PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Miscellaneous Agents Affecting Bone Structure and Mineralization

    BOXED WARNING

    Myocardial infarction, stroke

    Do not begin treatment with romosozumab in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits of romosozumab therapy outweigh the risks in patients with other cardiovascular risk factors. Monitor for signs and symptoms of myocardial infarction and stroke, and instruct patients to seek prompt medical care if symptoms occur. If a patient experiences a myocardial infarction or stroke during treatment, discontinue romosozumab. A higher incidence of major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, occurred in patients treated with romosozumab vs. those treated with alendronate during clinical trials.[64057]  

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral humanized IgG2 monoclonal antibody and sclerostin inhibitor
    Used for the treatment of osteoporosis in postmenopausal women at high risk for fracture or who have either failed or are intolerant to other therapy
    Associated with a higher incidence of major adverse cardiac events (MACE) vs. alendronate

    COMMON BRAND NAMES

    EVENITY

    HOW SUPPLIED

    EVENITY/Romosozumab Subcutaneous Inj Sol: 1.17mL, 105mg

    DOSAGE & INDICATIONS

    For the treatment of osteoporosis in postmenopausal women at high risk for fracture.
    Subcutaneous dosage
    Adult postmenopausal females

    210 mg subcutaneously once monthly for 12 months. Supplement calcium and vitamin D if dietary intake is inadequate.[64057] High fracture risk is defined as women with a history of osteoporotic fracture or multiple risk factors for fracture or those who have failed or are intolerant to other available osteoporosis therapy.[64057] Romosozumab may be considered for patients unable to use oral therapy and as initial therapy for those at very high fracture risk. Follow with a drug intended for long-term use, such as a bisphosphonate or denosumab, to prevent decline of bone density and loss of efficacy against fracture.  Romosozumab is also a treatment option for patients previously treated with teriparatide or abaloparatide.

    MAXIMUM DOSAGE

    Adults

    210 mg/month subcutaneously.

    Geriatric

    210 mg/month subcutaneously.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Romosozumab is a clear to opalescent, colorless to light yellow solution.
    Romosozumab should be administered by a health care provider.
    Limit the duration of treatment to 12 doses. The anabolic effect of romosozumab decreases after 12 monthly doses. Consider therapy with an anti-resorptive agent if osteoporosis treatment remains warranted.[64057]
    Ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia. Supplement with adequate calcium and vitamin D during treatment.
    Missed dose: If a dose is missed, administer it as soon as it can be rescheduled. Thereafter, schedule doses every month from the date of the last dose.[64057]

    Subcutaneous Administration

    Allow the product to warm at room temperature for a minimum of 30 minutes before injecting. Do not warm in any other way.
    Prepare 2 injection sites. Recommended injection sites include the thigh, abdomen, or outer area of the upper arm. Rotate injection sites with each dose. If using the same injection site, ensure that it is not the same spot on the injection site used for a previous injection.
    Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
    Use 2 separate syringes and 2 separate injections to administer the full romosozumab dose.
    Pull gray cap straight off needle.
    Inject subcutaneously.
    When done, gently lift syringe off skin.
    Repeat all steps with the second syringe to inject the full dose.[64057]

    STORAGE

    EVENITY:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard product that has been stored at room temperature for over 30 days
    - Discard unused portion. Do not store for later use.
    - Do not expose product to temperatures above 77 degrees F
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store at or below 77 degrees F for no more than 30 days if refrigeration is not available
    - Store in original container

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Romosozumab is contraindicated in patients with a history of systemic hypersensitivity to romosozumab or any component of the formulation. If an anaphylactic or other clinically significant allergic reaction occurs, discontinue romosozumab and treat as clinically indicated. Angioedema, erythema multiforme, dermatitis, rash, and urticaria have been reported with romosozumab use.[64057]

    Myocardial infarction, stroke

    Do not begin treatment with romosozumab in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits of romosozumab therapy outweigh the risks in patients with other cardiovascular risk factors. Monitor for signs and symptoms of myocardial infarction and stroke, and instruct patients to seek prompt medical care if symptoms occur. If a patient experiences a myocardial infarction or stroke during treatment, discontinue romosozumab. A higher incidence of major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, occurred in patients treated with romosozumab vs. those treated with alendronate during clinical trials.[64057]  

    Anemia, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, dental work, infection, radiation therapy

    Osteonecrosis of the jaw (ONJ) has been reported in patients receiving romosozumab. It is generally associated with tooth extraction and/or local infection with delayed healing; however, it may occur spontaneously. Perform a routine oral exam before starting romosozumab. Risk factors for ONJ include anemia, cancer, radiation therapy, coagulopathy, preexisting dental disease or infection, and poor oral hygiene. Concomitant use of other drugs associated with ONJ, including chemotherapy, bisphosphonates, denosumab, angiogenesis inhibitors, and corticosteroid therapy, may increase the risk of developing ONJ. For patients requiring invasive dental work, use clinical judgment to guide the management of each patient based on benefit-risk assessment. Refer patients who develop or are suspected of having ONJ to a dentist or oral surgeon for care. Dental surgery to treat ONJ may exacerbate the condition. Consider romosozumab discontinuation based on benefit-risk assessment.[64057] For antiresorptive therapy, which may follow romosozumab treatment, preventive measures and continued regular follow-up with a dentist are recommended to minimize the risk of osteonecrosis.[64058]

    Dialysis, hypocalcemia, renal failure, renal impairment

    Romosozumab is contraindicated in patients with preexisting hypocalcemia. Correct hypocalcemia before initiating romosozumab therapy. Monitor all patients for signs and symptoms of hypocalcemia. Patients with severe renal impairment (eGFR less than 30 mL/minute/1.73 m2) or renal failure requiring dialysis were at greater risk for hypocalcemia during clinical trials. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended in these patients. In all patients, ensure adequate intake of calcium and vitamin D. Instruct patients to seek medical care if symptoms of hypocalcemia develop.[64057]

