Denosumab (Xgeva)
Other products: Denosumab
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From MedlinePlus, U.S. National Library of Medicine
Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, biosimilars, Medicare Part D coverage.
RANK Ligand Inhibitor
Dosing in kidney impairment
Renal Impairment Two clinical trials were conducted in patients without cancer and with varying degrees of renal function. In one study, patients (N = 55) with varying degrees of renal function (ranging from normal through end-stage renal disease requiring dialysis) received a single 60 mg subcutaneous dose of denosumab.
In a second study, patients (N = 32) with severe renal dysfunction (creatinine clearance less than 30 mL/min and/or on dialysis) were given two 120 mg subcutaneous doses of denosumab. In both studies, greater risk of developing hypocalcemia was observed with increasing renal impairment, and with inadequate/no calcium supplementation.
Hypocalcemia was mild to moderate in severity in 96% of patients. Monitor calcium levels and calcium and vitamin D intake [see Warnings and Precautions, Adverse Reactions, and Clinical Pharmacology] .
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Preparation and administration
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Important Administration Instructions Xgeva should be administered by a healthcare provider. Xgeva is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally.
Preparation and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Xgeva is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles.
Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter. Prior to administration, Xgeva may be removed from the refrigerator and brought to room temperature up to 25°C (77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Xgeva in any other way [see How Supplied/Storage and Handling].
Use a 27-gauge needle to withdraw and inject the entire contents of the vial. Do not re-enter the vial. Discard vial after single entry.
Drug interactions
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- Denosumab (Xgeva)
Contraindications
Hypocalcemia ( 4.1 ) Known clinically significant hypersensitivity to Xgeva or denosumab products ( 4.2 )
4.1 Hypocalcemia Pre-existing hypocalcemia must be corrected prior to initiating therapy with Xgeva [s ee Warnings and Precautions ( 5.3 )] .
4.2 Hypersensitivity Xgeva is contraindicated in patients with known clinically significant hypersensitivity to Xgeva or denosumab products [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.2 )] .
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Unproven but suspected rare cause of clinically apparent liver injury.
Denosumab is a monoclonal antibody to the RANK ligand which plays an important role in bone remodeling. Denosumab is used in the therapy of osteoporosis and for bone metastases and rare bone tumors. Denosumab therapy has not been associated with serum enzyme elevations during therapy, nor has it been convincingly implicated in cases of clinically apparent drug induced liver injury with jaundice.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action, Xgeva can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are insufficient data with denosumab use in pregnant women to inform any drug associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 25-fold higher than the recommended human dose of Xgeva based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality; and absent lymph nodes, abnormal bone growth, and decreased neonatal growth [ see Data ] .
Apprise pregnant women of the potential risk to the fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”).
In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy starting at gestational day 20 and at a pharmacologically active dose 25-fold higher than the recommended human dose of Xgeva based on body weight, there was increased fetal loss during gestation, stillbirths, and postnatal mortality. Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia, and tooth malalignment; and decreased neonatal growth. At birth out to one month of age, infants had measurable blood levels of denosumab (22-621% of maternal levels).
Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal. There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this…
Breastfeeding (LactMed)
No information is available on the clinical use of denosumab during breastfeeding. Because denosumab is a large protein molecule with a molecular weight of about 147,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant’s gastrointestinal tract and absorption by the infant is probably minimal. Until more data become available, denosumab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Waiting for at least 2 weeks postpartum to resume therapy may minimize transfer to the infant.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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