Denosumab
PROLIA
What it isRANK ligand antibody preventing osteoclast maturation; osteoporosis and skeletal events in malignancy.
Why this oneIt needs no renal dose adjustment, unlike bisphosphonates, but advanced CKD sharply increases hypocalcemia risk.
What limits it⚑ Check and correct calcium before treatment; never stop without follow-on antiresorptive therapy because vertebral fractures can rebound.
FDA-approved for
- postmenopausal osteoporosis (2010)
- skeletal-related events in bone metastases
Off-label
- glucocorticoid-induced osteoporosis in men
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Multiple myeloma / bone metastasis from solid tumors | Adult | 120 mg SC q4wk | 120 mg SC q4wk | |
| Giant cell tumor of bone | Adult / skeletally mature adolescent | 120 mg SC q4wk + 120 mg on Days 8 and 15 of month 1 | 120 mg SC q4wk | |
| Hypercalcemia of malignancy | Adult | 120 mg SC q4wk + 120 mg on Days 8 and 15 of month 1 | 120 mg SC q4wk |
Renal CrCl <30 mL/min or on dialysis: increased hypocalcemia risk - supplement calcium and vitamin D (no dose change)
Hepatic Undefined
GCTB and hypercalcemia of malignancy: additional loading doses on Days 8 and 15 of the first month
Instructions
- SC only (upper arm, thigh, or abdomen) by a healthcare provider; not IV/IM/intradermal
- Administer calcium and vitamin D as needed to treat/prevent hypocalcemia
- Do not give other denosumab products concomitantly
Contraindications
- Hypocalcemia (correct pre-existing hypocalcemia before initiating)
Cautions
- Hypersensitivity/anaphylaxis - discontinue permanently if significant reaction
- Severe symptomatic hypocalcemia (fatal cases reported); monitor calcium
- Osteonecrosis of the jaw - oral exam first, avoid invasive dental procedures
- Atypical femoral fracture
- Hypercalcemia after discontinuation in GCTB / growing skeletons
- Multiple vertebral fractures after discontinuation
- Embryo-fetal toxicity - use effective contraception
Adverse reactions
- Bone metastasis: fatigue/asthenia, hypophosphatemia, nausea
- Multiple myeloma: diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, URTI, rash, headache
- GCTB: arthralgia, headache, nausea, back pain, fatigue, extremity pain
- Hypercalcemia of malignancy: nausea, dyspnea, decreased appetite, headache, edema, vomiting, anemia, constipation, diarrhea
Pregnancy Can cause fetal harm; advise effective contraception (insufficient human data)
Lactation No human data; weigh benefits of breastfeeding against maternal need
NO BOXED WARNINGS
Principal riskSevere rebound vertebral fractures if stopped without a follow-on agent
Cost, est. cash$300–$5,000/dose or month
Generic entry2025 (biosimilar)
Classes and tags
Clinical profile
Legacy pregnancy categoryC
Defining liabilityHypocalcemia, osteonecrosis and rebound vertebral fractures if stopped without transition therapy.
Mechanism of action: Denosumab ballicule
Open Denosumab in the interactive console ↗
Memory aids: mascots and interaction avatars
