5.5 Atypical Subtrochanteric and Diaphyseal Femoral FracturesAtypical low-energy or low trauma fractures of the femoral shaft have been reported in patients receiving
EVENITY [see Adverse Reactions (6.1)].
These fractures can occur anywhere in the femoral shaft fromjust 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 alsooccur in osteoporotic patients who have not been treated.
Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. Theymay 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.
During EVENITY 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 andshould be eva luated to rule out an incomplete femur fracture. Patient presenting with an atypical femurfracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruptionof EVENITY therapy should be considered based on benefit-risk assessment [see Clinical Studies (14)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
• Major adverse cardiac events [see Boxed Warning and Warnings and Precautions (5.1)]
• Hypersensitivity [see Contraindications (4) and Warnings and Precautions (5.2)]
• Hypocalcemia [see Contraindications (4) and Warnings and Precautions (5.3)]
• Osteonecrosis of the Jaw [see Warnings and Precautions (5.4)]
• Atypical Subtrochanteric and Diaphyseal Femoral Fractures [see Warnings and Precautions
(5.5)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed inthe clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug andmay not reflect the rates observed in practice.
The safety of EVENITY for the treatment of postmenopausal osteoporosis was eva luated in a multicenter,randomized, double-blind, placebo-controlled study (Study 1, NCT01575834) of 7180 postmenopausalwomen aged 55 to 90 years (mean age of 71 years). A total of 3581 and 3576 women received at least onedose of EVENITY and placebo, respectively, administered once every month during the 12-monthdouble-blind study period. Women received at least 500 mg calcium and 600 international units of
vitamin D supplementation daily and 77% received a loading dose of 50,000 to 60,000 international unitsof vitamin D within one week of randomization (if serum 25-hydroxyvitamin D concentrations were40 ng/mL or less).
The safety of EVENITY for the treatment of postmenopausal osteoporosis in patients at high risk offracture was eva luated in a multicenter, randomized, double-blind, alendronate-controlled study (Study 2,NCT01631214) of 4093 postmenopausal women aged 55 to 90 years (mean age of 74 years). A total of2040 and 2014 women received at least one dose of EVENITY and alendronate, respectively, during the12-month double-blind study period. Women received at least 500 mg calcium and 600 international unitsvitamin D supplementation daily and 74% received a loading dos |
