Denosumab – Uses, Dosage, Side Effects, Interaction Denosumab is a RANK ligand (RANKL) inhibitor used for the management of osteoporosis in patients at high risk for bone fractures. Denosumab is a novel, fully human IgG2 monoclonal antibody specific to receptor activator of nuclear factor kappa-B ligand (RANKL), suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases. Chemically, it consists of 2 heavy and 2 light chains. Each light chain consists of 215 amino acids. Each heavy chain consists of 448 amino acids with 4 intramolecular disulfides. FDA approved on June 1, 2010. Denosumab is a bone anti-resorptive drug used to treat osteoporosis and other bone-related disorders. FDA-approved indications include prevention of skeletal-related events (e.g., bone pain and fractures) secondary to multiple myeloma or bone metastases from solid tumors, giant cell tumors of the bone, hypercalcemia of malignancy, osteoporosis in postmenopausal women with osteoporosis at high risk for fracture as well as men with osteoporosis at high risk of fracture, glucocorticoid-induced osteoporosis, and bone loss. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of denosumab pertinent for interprofessional team members when denosumab therapy is appropriate to achieve optimal patient outcomes. Mechanism of action Denosumab is designed to target RANKL (RANK ligand), a protein that acts as the primary signal to promote bone removal/resorption. In many bone loss conditions, RANKL overwhelms the body’s natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors. Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function, and survival, thereby decreasing bone resorption and increasing bone mass and strength in both cortical and trabecular bone. In clinical studies, treatment with 60 mg of Prolia resulted in a reduction in the bone resorption marker serum type 1 C-telopeptide (CTX) by approximately 85% by 3 days. Consistent with the physiological coupling of bone formation and resorption in skeletal remodeling, subsequent reductions in bone formation markers (i.e. osteocalcin and procollagen type 1 N-terminal peptide [PlNP]) were observed starting 1 month after the first dose of Prolia. Indications Prolia is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture. It reduces the incidence of vertebral, nonvertebral, and hip fractures. Prolia is also indicated as a treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer. It can also be used in men with osteoporosis at high risk for fracture or in men receiving androgen deprivation therapy for nonmetastatic prostate cancer to increase bone mass. Xgeva is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Bone Fractures Bone Loss Bone pain Spinal Cord Compression Bone destruction Giant cell tumor of the bone High risk of fracture Osteoporosis Refractory Hypercalcemia of malignancy Postmenopausal women Men with osteoporosis Men and women receiving daily glucocorticoids Men receiving androgen deprivation therapy for nonmetastatic prostate cancer Women receiving adjuvant aromatase inhibitor therapy for breast cancer Use in Cancer Denosumab is approved to treat: Giant cell tumor of the bone that cannot be removed by surgery. It is used in adults and in adolescents whose bones have finished growing. Hypercalcemia of malignancy that got worse after treatment with bisphosphonates. These uses are approved for the Xgeva brand of denosumab. Denosumab is approved to prevent: Broken bones and other bone problems are caused by multiple myeloma or by solid tumors that have metastasized (spread) to the bone. This use is approved for the Xgeva brand of denosumab. Denosumab is also approved to increase bone mass in adults who have a high risk of breaking bones. It is used in the following types of cancer: Breast cancer in women receiving aromatase inhibitor therapy. Prostate cancer in men receiving androgen deprivation therapy. These uses are approved for the Prolia brand of denosumab. Denosumab is also being studied in the treatment of other conditions and types of cancer. FDA-approved Indications Prevention of skeletal-related events (e.g., bone pain and fractures) secondary to multiple myeloma or bone metastases from solid tumors. Used in conjunction with treatments for primary malignancy[rx] Giant cell tumor of the bone. Indicated in adults and skeletally mature adolescents with an unresectable tumor or when surgical resection would likely cause severe morbidity.[rx] Hypercalcemia of malignancy. This drug is indicated when hypercalcemia is refractory to bisphosphonate therapy. Osteoporosis. Indicated as therapy for postmenopausal women with osteoporosis at high risk for fracture. Indications also include the treatment of men with osteoporosis at high risk of fracture. A high risk for fracture is defined as those with multiple risk factors for fracture, a known history of an osteoporotic fracture, or those who have failed prior osteoporosis treatment (e.g., bisphosphonates).[rx] Glucocorticoid-induced osteoporosis. Indicated for treatment in patients of both sexes at high risk for fracture who are initiating or continuing systemic glucocorticoids at a dose greater than or equal to 7.5 mg of prednisone daily for an expected duration of at least six months.[rx] Bone loss. Indicated for treating androgen deprivation-induced bone loss and aromatase inhibitor-induced bone loss. The goal of therapy is to increase bone mass in men with prostate cancer receiving androgen deprivation therapy. In women, the treatment goal is to increase bone mass when receiving aromatase inhibitor therapy for breast cancer.[rx] Contraindications Anemia or Blood clotting problems or Cancer or Dental disease, history of or Dental implants, history of or Dentures that do not fit well or Diabetes or Fractures, history of or Gum disease or Hypoparathyroidism (underactive parathyroid gland), history of or Kidney problems, are severe and may require dialysis or Malabsorption syndrome (trouble absorbing food), history of or Mouth surgery, history of or Parathyroid surgery, history of or Thyroid surgery, history of or Tooth extraction, history of—May cause side effects to become worse. Ear infection or Eczema (skin problem) or Endocarditis (heart infection) or Skin infections or Skin rashes or Stomach infection or Urinary tract infection—Use with caution. This may make these conditions worse. Hypocalcemia (low calcium in the blood)—Should not be given to patients with this condition. Dosage Strengths: 60 mg/mL; 120 mg/1.7 mL Osteoporosis 60 mg subcutaneously once every 6 months Patients should be adequately supplemented with calcium and vitamin D, suggested as calcium 1000 mg/day and at least 400 IU vitamin D per day Postmenopausal women at high risk for fracture include those with a history of osteoporotic fracture, or multiple risk factors for fracture; this drug reduces the incidence of vertebral, nonvertebral, and hip fractures. Men with osteoporosis are at high risk for fracture including those with a history of osteoporotic fracture or multiple risk factors for fracture. Men and women initiating or continuing systemic glucocorticoids at a prednisone equivalent dose of 7.5 mg or greater for 6 months or longer are at high risk of fracture, especially with a history of osteoporotic fracture or multiple risk factors for fracture. Men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer have shown a reduced incidence of vertebral fractures with this drug. Giant Cell Tumor of Bone First Month: 120 mg subcutaneously on day 1, day 8, and day 15 Maintenance dose: 120 mg subcutaneously every 4 week Calcium and vitamin D should be administered to treat or prevent hypocalcemia. For