if discolored or cloudy, or if the solution contains many particles or foreign particulate matter
Prior to administration, remove from refrigerator bring to room temperature (up to 25°C/77°F); generally takes 15-30 minutes; do not warm in any other way
Latex allergy
- Prolia only
- People sensitive to latex should not handle the grey needle cap on the single-use prefilled syringe, which contains dry natural rubber (a derivative of latex)
SC Administration
SC administration only
Must be administered by healthcare professional
Use a 27-gauge needle to withdraw and inject the entire contents of the vial; do not reenter the vial
Do not administer intradermally, IM, or IV
Administer SC in upper arm, upper thigh, or abdomen
Administer calcium and vitamin D as needed to treat or prevent hypocalcemia
Avoid vigorous shaking of vial/syringe
Discard vial after single-dose or entry
Storage
Xgeva and Prolia
- Refrigerate at 2-8°C (36-46°F); do not freeze
- Once removed from refrigerator, preparation must be used within 14 days and not exposed to temperatures above 25°C (77°F)
- Protect from direct light and heat
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Prolia subcutaneous - | 60 mg/mL solution |  | |
| Xgeva subcutaneous - | 120 mg/1.7 mL (70 mg/mL) vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
denosumab subcutaneous
DENOSUMAB 4 WEEK (120 MG) - INJECTION
(den-OH-sue-mab)
COMMON BRAND NAME(S): Xgeva
USES: Denosumab is used to treat bone problems that may occur in people with multiple myeloma or in people with cancer that has spread to the bones. It is also used to treat high blood calcium levels (hypercalcemia) that may occur with cancer. It may also be used by adults (and teenagers who have reached their final adult height) to treat a certain disease called giant cell tumor of the bone, if they cannot use surgery to treat the disease.
HOW TO USE: This medication is given by injection under your skin in the upper arm, upper thigh, or abdomen by a healthcare professional as directed by your doctor, usually every 4 weeks. If you are using this medication to treat giant cell tumor of the bone or high blood calcium levels, your doctor may also direct you to receive additional doses once a week during weeks 2 and 3 of the first month of treatment.Use this medication regularly in order to get the most benefit from it. Remember to receive it every 4 weeks. It may help to mark your calendar with a reminder.You may also be instructed to take calcium and vitamin D supplements. Follow your doctor's instructions carefully.
SIDE EFFECTS: Tiredness, weakness, headache, back pain, diarrhea, and nausea may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: jaw pain, new or unusual thigh/hip/groin pain, bone/joint/muscle pain, shortness of breath.Denosumab may cause very serious (rarely fatal) low levels of calcium in the blood, especially if you have kidney problems. Take calcium and vitamin D as directed by your doctor. (See also How to Use section.) Get medical help right away if you have any symptoms of low calcium such as: severe muscle spasms/cramps, mental/mood changes (such as irritability or confusion), numbness/tingling (especially around lips/mouth or in fingers/toes), seizures, severe dizziness/fainting, fast/irregular heartbeat.Denosumab can affect your immune system. You may be more likely to get a serious infection, such as a skin, ear, stomach/gut, or bladder infection. Tell your doctor right away if you develop any signs of infection, such as: fever/chills, red/swollen/tender/warm skin (with or without pus), severe abdominal pain, ear pain/discharge, trouble hearing, frequent/painful/burning urination, pink/bloody urine.Denosumab can cause skin problems such as dryness, peeling, redness, itching, small bumps/patches, or blisters. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe allergic reaction. Get medical help right away if you develop any rash or if any of these symptoms persist or worsen.Denosumab may cause high levels of calcium in the blood weeks to months after treatment has stopped, especially if you have not reached your final adult height. Tell your doctor right away if you have any symptoms of high calcium after you have stopped using denosumab such as: nausea, vomiting, headache, unusual tiredness.After your treatment with denosumab is stopped, you may be at increased risk for bone fractures in your spine. This risk is greater if you have bone loss (osteoporosis) or have had broken bones. If your treatment is stopped, talk with your doctor about other medicines you can take.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before using denosumab, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: low level of calcium in the blood (hypocalcemia), kidney disease.Some people using denosumab may have serious jawbone problems. Your doctor should check your mouth before you start this medication. Tell your dentist that you are using this medication before you have any dental work done. To help prevent jawbone problems, have regular dental exams and learn how to keep your teeth and gums healthy. If you have jaw pain, tell your doctor and dentist right away.Before having any surgery (especially dental procedures), tell your doctor and dentist about this medication and all other products you use (including prescription drugs, nonprescription drugs, and herbal products).Denosumab is not recommended for use in children except for the treatment of giant cell tumor of the bone (see also Uses section). It may slow down a child's growth and affect tooth development.This medication must not be used during pregnancy. It may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. It is important to prevent pregnancy while using this medication and for at least 5 months after treatment. Females must use reliable forms of birth control during treatment and for at least 5 months after treatment. If you become pregnant or think you may be pregnant, tell your doctor right away.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Laboratory and/or medical tests (such as calcium/phosphorus levels, kidney function) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.Do not take this medication with any other product that contains denosumab.
MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule.
STORAGE: Not applicable. This medication is given in a clinic or doctor's office and will not be stored at home.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details.
Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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