Meta Information
ID:denosumab
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/intervention/calcium-supplements
Target name:
Calcium Supplements
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Denosumab potently inhibits bone resorption, which can lead to a rapid and severe drop in blood calcium levels (hypocalcemia). Adequate calcium intake is essential to maintain normal blood calcium levels during treatment.
Actionable advice:
You must take daily calcium supplements (at least 1000 mg) as prescribed by your doctor throughout your denosumab treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Hypocalcemia Advise the patient to adequately supplement with calcium and vitamin D and instruct them on the importance of maintaining serum calcium levels while receiving Denosumab-bmwo [see Warnings and Precautions (5.1) , Use in Specific Populations (8.6) ] .
Label source:
Action type:
informational_none
Target id:
/intervention/vitamin-d
Target name:
Vitamin D Supplements
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin D is required for the proper absorption of calcium from the gut. Without adequate vitamin D, calcium supplementation will be ineffective, increasing the risk of denosumab-induced hypocalcemia.
Actionable advice:
You must take daily vitamin D supplements (at least 400 IU) as prescribed by your doctor throughout your denosumab treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
intact parathyroid hormone (iPTH), serum calcium, 25(OH) vitamin D, and 1,25(OH)2 vitamin D prior to decisions regarding Enoby treatment.
Label source:
FDA label: Denosumab biosimilar Enoby (denosumab-qbde) — biosimilar to Prolia
Action type:
informational_none
Target id:
/condition/hypocalcemia
Target name:
Pre-existing Low Blood Calcium (Hypocalcemia)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Denosumab can cause severe, life-threatening hypocalcemia. Starting treatment in a patient who already has low calcium levels is contraindicated and can lead to serious complications like seizures or cardiac arrhythmias.
Actionable advice:
Denosumab should be avoided completely with uncorrected low blood calcium; it must be treated and normalized first.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Prolia can cause serious side effects including:
Increased risk of severe low calcium levels in your blood (hypocalcemia).
Label source:
Action type:
avoid
Target id:
/condition/renal-impairment
Target name:
Severe Kidney Disease (Renal Impairment)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Patients with severe kidney impairment (creatinine clearance <30 mL/min) or on dialysis have a significantly higher risk of developing severe hypocalcemia with denosumab due to impaired vitamin D metabolism.
Actionable advice:
This should be used with extreme caution and frequent calcium monitoring in those with severe kidney disease, and it is important to discuss the risks with a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In clinical studies, patients with advanced chronic kidney disease (i.e.,
eGFR < 30 mL/min/1.73 m2), including dialysis-dependent patients, were at greater risk of developing
hypocalcemia.
Label source:
Action type:
monitor
Target id:
/procedure/invasive-dental-procedure
Target name:
Invasive Dental Procedures (e.g., tooth extraction, implants)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Denosumab increases the risk of a rare but serious condition called osteonecrosis of the jaw (ONJ), where the jawbone fails to heal after minor trauma like a tooth extraction.
Actionable advice:
Complete any necessary invasive dental work before starting denosumab and maintain excellent oral hygiene during treatment.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Osteonecrosis of the Jaw
Advise patients to maintain good oral hygiene during treatment with Prolia and to inform their dentist
prior to dental procedures that they are receiving Prolia.
Label source:
Action type:
informational_none
Target id:
/procedure/discontinuation-of-denosumab
Target name:
Stopping Denosumab Treatment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Abruptly stopping denosumab leads to a rapid reversal of its effects, a surge in bone resorption above baseline, and a significant loss of bone mineral density, which is associated with a high risk of multiple vertebral fractures.
Actionable advice:
Denosumab should not be stopped without a specific plan to transition to another antiresorptive therapy to prevent rebound bone loss.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
After discontinuation of denosumab therapy, markers of bone resorption increased to levels 40% to 60% above pretreatment values but returned to baseline levels within 12 months.
Label source:
Action type:
informational_none
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Denosumab may cause fetal harm as the RANK/RANKL pathway is crucial for fetal immune system development and bone metabolism. It is contraindicated during pregnancy.
