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Romosozumab

Medically reviewed by Drugs.com. Last updated on Jul 25, 2019.

Pronunciation

(ROE moe SOZ ue mab)

Index Terms

  • Romosozumab-aqqg

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Evenity: Romosozumab-aqqg 105 mg per 1.17 mL (1.17 mL)

Brand Names: U.S.

  • Evenity

Pharmacologic Category

  • Monoclonal Antibody
  • Sclerostin Inhibitor

Pharmacology

Romosozumab inhibits sclerostin, a regulatory factor in bone metabolism that inhibits Wnt/Beta-catenin signaling pathway regulating bone growth (MacDonald 2009; McClung 2018); romosozumab increases bone formation and to a lesser extent, decreases bone resorption.

Distribution

Vdss: ~3.92 L

Metabolism

Has not been characterized; expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG

Onset of Action

Peak increase in bone formation marker procollagen type 1 N-telopeptide (P1NP) and peak decrease in bone resorption marker type 1 collagen C-telopeptide (CTX) observed 2 weeks after initiation. Increased histomorphometric indices of bone formation observed 2 months after therapy initiation.

Time to Peak

Median: 5 days (range: 2 to 7 days)

Duration of Action

CTX decrease persists throughout 12 months of therapy; P1NP returns to baseline by 9 months and declines at 12 months; anabolic effect wanes after 12 months of treatment. After discontinuation of therapy, an increase in CTX above baseline value occurs within 3 months. CTX, P1NP, and bone mineral density (BMD) return to baseline within ~12 months of discontinuing therapy.

Half-Life Elimination

12.8 days after 3 doses over 12-week period (ie, 1 dose every 4 weeks)

Special Populations Note

Weight: The exposure of romosozumab decreases with increasing body weight.

Use: Labeled Indications

Osteoporosis: Treatment of osteoporosis in postmenopausal women 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 available osteoporosis therapy

Limitations of use: The anabolic effect of romosozumab wanes after 12 monthly doses of therapy. Therefore, the duration of romosozumab use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered.

Contraindications

Hypersensitivity (eg, angioedema, erythema multiforme, urticaria) to romosozumab or any component of the formulation; uncorrected hypocalcemia

Dosing: Adult

Note: Administer in conjunction with supplemental calcium and vitamin D; in clinical trials patients received calcium 500 mg to 1 g/day and vitamin D 600 to 800 units/day.

Osteoporosis in postmenopausal females: SubQ: Two consecutive injections (105 mg each) for a total dose of 210 mg once monthly; treatment duration: 12 months. Note: After discontinuation, an increase in type 1 collagen C-telopeptide (CTX) above baseline levels occurred within 3 months. Bone mineral density (BMD) returns to approximately baseline levels within 12 months; if continued osteoporosis therapy is necessary following discontinuation, consider initiating anti-resorptive therapy.

Missed dose: If a dose is missed, administer as soon as it can be rescheduled; subsequent doses should be scheduled every month from the date of last dose.

Dosing: Geriatric

Refer to adult dosing.

Administration

SubQ: Each monthly dose consists of 2 consecutive SubQ injections.

Remove 2 syringes from carton and allow to sit at room temperature for at least 30 minutes before administration. Administer into the abdomen, thigh, or outer area of upper arm. Rotate injection sites; if the same injection site is chosen, do not inject into the same spot used for the first injection. Avoid areas of skin that are tender, bruised, red, hard, scarred, or with stretch marks. Solution in syringe should appear clear to opalescent, colorless to light yellow; do not use if cloudy, discolored, or contains particulate matter.

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. Upon removal from the refrigerator, may store at room temperature up to 25°C (77°F) in the original carton for up to 30 days. If not used within 30 days, discard. Do not expose to temperatures >25°C (77°F).

