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Hold clear finger grip. 

Gently slide green safety guard over 
needle and lock securely in place.  Do 
not grip green safety guard too firmly 
when sliding over needle. 

 
Immediately dispose of the syringe and needle cap in the nearest sharps container.  DO NOT put the 
needle cap back on the used syringe. 
 
Instructions for Single-use Vial 
For administration of Prolia from the single-use vial, use a 27-gauge needle to withdraw and inject the 
1 mL dose.  Do not re-enter the vial.  Discard vial and any liquid remaining in the vial. 
 
3 

DOSAGE FORMS AND STRENGTHS 



  1 mL of a 60 mg/mL solution in a single-use prefilled syringe 



  1 mL of a 60 mg/mL solution in a single-use vial 

 
4 

CONTRAINDICATIONS 

 
4.1 

Hypocalcemia 

 
Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia [see Warnings and 
Precautions (5.3)]. 
 
4.2 

Pregnancy 

 
Prolia may cause fetal harm when administered to a pregnant woman.  In utero denosumab exposure in 
cynomolgus monkeys resulted in increased fetal loss, stillbirths, and postnatal mortality, along with 
evidence of absent lymph nodes, abnormal bone growth and decreased neonatal growth.  Prolia is 
contraindicated in women who are pregnant.  If this drug is used during pregnancy, or if the patient 
becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus 
[see Use in Specific Populations (8.1)].   
 
4.3 

Hypersensitivity 

 
Prolia is contraindicated in patients with a history of systemic hypersensitivity to any component of the 
product.  Reactions have included anaphylaxis, facial swelling and urticaria [see Warnings and 
Precautions (5.2), Adverse Reactions (6.2)]. 

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5 

WARNINGS AND PRECAUTIONS 

 
5.1  

Drug Products with Same Active Ingredient 

 
Prolia contains the same active ingredient (denosumab) found in Xgeva.  Patients receiving Prolia should 
not receive Xgeva.  
 
5.2 

Hypersensitivity  

 
Clinically significant hypersensitivity including anaphylaxis has been reported with Prolia.  Symptoms 
have included hypotension, dyspnea, throat tightness, facial and upper airway edema, pruritus, and 
urticaria.  If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate 
therapy and discontinue further use of Prolia [see Contraindications (4.3), Adverse Reactions (6.2)]. 
 
5.3 

Hypocalcemia and Mineral Metabolism 

 
Hypocalcemia may be exacerbated by the use of Prolia.  Pre-existing hypocalcemia must be corrected 
prior to initiating therapy with Prolia.  In patients predisposed to hypocalcemia and disturbances of 
mineral metabolism (e.g. history of hypoparathyroidism, thyroid surgery, parathyroid surgery, 
malabsorption syndromes, excision of small intestine, severe renal impairment [creatinine 
clearance < 30 mL/min] or receiving dialysis), clinical monitoring of calcium and mineral levels 
(phosphorus and magnesium) is highly recommended within 14 days of Prolia injection.  In some 
postmarketing cases, hypocalcemia persisted for weeks or months and required frequent monitoring and 
intravenous and/or oral calcium replacement, with or without vitamin D. 
 
Hypocalcemia following Prolia administration is a significant risk in patients with severe renal 
impairment [creatinine clearance < 30 mL/min] or receiving dialysis.  These patients may also develop 
marked elevations of serum parathyroid hormone (PTH).  Instruct all patients with severe renal 
impairment, including those receiving dialysis, about the symptoms of hypocalcemia and the importance 
of maintaining calcium levels with adequate calcium and vitamin D supplementation. 
 
Adequately supplement all patients with calcium and vitamin D [see Dosage and Administration (2.1), 
Contraindications (4.1), Adverse Reactions (6.1), and Patient Counseling Information (17.3)]. 
 
