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. |
| Molecular Weight | 718.8 |
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 | No human data; animal studies show no evidence of harm, but insufficient human data to determine safety. Use only if clearly needed. |
| 2nd trimester | No human data; animal studies show no evidence of harm, but insufficient human data to determine safety. Use only if clearly needed. |
| 3rd trimester | No human data; animal studies show no evidence of harm, but insufficient human data to determine safety. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for VOXZOGO (VOXZOGO).
| Placental transfer | Likely crosses placenta due to low molecular weight (718.8 Da); no specific human data. In rats, fetal exposure was observed at maternal doses ≥2 times the human exposure. |
| Breastfeeding | No human data on excretion in breast milk; likely present due to small molecular size. Consider developmental benefits of breastfeeding vs. potential adverse effects. Monitor infant for hypoglycemia as vosoritide may affect growth hormone pathway. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Hypersensitivity to vosoritide or any excipientsChildren with epiphyseal closure (confirmed via bone age assessment)
| 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. |
| Food/Dietary | No significant food interactions have been reported. May be taken without regard to meals. |
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| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
| Clinical Pearls |
| Vosoritide (VOXZOGO) is a C-type natriuretic peptide analog approved for children with achondroplasia aged 5 years and older with open growth plates. Monitor growth velocity and height SDS regularly. Injection site reactions are common; rotate sites. Use with caution in patients with hepatic impairment due to potential for increased exposure. Not recommended for severe renal impairment (eGFR <30 mL/min/1.73m²). |
| Patient Advice | Administer by subcutaneous injection daily at the same time each day. · Rotate injection sites among abdomen, thigh, and upper arm to prevent lipodystrophy. · Do not miss doses; if a dose is missed, skip it and resume next scheduled dose. · Store vials in refrigerator (2°C to 8°C); do not freeze. Protect from light. · Common side effects include injection site reactions, vomiting, and decreased blood pressure. · Inform your doctor if you experience signs of allergic reaction (rash, itching, swelling). · Your child will need regular height measurements and blood pressure monitoring. · Pregnancy and breastfeeding: avoid as safety not established. |