    Pregnancy

    Romosozumab is not indicated for use in women of reproductive potential, including during pregnancy. During animal studies in pregnant rats, skeletal malformations including syndactyly and polydactyly occurred in 1 of 75 litters of a dam who received weekly subcutaneous doses of romosozumab equivalent to at least 32 times the clinical exposure observed in humans after a monthly subcutaneous dose of 210 mg based on AUC comparison. Femoral periosteal and endocortical circumferences were slightly decreased in the offspring of rats given romosozumab at weekly doses equivalent to 1.4, 18, or 54 times the clinical exposure after a monthly subcutaneous dose of 210 mg based on AUC comparison from 6 weeks before cohabitation through mating and lactation. Cortical thickness was increased at a dose 56 times the expected clinical exposure, and femoral metaphyseal bone mineral density was slightly decreased at doses equivalent to 18 to 54 times the expected clinical exposure.[64057]

    Breast-feeding

    Romosozumab is not indicated for use in women of reproductive potential, including during breast-feeding. In pregnant rats given romosozumab at weekly doses equivalent to 1.4, 18, or 54 times the clinical exposure after a monthly subcutaneous dose of 210 mg based on AUC comparison from 6 weeks before cohabitation through mating and lactation, romosozumab was dose-dependently present in offspring serum on postnatal day 21 at 0.01 to 2.4 times maternal exposure due to maternal and/or lactational exposure.[64057]

    ADVERSE REACTIONS

    Severe

    bone fractures / Delayed / 0-1.0
    myocardial infarction / Delayed / 0.3-0.8
    stroke / Early / 0.2-0.6
    angioedema / Rapid / 0-0.1
    erythema multiforme / Delayed / 0-0.1

    Moderate

    antibody formation / Delayed / 18.1-18.1
    peripheral edema / Delayed / 1.7-2.4
    erythema / Early / 1.4-1.4
    hypocalcemia / Delayed / 0-1.0

    Mild

    arthralgia / Delayed / 8.1-13.1
    headache / Early / 5.2-6.6
    injection site reaction / Rapid / 4.9-4.9
    asthenia / Delayed / 2.3-2.5
    insomnia / Early / 1.7-2.0
    paresthesias / Delayed / 1.4-2.0
    rash / Early / 1.1-1.1
    urticaria / Rapid / 0.4-0.4

    DRUG INTERACTIONS

    There are no drug interactions associated with Romosozumab products.

    PREGNANCY AND LACTATION

    Pregnancy

    Romosozumab is not indicated for use in women of reproductive potential, including during pregnancy. During animal studies in pregnant rats, skeletal malformations including syndactyly and polydactyly occurred in 1 of 75 litters of a dam who received weekly subcutaneous doses of romosozumab equivalent to at least 32 times the clinical exposure observed in humans after a monthly subcutaneous dose of 210 mg based on AUC comparison. Femoral periosteal and endocortical circumferences were slightly decreased in the offspring of rats given romosozumab at weekly doses equivalent to 1.4, 18, or 54 times the clinical exposure after a monthly subcutaneous dose of 210 mg based on AUC comparison from 6 weeks before cohabitation through mating and lactation. Cortical thickness was increased at a dose 56 times the expected clinical exposure, and femoral metaphyseal bone mineral density was slightly decreased at doses equivalent to 18 to 54 times the expected clinical exposure.[64057]

    Romosozumab is not indicated for use in women of reproductive potential, including during breast-feeding. In pregnant rats given romosozumab at weekly doses equivalent to 1.4, 18, or 54 times the clinical exposure after a monthly subcutaneous dose of 210 mg based on AUC comparison from 6 weeks before cohabitation through mating and lactation, romosozumab was dose-dependently present in offspring serum on postnatal day 21 at 0.01 to 2.4 times maternal exposure due to maternal and/or lactational exposure.[64057]

    MECHANISM OF ACTION

    Romosozumab inhibits the action of sclerostin, a regulatory factor in bone metabolism, which leads to increased bone formation and, to a lesser extent, decreased bone resorption. Animal studies demonstrated that romosozumab increases trabecular and cortical bone mass and improves bone structure and strength through stimulation of new bone formation on trabecular and cortical bone surfaces by increasing osteoblastic activity.[64057]

    PHARMACOKINETICS

    Romosozumab is administered subcutaneously. Romosozumab exhibits nonlinear pharmacokinetics. The estimated volume of distribution at steady-state is approximately 3.92 L. Romosozumab is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG. The clearance of romosozumab decreases as the dose increases. The estimated mean systemic clearance (CL/F) of romosozumab was 0.38 mL/hour/kg after a single subcutaneous dose of 3 mg/kg. The mean effective half-life was 12.8 days after 3 doses of 3 mg/kg every 4 weeks.[64057]
     
    Affected cytochrome P450 isoenzymes and/or drug transporters: none

    Subcutaneous Route

    After a single 210 mg dose in healthy volunteers, mean (standard deviation [SD]) romosozumab Cmax was 22.2 (5.8) mcg/mL and mean (SD) AUC was 389 (127) mcg x day/mL. Steady-state concentrations were achieved by month 3 after monthly administration of 210 mg to postmenopausal women. Mean trough romosozumab concentrations at months 3, 6, 9, and 12 ranged from 8 to 13 mcg/mL. Romosozumab exhibited nonlinear pharmacokinetics with exposure increasing greater than dose proportionally (e.g., 550-fold mean AUC increase for a 100-fold increase in the subcutaneous dose ranging from 0.1 to 10 mg/kg). Median Tmax is 5 days (range 2 to 7 days).[64057]