Hypocalcaemia: Transient hypocalcaemia has been observed in patients receiving EVENITY. Correct hypocalcaemia prior to initiating therapy with EVENITY [see Contraindications, Adverse Reactions, and Use in Pregnancy & Lactation].
Monitor patients for signs and symptoms of hypocalcaemia. Patients should be adequately supplemented with calcium and vitamin D [see Pharmacology: Pharmacodynamics under Actions].
Hypersensitivity: Clinically significant hypersensitivity reactions, including angio-oedema, erythema multiforme, and urticaria occurred in the EVENITY group in clinical trials. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of EVENITY [see Contraindications and Adverse Reactions].
Myocardial Infarction, Stroke and Cardiovascular Death: In a randomised controlled trial in postmenopausal women, there was a higher rate of major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, in patients treated with EVENITY compared to those treated with alendronate.
In two large, controlled fracture trials of EVENITY for the treatment of osteoporosis in postmenopausal women, cardiovascular events of myocardial infarction (MI) and stroke were prospectively adjudicated. In the active-controlled trial (N = 4054) during the 12-month double blind EVENITY treatment phase, MI occurred in 16 women (0.8%) in the EVENITY arm and 5 (0.2%) in the alendronate arm; stroke occurred in 13 women (0.6%) in the EVENITY arm and 7 (0.3%) in the alendronate arm. These events occurred in patients with and without a history of MI or stroke. In the placebo-controlled trial (N = 7157) during the 12-month double blind EVENITY treatment phase, MI occurred in 9 women (0.3%) in the EVENITY arm and 8 (0.2%) in the placebo arm; stroke occurred in 8 women (0.2%) in the EVENITY arm and 10 (0.3%) in the placebo arm. These events occurred in patients with and without a history of MI or stroke.
A causal relationship between EVENITY and these events has not been established. In both trials, most participants had common risk factors for cardiovascular disease, and within each trial, cardiovascular risk factors were balanced between treatment arms. Consider the benefit-risk in patients at increased risk for MI or stroke. Patients should be instructed to watch for symptoms of MI and stroke and to seek prompt medical attention if symptoms occur. If a patient experiences a myocardial infarction or stroke during therapy, consider discontinuation of EVENITY.
EVENITY should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Treating physician should assess patient for risk of CV before treatment.
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 rarely in patients receiving EVENITY in the clinical trials.
Prior to treatment, a dental examination with appropriate preventative dentistry should be considered in patients with possible risk factors. Before commencing invasive dental procedures, patients and their dentist should be advised of the risks and reports of osteonecrosis of the jaw so that dental symptoms, including toothache, developing during treatment can be fully assessed for cause before treatment of the tooth commences.
Patients who are suspected of having or who develop ONJ while on EVENITY should receive care by a dentist or an oral surgeon. Discontinuation of EVENITY therapy should be considered based on individual benefit-risk assessment.
Atypical Femoral Fracture: Atypical low-energy or low-trauma fracture of the femoral shaft, which can occur spontaneously, has occurred rarely in patients receiving EVENITY in the clinical trials. Any patient who presents with new or unusual thigh, hip, 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 EVENITY therapy should be considered based on individual benefit-risk assessment.
Effects on Ability to Drive and Use Machines: No studies on the effect on the ability to drive or use heavy machinery have been performed in patients receiving EVENITY.
Hepatic Impairment: No clinical studies have been conducted to evaluate the effect of hepatic impairment.
Renal Impairment: No dose adjustment is required in patients with renal impairment. There is limited experience in patients with eGFR < 30 mL/min.
Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m2) or receiving dialysis are at greater risk of developing hypocalcaemia [see Contraindications and Precautions]. Monitoring of calcium levels is highly recommended. Adequate intake of calcium and vitamin D is important in patients with severe renal impairment or receiving dialysis.
Use in Children: The safety and efficacy of EVENITY have not been established in paediatric patients [see Pharmacology: Preclinical Safety Data/Nonclinical Toxicology under Actions].
Use in the Elderly: Of the 6525 postmenopausal women with osteoporosis treated with EVENITY in clinical studies, 5222 (80%) were ≥ 65 years old and 2385 (36.6%) were ≥ 75 years old. No overall differences in safety or efficacy were observed among these patients and younger patients.