Evenity

— THERAPEUTIC CATEGORIES —
  • Bone disorders
PAGE CONTENTS
  • Jump to Section
  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Evenity Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Romosozumab-aqqg 105mg/1.17mL; per prefilled syringe; soln for SC inj; preservative-free.

    Pharmacological Class

    Sclerostin inhibitor.

    How Supplied

    Single-use prefilled syringes—2

    Storage

    Refrigerate at 2° C to 8° C (36° F to 46° F) in the original carton to protect from light. Do not freeze. Do not shake.  

    If removed from the refrigerator, Evenity can be kept at room temperature up to 25° C (77° F) in the original carton and must be used within 30 days. If not used within 30 days, discard Evenity.     

    Do not expose Evenity to temperatures above 25° C (77° F).

    Manufacturer

    Amgen, Inc.

    Generic Availability

    NO

    Mechanism of Action

    Romosozumab-aqqg is a humanized monoclonal antibody (IgG2) that inhibits the action of sclerostin, a regulatory factor in bone metabolism. It increases bone formation and, to a lesser extent, decreases bone resorption.

    Evenity Indications

    Indications

    In postmenopausal women with osteoporosis: at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other therapy.

    Limitations of Use

    Duration limited to 12 monthly doses; consider anti-resorptive agent if continued therapy for osteoporosis warranted.

    Evenity Dosage and Administration

    Adult

    Should be administered by a healthcare professional. Give as SC inj in abdomen, thigh or upper arm; rotate inj sites. 210mg once monthly (given as 2 separate syringes consecutively) for 12 months. Supplement with calcium and Vit.D during treatment.

    Children

    Not established.

    Evenity Contraindications

    Contraindications

    Hypocalcemia.

    Evenity Boxed Warnings

    Boxed Warning

    Potential risk of myocardial infarction, stroke and cardiovascular death.

    Evenity Warnings/Precautions

    Warnings/Precautions

    Increased risk of major adverse cardiac events; monitor. MI or stroke within previous year: do not initiate. Discontinue if MI, stroke, anaphylaxis, other hypersensitivity reaction occurs. Correct hypocalcemia prior to initiating; monitor for signs/symptoms. Monitor for osteonecrosis of the jaw (ONJ). Do baseline oral exam if risks for ONJ exist (eg, tooth extraction, oral surgery, poor oral hygiene, and/or other pre-existing dental disease, infection, cancer, radiotherapy, anemia, coagulopathy); discontinue based on risk/benefit assessment. Maintain good oral hygiene. Evaluate for atypical fractures if thigh/groin pain develops; consider interrupting therapy based on risk/benefit assessment. Do not inj areas where skin is tender, bruised, red, hard, or scars or stretch marks. Severe renal impairment or on dialysis: monitor serum calcium and adequately supplement with Vit.D and calcium. Women of reproductive potential, pregnancy, nursing mothers: not indicated.

    Warnings/Precautions

    Major Adverse Cardiac Events (MACE) 

    • Evenity should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. 
    • Consider the benefits vs risks in those with other cardiovascular risk factors. 
    • Monitor for signs/symptoms of myocardial infarction and stroke; instruct patients to seek medical attention if symptoms occur. 
    • Evenity should be discontinued if a patient experiences a myocardial infarction or stroke during therapy.

    Hypersensitivity Reactions 

    • Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticaria have occurred in Evenity-treated patients. 
    • Initiate appropriate therapy and discontinue further use if an anaphylactic or other clinically significant allergic reaction occurs.

    Hypocalcemia

    • Hypocalcemia has occurred in patients receiving Evenity.
    • Correct hypocalcemia prior to initiation. 
    • Monitor for signs/symptoms of hypocalcemia. 
    • Patients should be adequately supplemented with calcium and vitamin D while on Evenity.
    • Increased risk of developing hypocalcemia in those with severe renal impairment (eGFR 15–29 mL/min/1.73m2) or receiving dialysis; monitor serum calcium and adequately supplement these patients with calcium and vitamin D.