the treatment of patients with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity Osteolytic Bone Metastases of Solid Tumors 120 mg subcutaneously every 4 weeks Calcium and vitamin D should be administered to treat or prevent hypocalcemia. For the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors Hypercalcemia of Malignancy First Month: 120 mg subcutaneously on day 1, day 8, and day 15 Maintenance dose: 120 mg subcutaneously every 4 weeks For the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. Pediatric Dose for Giant Cell Tumor of Bone 13 years or older and having reached skeletal maturity: First Month: 120 mg subcutaneously on day 1, day 8, and day 15 Maintenance dose: 120 mg subcutaneously every 4 weeks Calcium and vitamin D should be administered to treat or prevent hypocalcemia. In clinical trials, skeletal maturity was defined by at least 1 mature long bone (e.g., closed epiphyseal growth plate of the humerus) and a body weight of 45 kg or more. For the treatment of skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. Administration advice: For subcutaneous administration only; do not administer IV, IM, or intradermally Subcutaneous administration should be in the upper arm, upper thigh, or abdomen This drug should be administered by a healthcare professional Patients should receive 1 dose subcutaneously every 6 months Patients should be receiving calcium 1000 mg/day and at least 400 IU vitamin D daily Individuals sensitive to latex should not handle the gray needle cap as it contains dry natural rubber (a derivative of latex) Missed dose: Administer as soon as convenient, thereafter, schedule injections 6 months from the date of the last injection Side Effects The Most Common red, dry, or itchy skin oozing or crusty blisters on the skin peeling skin back pain pain in your arms swelling of arms or legs muscle or joint pain nausea diarrhea constipation abdominal pain headache muscle stiffness, twitching, cramps, or spasms numbness or tingling in your fingers, toes, or around your mouth hives, rash, itching, difficulty breathing or swallowing, swelling of the face, eyes, throat, tongue or lips, fever or chills redness, tenderness, swelling or warmth of area of skin fever, cough, shortness of breath ear drainage or severe ear pain frequent or urgent need to urinate, burning feeling when you urinate severe abdominal pain painful or swollen gums, loosening of the teeth, numbness or heavy feeling in the jaw, poor healing of the jaw unusual bleeding or bruising nausea, vomiting, headache, and decreased alertness after stopping denosumab and for up to 1 year afterward More Common Back pain blistering, crusting, irritation, itching, or reddening of the skin bloody or cloudy urine cracked, dry, or scaly skin difficult, burning, or painful urination frequent urge to urinate muscle or bone pain pain in the arms or legs rash skin rash, encrusted, scaly, and oozing swelling Arm or jaw pain bloating or swelling of the face, arms, hands, lower legs, or feet body aches or pain chest pain or discomfort chest tightness or heaviness chills confusion congestion cough difficulty with breathing difficulty with moving dryness or soreness of the throat ear congestion fast or irregular heartbeat fever headache hoarseness joint pain loss of voice muscle cramps in the hands, arms, feet, legs, or face muscle stiffness numbness and tingling around the mouth, fingertips, hands, or feet pain in the lower back, bottom, upper leg, or hips painful blisters on the trunk of the body pale skin rapid weight gain runny or stuffy nose seizures sneezing stomach cramps swollen joints tender, swollen glands in the neck tremor trouble swallowing troubled breathing with exertion unusual bleeding or bruising unusual tiredness or weakness unusual weight gain or loss voice changes Rare Blood in the stool change in bowel habits clear or bloody discharge from the nipple constipation darkened urine difficulty with eating dimpling of the breast skin indigestion inverted nipple itching, pain, redness, swelling, tenderness, or warmth on the skin loss of appetite lower back or side pain lump in the breast or under the arm lump or swelling in the abdomen or stomach nausea pains in the stomach, side, or abdomen, possibly radiating to the back persistent crusting or scaling of the nipple raised, firm, and bright red patches of the skin on the arm or leg redness or swelling of the breast sore on the skin of the breast that does not heal stomach discomfort unexplained weight loss vomiting yellow eyes or skin Heavy feeling in the jaw loose teeth pain, swelling, or numbness in the mouth or jaw Drug interaction DRUG INTERACTION Abatacept The risk or severity of adverse effects can be increased when Denosumab is combined with Abatacept. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Denosumab. Adalimumab The risk or severity of adverse effects can be increased when Denosumab is combined with Adalimumab. Adenovirus The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Denosumab. Aducanumab The risk or severity of adverse effects can be increased when Denosumab is combined with Aducanumab. Aldesleukin The risk or severity of adverse effects can be increased when Denosumab is combined with Aldesleukin. Alefacept The risk or severity of adverse effects can be increased when Denosumab is combined with Alefacept. Alemtuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Alemtuzumab. Alirocumab The risk or severity of adverse effects can be increased when Denosumab is combined with Alirocumab. Allogeneic The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Denosumab. Altretamine The risk or severity of adverse effects can be increased when Denosumab is combined with Altretamine. Amivantamab The risk or severity of adverse effects can be increased when Denosumab is combined with Amivantamab. Amsacrine The risk or severity of adverse effects can be increased when Denosumab is combined with Amsacrine. Anakinra The risk or severity of adverse effects can be increased when Denosumab is combined with Anakinra. Anifrolumab The risk or severity of adverse effects can be increased when Denosumab is combined with Anifrolumab. Ansuvimab The risk or severity of adverse effects can be increased when Denosumab is combined with Ansuvimab. Anthrax immune The therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Denosumab. Anthrax vaccine The risk or severity of infection can be increased when Anthrax vaccine is combined with Denosumab. Antilymphocyte The risk or severity of adverse effects can be increased when Denosumab is combined with Antilymphocyte immunoglobulin (horse). Antithymocyte The risk or severity of adverse effects can be increased when Denosumab is combined with Antithymocyte immunoglobulin (rabbit). Apremilast The risk or severity of adverse effects can be increased when Denosumab is combined with Apremilast. Arsenic trioxide The risk or severity of adverse effects can be increased when Denosumab is combined with Arsenic trioxide. Asfotase alfa The risk or severity of adverse effects can be increased when Denosumab is combined with Asfotase alfa. COVID-19 Vaccine The therapeutic efficacy of AstraZeneca COVID-19 Vaccine can be decreased when used in combination with Denosumab. Atezolizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Atezolizumab. Atoltivimab The risk or severity of adverse effects can be increased when Denosumab is combined with Atoltivimab. Avelumab The risk or severity of adverse effects can be increased when Denosumab is combined with Avelumab. Azacitidine The risk or severity of adverse effects can be increased when Denosumab is combined with Azacitidine. Azathioprine The risk or severity of adverse effects can be increased when Denosumab is combined with Azathioprine. Bacillusantigen The risk or severity of infection can be increased when Bacillus calmette-guerin substrain connaught live antigen is combined with Denosumab. Bacillus live antigen The therapeutic efficacy of Bacillus calmette-guerin substrain russian BCG-I live antigen can be decreased when used in combination with Denosumab. Bacillus The risk or severity of infection can be increased when Bacillus calmette-guerin substrain tice live antigen is combined with Denosumab. Bamlanivimab The risk or severity of adverse effects can be increased when Denosumab is combined with Bamlanivimab. Baricitinib The risk or severity of adverse effects can be increased when Denosumab is combined with Baricitinib. Basiliximab The risk or severity of adverse effects can be increased when Denosumab is combined with Basiliximab. BCG vaccine The risk or severity of infection can be increased when BCG vaccine is combined with Denosumab. Bebtelovimab The risk or severity of adverse effects can be increased when Denosumab is combined with Bebtelovimab. Beclomethasone The risk or severity of adverse effects can be increased when Denosumab is combined with Beclomethasone dipropionate. Belantamab The risk or severity of adverse effects can be increased when Denosumab is combined with Belantamab mafodotin. Belatacept The risk or severity of adverse effects can be increased when Denosumab is combined with Belatacept. Belimumab The risk or severity of adverse effects can be increased when Denosumab is combined with Belimumab. Belinostat The risk or severity of adverse effects can be increased when Denosumab is combined with Belinostat. Belumosudil The risk or severity of adverse effects can be increased when Denosumab is combined with Belumosudil. Bendamustine The risk or severity of adverse effects can be increased when Denosumab is combined with Bendamustine. Benralizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Benralizumab. Besilesomab The risk or severity of adverse effects can be increased when Denosumab is combined with Besilesomab. Betamethasone The risk or severity of adverse effects can be increased when Denosumab is combined with Betamethasone. Bevacizumab The risk or severity of adverse effects can be increased when Bevacizumab is combined with Denosumab. Bexarotene The risk or severity of adverse effects can be increased when Denosumab is combined with Bexarotene. Bezlotoxumab The risk or severity of adverse effects can be increased when Denosumab is combined with Bezlotoxumab. Bimekizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Bimekizumab. Bleomycin The risk or severity of adverse effects can be increased when Denosumab is combined with Bleomycin. Blinatumomab The risk or severity of adverse effects can be increased when Denosumab is combined with Blinatumomab. Bordetella The therapeutic efficacy of Bordetella pertussis toxoid antigen (formaldehyde, glutaraldehyde inactivated) can be decreased when used in combination with Denosumab. Bortezomib The risk or severity of adverse effects can be increased when Denosumab is combined with Bortezomib. Bosutinib The risk or severity of adverse effects can be increased when Denosumab is combined with Bosutinib. Brentuximab vedotin The risk or severity of adverse effects can be increased when Denosumab is combined with Brentuximab vedotin. Brodalumab The risk or severity of adverse effects can be increased when Denosumab is combined with Brodalumab. Brolucizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Brolucizumab. Budesonide The risk or severity of adverse effects can be increased when Denosumab is combined with Budesonide. Burosumab The risk or severity of adverse effects can be increased when Denosumab is combined with Burosumab. Busulfan The risk or severity of adverse effects can be increased when Denosumab is combined with Busulfan. Cabazitaxel The risk or severity of adverse effects can be increased when Denosumab is combined with Cabazitaxel. Canakinumab The risk or severity of adverse effects can be increased when Denosumab is combined with Canakinumab. Capecitabine The risk or severity of adverse effects can be increased when Denosumab is combined with Capecitabine. Caplacizumab The risk or severity of adverse effects can be increased when Caplacizumab is combined with Denosumab. Capromab pendetide The risk or severity of adverse effects can be increased when Capromab pendetide is combined with Denosumab. Carbamazepine The risk or severity of adverse effects can be increased when Denosumab is combined with Carbamazepine. Carboplatin The risk or severity of adverse effects can be increased when Denosumab is combined with Carboplatin. Carfilzomib The risk or severity of adverse effects can be increased when Denosumab is combined with Carfilzomib. Carmustine The risk or severity of adverse effects can be increased when Denosumab is combined with Carmustine. Casirivimab The risk or severity of adverse effects can be increased when Denosumab is combined with Casirivimab. Catumaxomab The risk or severity of adverse effects can be increased when Catumaxomab is combined with Denosumab. Cemiplimab The risk or severity of adverse effects can be increased when Denosumab is combined with Cemiplimab. Certolizumab pegol The risk or severity of adverse effects can be increased when Denosumab is combined with Certolizumab pegol. Cetuximab The risk or severity of adverse effects can be increased when Cetuximab is combined with Denosumab. Chlorambucil The risk or severity of adverse effects can be increased when Denosumab is combined with Chlorambucil. Chloramphenicol The risk or severity of adverse effects can be increased when Denosumab is combined with Chloramphenicol. Ciclesonide The risk or severity of adverse effects can be increased when Denosumab is combined with Ciclesonide. Cilgavimab The risk or severity of adverse effects can be increased when Denosumab is combined with Cilgavimab. Cisplatin The risk or severity of adverse effects can be increased when Denosumab is combined with Cisplatin. Cladribine The risk or severity of adverse effects can be increased when Denosumab is combined with Cladribine. Clobetasol The risk or severity of adverse effects can be increased when Denosumab is combined with Clobetasol propionate. Clofarabine The risk or severity of adverse effects can be increased when Denosumab is combined with Clofarabine. Clostridium The therapeutic efficacy of Clostridium tetani toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Denosumab. C estrogens Conjugated estrogens may increase the thrombogenic activities of Denosumab. Corticotropin The risk or severity of adverse effects can be increased when Denosumab is combined with Corticotropin. Cortisone acetate The risk or severity of adverse effects can be increased when Denosumab is combined with Cortisone acetate. Corynebacterium The therapeutic efficacy of Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) can be decreased when used in combination with Denosumab. Cyclophosphamide The risk or severity of adverse effects can be increased when Denosumab is combined with Cyclophosphamide. Cyclosporine Denosumab may increase the immunosuppressive activities of Cyclosporine. Cytarabine The risk or severity of adverse effects can be increased when Denosumab is combined with Cytarabine. Dacarbazine The risk or severity of adverse effects can be increased when Denosumab is combined with Dacarbazine. Dactinomycin The risk or severity of adverse effects can be increased when Denosumab is combined with Dactinomycin. Daratumumab