Denosumab-Kyqq
FDA Drug Information • Also known as: Aukelso, Bosaya
- Brand Names
- Aukelso, Bosaya
- Drug Class
- RANK Ligand Inhibitor [EPC]
- Route
- SUBCUTANEOUS
- Dosage Form
- INJECTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Denosumab-kyqq is a human IgG2 monoclonal antibody that binds to human RANKL. Denosumab-kyqq has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. Aukelso (denosumab-kyqq) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale yellow solution. Each single-dose vial contains 120 mg denosumab-kyqq, glacial acetic acid (0.397 mg), polysorbate 20 (0.17 mg), sodium acetate (1.828 mg), sorbitol (79.9 mg), Water for Injection (USP), and may contain sodium hydroxide/acetic acid to adjust pH to 5.2.
What Is Denosumab-Kyqq Used For?
1 INDICATIONS AND USAGE Aukelso is a RANK ligand (RANKL) inhibitor indicated for: Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. ( 1.1 ) Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. ( 1.2 , 14.3 ) Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. ( 1.3 ) 1.1 Multiple Myeloma and Bone Metastasis from Solid Tumors Aukelso is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. 1.2 Giant Cell Tumor of Bone Aukelso is indicated for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity [see Clinical Trials (14.2) ] . 1.3 Hypercalcemia of Malignancy Aukelso is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Aukelso should be administered by a healthcare provider. ( 2.1 ) Aukelso is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally. ( 2.1 ) Multiple Myeloma and Bone Metastasis from Solid Tumors: Administer 120 mg every 4 weeks as a subcutaneous injection in the upper arm, upper thigh, or abdomen. ( 2.2 ) Giant Cell Tumor of Bone: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. ( 2.3 ) Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia. ( 2.2 , 2.3 ) Hypercalcemia of Malignancy: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. ( 2.4 ) 2.1 Important Administration Instructions Aukelso should be administered by a healthcare provider. Aukelso is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally. 2.2 Multiple Myeloma and Bone Metastasis from Solid Tumors The recommended dose of Aukelso is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia [see Warnings and Precautions (5.3) ]. 2.3 Giant Cell Tumor of Bone The recommended dose of Aukelso is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia [see Warnings and Precautions (5.3) ]. 2.4 Hypercalcemia of Malignancy The recommended dose of Aukelso is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. 2.5 Preparation and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Aukelso is a clear to slightly opalescent, colorless to pale yellow solution. Do not use if the solution is discolored or cloudy or if the solution contains visible particles or foreign particulate matter. Prior to administration, Aukelso 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 Aukelso in any other way [see How Supplied/Storage and Handling (16) ]. 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.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed below and elsewhere in the labeling: Hypersensitivity [see Warnings and Precautions (5.2) ] Hypocalcemia [see Warnings and Precautions (5.3) and Use in Specific Populations (8.6) ] Osteonecrosis of the Jaw [see Warnings and Precautions (5.4) ] Atypical Subtrochanteric and Diaphyseal Femoral Fracture [see Warnings and Precautions (5.5) ] Hypercalcemia following treatment discontinuation in patients with giant cell tumor of bone and in patients with growing skeletons [see Warnings and Precautions (5.6) and Use in Specific Populations (8.4) ] Multiple vertebral fractures (MVF) following treatment discontinuation [see Warnings and Precautions (5.7) ] Bone Metastasis from Solid Tumors: Most common adverse reactions (≥ 25%) were fatigue/asthenia, hypophosphatemia, and nausea. ( 6.1 ) Multiple Myeloma: Most common adverse reactions (≥ 10%) were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. ( 6.1 ) Giant Cell Tumor of Bone: Most common adverse reactions (≥ 10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. ( 6.1 ) Hypercalcemia of Malignancy: Most common adverse reactions (> 20%) were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Biocon Biologics at 1-833-986-1468 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Bone Metastasis from Solid Tumors The safety of denosumab was evaluated in three randomized, double-blind, double-dummy trials [see Clinical Trials (14.1) ] in which a total of 2841 patients with bone metastasis from prostate cancer, breast cancer, or other solid tumors, or lytic bony lesions from multiple myeloma received at least one dose of denosumab. In Studies 20050136, 20050244, and 20050103, patients were randomized to receive either 120 mg of denosumab every 4 weeks as a subcutaneous injection or 4 mg (dose adjusted for reduced renal function) of zoledronic acid every 4 weeks by intravenous (IV) infusion. Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure. During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required. The median duration of exposure to denosumab was 12 months (range: 0.1-41) and median duration on-study was 13 months (range: 0.1-41). Of patients who received denosumab, 46% were female. Eighty-five percent were White, 5% Hispanic/Latino, 6% Asian, and 3% Black. The median age was 63 years (range: 18-93). Seventy-five percent of patients who received denosumab received concomitant chemotherapy. The most common adverse reactions in patients (incidence greater than or equal to 25%) were fatigue/asthenia, hypophosphatemia, and nausea (see Table 1). The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation of denosumab were osteonecrosis and hypocalcemia. Table 1. Selected a Adverse Reactions of Any Severity (Studies 20050136, 20050244, and 20050103) Body System Denosumab n = 2841 % Zoledronic Acid n = 2836 % GASTROINTESTINAL Nausea 31 32 Diarrhea 20 19 GENERAL Fatigue/Asthenia 45 46 INVESTIGATIONS...
Contraindications
4 CONTRAINDICATIONS Hypocalcemia ( 4.1 ) Known clinically significant hypersensitivity to denosumab products (4.2 ) 4.1 Hypocalcemia Pre-existing hypocalcemia must be corrected prior to initiating therapy with Aukelso [see Warnings and Precautions (5.3) ]. 4.2 Hypersensitivity Aukelso is contraindicated in patients with known clinically significant hypersensitivity to denosumab products [see Warnings and Precautions (5.2) and Adverse Reactions (6.2) ] .
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action, denosumab products can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are insufficient data with denosumab products 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 denosumab 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 denosumab 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...
Overdosage
10 OVERDOSAGE There is no experience with overdosage of denosumab products.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Aukelso (denosumab-kyqq) injection is a clear to slightly opalescent, colorless to pale yellow solution supplied in a single-dose vial. The vial stopper is not made with natural rubber latex. 120 mg/1.7 mL (70 mg/mL) 1 vial per carton NDC 83257-030-11 Store Aukelso refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Prior to administration, Aukelso may be allowed to reach room temperature up to 25°C (77°F) in the original container. Once removed from the refrigerator, Aukelso must not be exposed to temperatures above 25°C (77°F) and must be used within 30 days. Discard Aukelso if not used within the 30 days. Do not use Aukelso after the expiry date printed on the label. Protect Aukelso from direct light and heat. Avoid vigorous shaking of Aukelso.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.