    Osteonecrosis of the Jaw

    • Osteonecrosis of the jaw (ONJ) can occur spontaneously and  is generally associated with tooth extraction and/or local infection with delayed healing. 
    • Perform a routine oral examination prior to initiation of treatment. 
    • Concomitant drugs associated with ONJ (eg, 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, preexisting dental disease or infection, anemia, and coagulopathy.
    • Patients who require invasive dental procedures, should be guided based on benefit/risk assessment. 
    • Patients who are suspected of having or who develop ONJ while on Evenity should receive care by a dentist or an oral surgeon. In these patients, dental surgery to treat ONJ may exacerbate the condition. 
    • Discontinuation of Evenity should be considered based on benefit/risk assessment.

    Atypical Subtrochanteric and Diaphyseal Femoral Fractures

    • Atypical low-energy or low trauma fractures of the femoral shaft can occur; causality has not been established as these fractures also occur in osteoporotic patients who have not been treated. 
    • Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area.
    • Advise patients to report new or unusual thigh, hip, or groin pain during treatment; evaluate for incomplete femur fracture if occurs. 
    • Interruption of Evenity should be considered based on benefit/risk assessment.

    Pregnancy Considerations

    Not indicated for use in women of reproductive potential.

    Nursing Mother Considerations

    Not indicated for use in women of reproductive potential.

    Pediatric Considerations

    Safety and effectiveness have not been established.

    Geriatric Considerations

    No overall differences in safety or efficacy were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

    Renal Impairment Considerations

    No dose adjustment is required in patients with renal impairment.  

    Monitor calcium concentrations; should adequately supplement with calcium and vitamin D in those who have severe renal impairment or are receiving dialysis.

    Evenity Pharmacokinetics

    Absorption

    The median time to maximum concentration (Tmax) is 5 days (range: 2 to 7 days).

    Distribution

    The estimated volume of distribution at steady-state is ~3.92 L. 

    Metabolism

    Romosozumab-aqqg is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG. 

    Elimination

    The mean effective half-life was 12.8 days after 3 doses of 3 mg/kg (the approved recommended dosage for a 70 kg woman) every 4 weeks.

    Evenity Interactions

    Interactions

    Increased risk of ONJ with concomitant corticosteroids, chemotherapy, bisphosphonates, angiogenesis inhibitors or denosumab.

    Evenity Adverse Reactions

    Adverse Reactions

    Arthralgia, headache, muscle spasms, peripheral edema, asthenia, neck pain, insomnia, paresthesia; hypersensitivity, atypical subtrochanteric and diaphyseal femoral fractures.

    Evenity Clinical Trials

    Clinical Trials

    Study 1 (ClinicalTrials.gov: NCT01575834): 
    A randomized, double-blind, placebo-controlled study of postmenopausal women aged 55 to 90 years (mean age of 71 years) with bone mineral density (BMD) T-score less than or equal to -2.5 at the total hip or femoral neck.

    Women were randomized to receive subcutaneous injections of either Evenity (N=3589) or placebo (N=3591) for 12 months, with 500 to 1000 mg calcium and 600 to 800 international units vitamin D supplementation daily. At baseline, 18% of women had a vertebral fracture. After the 12-month treatment period, women in both arms transitioned to open-label anti-resorptive therapy (denosumab) for 12 months while remaining blinded to their initial treatment. 

    The coprimary efficacy endpoints were new vertebral fracture at month 12 and month 24. 

    Effect on Fractures 

    • Evenity significantly reduced the incidence of new vertebral fractures through month 12 compared to placebo (0.5% vs 1.8%; P <.001, respectively). In addition, the significant reduction in fracture risk persisted through the second year in women who received Evenity during the first year and transitioned to denosumab compared to those who transitioned from placebo to denosumab (0.6% vs 2.5%; P <.001, respectively).
    • Evenity significantly reduced the incidence of clinical fracture (a composite endpoint of symptomatic vertebral fracture and nonvertebral fracture) at 12 months. However, 88% of these clinical fractures were nonvertebral fractures and the incidence of nonvertebral fractures was not statistically significantly different when comparing Evenity-treated women to placebo-treated women at month 12 or month 24. 

