EVENITY

1 Dosing Considerations EVENITY is administered subcutaneously. EVENITY should be administered by a health care professional or an individual trained by a health care professional. EVENITY Product Monograph Page 5 of 38 After initial training in proper subcutaneous injection technique, an individual may self-inject EVENITY if a physician determines that is appropriate and with medical follow-up as necessary.

2 Recommended Dose and Dosage Adjustment The recommended dose of EVENITY is 210 mg administered once every month as two consecutive subcutaneous injections of 105 mg each using the single-dose prefilled syringes for 12 doses. Patients should be adequately supplemented with calcium and vitamin D (see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and CLINICAL TRIALS).

Limit duration of use to 12 monthly doses. When a patient has completed the 12 months of EVENITY therapy, and osteoporosis therapy remains warranted, continued therapy with an anti- resorptive agent should be considered (see ACTION AND CLINICAL PHARMACOLOGY and CLINICAL TRIALS).

In the absence of a follow on anti-resorptive therapy, bone mineral density (BMD) gains trend toward pre-treatment levels following cessation of EVENITY. Health Canada has not authorized an indication for pediatric use. 73 m2) or end-stage renal disease (ESRD) requiring hemodialysis; however, EVENITY should be used with caution (see WARNINGS AND PRECAUTIONS, Renal Impairment).

3 Administration To administer the recommended dose of 210 mg, give two consecutive subcutaneous injections of 105 mg each. Visually inspect EVENITY for particles and discolouration prior to administration. EVENITY is a clear to opalescent, colourless to light yellow solution.

Do not use if the solution is cloudy or discoloured or contains particles. Administer EVENITY in the abdomen, thigh, or upper arm subcutaneously. If you want to use the same injection site, make sure it is not the same spot on the injection site you used for a previous injection.

Do not inject into areas where the skin is tender, bruised, red, or hard. Comprehensive instructions for the administration of EVENITY are provided in the Patient Medication Information – How to take EVENITY section. 4 Missed Dose If an EVENITY dose is missed, administer as soon as it can be rescheduled.

8% (29/3581) in the EVENITY group. 1% in the EVENITY group. 1% in the EVENITY group. 6%). 1%) in the EVENITY group). 5% (30/2040) in the EVENITY group. 9% in the EVENITY group. 2% in the EVENITY group. 2%). 2 Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Treatment of Postmenopausal Osteoporosis in Women at High Risk of Fracture Study 1 (FRAME) (placebo-controlled) The safety of EVENITY in the treatment of postmenopausal osteoporosis in women at high risk of fracture was demonstrated in a multicenter, randomized, double-blind, placebo-controlled study of 7180 postmenopausal women aged 55 to 90 years (mean age of 71 years).

EVENITY Product Monograph Page 10 of 38 A total of 3581 and 3576 patients received at least 1 dose of EVENITY and placebo, respectively, administered once every month during the 12-month double-blind study period. Patients received at least 500 mg calcium and 600 international units (IU) vitamin D supplementation daily.

Most patients (77%) received a loading dose of 50,000 to 60,000 IU of vitamin D within one week of randomization if their serum 25-hydroxyvitamin D concentrations were 40 ng/mL or less. Study 2 (ARCH) (alendronate-controlled) The safety of EVENITY in the treatment of postmenopausal osteoporosis in women at high risk of fracture was demonstrated in a multicenter, randomized, double-blind, alendronate-controlled study of 4093 postmenopausal women aged 55 to 90 years (mean age of 74 years).

A total of 2040 and 2014 patients received at least 1 dose of EVENITY and alendronate, respectively, with EVENITY administered once every month during the 12-month double-blind study period. A total of 3462 patients received at least 1 dose of alendronate in the open-label period.

Please see the Serious Warnings and Precautions Box at the beginning of Part I:

Health Professional Information. General Patients should be adequately supplemented with calcium and vitamin D during EVENITY treatment (see CONTRAINDICATIONS, and WARNINGS AND PRECAUTIONS, Endocrine and Metabolism -- Hypocalcemia).

Bone 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 and has occurred in EVENITY- treated patients in clinical trials (see Clinical Trial Adverse Reactions).

Evaluate patients for risk factors for ONJ before starting treatment. A dental examination with appropriate preventative dentistry is recommended prior to treatment with EVENITY in patients with risk factors for ONJ. g. g. g. periodontal and/or other pre-existing dental disease, ill- fitting dentures, anemia, coagulopathy, and infection).

Patients should maintain good oral hygiene practices during treatment with EVENITY. Patients should receive routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling during treatment with EVENITY.

For patients in whom invasive dental procedures cannot be avoided, the clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit-risk assessment. Patients who are suspected of having or who develop ONJ during treatment with EVENITY should receive care by a dentist or an oral surgeon.

Consider discontinuation of EVENITY treatment based on an individual benefit-risk assessment. Atypical Femoral Fractures Atypical low-energy or low-trauma fractures of the femoral shaft, which can occur spontaneously, have been reported in patients treated with EVENITY (see Clinical Trial Adverse Reactions).

 EVENITY is contraindicated in patients who are hypersensitive to romosozumab or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see Table 1 Dosage Forms, Strengths, Composition and Packaging.

 EVENITY is contraindicated in patients with hypocalcemia. Correct pre-existing hypocalcemia prior to initiating treatment with EVENITY (see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS).