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Drug overview for XGEVA (denosumab):
Generic name: DENOSUMAB (den-OH-sue-mab)
Drug class: Hypercalcemia Agents
Therapeutic class: Endocrine
Denosumab, a fully human monoclonal antibody that is specific for the receptor activator of nuclear factor kappa-B ligand (RANKL) and acts as a RANKL inhibitor, is a bone resorption inhibitor.
Denosumab (Prolia(R)) is used in the treatment of osteoporosis in postmenopausal women and men at high risk for fracture, in the treatment of glucocorticoid-induced osteoporosis in patients at high risk for fracture, and to increase bone mass in patients at high risk for fracture who are receiving androgen deprivation or aromatase inhibitor therapy. Denosumab (Xgeva(R)) is used to prevent skeletal-related events (SREs) in patients with multiple myeloma or with bone metastases from solid tumors. Denosumab (Xgeva(R)) also is used for the treatment of giant cell tumor of bone and for the treatment of bisphosphonate-refractory hypercalcemia associated with malignant neoplasms; denosumab has been designated an orphan drug by FDA for these uses.
Generic name: DENOSUMAB (den-OH-sue-mab)
Drug class: Hypercalcemia Agents
Therapeutic class: Endocrine
Denosumab, a fully human monoclonal antibody that is specific for the receptor activator of nuclear factor kappa-B ligand (RANKL) and acts as a RANKL inhibitor, is a bone resorption inhibitor.
Denosumab (Prolia(R)) is used in the treatment of osteoporosis in postmenopausal women and men at high risk for fracture, in the treatment of glucocorticoid-induced osteoporosis in patients at high risk for fracture, and to increase bone mass in patients at high risk for fracture who are receiving androgen deprivation or aromatase inhibitor therapy. Denosumab (Xgeva(R)) is used to prevent skeletal-related events (SREs) in patients with multiple myeloma or with bone metastases from solid tumors. Denosumab (Xgeva(R)) also is used for the treatment of giant cell tumor of bone and for the treatment of bisphosphonate-refractory hypercalcemia associated with malignant neoplasms; denosumab has been designated an orphan drug by FDA for these uses.
DRUG IMAGES
XGEVA 120 MG/1.7 ML VIAL
The following indications for XGEVA (denosumab) have been approved by the FDA:
Indications:
Giant cell tumor of bone
Humoral hypercalcemia of malignancy
Prevention of skeletal related events associated with bone metastases from solid tumor
Prevention of skeletal related events in multiple myeloma
Professional Synonyms:
Hypercalcemia associated with cancer
Hypercalcemia associated with malignancy
Hypercalcemia of malignancy
Malignant hypercalcemia
Indications:
Giant cell tumor of bone
Humoral hypercalcemia of malignancy
Prevention of skeletal related events associated with bone metastases from solid tumor
Prevention of skeletal related events in multiple myeloma
Professional Synonyms:
Hypercalcemia associated with cancer
Hypercalcemia associated with malignancy
Hypercalcemia of malignancy
Malignant hypercalcemia
The following dosing information is available for XGEVA (denosumab):
Correct preexisting hypocalcemia prior to initiation of denosumab treatment. Supplementation with calcium and vitamin D may be required during denosumab treatment. All patients treated with denosumab for osteoporosis or bone loss indications should receive 1000 mg of calcium daily and >=400 IU of vitamin D daily.
Administer denosumab by subcutaneous injection using single-dose prefilled syringes (Prolia(R)) or single-use vials (Xgeva(R)). Subcutaneous injections of denosumab should be made into the upper arm, upper thigh, or abdomen. Do not administer IV, or by IM or intradermal injection.
For osteoporosis or bone loss indications, denosumab is available as a preservative-free 60-mg/mL solution (Prolia(R)) in single-use prefilled syringes for administration by a health-care professional. For cancer-related indications, denosumab is available as a preservative-free 120-mg/1.7-mL solution (Xgeva(R)) in single-use vials.
Store denosumab at 2-8degreesC in the original container; do not freeze. After removal from refrigeration, do not expose to temperatures exceeding 25degreesC, or to direct light or heat. Use within 14 days after removal from refrigeration and discard if not used within 14 days.