    Effect on Bone Mineral Density (BMD) 

    • Evenity significantly increased BMD at the lumbar spine, total hip, and femoral neck compared with placebo at month 12. The treatment differences in BMD were 12.7% at the lumbar spine, 5.8% at the total hip, and 5.2% at the femoral neck.

     

    Study 2 (ClinicalTrials.gov: NCT01631214): 
    A randomized, double-blind, alendronate-controlled study of postmenopausal women aged 55 to 90 years (mean age of 74 years) with BMD T-score less than or equal to -2.5 at the total hip or femoral neck and either one moderate or severe vertebral fracture or two mild vertebral fractures, or BMD T-score less than or equal to -2.0 at the total hip or femoral neck and either two moderate or severe vertebral fractures or a history of a proximal femur fracture. 

    Women were randomized (1:1) to receive either monthly subcutaneous injections of Evenity (N=2046) or oral alendronate 70 mg weekly (N=2047) for 12 months, with 500 to 1000 mg calcium and 600 to 800 international units vitamin D supplementation daily. After the 12-month treatment period, women in both arms transitioned to open-label alendronate 70 mg weekly while remaining blinded to their initial treatment. 

    This was an event driven trial. The two primary efficacy endpoints were the incidence of morphometric vertebral fracture at 24 months and time to the first clinical fracture through the primary analysis period, which ended when at least 330 patients had a clinical fracture and all patients had completed the 24-month visit. Clinical fracture was a composite endpoint of nonvertebral fracture and symptomatic vertebral fracture. The median duration of follow-up for the primary analysis period was 33 months.

    Effect on Fractures  

    • Evenity significantly reduced the incidence of new vertebral fracture at 24 months compared to alendronate alone (4.1% vs 8.0%; P <.001, respectively).
    • Evenity significantly reduced the risk of clinical fracture through the end of the primary analysis period compared to alendronate alone (9.7% vs 13.0%, respectively), with a hazard ratio of 0.73 (95% CI, 0.61-0.88; P <.001).
    • Evenity followed by alendronate also significantly reduced the risk of nonvertebral fracture through the primary analysis period (median follow-up of 33 months), with a hazard ratio of 0.81 (95% CI, 0.66-0.99; P =0.04) compared to alendronate alone. 

    Effect on Bone Mineral Density (BMD) 

    • Evenity significantly increased BMD at the lumbar spine, total hip, and femoral neck compared with alendronate at month 12. The treatment differences in BMD were 8.7% at the lumbar spine, 3.3% at the total hip, and 3.2% at the femoral neck. 

    Evenity Note

    Not Applicable

    Evenity Patient Counseling

    Patient Counseling

    Major Adverse Cardiac Events 

    • Advise patients to seek immediate medical attention if they experience signs or symptoms of a myocardial infarction or stroke.

    Hypersensitivity Reactions 

    • Advise patients to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction including angioedema, erythema multiforme, dermatitis, rash, and urticaria.

    Calcium and Vitamin D Supplements to Prevent Hypocalcemia 

    • Advise patients to take calcium and vitamin D supplements daily to reduce the risk of hypocalcemia.
    • Advise patients to seek immediate medical attention for symptoms of hypocalcemia.

    Osteonecrosis of the Jaw 

    • Advise patients to practice good oral hygiene during treatment with Evenity and tell their dentist that they are receiving Evenity before having dental work.

    Atypical Femoral Fracture 

    • Advise patients to report signs and symptoms that could be consistent with impending atypical femoral fracture including new or unusual thigh, hip, or groin pain.

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