EVENITY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVENITY (EVENITY).
Sclerostin inhibitor; monoclonal antibody that binds to sclerostin, increasing bone formation and decreasing bone resorption.
| Metabolism | Catabolized by general protein degradation pathways; no CYP450-mediated metabolism. |
| Excretion | Renal: minimal; Fecal: eliminated via reticuloendothelial system (RES) degradation, not intact drug; no significant biliary excretion. |
| Half-life | Terminal half-life (t1/2) approximately 26 days; due to FcRn-mediated recycling of the monoclonal antibody, supporting monthly dosing. |
| Protein binding | <1%; not bound to plasma proteins; binds to target sclerostin with high affinity. |
| Volume of Distribution | Vd ~6.4 L (approximately 0.09 L/kg), indicating limited extravascular distribution, primarily confined to plasma and interstitial fluid. |
| Bioavailability | Subcutaneous: approximately 82% absolute bioavailability. |
| Onset of Action | Subcutaneous: reduction in bone resorption markers (e.g., sCTX-1) within 1 week; effects on BMD measurable at 1 month. |
| Duration of Action | Bone turnover markers return to baseline ~9 months after last dose; effects on BMD persist for up to 12 months. Clinical trials show sustained fracture risk reduction with monthly dosing. |
210 mg subcutaneously once every month.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to severe renal impairment (CrCl ≥15 mL/min). Not studied in end-stage renal disease (CrCl <15 mL/min) or on dialysis. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established; no approved pediatric dose. |
| Geriatric use | No dose adjustment required based on age. Same dosing as younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVENITY (EVENITY).
| Breastfeeding | Unknown whether romosozumab is excreted in human milk. No M/P ratio available. Due to potential for serious adverse reactions in nursing infants, including effects on bone development, breastfeeding is not recommended during treatment and for at least 5 months after last dose. |
| Teratogenic Risk | EVENITY (romosozumab) is contraindicated in pregnancy. Based on animal studies, there is evidence of fetal harm including skeletal malformations and reduced fetal growth, likely due to inhibition of sclerostin leading to altered bone development. Risk in first trimester is unknown but concern exists due to potential placental transfer of IgG antibodies. In second and third trimesters, there is a clear risk of fetal skeletal abnormalities and growth restriction. |
■ FDA Black Box Warning
Increased risk of myocardial infarction, stroke, and cardiovascular death. Should not be initiated in patients with a history of myocardial infarction or stroke.
| Serious Effects |
Hypocalcemia; history of myocardial infarction or stroke.
| Precautions | Hypersensitivity reactions including angioedema, urticaria, and rash; hypocalcemia; osteonecrosis of the jaw; atypical femoral fractures; serious infections. |
Loading safety data…
| Fetal Monitoring | If inadvertent exposure occurs during pregnancy, perform fetal ultrasound to assess skeletal development, including long bones and ribs. Monitor for oligohydramnios. Postnatally, evaluate infant for hypocalcemia, skeletal abnormalities, and growth parameters. No specific maternal monitoring required beyond standard obstetric care. |
| Fertility Effects | In animal studies, romosozumab did not impair male or female fertility. However, no human data are available. The effect on human fertility is unknown. |