Do not use after the expiration date stated on the label. Do not shake denosumab vigorously. Prior to administration, denosumab may be warmed to room temperature by allowing the drug to stand in the original container at room temperature (<=25degreesC) for approximately 15-30 minutes; do not use other methods to warm the drug.
Denosumab should appear clear, colorless to pale yellow, and may contain trace amounts of translucent to white proteinaceous particles; do not use the solution if it is discolored, cloudy, or contains many particles or foreign matter. When denosumab is administered using the prefilled syringe, remove the gray needle cap and administer all of the solution by subcutaneous injection. Do not place the gray needle cap back on the needle.
After the injection is complete, activate the green needle guard to prevent accidental needle sticks. To activate the needle guard, hold the clear plastic finger grip with one hand, with the needle pointed away from the body; with the other hand, grasp the green safety guard at its base and gently slide it toward the needle until the safety guard locks securely in place. The needle guard will render the unit useless if activated prior to administering the injection.
When denosumab is administered using the single-use vial, use a 27-gauge needle to withdraw and inject the entire contents of the vial subcutaneously. Do not re-enter the vial, and discard any remaining solution along with the vial.
For osteoporosis or bone loss indications, denosumab is available as a preservative-free 60-mg/mL solution (Prolia(R)) in single-use prefilled syringes for administration by a health-care professional. For cancer-related indications, denosumab is available as a preservative-free 120-mg/1.7-mL solution (Xgeva(R)) in single-use vials.
Store denosumab at 2-8degreesC in the original container; do not freeze. After removal from refrigeration, do not expose to temperatures exceeding 25degreesC, or to direct light or heat. Use within 14 days after removal from refrigeration and discard if not used within 14 days.
Do not use after the expiration date stated on the label. Do not shake denosumab vigorously. Prior to administration, denosumab may be warmed to room temperature by allowing the drug to stand in the original container at room temperature (<=25degreesC) for approximately 15-30 minutes; do not use other methods to warm the drug.
Denosumab should appear clear, colorless to pale yellow, and may contain trace amounts of translucent to white proteinaceous particles; do not use the solution if it is discolored, cloudy, or contains many particles or foreign matter. When denosumab is administered using the prefilled syringe, remove the gray needle cap and administer all of the solution by subcutaneous injection. Do not place the gray needle cap back on the needle.
After the injection is complete, activate the green needle guard to prevent accidental needle sticks. To activate the needle guard, hold the clear plastic finger grip with one hand, with the needle pointed away from the body; with the other hand, grasp the green safety guard at its base and gently slide it toward the needle until the safety guard locks securely in place. The needle guard will render the unit useless if activated prior to administering the injection.
When denosumab is administered using the single-use vial, use a 27-gauge needle to withdraw and inject the entire contents of the vial subcutaneously. Do not re-enter the vial, and discard any remaining solution along with the vial.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| XGEVA 120 MG/1.7 ML VIAL | Maintenance | Adults inject 1.7 milliliters (120 mg) by subcutaneous route every 4 weeks |
No generic dosing information available.
The following drug interaction information is available for XGEVA (denosumab):
There are 0 contraindications.
There are 2 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3) |
VYVGART, VYVGART HYTRULO |
| IgG Antibodies and Derivatives/Nipocalimab-aahu SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3) |
IMAAVY |
There are 1 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3) |
RYSTIGGO |
The following contraindication information is available for XGEVA (denosumab):
Drug contraindication overview.
*Hypocalcemia (correct preexisting hypocalcemia prior to initiating denosumab). *History of clinically important hypersensitivity (e.g., systemic hypersensitivity) to denosumab or any component in the formulation. *The preparation of denosumab labeled for use in the treatment of osteoporosis or bone loss (Prolia(R)) is contraindicated in pregnant women.
*Hypocalcemia (correct preexisting hypocalcemia prior to initiating denosumab). *History of clinically important hypersensitivity (e.g., systemic hypersensitivity) to denosumab or any component in the formulation. *The preparation of denosumab labeled for use in the treatment of osteoporosis or bone loss (Prolia(R)) is contraindicated in pregnant women.