The risk or severity of adverse effects can be increased when Denosumab is combined with Daratumumab. Dasatinib The risk or severity of adverse effects can be increased when Denosumab is combined with Dasatinib. Daunorubicin The risk or severity of adverse effects can be increased when Denosumab is combined with Daunorubicin. Decitabine The risk or severity of adverse effects can be increased when Denosumab is combined with Decitabine. Deflazacort The risk or severity of adverse effects can be increased when Denosumab is combined with Deflazacort. Desoximetasone The risk or severity of adverse effects can be increased when Denosumab is combined with Desoximetasone. You Might Also Read Tramadol Indications, Contraindications, Warning Deucravacitinib The risk or severity of adverse effects can be increased when Denosumab is combined with Deucravacitinib. Dexamethasone The risk or severity of adverse effects can be increased when Denosumab is combined with Dexamethasone. Dexrazoxane The risk or severity of adverse effects can be increased when Denosumab is combined with Dexrazoxane. Dienestrol Dienestrol may increase the thrombogenic activities of Denosumab. Diethylstilbestrol Diethylstilbestrol may increase the thrombogenic activities of Denosumab. Difluocortolone The risk or severity of adverse effects can be increased when Denosumab is combined with Difluocortolone. Digoxin Immune The risk or severity of adverse effects can be increased when Digoxin Immune Fab (Ovine) is combined with Denosumab. Dimethyl fumarate The risk or severity of adverse effects can be increased when Denosumab is combined with Dimethyl fumarate. Dinutuximab The risk or severity of adverse effects can be increased when Denosumab is combined with Dinutuximab. Diroximel fumarate The risk or severity of adverse effects can be increased when Denosumab is combined with Diroximel fumarate. Docetaxel The risk or severity of adverse effects can be increased when Denosumab is combined with Docetaxel. Dostarlimab The risk or severity of adverse effects can be increased when Denosumab is combined with Dostarlimab. Doxorubicin The risk or severity of adverse effects can be increased when Denosumab is combined with Doxorubicin. Dulaglutide The risk or severity of adverse effects can be increased when Denosumab is combined with Dulaglutide. Dupilumab The risk or severity of adverse effects can be increased when Denosumab is combined with Dupilumab. Durvalumab The risk or severity of adverse effects can be increased when Denosumab is combined with Durvalumab. Ebola Zaire vaccine The therapeutic efficacy of Ebola Zaire vaccine (live, attenuated) can be decreased when used in combination with Denosumab. Eculizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Eculizumab. Efalizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Efalizumab. Eflapegrastim The risk or severity of adverse effects can be increased when Denosumab is combined with Eflapegrastim. Eftrenonacog alfa The risk or severity of adverse effects can be increased when Denosumab is combined with Eftrenonacog alfa. Elotuzumab The risk or severity of adverse effects can be increased when Elotuzumab is combined with Denosumab. Emapalumab The risk or severity of adverse effects can be increased when Denosumab is combined with Emapalumab. Emicizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Emicizumab. Epirubicin The risk or severity of adverse effects can be increased when Denosumab is combined with Epirubicin. Eptinezumab The risk or severity of adverse effects can be increased when Denosumab is combined with Eptinezumab. Erenumab The risk or severity of adverse effects can be increased when Denosumab is combined with Erenumab. Eribulin The risk or severity of adverse effects can be increased when Denosumab is combined with Eribulin. Esterified Esterified estrogens may increase the thrombogenic activities of Denosumab. Estetrol Estetrol may increase the thrombogenic activities of Denosumab. Estradiol Estradiol may increase the thrombogenic activities of Denosumab. Estradiol acetate Estradiol acetate may increase the thrombogenic activities of Denosumab. Estradiol benzoate Estradiol benzoate may increase the thrombogenic activities of Denosumab. Estradiol cypionate Estradiol cypionate may increase the thrombogenic activities of Denosumab. Estradiol valerate Estradiol valerate may increase the thrombogenic activities of Denosumab. Estramustine The risk or severity of adverse effects can be increased when Denosumab is combined with Estramustine. Estriol Estriol may increase the thrombogenic activities of Denosumab. Estrone Estrone may increase the thrombogenic activities of Denosumab. Estrone sulfate Estrone sulfate may increase the thrombogenic activities of Denosumab. Etanercept The risk or severity of adverse effects can be increased when Denosumab is combined with Etanercept. Ethinylestradiol Ethinylestradiol may increase the thrombogenic activities of Denosumab. Etoposide The risk or severity of adverse effects can be increased when Denosumab is combined with Etoposide. Everolimus The risk or severity of adverse effects can be increased when Denosumab is combined with Everolimus. Evolocumab The risk or severity of adverse effects can be increased when Denosumab is combined with Evolocumab. Famtozinameran The therapeutic efficacy of Famtozinameran can be decreased when used in combination with Denosumab. Fanolesomab The risk or severity of adverse effects can be increased when Denosumab is combined with Fanolesomab. Filgotinib The risk or severity of adverse effects can be increased when Denosumab is combined with Filgotinib. Fingolimod The risk or severity of adverse effects can be increased when Denosumab is combined with Fingolimod. Floxuridine The risk or severity of adverse effects can be increased when Denosumab is combined with Floxuridine. Flucytosine The risk or severity of adverse effects can be increased when Denosumab is combined with Flucytosine. Fludarabine The risk or severity of adverse effects can be increased when Denosumab is combined with Fludarabine. Fludrocortisone The risk or severity of adverse effects can be increased when Denosumab is combined with Fludrocortisone. Flumethasone The risk or severity of adverse effects can be increased when Denosumab is combined with Flumethasone. Flunisolide The risk or severity of adverse effects can be increased when Denosumab is combined with Flunisolide. Fluocinolone acetonide The risk or severity of adverse effects can be increased when Denosumab is combined with Fluocinolone acetonide. Fluocinonide The risk or severity of adverse effects can be increased when Denosumab is combined with Fluocinonide. Fluocortolone The risk or severity of adverse effects can be increased when Denosumab is combined with Fluocortolone. Fluorometholone The risk or severity of adverse effects can be increased when Denosumab is combined with Fluorometholone. Fluorouracil The risk or severity of adverse effects can be increased when Denosumab is combined with Fluorouracil. Fluprednisolone The risk or severity of adverse effects can be increased when Denosumab is combined with Fluprednisolone. Fluticasone The risk or severity of adverse effects can be increased when Denosumab is combined with Fluticasone. Fluticasone furoate The risk or severity of adverse effects can be increased when Denosumab is combined with Fluticasone furoate. Fluticasone The risk or severity of adverse effects can be increased when Denosumab is combined with Fluticasone propionate. Fremanezumab The risk or severity of adverse effects can be increased when Denosumab is combined with Fremanezumab. Galcanezumab