Denosumab

Denosumabis a human IgG2monoclonal antibody用于治疗骨马的问题y occur with cancer that has spread (metastasized) to the bones.

Denosumab is available under the following different brand names:ProliaandXgeva.

Dosage Forms and Strengths

Subcutaneous injection

• Prolia: 60mg/mL (1mL prefilled syringe or 1mL vial) (adult only)
• Xgeva: 70mg/mL (120mg/1.7mL vial) (adult and pediatric)

Dosage Considerations – Should be Given as Follows:

Osteoporosis

• Treatment of men andpostmenopausalwomen with osteoporosis who are at high risk forfracture; treatment to increase bone mass in men at high risk for fracture who are receivingandrogendeprivation therapy for non-metastaticprostate cancer; treatment to increase bone mass in women at high risk for fracture who are receivingadjuvantaromatase inhibitortherapy forbreast cancer
• Prolia: 60 mg subcutaneously (SC) every 6 months
• Supplement with calcium 1000 mg/day andvitamin D400 IU/day

AromataseInhibitor Induced Bone Loss

• Women with breast cancer: 60 mg (Prolia) subcutaneously (SC) every 6 months

Androgen Deprivation Induced Bone Loss

• Men withprostatecancer: 60 mg (Prolia) subcutaneously (SC) every 6 months

Skeletal-Related Events

• Prevention of skeletal-related events (SREs; e.g., bone fractures and pain) in patients with bone metastases from solid tumors
• Xgeva: 120 mg (1.7 mL) subcutaneously (SC) every 4 weeks

Giant Cell Tumor

• Adult: Treatment of adults and skeletally mature adolescents with giant cell tumor of bone in whom surgical切除is impossible or is likely to result in severe morbidity
• Xgeva: 120 mg subcutaneously (SC) every 4 weeks with additional 120 mg on days 8 and 15 during first month of therapy
• 儿科:治疗只是成熟进入青春期nts with giant cell tumor of bone in whom surgical resection is impossible or is likely to result in severe morbidity
• Xgeva: 120 mg SC every 4 weeks, with additional 120 mg on days 8 and 15 during first month of therapy

HypercalcemiaofMalignancy

• Indicated for treatment of hypercalcemia of malignancyrefractorytobisphosphonatetherapy
• Xgeva: 120 mg subcutaneously (SC) every 4 weeks
• Give 2 additional 120 mg doses during the first month of therapy on Days 8 and 15

Administration

• Must be administered by healthcare professional
• Administer SC in upper arm, upper thigh, or abdomen; do NOT administer intradermally, intramuscularly (IM), or intravenously (IV)
• Administer calcium and vitamin D as needed to treat or preventhypocalcemia
• 避免剧烈的摇瓶/注射器
• Storage
  • Store refrigerated at 2-8°C (36-46°F)
  • Once removed from refrigerator, preparation must be used within 14 days

Common side effects of denosumab include:

• Back pain
• Extremity pain
• Musculoskeletal pain
• Hypercholesterolemia
• Cystitis
• Upper respiratory tract infection
• New malignancies
• Sciatica
• Nonfatal serious infection
• Bone pain
• Anemia
• Upper abdominal pain
• Rash
• Gas (flatulence)
• Osteonecrosis of jaw
• Itching
• Low blood calcium (hypocalcemia)
• Tiredness
• Weakness
• Headache
• Joint pain
• Diarrhea
• Nausea

Serious side effects of denosumab include:

• Serious infection of abdomen resulting in hospitalization
• Serious infection ofurinary tractresulting in hospitalization
• Serious infection resulting in death
• Pancreatitis
• Serious infection of ear resulting in hospitalization
• Jaw pain
• New or unusual thigh/hip/groinpain
• Bone/joint/muscle pain
• Shortness of breath

Postmarketing side effects of denosumab reported include:

• Hypocalcemia
• Marked elevation in PTH in patients with severe renal impairment or receivingdialysis
• Multiple vertebral fractures following discontinuation of Prolia

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Denosumab has no known severe interactions with other drugs.
• Serious interactions of denosumab include:
  • daclizumab
  • 流感virus vaccinetrivalent, adjuvanted
• Denosumab has moderate interactions with at least 105 different drugs.
• Denosumab has no known mild interactions with other drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

Warnings

This medication contains denosumab. Do not take Prolia or Xgeva if you are allergic to denosumab or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

History of systemic hypersensitivity, includinganaphylaxis, facial swelling, andurticaria

Preexisting hypocalcemia

Effects of Drug Abuse

• No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Denosumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Denosumab?"