There are 0 contraindications.
There are 6 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
| Congenital long QT syndrome |
| Hypocalcemia |
| Pregnancy |
| Severe infection |
There are 6 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Diabetes mellitus |
| Hypoparathyroidism |
| Invasive dental procedure |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
| Periodontitis |
| Thyroid surgery |
The following adverse reaction information is available for XGEVA (denosumab):
Adverse reaction overview.
Adverse effects reported in clinical trials in >5% of patients receiving denosumab for the treatment of osteoporosis and reported more frequently with the drug than with placebo include back pain, extremity pain, musculoskeletal pain, hypercholesterolemia, and cystitis (in postmenopausal women) or back pain, arthralgia, and nasopharyngitis (in men). Adverse effects reported in clinical trials in >3% of patients receiving denosumab for the treatment of glucocorticoid-induced osteoporosis and reported more frequently with denosumab than with risedronate include back pain, hypertension, bronchitis, and headache. In clinical trials in patients receiving androgen deprivation or aromatase inhibitor therapy, adverse effects reported in >=10% of patients receiving denosumab for treatment of bone loss and reported more frequently with the drug than with placebo include arthralgia and back pain.
Musculoskeletal and extremity pain have also been reported. Adverse effects reported in clinical trials in >=25% of patients with bone metastases from solid tumors receiving denosumab include fatigue/asthenia, hypophosphatemia, and nausea. Adverse effects reported in clinical trials in >=10% of patients with multiple myeloma receiving denosumab include diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory infection, rash, and headache.
Adverse effects reported in clinical trials in >=10% of patients receiving denosumab for treatment of giant cell tumor of bone include arthralgia, headache, nausea, back pain, fatigue, and extremity pain. Adverse effects reported in clinical trials in >20% of patients receiving denosumab for bisphosphonate-refractory hypercalcemia of malignancy include nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.
Adverse effects reported in clinical trials in >5% of patients receiving denosumab for the treatment of osteoporosis and reported more frequently with the drug than with placebo include back pain, extremity pain, musculoskeletal pain, hypercholesterolemia, and cystitis (in postmenopausal women) or back pain, arthralgia, and nasopharyngitis (in men). Adverse effects reported in clinical trials in >3% of patients receiving denosumab for the treatment of glucocorticoid-induced osteoporosis and reported more frequently with denosumab than with risedronate include back pain, hypertension, bronchitis, and headache. In clinical trials in patients receiving androgen deprivation or aromatase inhibitor therapy, adverse effects reported in >=10% of patients receiving denosumab for treatment of bone loss and reported more frequently with the drug than with placebo include arthralgia and back pain.
Musculoskeletal and extremity pain have also been reported. Adverse effects reported in clinical trials in >=25% of patients with bone metastases from solid tumors receiving denosumab include fatigue/asthenia, hypophosphatemia, and nausea. Adverse effects reported in clinical trials in >=10% of patients with multiple myeloma receiving denosumab include diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory infection, rash, and headache.
Adverse effects reported in clinical trials in >=10% of patients receiving denosumab for treatment of giant cell tumor of bone include arthralgia, headache, nausea, back pain, fatigue, and extremity pain. Adverse effects reported in clinical trials in >20% of patients receiving denosumab for bisphosphonate-refractory hypercalcemia of malignancy include nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.