Actionable advice:
Denosumab should be avoided completely by anyone who is pregnant or planning to become pregnant.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node
agenesis and led to postnatal impairment of dentition and bone growth.
Label source:
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known if denosumab is excreted in human milk, but due to the potential for serious adverse reactions in nursing infants, it is not recommended.
Actionable advice:
Denosumab should be avoided while breastfeeding; it is important to discuss alternatives with a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
17 of 31
Reference ID: 5596256
8.2 Lactation
Risk Summary
There is no information regarding the presence of denosumab in human milk, the effects on the breastfed
infant, or the effects on milk production.
Label source:
Action type:
avoid
Target id:
/biomarker/serum-calcium
Target name:
Serum Calcium Level Check (Post-Dose) (Post Administration)
Severity:
major
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
336
Description:
Blood calcium levels can drop after a denosumab injection, typically reaching their lowest point around day 10. Monitoring is essential to detect and treat hypocalcemia, especially in high-risk patients.
Actionable advice:
Serum calcium level should be checked within 14 days after the injection, especially for people with kidney disease.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
history of hypoparathyroidism, thyroid surgery, parathyroid
surgery, malabsorption syndromes, excision of small intestine, treatment with other calcium-lowering
drugs), assess serum calcium and mineral levels (phosphorus and magnesium) 10 to14 days after Prolia
injection.
Label source:
Action type:
monitor
Target id:
/class/immunosuppressants
Target name:
Immunosuppressant Medications
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Denosumab can affect immune function and may increase the risk of serious infections. Combining it with other immunosuppressive drugs (like corticosteroids or calcineurin inhibitors) could further elevate this risk.
Actionable advice:
This is best used with caution, and it is a good idea to monitor closely for signs of infection when taken with other immunosuppressants.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Patients on concomitant immunosuppressant agents or with impaired immune systems may be at
increased risk for serious infections.
Label source:
Action type:
monitor
Target id:
/intervention/bisphosphonates
Target name:
Bisphosphonates (e.g., Alendronate, Zoledronic Acid)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Concomitant use of denosumab with bisphosphonates is not recommended as it could increase the risk of over-suppression of bone turnover, leading to adverse events like ONJ or atypical fractures, without added benefit.
Actionable advice:
Denosumab is best not used concurrently with bisphosphonates or other antiresorptive therapies.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
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.
Label source:
Action type:
avoid
Target id:
/class/live-vaccines
Target name:
Live Attenuated Vaccines
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
As denosumab can modulate the immune system, there is a theoretical risk that it could reduce the efficacy of live vaccines or increase the risk of infection from the vaccine virus itself.
Actionable advice:
Live vaccines are best avoided during treatment with denosumab.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Denosumab inhibits RANKL, which modulates immune-cell development; while no formal contraindication exists on the FDA label for live vaccines, immunomodulatory mechanism supports caution and adherence to standard ACIP guidance on live vaccines during immune-modulating biologic therapy.
Label source:
Expert review: mechanism-based caution per ACIP guidance for immunomodulatory therapies
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/condition/history-of-hypersensitivity-to-denosumab
Target name:
History of Allergic Reaction to Denosumab
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Prior hypersensitivity reactions, which can include anaphylaxis, rash, and urticaria, are an absolute contraindication to further use of the drug.
Actionable advice:
Denosumab should be avoided completely by anyone with a known allergy to it or its components.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The following adverse reactions have been identified during post-approval use of denosumab products: Drug-related hypersensitivity reactions: anaphylaxis, rash, urticaria, facial swelling, and erythema.
Label source:
Action type:
avoid
Target id:
/condition/pre-existing-dermatitis-eczema
Target name:
Pre-existing Dermatitis or Eczema
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Denosumab can cause skin-related side effects, including dermatitis, rashes, and eczema. Individuals with a history of these conditions may be more susceptible or experience exacerbations.
Actionable advice:
It is worth watching the skin for new or worsening rashes while on denosumab and reporting them to a doctor.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Dermatologic Adverse Reactions Epidermal and dermal adverse events (such as dermatitis, eczema, and rashes) were reported in 16 patients (4.2%) in the active-control group and 15 patients (3.8%) in the denosumab group.
Label source:
Action type:
monitor