5.4 

Osteonecrosis of the Jaw  

 
Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth 
extraction and/or local infection with delayed healing.  ONJ has been reported in patients receiving 
denosumab [see Adverse Reactions (6.1)].  A routine oral exam should be performed by the prescriber 
prior to initiation of Prolia treatment.  A dental examination with appropriate preventive dentistry is 
recommended prior to treatment with Prolia in patients with risk factors for ONJ such as invasive dental 
procedures (e.g. tooth extraction, dental implants, oral surgery), diagnosis of cancer, concomitant 
therapies (e.g. chemotherapy, corticosteroids, angiogenesis inhibitors), poor oral hygiene, and co-morbid 
disorders (e.g. periodontal and/or other pre-existing dental disease, anemia, coagulopathy, infection, ill-
fitting dentures).  Good oral hygiene practices should be maintained during treatment with Prolia.  
Concomitant administration of drugs associated with ONJ may increase the risk of developing ONJ. 
 
For patients requiring invasive dental procedures, clinical judgment of the treating physician and/or oral 
surgeon should guide the management plan of each patient based on individual benefit-risk assessment. 
 

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Patients who are suspected of having or who develop ONJ while on Prolia should receive care by a dentist 
or an oral surgeon.  In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.  
Discontinuation of Prolia therapy should be considered based on individual benefit-risk assessment. 
 
5.5 

Atypical Subtrochanteric and Diaphyseal Femoral Fractures 

 
Atypical low-energy or low trauma fractures of the shaft have been reported in patients receiving Prolia 
[see Adverse Reactions (6.1)].  These fractures can occur anywhere in the femoral shaft from just below 
the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation 
without evidence of comminution.  Causality has not been established as these fractures also occur in 
osteoporotic patients who have not been treated with anti-resorptive agents. 
 
Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area.  They 
may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, 
aching thigh pain, weeks to months before a complete fracture occurs.  A number of reports note that 
patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture.  
 
During Prolia treatment, patients should be advised to report new or unusual thigh, hip, or groin pain.  
Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and 
should be evaluated to rule out an incomplete femur fracture.  Patient presenting with an atypical femur 
fracture should also be assessed for symptoms and signs of fracture in the contralateral limb.  Interruption 
of Prolia therapy should be considered, pending a risk/benefit assessment, on an individual basis.   
 
5.6 

Serious Infections 

In a clinical trial of over 7800 women with postmenopausal osteoporosis, serious infections leading to 
hospitalization were reported more frequently in the Prolia group than in the placebo group [see Adverse 
Reactions (6.1)].  Serious skin infections, as well as infections of the abdomen, urinary tract, and ear, 
were more frequent in patients treated with Prolia.  Endocarditis was also reported more frequently in 
Prolia-treated patients.  The incidence of opportunistic infections was similar between placebo and Prolia 
groups, and the overall incidence of infections was similar between the treatment groups.  Advise patients 
to seek prompt medical attention if they develop signs or symptoms of severe infection, including 
cellulitis.   

Patients on concomitant immunosuppressant agents or with impaired immune systems may be at 
increased risk for serious infections.  Consider the benefit-risk profile in such patients before treating with 
Prolia.  In patients who develop serious infections while on Prolia, prescribers should assess the need for 
continued Prolia therapy. 
 
5.7 

Dermatologic Adverse Reactions  

 
In a large clinical trial of over 7800 women with postmenopausal osteoporosis, epidermal and dermal 
adverse events such as dermatitis, eczema, and rashes occurred at a significantly higher rate in the Prolia 
group compared to the placebo group.  Most of these events were not specific to the injection site 
[see Adverse Reactions (6.1)].  Consider discontinuing Prolia if severe symptoms develop.  
 
5.8 

Musculoskeletal Pain 

 
In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain has 
been reported in patients taking Prolia [see Adverse Reactions (6.2)].  The time to onset of symptoms 

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varied from one day to several months after starting Prolia.  Consider discontinuing use if severe 
symptoms develop [see Patient Counseling Information (17.8)]. 
 
5.9 

Suppression of Bone Turnover  

 
In clinical trials in women with postmenopausal osteoporosis, treatment with Prolia resulted in significant 
suppression of bone remodeling as evidenced by markers of bone turnover and bone histomorphometry 
[see Clinical Pharmacology (12.2) and Clinical Studies (14.1)].  The significance of these findings and 
the effect of long-term treatment with Prolia are unknown.  The long-term consequences of the degree of 
suppression of bone remodeling observed with Prolia may contribute to adverse outcomes such as 
osteonecrosis of the jaw, atypical fractures, and delayed fracture healing.  Monitor patients for these 
consequences. 
 
