Class: Bone Anabolic Agents
Chemical Name: Anti-(human sclerostin) (human-mouse monoclonal 785A070802 heavy chain), disulfide with human-mouse monoclonal 785A070802 κ-chain, dimer immunoglobulin G2
Molecular Formula: C6452H9926N1714O2040S54
CAS Number: 909395-70-6
May increase risk of MI, stroke, and cardiovascular death. (See Cardiac Effects under Cautions.)
Do not initiate in patients with a history of MI or stroke within the past year. In those with other cardiovascular risk factors, consider whether benefits of the drug outweigh risks.
If patient experiences an MI or stroke, discontinue romosozumab.
Bone anabolic agent; humanized anti-sclerostin monoclonal antibody.
Uses for Romosozumab-aqqg
Treatment of osteoporosis in postmenopausal women at high risk of fracture, defined as history of osteoporotic fracture or multiple risk factors for fracture.
Treatment of osteoporosis in postmenopausal women following failure of or intolerance to other available osteoporosis therapies.
Anabolic effect wanes after 12 months of therapy; limit duration of romosozumab therapy to 12 months. (See Absorption under Pharmacokinetics.) If continued treatment of osteoporosis needed, consider use of a bone resorption inhibitor.
In addition to adequate intake of calcium/vitamin D and other lifestyle modifications (e.g., exercise, avoidance of excessive alcohol and tobacco use), experts recommend that pharmacologic therapy for osteoporosis be considered in postmenopausal women and in men ≥50 years of age with high risk of fractures (generally those who have experienced a previous hip or vertebral fracture or who have low bone mineral density [BMD]); pharmacologic therapy also may be considered in postmenopausal women and in men ≥50 years of age with low bone mass, although there is less evidence supporting overall fracture risk reduction in such patients.
Use of a drug with proven antifracture efficacy is recommended.
Individualize choice of therapy based on potential benefits (with respect to fracture risk reduction) and adverse effects of therapy, patient preferences, comorbidities, and risk factors.
Some experts recommend romosozumab (for up to 1 year) as a treatment option in postmenopausal women with osteoporosis at very high risk for fracture, such as those with severe osteoporosis (i.e., T-score below −2.5 and fractures) or multiple vertebral fractures, to reduce risk of vertebral, hip, and nonvertebral fractures; following completion of romosozumab treatment course, administer other antiresorptive therapy to maintain bone mineral density (BMD) gains and reduce fracture risk. Avoid use in women at high risk for cardiovascular disease or stroke (i.e., history of MI or stroke) pending further characterization of the drug’s cardiovascular risks. (See Cardiac Effects under Cautions.)
Romosozumab-aqqg Dosage and Administration
Patients should receive adequate supplemental calcium and vitamin D during romosozumab therapy.
Administer by sub-Q injection by health-care professional into abdomen, anterior thigh, or outer aspect of upper arm; do not administer IV or by IM injection.
Available in single-use prefilled syringes containing 105 mg of romosozumab-aqqg in 1.17 mL of solution. Single 210-mg dose requires administration of entire contents of 2 prefilled syringes sequentially at separate sites.
Use different injection site each time the drug is administered. If an injection site is used again, avoid site of the previous injection.
Do not inject into areas of skin that are tender, bruised, red, or hard. Avoid scars and stretch marks; avoid injections within 2 inches of navel.
Prior to administration, allow solution to warm at room temperature for ≥30 minutes; do not use other methods to warm the drug.
Solution should appear clear to opalescent and colorless to light yellow; do not use if it is cloudy, discolored, or contains particles.
Do not shake the drug.
Treatment in Postmenopausal Women at High Risk for FractureSub-Q
210 mg once every month for 12 months.
Administer a missed dose as soon as it can be rescheduled; give subsequent doses once monthly from the date of administered dose.
Treatment in Postmenopausal Women at High Risk for FractureSub-Q
Do not exceed 12 months’ duration. Anabolic effect wanes after 12 months. (See Absorption under Pharmacokinetics.) If continued treatment needed, consider use of a bone resorption inhibitor.
Manufacturer makes no specific dosage recommendations. (See Hepatic Impairment under Cautions.)
Dosage adjustment not needed.
Manufacturer makes no special dosage recommendations. Most patients in clinical trials were ≥65 years of age. (See Geriatric Use under Cautions.)