There are 29 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Dyspnea |
Hypertension Hypokalemia Hypomagnesemia |
| Rare/Very Rare |
|---|
|
Anaphylaxis Angina Aseptic necrosis of jaw bone Atypical femoral fracture Cataracts Cellulitis Cholesteatoma of external ear Dental abscess DRESS syndrome Endocarditis Erysipelas Hypercalcemia Hyperparathyroidism Hypersensitivity angiitis Hypersensitivity drug reaction Hypocalcemia Hypotension Infection Malignancy Osteonecrosis of external auditory canal Pancreatitis Polymyalgia rheumatica Severe infection Throat constriction Vasculitis |
There are 49 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Back pain Fatigue General weakness Hypophosphatemia Musculoskeletal pain Nausea |
Allergic dermatitis Anemia Anorexia Arthralgia Bone pain Bronchitis Constipation Cough Cystitis Diarrhea Dizziness Dyspepsia Eczema Flatulence Gastroesophageal reflux disease Headache disorder Hypercholesterolemia Infection of ear Insomnia Pain in extremities Peripheral edema Pharyngitis Pruritus of skin Sciatica Skin inflammation Skin rash Spinal osteoarthritis Upper abdominal pain Upper respiratory infection Urinary tract infection Vertigo Vomiting |
| Rare/Very Rare |
|---|
|
Alopecia Ear itching Earache Erythema Facial edema Hearing loss Herpes zoster Impacted cerumen Lichenoid dermatitis drug eruption Tinnitus Urticaria |
The following precautions are available for XGEVA (denosumab):
Safety and efficacy of denosumab (Xgeva(R)) have been established for treatment of giant cell tumor of bone in skeletally mature adolescents (12-16 years of age). Safety and efficacy of denosumab have not been established for any other indication in pediatric patients. Safety and efficacy of denosumab (Prolia(R)) have not been established in pediatric patients.
Cases of hypercalcemia (some requiring hospitalization and/or complicated by acute kidney injury) have been reported in clinical trials of pediatric patients with osteogenesis imperfecta treated with denosumab. In pediatric patients <4 years of age, denosumab may adversely affect long-bone growth and dentition based on evidence from animal studies. Clinically important hypercalcemia has been reported following discontinuance of denosumab therapy in pediatric patients with growing skeletons who received the drug for treatment of giant cell tumor of bone or for other off-label uses. Based on animal data, denosumab potentially may impair bone growth in children with open growth plates and may inhibit eruption of dentition.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Cases of hypercalcemia (some requiring hospitalization and/or complicated by acute kidney injury) have been reported in clinical trials of pediatric patients with osteogenesis imperfecta treated with denosumab. In pediatric patients <4 years of age, denosumab may adversely affect long-bone growth and dentition based on evidence from animal studies. Clinically important hypercalcemia has been reported following discontinuance of denosumab therapy in pediatric patients with growing skeletons who received the drug for treatment of giant cell tumor of bone or for other off-label uses. Based on animal data, denosumab potentially may impair bone growth in children with open growth plates and may inhibit eruption of dentition.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Based on findings from animal studies and the mechanism of action of denosumab, the drug may cause fetal harm if administered to pregnant women. Reproduction studies in monkeys have demonstrated fetal loss, stillbirth, postnatal mortality, evidence of absent lymph nodes, abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia, tooth malalignment, and decreased neonatal growth. Some of the observed bone abnormalities recovered once drug exposure ceased following birth.
No evidence of maternal harm was observed prior to labor in the studies. A study in mice found that absence of receptor activator of nuclear factor kappa-B ligand (RANKL; the target of denosumab) resulted in fetal lymph node agenesis and postnatal impairment of bone growth and dentition. Apprise pregnant women and females of reproductive potential of the potential drug-associated risk to the fetus.
No evidence of maternal harm was observed prior to labor in the studies. A study in mice found that absence of receptor activator of nuclear factor kappa-B ligand (RANKL; the target of denosumab) resulted in fetal lymph node agenesis and postnatal impairment of bone growth and dentition. Apprise pregnant women and females of reproductive potential of the potential drug-associated risk to the fetus.
It is not known whether denosumab is distributed into human milk; the effects of the drug on breast-fed infants or on milk production are also unknown. Denosumab is distributed into milk in monkeys in concentrations of <=0.5% of those attained in serum at <=1 month after the last dose.