The risk or severity of adverse effects can be increased when Denosumab is combined with Galcanezumab. Gallium nitrate The risk or severity of adverse effects can be increased when Denosumab is combined with Gallium nitrate. Gemcitabine The risk or severity of adverse effects can be increased when Denosumab is combined with Gemcitabine. Gemtuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Gemtuzumab ozogamicin. Glatiramer The risk or severity of adverse effects can be increased when Denosumab is combined with Glatiramer. Golimumab The risk or severity of adverse effects can be increased when Denosumab is combined with Golimumab. Guselkumab The risk or severity of adverse effects can be increased when Denosumab is combined with Guselkumab. Haemophilus The therapeutic efficacy of Haemophilus influenzae type B strain 20752 capsular polysaccharide tetanus toxoid conjugate antigen can be decreased when used in combination with Denosumab. Hepatitis A Vaccine The therapeutic efficacy of Hepatitis A Vaccine can be decreased when used in combination with Denosumab. Hepatitis B The risk or severity of adverse effects can be increased when Hepatitis B immune globulin is combined with Denosumab. Hepatitis B Vaccine The therapeutic efficacy of Hepatitis B Vaccine (Recombinant) can be decreased when used in combination with Denosumab. Human antigen The risk or severity of infection can be increased when Human adenovirus e serotype 4 strain cl-68578 antigen is combined with Denosumab. cytomegalovirus The risk or severity of adverse effects can be increased when Denosumab is combined with Human cytomegalovirus immune globulin. immunoglobulin G The risk or severity of adverse effects can be increased when Human immunoglobulin G is combined with Denosumab. Human Rho The risk or severity of adverse effects can be increased when Denosumab is combined with Human Rho(D) immune globulin. Human varicella The risk or severity of adverse effects can be increased when Denosumab is combined with Human varicella-zoster immune globulin. Hydrocortisone The risk or severity of adverse effects can be increased when Denosumab is combined with Hydrocortisone acetate. Hydrocortisone The risk or severity of adverse effects can be increased when Denosumab is combined with Hydrocortisone butyrate. Hydrocortisone The risk or severity of adverse effects can be increased when Denosumab is combined with Hydrocortisone succinate. Hydroxychloroquine The risk or severity of adverse effects can be increased when Denosumab is combined with Hydroxychloroquine. Hydroxyurea The risk or severity of adverse effects can be increased when Denosumab is combined with Hydroxyurea. Ibalizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Ibalizumab. Ibritumomab The risk or severity of adverse effects can be increased when Denosumab is combined with Ibritumomab tiuxetan. Ibrutinib The risk or severity of adverse effects can be increased when Denosumab is combined with Ibrutinib. Idarubicin The risk or severity of adverse effects can be increased when Denosumab is combined with Idarubicin. Idarucizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Idarucizumab. Idelalisib The risk or severity of adverse effects can be increased when Denosumab is combined with Idelalisib. Ifosfamide The risk or severity of adverse effects can be increased when Denosumab is combined with Ifosfamide. Imatinib The risk or severity of adverse effects can be increased when Denosumab is combined with Imatinib. Imdevimab The risk or severity of adverse effects can be increased when Denosumab is combined with Imdevimab. Imlifidase The therapeutic efficacy of Denosumab can be decreased when used in combination with Imlifidase. Indomethacin The risk or severity of adverse effects can be increased when Denosumab is combined with Indomethacin. Inebilizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Inebilizumab. Infliximab The risk or severity of adverse effects can be increased when Denosumab is combined with Infliximab. You Might Also Read Phytoestrogen - Nutritional Value, Health Benefits, Recipes Lanadelumab The risk or severity of adverse effects can be increased when Denosumab is combined with Lanadelumab. Leflunomide The risk or severity of adverse effects can be increased when Denosumab is combined with Leflunomide. Lenalidomide The risk or severity of adverse effects can be increased when Denosumab is combined with Lenalidomide. Linezolid The risk or severity of adverse effects can be increased when Denosumab is combined with Linezolid. Lomustine The risk or severity of adverse effects can be increased when Denosumab is combined with Lomustine. Loncastuximab The risk or severity of adverse effects can be increased when Denosumab is combined with Loncastuximab tesirine. Lopinavir The serum concentration of Denosumab can be increased when it is combined with Lopinavir. Maftivimab The risk or severity of adverse effects can be increased when Denosumab is combined with Maftivimab. Magnesium The serum concentration of Magnesium can be decreased when it is combined with Denosumab. Margetuximab The risk or severity of adverse effects can be increased when Denosumab is combined with Margetuximab. Measles virus The therapeutic efficacy of Measles virus vaccine live attenuated can be decreased when used in combination with Denosumab. Mechlorethamine The risk or severity of adverse effects can be increased when Denosumab is combined with Mechlorethamine. Melphalan The risk or severity of adverse effects can be increased when Denosumab is combined with Melphalan. Meningococca The therapeutic efficacy of Meningococcal (groups A, C, Y and W-135) oligosaccharide diphtheria CRM197 conjugate vaccine can be decreased when used in combination with Denosumab. Mepolizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Mepolizumab. Meprednisone The risk or severity of adverse effects can be increased when Denosumab is combined with Meprednisone. Mercaptopurine The risk or severity of adverse effects can be increased when Denosumab is combined with Mercaptopurine. Mestranol Mestranol may increase the thrombogenic activities of Denosumab. Methimazole The risk or severity of adverse effects can be increased when Denosumab is combined with Methimazole. Methotrexate The risk or severity of adverse effects can be increased when Denosumab is combined with Methotrexate. Methylprednisolone The risk or severity of adverse effects can be increased when Denosumab is combined with Methylprednisolone. Mirvetuximab The risk or severity of adverse effects can be increased when Denosumab is combined with Mirvetuximab Soravtansine. Mitomycin The risk or severity of adverse effects can be increased when Denosumab is combined with Mitomycin. Mitoxantrone The risk or severity of adverse effects can be increased when Denosumab is combined with Mitoxantrone. Moderna COVID-19 The therapeutic efficacy of Moderna COVID-19 Vaccine can be decreased when used in combination with Denosumab. Modified vaccinia The therapeutic efficacy of Modified vaccinia ankara can be decreased when used in combination with Denosumab. Mogamulizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Mogamulizumab. Mometasone furoate The risk or severity of adverse effects can be increased when Denosumab is combined with Mometasone furoate. Monomethyl fumarate The risk or severity of adverse effects can be increased when Denosumab is combined with Monomethyl fumarate. Mosunetuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Mosunetuzumab. Mumps virus The therapeutic efficacy of Mumps virus strain B level jeryl lynn live antigen can be decreased when used in combination with Denosumab. Muromonab