Cautions for Romosozumab-aqqg
Hypocalcemia (preexisting hypocalcemia must be corrected prior to initiating romosozumab).
History of systemic hypersensitivity reaction (e.g., angioedema, erythema multiforme, urticaria) to romosozumab or any ingredient in the formulation.
May increase risk of MI, stroke, and cardiovascular death.
Higher incidence of major adverse cardiovascular events (composite end point of cardiovascular death, nonfatal MI, and nonfatal stroke) observed in a clinical trial in postmenopausal women receiving romosozumab-aqqg compared with those receiving alendronate (2 versus 1.1%). In another clinical trial, incidence of such events was balanced between the romosozumab-aqqg and placebo groups (0.8% in each group).
Manufacturer states do not initiate in patients with a history of MI or stroke within the past year. In those with other cardiovascular risk factors, consider whether benefits of the drug outweigh risks.
Monitor for signs and symptoms of MI and stroke. If patient experiences an MI or stroke, discontinue romosozumab.
Hypersensitivity reactions (e.g., angioedema, erythema multiforme, dermatitis, rash, urticaria) reported.
If anaphylactic or other clinically important hypersensitivity reaction occurs, initiate appropriate therapy and permanently discontinue romosozumab.
Other Warnings and Precautions
Hypocalcemia reported. Patients with severe renal impairment (estimated GFR [eGFR] 15–29 mL/minute per 1.73 m2) or receiving dialysis are at increased risk of developing hypocalcemia.
Correct preexisting hypocalcemia before initiating romosozumab.
All patients should receive adequate supplemental calcium and vitamin D; monitor for manifestations of hypocalcemia.
In patients with severe renal impairment or receiving dialysis, monitor serum calcium concentrations and provide adequate supplemental calcium and vitamin D.
Osteonecrosis of the Jaw (ONJ)
ONJ reported. May occur spontaneously, but generally associated with tooth extraction and/or local infection with delayed healing.
Risk factors include concomitant use of other drugs associated with ONJ (e.g., chemotherapy, bisphosphonates, denosumab, angiogenesis inhibitors, corticosteroids), cancer, radiation therapy, poor oral hygiene, preexisting dental disease or infection, anemia, and coagulopathy.
Perform routine oral examination before initiating romosozumab. Patients should maintain good oral hygiene during treatment.
For patients requiring invasive dental procedures, use clinical judgment and assessment of benefits and risks to guide treatment plan. Patients with suspected or confirmed ONJ should receive care from a dentist or oral surgeon; consider discontinuing romosozumab. Dental surgery to treat ONJ may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral Fracture
Atypical low-energy or low-trauma fractures of the femur reported. Such fractures can occur anywhere along the femoral shaft from just below the lesser trochanter to above the supracondylar flare and have transverse or short oblique orientation without evidence of comminution.
May be bilateral and often occur with minimal or no trauma to affected area. Many patients report dull or aching thigh pain weeks to months before a complete fracture occurs.
Causality not established; such fractures also reported in untreated osteoporotic patients.
Suspect atypical fracture in patients presenting with thigh or groin pain and evaluate to rule out incomplete femur fracture. Assess patients with atypical femur fracture for fracture in contralateral limb; consider interruption of romosozumab therapy.
Immunogenicity and Antibody Formation
Romosozumab-binding antibodies, including neutralizing antibodies, reported. Presence of antibodies associated with lower serum concentrations of the drug, but generally not associated with changes in efficacy or safety.
Skeletal abnormalities (e.g., syndactyly, polydactyly) and minimal to slight decreases in femoral BMD and/or cortical circumference reported in animal reproduction studies.
Not indicated for use in women of childbearing potential.
Detected postnatally in dose-dependent concentrations in serum of rat pups as the result of exposure during gestation and/or nursing.
Not indicated for use in women of childbearing potential.
Safety and efficacy not established in pediatric patients.
In 2 pivotal studies of romosozumab-aqqg for treatment of postmenopausal osteoporosis, 80% of women were ≥65 years of age and 37% were ≥75 years of age. No overall differences in safety or efficacy observed between these women and younger women; other reported clinical experience identified no age-related differences in response. However, greater sensitivity of some older individuals cannot be ruled out.
