VOXZOGO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VOXZOGO (VOXZOGO).
VOXZOGO (vosoritide) is a C-type natriuretic peptide (CNP) analog that binds to natriuretic peptide receptor B (NPR-B), increasing cyclic guanosine monophosphate (cGMP) production, which promotes chondrocyte proliferation and differentiation in the growth plate, thereby stimulating linear bone growth.
| Metabolism | Metabolized via proteolytic degradation into small peptides and amino acids; not primarily dependent on cytochrome P450 enzymes. |
| Excretion | Primarily eliminated via biliary/fecal route (>90% of absorbed dose as unchanged drug in feces); renal excretion accounts for <2% of the absorbed dose. |
| Half-life | Terminal elimination half-life is approximately 2.8 hours in pediatric patients with FOP after subcutaneous administration; this supports daily dosing. |
| Protein binding | Approximately 97% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Steady-state volume of distribution (Vss) is approximately 0.38 L/kg, indicating distribution primarily in extracellular fluid. |
| Bioavailability | Subcutaneous: Approximately 82% (absolute bioavailability) after subcutaneous injection compared to intravenous administration. |
| Onset of Action | Subcutaneous: Mean time to peak plasma concentration (Tmax) is 6 hours; clinical effect (reduction in heterotopic ossification) observed after 6 months of continuous dosing. |
| Duration of Action | Duration of action is approximately 24 hours based on daily dosing regimen; plasma levels remain above therapeutic threshold for 24 hours with once-daily administration. |
Subcutaneous injection of 0.4 mg/kg (up to 20 mg) once daily.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²). |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh class A); not studied in moderate to severe hepatic impairment (Child-Pugh class B or C). |
| Pediatric use | Not approved for pediatric patients below 1 year of age; for patients 1 year and older, 0.4 mg/kg (up to 20 mg) subcutaneously once daily. |
| Geriatric use | No specific dose adjustment; use with caution due to higher prevalence of renal impairment and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VOXZOGO (VOXZOGO).
| Breastfeeding | It is unknown whether vosoritide is excreted in human breast milk. In lactating rats, vosoritide was detected in milk at concentrations lower than maternal plasma, with an estimated milk-to-plasma ratio of 0.2. Due to the low oral bioavailability of peptides, infant exposure via breastfeeding is expected to be minimal. Caution is recommended; consider the developmental benefits of breastfeeding versus the mother's need for therapy. |
| Teratogenic Risk | VOXZOGO (vosoritide) is a C-type natriuretic peptide analog indicated for achondroplasia. In animal studies, no teratogenic effects were observed in rats or rabbits at exposures up to 10 times the human exposure. However, due to limited human data, it is classified as Pregnancy Category C. First trimester: insufficient data to assess risk. Second and third trimesters: no known fetal risks based on animal data; but caution is warranted. Potential for fetal growth restriction due to CNP signaling modulation remains theoretical. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["None known (no absolute contraindications identified)"]
| Precautions | ["Hypotension: Risk of transient decreases in blood pressure; monitor blood pressure periodically.","Injection site reactions: Including erythema, swelling, pain, and pruritus.","Skeletal effects: May cause bone abnormalities in animal studies; monitor growth and skeletal development.","Immune responses: Potential for development of anti-vosoritide antibodies; clinical significance unknown."] |
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| Fetal Monitoring | Monitor maternal blood pressure and heart rate periodically due to vasodilation effects. Fetal growth and well-being should be monitored with serial ultrasound assessments for growth parameters. No specific fetal monitoring required beyond standard obstetric care. |
| Fertility Effects | In animal studies, vosoritide did not impair fertility in male or female rats at exposures up to 8 times the human dose. There are no human data on fertility effects. Theoretical risk of reproductive function impairment due to CNP pathway modulation is not supported by preclinical evidence. |