Cautions

• Denosumab is available as 2 distinct brands (Prolia and Xgeva) that have different dosage strengths for their respective indications; do not use concurrently.
• Low blood calcium (hypocalcemia) may occur; monitor calcium levels during therapy, especially in the first weeks of initiating therapy, and adequately supplement all patients with calcium and vitamin D.
• Severe symptomatic hypocalcemia has been reported; hypocalcemia may worsen, especially in patients who have CrCl less than 30 mL/minute or are onhemodialysis.
• Serious infections (includingcellulitis) anddermatologicreactions (e.g.,dermatitis, rashes,eczema) have been reported; advise patients to seek prompt medical attention if they develop signs or symptoms of infection, including cellulitis; consider discontinuing therapy if severe symptoms develop.
• Hypersensitivity (including anaphylaxis) has been reported.
• Bone turnover suppression may increase risk for osteonecrosis of jaw; perform an oral examination prior to initiating therapy; osteonecrosis of the jaw, can occur spontaneously and is generally associated with tooth extraction and/or local infection with delayed healing; known risk factors include invasive dental procedures (e.g., tooth extraction, dental implants, boney surgery), diagnosis of cancer, concomitant therapies (e.g.,chemotherapy, corticosteroids,angiogenesisinhibitors), poor oral hygiene, and co-morbid disorders; risk of osteonecrosis of the jaw may increase with duration of therapy.
• Significant suppression demonstrated; monitor for consequences of bone over-suppression.
• Severe and occasionally incapacitating bone, joint, and/or muscle pain has been reported; discontinue use if severe symptoms develop.
• Monitor patients for signs and symptoms of high blood calcium (hypercalcemia) and treat appropriately.
• Atypicalfemoralfracture has been reported; evaluate patients with thigh or groin pain to rule out a femoral fracture.
• Following discontinuation of Prolia treatment, fracture risk increases, including risk of multiple vertebral fractures.
• Pancreatitis reported in clinical trials.
• Pediatric use is not recommended; drug may impair bone growth in children with open growth plates and may inhibit eruption of dentition.
• Latexallergy: If sensitive to latex, do not handle gray needle cap on single-use prefilled syringe, which contains dry natural rubber (a derivative of latex).
• Pregnancy; females of reproductive potential should be advised to use highly effective contraception during therapy and for at least 5 months after last dose (Prolia).
• Not indicated for the prevention of skeletal-related events in patients withmultiple myeloma.
• Use caution in patients with renal impairment less than 30 mL/minute) or patients on dialysis; risk of hypocalcemia increased; dose adjustment not necessary when administered at 60 mg every 6 months; once monthly dosing not evaluated in patients with renal impairment.
• Not for intravenous,intradermal, orintramuscularadministration.

Pregnancy and Lactation

• Do not use denosumab in pregnancy. The risks involved outweigh potential benefits. Safer alternatives exist.
• On the basis of animal studies, denosumab may cause fetal harm when administered pregnant women. In utero, there were results in increased fetal loss, stillbirths, and postnatal mortality, including absent lymph nodes, abnormal bone growth, and decreasedneonatalgrowth.
• Women with reproductive potential must use highly effective contraception during therapy and for 5 months or more after the last dose of denosumab.
• On the basis of animal studies in pregnant mice lacking the RANK/RANK ligand (RANKL) signaling pathway that have shown altered maturation of the maternalmammary gland, leading to impaired lactation post partum, maternal exposure during pregnancy may impair mammaryglanddevelopment and lactation.
• It is unknown whether denosumab is distributed in breast milk; caution is advised if breastfeeding.