Not studied in individuals with hepatic impairment. Not expected to be eliminated by hepatic metabolic pathways.
Patients with severe renal impairment (eGFR 15–29 mL/minute per 1.73 m2) or receiving dialysis: Increased risk of hypocalcemia; monitor serum calcium concentrations and provide adequate supplemental calcium and vitamin D.
No dosage adjustment required in patients with renal impairment. (See Special Populations under Pharmacokinetics.)
Common Adverse Effects
Interactions for Romosozumab-aqqg
Low risk of pharmacokinetic drug interactions.
Exhibits nonlinear pharmacokinetics with exposure increasing in more than dose-proportional manner.
Following sub-Q administration, peak plasma concentrations occur at approximately 5 days.
Steady-state concentrations achieved within 3 months when administered once monthly.
Maximum effect on markers of bone formation (145% increase in procollagen type 1 N-telopeptide [P1NP] concentration) and bone resorption (55% decrease in type 1 collagen C-telopeptide [CTX]) observed 2 weeks following initiation of romosozumab-aqqg therapy in postmenopausal women with osteoporosis.
P1NP concentrations declined to concentrations observed in placebo recipients at 9 months of treatment; following drug discontinuance, concentrations returned to baseline within 12 months.
CTX concentrations remained below concentrations observed in placebo recipients throughout 12 months of treatment; following drug discontinuance, concentrations initially increased above baseline, then returned toward baseline by 12 months.
Renal impairment, including end-stage renal disease requiring dialysis: No clinically important differences in pharmacokinetics.
End-stage renal disease not requiring dialysis: Effect on pharmacokinetics not known.
Body weight: Exposure decreases with increasing body weight.
Age (range: 20–89 years), sex, race, disease state (low bone mass or osteoporosis), and prior exposure to alendronate do not appear to affect pharmacokinetics.
Metabolic pathway not studied; expected to be catabolized to small peptides and amino acids in similar manner as endogenous IgG.
Exhibits nonlinear pharmacokinetics with clearance decreasing as dose increases.
Injection for Sub-Q Use
2–8°C in original carton to protect from light; do not freeze or expose to temperatures >25°C.
Use within 30 days after removal from refrigerator.
Humanized monoclonal IgG2 antibody that binds to and inhibits sclerostin; a bone anabolic agent.
Sclerostin (a regulatory factor in bone metabolism with inhibitory effect on bone formation) binds to low-density lipoprotein receptor-related protein (LRP) 5 and LRP6 co-receptors, which prevents Wnt from binding to the frizzled family receptor and LRP co-receptors, leading to down-regulation of the canonical Wnt signaling pathway. Down-regulation of this pathway results in inhibition of osteoblast differentiation and decreased bone formation.
Binding of romosozumab to sclerostin results in activation of the canonical Wnt signaling pathway, which increases bone formation and, to a lesser extent, decreases bone resorption.
Causes rapid increase in bone formation markers (e.g., P1NP, osteocalcin, bone-specific alkaline phosphatase [BSAP]) and decrease in bone resorption markers (e.g., CTX). (See Absorption under Pharmacokinetics.)
Advice to Patients
Importance of instructing patients to read the manufacturer’s patient information (medication guide).
Importance of receiving adequate supplemental calcium and vitamin D during romosozumab therapy to reduce the risk of hypocalcemia, and importance of seeking medical attention if signs or symptoms of hypocalcemia (e.g., spasms, twitches, muscle cramps, numbness or tingling in fingers, toes, or near the mouth) develop.
Advise patients to seek immediate medical attention if they experience signs or symptoms of an MI or stroke.
Advise patients to seek immediate medical attention if they experience signs or symptoms of a hypersensitivity reaction (e.g., angioedema, erythema multiforme, dermatitis, rash, urticaria).
Importance of maintaining good oral hygiene during treatment with romosozumab. Advise patients to inform their dentist that they are receiving romosozumab prior to having dental work performed.
Advise patients to report signs and symptoms consistent with impending atypical femoral fracture (e.g., new or unusual thigh, hip, or groin pain).
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Injection, for subcutaneous use
105 mg/1.17 mL
Evenity (available in single-use prefilled syringes)
AHFS DI Essentials™. © Copyright 2022, Selected Revisions June 8, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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