].
5 WARNINGS AND PRECAUTIONS
5.1 Major Adverse Cardiac Events (MACE)
In a randomized controlled trial in postmenopausal women, there was a higher rate of major adversecardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction andnonfatal stroke, in patients treated with EVENITY compared to those treated with alendronate [see BoxedWarning and Adverse Reactions (6.1)].
EVENITY should not be initiated in patients who have had a myocardial infarction or stroke within thepreceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular riskfactors. Monitor for signs and symptoms of myocardial infarction and stroke and instruct patients to seekprompt medical attention if symptoms occur. If a patient experiences a myocardial infarction or strokeduring therapy, EVENITY should be discontinued.
5.2 Hypersensitivity Reactions
Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticariahave occurred in EVENITY-treated patients. If an anaphylactic or other clinically significant allergicreaction occurs, initiate appropriate therapy and discontinue further use of EVENITY [seeContraindications (4) and Adverse Reactions (6.1)].
5.3 Hypocalcemia
Hypocalcemia has occurred in patients receiving EVENITY. Correct hypocalcemia prior to initiating
EVENITY [see Contraindications (4), Adverse Reactions (6.1) and Use in Specific Populations (8.7)].
Monitor patients for signs and symptoms of hypocalcemia. Patients should be adequately supplemented
with calcium and vitamin D while on EVENITY [see Dosage and Administration (2.2) and Clinical
Studies (14.1)].
Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to29 mL/min/1.73 m2) or receiving dialysis are at greater risk of developing hypocalcemia. Monitor serumcalcium and adequately supplement patients who have severe renal impairment or are receiving dialysiswith calcium and vitamin D. Instruct patients with severe renal impairment, including those receiving
dialysis, about the symptoms of hypocalcemia and the importance of maintaining calcium levels withadequate calcium and vitamin D supplementation.
5.4 Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with toothextraction and/or local infection with delayed healing, and has been reported in patients receivingEVENITY. A routine oral examination should be performed by the prescriber prior to initiation ofEVENITY treatment. Concomitant administration of drugs associated with ONJ (chemotherapy,bisphosphonates, denosumab, angiogenesis inhibitors, and corticosteroids) may increase the risk of
developing ONJ. Other risk factors for ONJ include cancer, radiotherapy, poor oral hygiene, pre-existingdental disease or infection, anemia, and coagulopathy [see Adverse Reactions (6.1)].
For patients requiring invasive dental procedures, clinical judgment of the treating physician and/or oralsurgeon should guide the management plan of each patient based on benefit-risk assessment. Patients whoare suspected of having or who develop ONJ while on EVENITY should receive care by a dentist or anoral surgeon. In these patients, dental surgery to treat ONJ may exacerbate the condition. Discontinuationof EVENITY should be considered based on benefit-risk assessment.
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