The risk or severity of adverse effects can be increased when Denosumab is combined with Muromonab. Mycophenolate The risk or severity of adverse effects can be increased when Denosumab is combined with Mycophenolate mofetil. Mycophenolic acid The risk or severity of adverse effects can be increased when Denosumab is combined with Mycophenolic acid. Natalizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Natalizumab. Necitumumab The risk or severity of adverse effects can be increased when Denosumab is combined with Necitumumab. Nelarabine The risk or severity of adverse effects can be increased when Denosumab is combined with Nelarabine. Nilotinib The risk or severity of adverse effects can be increased when Denosumab is combined with Nilotinib. Nivolumab The risk or severity of adverse effects can be increased when Denosumab is combined with Nivolumab. Nuvaxovid The therapeutic efficacy of Nuvaxovid can be decreased when used in combination with Denosumab. Obiltoxaximab The risk or severity of adverse effects can be increased when Obiltoxaximab is combined with Denosumab. Obinutuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Obinutuzumab. Ocrelizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Ocrelizumab. Odesivimab The risk or severity of adverse effects can be increased when Denosumab is combined with Odesivimab. Ofatumumab The risk or severity of adverse effects can be increased when Denosumab is combined with Ofatumumab. Olaparib The risk or severity of adverse effects can be increased when Denosumab is combined with Olaparib. Olaratumab The risk or severity of adverse effects can be increased when Olaratumab is combined with Denosumab. Omalizumab The risk or severity of adverse effects can be increased when Omalizumab is combined with Denosumab. Oxaliplatin The risk or severity of adverse effects can be increased when Denosumab is combined with Oxaliplatin. Ozanimod The risk or severity of adverse effects can be increased when Denosumab is combined with Ozanimod. Paclitaxel The risk or severity of adverse effects can be increased when Denosumab is combined with Paclitaxel. Palbociclib The risk or severity of adverse effects can be increased when Denosumab is combined with Palbociclib. Palivizumab The risk or severity of adverse effects can be increased when Palivizumab is combined with Denosumab. Panitumumab The risk or severity of adverse effects can be increased when Panitumumab is combined with Denosumab. Panobinostat The risk or severity of adverse effects can be increased when Denosumab is combined with Panobinostat. Pazopanib The risk or severity of adverse effects can be increased when Denosumab is combined with Pazopanib. Pegaspargase The risk or severity of adverse effects can be increased when Denosumab is combined with Pegaspargase. Pegcetacoplan The risk or severity of adverse effects can be increased when Denosumab is combined with Pegcetacoplan. Peginterferon alfa-2a The risk or severity of adverse effects can be increased when Denosumab is combined with Peginterferon alfa-2a. Peginterferon alfa-2b The risk or severity of adverse effects can be increased when Denosumab is combined with Peginterferon alfa-2b. Peginterferon beta-1a The risk or severity of adverse effects can be increased when Denosumab is combined with Peginterferon beta-1a. Pembrolizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Pembrolizumab. Pemetrexed The risk or severity of adverse effects can be increased when Denosumab is combined with Pemetrexed. Penicillamine The risk or severity of adverse effects can be increased when Denosumab is combined with Penicillamine. Pentostatin The risk or severity of adverse effects can be increased when Denosumab is combined with Pentostatin. Pertussis vaccine The therapeutic efficacy of Pertussis vaccine can be decreased when used in combination with Denosumab. Pertuzumab The risk or severity of adverse effects can be increased when Pertuzumab is combined with Denosumab. Phenylalanine The risk or severity of adverse effects can be increased when Denosumab is combined with Phenylalanine. Pimecrolimus The risk or severity of adverse effects can be increased when Pimecrolimus is combined with Denosumab. Pirfenidone The risk or severity of adverse effects can be increased when Denosumab is combined with Pirfenidone. Polatuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Polatuzumab vedotin. Polyestradiol Polyestradiol phosphate may increase the thrombogenic activities of Denosumab. Pomalidomide The risk or severity of adverse effects can be increased when Denosumab is combined with Pomalidomide. Ponatinib The risk or severity of adverse effects can be increased when Denosumab is combined with Ponatinib. Ponesimod The risk or severity of adverse effects can be increased when Denosumab is combined with Ponesimod. Pralatrexate The risk or severity of adverse effects can be increased when Denosumab is combined with Pralatrexate. Prednisolone The risk or severity of adverse effects can be increased when Denosumab is combined with Prednisolone. Prednisone The risk or severity of adverse effects can be increased when Denosumab is combined with Prednisone. Procarbazine The risk or severity of adverse effects can be increased when Denosumab is combined with Procarbazine. Propylthiouracil The risk or severity of adverse effects can be increased when Denosumab is combined with Propylthiouracil. Quinestrol Quinestrol may increase the thrombogenic activities of Denosumab. Rabies immune The therapeutic efficacy of Rabies immune globulin, human can be decreased when used in combination with Denosumab. Rabies antigen, A The therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Denosumab. Rabies antigen, The therapeutic efficacy of Rabies virus inactivated antigen, B can be decreased when used in combination with Denosumab. Raltitrexed The risk or severity of adverse effects can be increased when Denosumab is combined with Raltitrexed. Ramucirumab The risk or severity of adverse effects can be increased when Ramucirumab is combined with Denosumab. Ranibizumab The risk or severity of adverse effects can be increased when Ranibizumab is combined with Denosumab. Ravulizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Ravulizumab. Raxibacumab The risk or severity of adverse effects can be increased when Denosumab is combined with Raxibacumab. Reslizumab The risk or severity of adverse effects can be increased when Reslizumab is combined with Denosumab. Rilonacept The risk or severity of adverse effects can be increased when Denosumab is combined with Rilonacept. Risankizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Risankizumab. Rituximab The risk or severity of adverse effects can be increased when Denosumab is combined with Rituximab. Roflumilast Roflumilast may increase the immunosuppressive activities of Denosumab. Romosozumab The risk or severity of adverse effects can be increased when Denosumab is combined with Romosozumab. Ropeginterferon The risk or severity of adverse effects can be increased when Denosumab is combined with Ropeginterferon alfa-2b. Rotavirus vaccine The therapeutic efficacy of Rotavirus vaccine can be decreased when used in combination with Denosumab. Rubella virus vaccine The risk or severity of infection can be increased when Rubella virus vaccine is combined with Denosumab. Ruxolitinib The risk or severity of adverse effects can be increased when Denosumab is combined with Ruxolitinib. Sacituzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Sacituzumab govitecan. Sarilumab The risk or severity of adverse effects can be increased when Denosumab is combined with Sarilumab. Satralizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Satralizumab. Secukinumab The risk or severity of adverse effects can be increased when Denosumab is combined with Secukinumab. Siltuximab The risk or severity of adverse effects can be increased when Denosumab is combined with Siltuximab. Siponimod The risk or severity of adverse effects can be increased when Denosumab is combined with Siponimod. Sipuleucel-T The therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Denosumab. Sirolimus The risk or severity of adverse effects can be increased when Denosumab is combined with Sirolimus. Smallpox The therapeutic efficacy of Smallpox (Vaccinia) Vaccine, Live can be decreased when used in combination with Denosumab. Sorafenib The risk or severity of adverse effects can be increased when Denosumab is combined with Sorafenib. Sotrovimab The risk or severity of adverse effects can be increased when Denosumab is combined with Sotrovimab. Spesolimab The risk or severity of adverse effects can be increased when Denosumab is combined with Spesolimab. Streptozocin The risk or severity of adverse effects can be increased when Denosumab is combined with Streptozocin. Sulesomab The risk or severity of adverse effects can be increased when Denosumab is combined with Sulesomab. Sulfamethoxazole The risk or severity of myelosuppression can be increased when Sulfamethoxazole is combined with Denosumab. Sulfasalazine The risk or severity of adverse effects can be increased when Denosumab is combined with Sulfasalazine. Sunitinib The risk or severity of adverse effects can be increased when Denosumab is combined with Sunitinib. Sutimlimab The risk or severity of adverse effects can be increased when Denosumab is combined with Sutimlimab. S Estrogens, A Synthetic Conjugated Estrogens, A may increase the thrombogenic activities of Denosumab. S Estrogens, B Synthetic Conjugated Estrogens, B may increase the thrombogenic activities of Denosumab. Tacrolimus The risk or severity of adverse effects can be increased when Denosumab is combined with Tacrolimus. Tafasitamab The risk or severity of adverse effects can be increased when Denosumab is combined with Tafasitamab. Temozolomide The risk or severity of adverse effects can be increased when Denosumab is combined with Temozolomide. Temsirolimus The risk or severity of adverse effects can be increased when Denosumab is combined with Temsirolimus. Teniposide The risk or severity of adverse effects can be increased when Denosumab is combined with Teniposide. Teplizumab The risk or severity of adverse effects can be increased when Teplizumab is combined with Denosumab. Teprotumumab The risk or severity of adverse effects can be increased when Denosumab is combined with Teprotumumab. Teriflunomide The risk or severity of adverse effects can be increased when Denosumab is combined with Teriflunomide. Tetanus immune The risk or severity of adverse effects can be increased when Denosumab is combined with Tetanus immune globulin, human. Tezepelumab The risk or severity of adverse effects can be increased when Denosumab is combined with Tezepelumab. Thalidomide The risk or severity of adverse effects can be increased when Denosumab is combined with Thalidomide. Thiotepa The risk or severity of adverse effects can be increased when Denosumab is combined with Thiotepa. Tibolone Tibolone may increase the thrombogenic activities of Denosumab. Tick-borne encephalitis The therapeutic efficacy of Tick-borne encephalitis vaccine (whole virus, inactivated) can be decreased when used in combination with Denosumab. Tildrakizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Tildrakizumab. Tioguanine The risk or severity of adverse effects can be increased when Denosumab is combined with Tioguanine. Tisotumab vedotin The risk or severity of adverse effects can be increased when Denosumab is combined with Tisotumab vedotin. Tixagevimab The risk or severity of adverse effects can be increased when Denosumab is combined with Tixagevimab. Tixocortol The risk or severity of adverse effects can be increased when Denosumab is combined with Tixocortol. Tocilizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Tocilizumab. Tofacitinib The risk or severity of adverse effects can be increased when Denosumab is combined with Tofacitinib. Topotecan The risk or severity of adverse effects can be increased when Denosumab is combined with Topotecan. Tositumomab The risk or severity of adverse effects can be increased when Denosumab is combined with Tositumomab. Trabectedin The risk or severity of adverse effects can be increased when Denosumab is combined with Trabectedin. Tralokinumab The risk or severity of adverse effects can be increased when Denosumab is combined with Tralokinumab. Trastuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Trastuzumab. Trastuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Trastuzumab deruxtecan. Trastuzumab The risk or severity of adverse effects can be increased when Denosumab is combined with Trastuzumab emtansine. Tremelimumab The risk or severity of adverse effects can be increased when Denosumab is combined with Tremelimumab. Tretinoin The risk or severity of adverse effects can be increased when Denosumab is combined with Tretinoin. Triamcinolone The risk or severity of adverse effects can be increased when Denosumab is combined with Triamcinolone. Trifluridine The risk or severity of adverse effects can be increased when Denosumab is combined with Trifluridine. Trilostane The risk or severity of adverse effects can be increased when Denosumab is combined with Trilostane. Typhoid vaccine The therapeutic efficacy of Typhoid vaccine can be decreased when used in combination with Denosumab. Typhoid Vaccine The risk or severity of infection can be increased when Typhoid Vaccine Live is combined with Denosumab. Typhoid Vi The therapeutic efficacy of Typhoid Vi polysaccharide vaccine can be decreased when used in combination with Denosumab. Upadacitinib The risk or severity of adverse effects can be increased when Denosumab is combined with Upadacitinib. Ustekinumab The risk or severity of adverse effects can be increased when Ustekinumab is combined with Denosumab. Varicella zoster vaccine The risk or severity of infection can be increased when Varicella zoster vaccine (live/attenuated) is combined with Denosumab. Varicella zoster vaccine The therapeutic efficacy of Varicella zoster vaccine (recombinant) can be decreased when used in combination with Denosumab. Vedolizumab The risk or severity of adverse effects can be increased when Denosumab is combined with Vedolizumab. Vibrio cholerae The therapeutic efficacy of Vibrio cholerae CVD 103-HgR strain live antigen can be decreased when used in combination with Denosumab. Vilanterol The risk or severity of adverse effects can be increased when Denosumab is combined with Vilanterol. Vinblastine The risk or severity of adverse effects can be increased when Denosumab is combined with Vinblastine. Vincristine The risk or severity of adverse effects can be increased when Denosumab is combined with Vincristine. Vindesine The risk or severity of adverse effects can be increased when Denosumab is combined with Vindesine. Vinorelbine The risk or severity of adverse effects can be increased when Denosumab is combined with Vinorelbine. Voclosporin The risk or severity of adverse effects can be increased when Denosumab is combined with Voclosporin. Vorinostat The risk or severity of adverse effects can be increased when Denosumab is combined with Vorinostat. Yellow fever vaccine The risk or severity of infection can be increased when Yellow fever vaccine is combined