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%: Neuromuscular & skeletal: Arthralgia (8% to 13%)

1% to 10%:

Cardiovascular: Cardiac disorder (2%), peripheral edema (2%)

Central nervous system: Headache (5% to 7%), insomnia (2%), paresthesia (1%)

Dermatologic: Skin rash (1%)

Hypersensitivity: Hypersensitivity reaction (7%)

Local: Injection site reaction (5%), pain at injection site (2%), erythema at injection site (1%)

Neuromuscular & skeletal: Muscle spasm (3% to 5%), asthenia (3%), neck pain (2%)

<1%, postmarketing, and/or case reports: Acute myocardial infarction, angioedema, cerebrovascular accident, dermatitis, erythema multiforme, femur fracture, hypocalcemia, osteonecrosis of the jaw, urticaria

ALERT: U.S. Boxed Warning

Potential risk of myocardial infarction, stroke and cardiovascular death

Romosozumab may increase the risk of myocardial infarction, stroke, and cardiovascular death. Romosozumab should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors. If a patient experiences a myocardial infarction or stroke during therapy, romosozumab should be discontinued.

Warnings/Precautions

Concerns related to adverse effects:

• Bone fractures: Atypical femur fractures have been reported in patients receiving romosozumab. The fractures may occur anywhere along the femoral shaft (may be bilateral) and commonly occur with minimal to no trauma to the area. Some patients experience prodromal pain weeks or months before the fracture occurs. New or unusual thigh, hip, or groin pain should be reported to health care provider; any patient with thigh or groin pain should be suspected of having an atypical femur fracture and should be evaluated to rule out an incomplete femur fracture. If an atypical fracture is present, assess for signs/symptoms of fracture in contralateral limb. Consider interruption of therapy based on benefits/risks.

• Cardiovascular events: [US Boxed Warning]: Romosozumab may increase the risk of MI, stroke, and cardiovascular death and should not be initiated in patients who have had an MI or stroke within the previous year. Consider benefits/risks of therapy in patients with other cardiovascular risk factors. Discontinue use if MI or stroke occurs during therapy.

• Hypocalcemia: Hypocalcemia may occur. Correct hypocalcemia prior to initiation of therapy (contraindicated in patients with uncorrected hypocalcemia). Ensure adequate supplementation with calcium and vitamin D during therapy and monitor calcium levels closely, particularly in patients predisposed to hypocalcemia (eg, severe renal impairment and/or receiving dialysis).

• Hypersensitivity: Hypersensitivity reactions (eg, angioedema, erythema multiforme, urticaria, rash, dermatitis) have occurred; discontinue use for serious reactions (eg, anaphylaxis) and treat appropriately.

• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients receiving romosozumab. Known risk factors for MRONJ include tooth extraction or other invasive dental procedures, cancer diagnosis, radiotherapy, concomitant therapy (eg, angiogenesis inhibitors, bisphosphonates, chemotherapy, corticosteroids, denosumab), poor oral hygiene, and comorbid disorders (anemia, coagulopathy, infection, preexisting dental or periodontal disease). Routine oral exam is recommended prior to initiation of therapy; patients should maintain good oral hygiene during treatment. Consider risk/benefits of therapy in patients requiring invasive dental procedures. Patients developing ONJ during therapy should receive care by an oral surgeon or dentist; consider discontinuation of therapy based on risk/benefit assessment.

Monitoring Parameters

Signs/symptoms of hypersensitivity; signs/symptoms of adverse cardiovascular events; serum calcium

Osteoporosis recommendations: Bone mineral density (BMD) should usually be evaluated every 1 to 3 years while on osteoporosis therapy (maximum duration of romosozumab therapy is 1 year; following discontinuation of romosozumab, BMD response decreases to baseline within 1 year); monitoring bone turnover markers (eg, CTX for antiresorptive therapy or P1NP for bone anabolic therapy) may be considered, typically at baseline and 3 to 6 months (Note: Due to diurnal and food effects on bone turnover markers, samples should be collected in the morning and while fasting [resorption markers]) (AACE/ACE [Camacho 2016]; Endocrine Society [Eastell 2019]; NOF [Cosman 2014]).

Pregnancy Considerations

Romosozumab is a humanized monoclonal antibody (IgG2). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Romosozumab is not indicated for use in females of reproductive potential.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience joint pain or headache. Have patient report immediately to prescriber signs of a heart attack (chest pain; pain in arms, back, neck, jaw, or abdomen; shortness of breath; cold sweats; severe dizziness; passing out; or severe nausea or vomiting); signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes); signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures); groin, hip, or thigh pain; jaw edema; or jaw pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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