6 

ADVERSE REACTIONS 

 
The following serious adverse reactions are discussed below and also elsewhere in the labeling: 
 



  Hypocalcemia [see Warnings and Precautions (5.3)] 



  Serious Infections [see Warnings and Precautions (5.6)] 



  Dermatologic Adverse Reactions [see Warnings and Precautions (5.7)] 



  Osteonecrosis of the Jaw [see Warnings and Precautions (5.4)] 



  Atypical Subtrochanteric and Diaphyseal Femoral Fractures [see Warnings and Precautions (5.5)] 

 
The most common adverse reactions reported with Prolia in patients with postmenopausal osteoporosis 

are back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis. 

 
The most common adverse reactions reported with Prolia in men with osteoporosis are back pain, 
arthralgia, and nasopharyngitis. 
 
The most common (per patient incidence ≥ 10%) adverse reactions reported with Prolia in patients with 
bone loss receiving androgen deprivation therapy for prostate cancer or adjuvant aromatase inhibitor 
therapy for breast cancer are arthralgia and back pain.  Pain in extremity and musculoskeletal pain have 
also been reported in clinical trials.   

The most common adverse reactions leading to discontinuation of Prolia in patients with postmenopausal 
osteoporosis are back pain and constipation.  
 
The Prolia Postmarketing Active Safety Surveillance Program is available to collect information from 
prescribers on specific adverse events.  Please see

www.proliasafety.com

 o

r call 1-800-772-6436 for more 

information about this program. 

 
6.1 

Clinical Trials Experience 

 
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed 
in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug 
and may not reflect the rates observed in clinical practice.   
 

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Treatment of Postmenopausal Women with Osteoporosis  
 
The safety of Prolia in the treatment of postmenopausal osteoporosis was assessed in a 3-year, 
randomized, double-blind, placebo-controlled, multinational study of 7808 postmenopausal women aged 
60 to 91 years.  A total of 3876 women were exposed to placebo and 3886 women were exposed to Prolia 
administered subcutaneously once every 6 months as a single 60 mg dose.  All women were instructed to 
take at least 1000 mg of calcium and 400 IU of vitamin D supplementation per day. 
 
The incidence of all-cause mortality was 2.3% (n = 90) in the placebo group and 1.8% (n = 70) in the 
Prolia group.  The incidence of nonfatal serious adverse events was 24.2% in the placebo group and 
25.0% in the Prolia group.  The percentage of patients who withdrew from the study due to adverse events 
was 2.1% and 2.4% for the placebo and Prolia groups, respectively.  
 
Adverse reactions reported in ≥ 2% of postmenopausal women with osteoporosis and more frequently in 
the Prolia-treated women than in the placebo-treated women are shown in the table below.  
 

Table 1. Adverse Reactions Occurring in ≥ 2% of Patients with Osteoporosis and More Frequently 

than in Placebo-treated Patients  

SYSTEM ORGAN CLASS 
    Preferred Term 

Prolia 

(N = 3886) 

n (%) 

Placebo 

(N = 3876) 

n (%) 

 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 

Anemia 

129 (3.3) 

107 (2.8) 

 
CARDIAC DISORDERS 

Angina pectoris 

101 (2.6) 

87 (2.2) 

Atrial fibrillation 

79 (2.0) 

77 (2.0) 

 
EAR AND LABYRINTH DISORDERS 

Vertigo 

195 (5.0) 

187 (4.8) 

 
GASTROINTESTINAL DISORDERS 

Abdominal pain upper 

129 (3.3) 

111 (2.9) 

Flatulence 

84 (2.2) 

53 (1.4) 

Gastroesophageal reflux disease 

80 (2.1) 

66 (1.7) 

 
GENERAL DISORDERS AND ADMINISTRATION 
SITE CONDITIONS 

Edema peripheral 

189 (4.9) 

155 (4.0) 

Asthenia 

90 (2.3) 

73 (1.9) 

 
INFECTIONS AND INFESTATIONS 

Cystitis 

228 (5.9) 

225 (5.8) 

Upper respiratory tract infection 

190 (4.9) 

167 (4.3) 

Pneumonia 

152 (3.9) 

150 (3.9)