with Denosumab. Zidovudine The risk or severity of adverse effects can be increased when Denosumab is combined with Zidovudine. You Might Also Read Hydrocortisone - Uses, Side Effects, InteractionsPregnancy and Lactation FDA Pregnancy Category C Pregnancy There are no adequate and well-controlled studies of Prolia in pregnant women. In genetically engineered mice in which RANK ligand (RANKL) was turned off by gene removal (a “knockout mouse”), the absence of RANKL (the target of denosumab) caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice also showed altered maturation of the maternal mammary gland, leading to impaired lactation postpartum. Prolia should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Women who become pregnant during Prolia treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. In an embryofetal developmental study, cynomolgus monkeys received subcutaneous denosumab weekly during organogenesis at doses up to 13-fold higher than the recommended human dose of 60 mg administered once every 6 months based on body weight (mg/kg). No evidence of maternal toxicity or fetal harm was observed. However, this study only assessed fetal toxicity during a period equivalent to the first trimester, and fetal lymph nodes were not examined. Monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses, with the largest amount transferred during the third trimester. Potential adverse developmental effects resulting from exposures during the second and third trimesters have not been assessed in animals Lactation It is not known whether Prolia is excreted into human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Prolia, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. Maternal exposure to Prolia during pregnancy may impair mammary gland development and lactation based on animal studies in pregnant mice lacking the RANK/RANKL signaling pathway that have shown altered maturation of the maternal mammary gland, leading to impaired lactation postpartum How should this medicine be used? Denosumab injection comes as a solution (liquid) to be injected subcutaneously (under the skin) in your upper arm, upper thigh, or stomach area. It is usually injected by a doctor or nurse in a medical office or clinic. Denosumab injection (Prolia) is usually given once every 6 months. When denosumab injection (Xgeva) is used to reduce the risk of fractures from multiple myeloma, or cancer that has spread to the bones, it is usually given once every 4 weeks. When denosumab injection (Xgeva) is used to treat giant cell tumor of bone, or high calcium levels caused by cancer, it is usually given every 7 days for the first three doses (on day 1, day 8, and day 15) and then once every 4 weeks starting 2 weeks after the first three doses. Your doctor will tell you to take supplements of calcium and vitamin D while you are being treated with denosumab injection. Take these supplements exactly as directed. When denosumab injection (Prolia) is used to treat osteoporosis or bone loss, your doctor or pharmacist will give you the manufacturer’s patient information sheet (Medication Guide) when you begin treatment with denosumab injection and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer’s website to obtain the Medication Guide. What special precautions should I follow? Before receiving a denosumab injection, tell your doctor and pharmacist if you are allergic to denosumab (Prolia, Xgeva), any other medications, latex, or any of the ingredients in denosumab injection. Ask your pharmacist or check the Medication Guide for a list of the ingredients. you should know that denosumab injection is available under the brand names Prolia and Xgeva. You should not receive more than one product containing denosumab at the same time. Be sure to tell your doctor if you are being treated with either of these medications. tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: angiogenesis inhibitors such as axitinib (Inlyta), bevacizumab (Avastin), everolimus (Afinitor, Zortress), pazopanib (Votrient), sorafenib (Nexavar), or sunitinib (Sutent); bisphosphonates such as alendronate (Binosto, Fosamax), etidronate, ibandronate (Boniva), pamidronate, risedronate (Actonel, Atelvia), zoledronic acid (Reclast); cancer chemotherapy medications; medications that suppress the immune system such as azathioprine (Azasan, Imuran), cyclosporine (Gengraf, Neoral, Sandimmune), methotrexate (Otrexup, Rasuvo, Trexall, Xatmep), sirolimus (Rapamune), and tacrolimus (Astagraf XL, Envarsus, Prograf); steroids such as dexamethasone, methylprednisolone (A-Methapred, Depo-Medrol, Medrol, Solu-Medrol), and prednisone (Rayos); or medications used to lower your calcium levels, such as cinacalcet (Sensipar). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. tell your doctor if you have or have ever had a low level of calcium in your blood. Your doctor will probably check the level of calcium in your blood before you begin treatment and will probably tell you not to receive denosumab injection if the level is too low. tell your doctor if you are receiving dialysis treatments or if you have or have ever had anemia (a condition in which the red blood cells do not bring enough oxygen to all the parts of the body); cancer; any type of infection, especially in your mouth; problems with your mouth, teeth, gums, or dentures; dental or oral surgery (teeth removed, dental implants); any condition that stops your blood from clotting normally; any condition that decreases the functioning of your immune system; surgery on your thyroid gland or parathyroid gland (a small gland in the neck); surgery to remove part of your small intestine; problems with your stomach or intestine that make it difficult for your body to absorb nutrients; polymyalgia rheumatic (disorder that causes muscle pain and weakness); diabetes, or parathyroid or kidney disease. tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. You will need to have a negative pregnancy test before starting treatment with a denosumab injection. You should not become pregnant while you are receiving a denosumab injection. You should use a reliable method of birth control to prevent pregnancy while you are receiving a denosumab injection and for at least 5 months after your final treatment. If you become pregnant while receiving a denosumab injection, or within 5 months of your treatment, call your doctor immediately. Denosumab may harm the fetus. you should know that denosumab injection may cause osteonecrosis of the jaw (ONJ, a serious condition of the jaw bone), especially if you have dental surgery or treatment while you are receiving this medication. A dentist should examine your teeth and perform any needed treatments, including cleaning or fixing ill-fitted dentures, before you start to receive a denosumab injection. Be sure to brush your teeth and clean your mouth properly while you are receiving a denosumab injection. Talk to your doctor before having any dental treatments while you are receiving this medication. References https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125320s5s6lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/125320s205lbl.pdf https://www.fda.gov/drugs/drug-safety-and-availability/fda-investigating-risk-severe-hypocalcemia-patients-dialysis-receiving-osteoporosis-medicine-prolia https://www.drugs.com/mtm/denosumab.html https://medlineplus.gov/druginfo/meds/a610023.html https://pubchem.ncbi.nlm.nih.gov/substance/178103468 https://go.drugbank.com/drugs/DB06643 https://www.mayoclinic.org/drugs-supplements/denosumab-subcutaneous-route/side-effects/drg-20074315 https://www.ncbi.nlm.nih.gov/books/NBK535388/ Show More