Studies in pregnant RANKL knockout mice indicate that denosumab exposure during pregnancy may impair maternal mammary gland development and lactation; however, no such impairment was observed in monkeys. The manufacturer of Prolia(R) recommends to not breast-feed during treatment with denosumab. The manufacturer of Xgeva(R) states to consider the developmental and health benefits of breast-feeding along with the mother's clinical need for treatment with denosumab and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
Studies in pregnant RANKL knockout mice indicate that denosumab exposure during pregnancy may impair maternal mammary gland development and lactation; however, no such impairment was observed in monkeys. The manufacturer of Prolia(R) recommends to not breast-feed during treatment with denosumab. The manufacturer of Xgeva(R) states to consider the developmental and health benefits of breast-feeding along with the mother's clinical need for treatment with denosumab and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients. When the total number of patients studied in clinical trials of denosumab for osteoporosis or bone loss indications is considered, 76% were >=65 years of age, while 27% were >=75 years of age; in clinical trials in men with osteoporosis or in patients with glucocorticoid-induced osteoporosis, 55 or 47%, respectively, of patients were >=65 years of age, while 16 or 17%, respectively, were >=75 years of age. Of the total number of patients studied in clinical trials of denosumab for cancer-related indications, 44-45% were >=65 years of age, while 16-17% were >=75 years of age. Although no overall differences in efficacy or safety were observed between geriatric and younger patients and other clinical experience has revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.
The following prioritized warning is available for XGEVA (denosumab):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for XGEVA (denosumab)'s list of indications:
| Giant cell tumor of bone | |
| C40 | Malignant neoplasm of bone and articular cartilage of limbs |
| C40.0 | Malignant neoplasm of scapula and long bones of upper limb |
| C40.00 | Malignant neoplasm of scapula and long bones of unspecified upper limb |
| C40.01 | Malignant neoplasm of scapula and long bones of right upper limb |
| C40.02 | Malignant neoplasm of scapula and long bones of left upper limb |
| C40.1 | Malignant neoplasm of short bones of upper limb |
| C40.10 | Malignant neoplasm of short bones of unspecified upper limb |
| C40.11 | Malignant neoplasm of short bones of right upper limb |
| C40.12 | Malignant neoplasm of short bones of left upper limb |
| C40.2 | Malignant neoplasm of long bones of lower limb |
| C40.20 | Malignant neoplasm of long bones of unspecified lower limb |
| C40.21 | Malignant neoplasm of long bones of right lower limb |
| C40.22 | Malignant neoplasm of long bones of left lower limb |
| C40.3 | Malignant neoplasm of short bones of lower limb |
| C40.30 | Malignant neoplasm of short bones of unspecified lower limb |
| C40.31 | Malignant neoplasm of short bones of right lower limb |
| C40.32 | Malignant neoplasm of short bones of left lower limb |
| C40.8 | Malignant neoplasm of overlapping sites of bone and articular cartilage of limb |
| C40.80 | Malignant neoplasm of overlapping sites of bone and articular cartilage of unspecified limb |
| C40.81 | Malignant neoplasm of overlapping sites of bone and articular cartilage of right limb |
| C40.82 | Malignant neoplasm of overlapping sites of bone and articular cartilage of left limb |
| C40.9 | Malignant neoplasm of unspecified bones and articular cartilage of limb |
| C40.90 | Malignant neoplasm of unspecified bones and articular cartilage of unspecified limb |
| C40.91 | Malignant neoplasm of unspecified bones and articular cartilage of right limb |
| C40.92 | Malignant neoplasm of unspecified bones and articular cartilage of left limb |
| C41 | Malignant neoplasm of bone and articular cartilage of other and unspecified sites |
| C41.0 | Malignant neoplasm of bones of skull and face |
| C41.1 | Malignant neoplasm of mandible |
| C41.2 | Malignant neoplasm of vertebral column |
| C41.3 | Malignant neoplasm of ribs, sternum and clavicle |
| C41.4 | Malignant neoplasm of pelvic bones, sacrum and coccyx |
| C41.9 | Malignant neoplasm of bone and articular cartilage, unspecified |
| D48.0 | Neoplasm of uncertain behavior of bone and articular cartilage |
| Humoral hypercalcemia of malignancy | |
| E83.52 | Hypercalcemia |
| Prevention of skeletal related event in multiple myeloma | |
| C90.0 | Multiple myeloma |
| C90.00 | Multiple myeloma not having achieved remission |
| C90.02 | Multiple myeloma in relapse |
| Prevention of skeletal related events in bone metastases | |
| C79.51 | Secondary malignant neoplasm of bone |
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