Dosing & Uses
See Pediatric Dosing
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 0.4mg/vial
- 0.56mg/vial
- 1.2mg/vial
Achondroplasia
Indicated to increase linear growth in pediatric patients aged ≥5 years who have achondroplasia with open epiphyses
≥5 years
- Recommended dosage based on actual body weight (ABW)
- 10-11 kg: 0.24 mg SC qDay
- 12-16 kg: 0.28 mg SC qDay
- 17-21 kg: 0.32 mg SC qDay
- 22-32 kg: 0.4 mg SC qDay
- 33-43 kg: 0.5 mg SC qDay
- 44-59 kg: 0.6 mg SC qDay
- 60-89 kg: 0.7 mg SC qDay
- ≥90 kg: 0.8 mg SC qDay
Dosage Modifications
Renal impairment
- Pharmacokinetics have not been evaluated
- eGFR ≥60 mL/min/1.73 m2: No dosage adjustment necessary
- eGFR <60 mL/min/1.73 m2: Not recommended
Hepatic impairment
- Effect of hepatic impairment on pharmacokinetics is unknown
Dosing Considerations
Growth monitoring
- Monitor and assess body weight, growth, and physical development regularly q3-6 months
- Adjust dosage according to patient’s ABW
- Permanently discontinue upon confirmation of no further growth potential, indicated by closure of epiphyses
Adverse Effects
>10%
Injection site erythema (75%)
Injection site swelling (62%)
Vomiting (27%)
Injection site urticaria (25%)
Arthralgia (15%)
Decreased blood pressure (13%)
Gastroenteritis (13%)
1-10%
Diarrhea (10%)
Dizziness (10%)
Ear pain (10%)
Influenza (10%)
Fatigue (8%)
Seasonal allergy (7%)
Dry skin (5%)
Warnings
Contraindications
None
Cautions
Risk of low blood pressure
- Transient decreases in blood pressure were observed
- Subjects with significant cardiac or vascular disease and patients on antihypertensive medicinal products were excluded from participation in clinical trials
- To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, fatigue and/or nausea), instruct patient to be well hydrated (~240-300 mL within hour before SC injection) and have adequate food intake before administration
Pregnancy & Lactation
Pregnancy
No available data are available on use in pregnant females to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal data
- There was no evidence of embryofetal toxicity or congenital malformations when pregnant rats and rabbits were administered vosoritide SC at doses equivalent to 14-times and 200-times, respectively, the exposure at the maximum recommended human dose
Lactation
There is no information regarding the presence of vosoritide in human milk, effects on the breastfed infant, or effects on milk production
Vosoritide is present in rat milk
When a drug is present in animal milk, it will likely be present in human milk
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Analog of C-type natriuretic peptide (CNP); this peptide binds to natriuretic-peptide receptor B (NPR B), which induces synthesis of cGMP molecules, which, in turn, inhibits the MAPK pathway
Inhibition of the MAPK pathway leads to increased extracellular matrix (ECM), which, in conjunction with chondrocytes, serves as a template for bone via endochondral ossification
Achondroplasia is caused by a mutation in the gene that encodes for fibroblast growth factor receptor 3 (FGFR3), causing it to be permanently active; FGFR3 signaling activates 2 intracellular signaling cascades that lead to a lower proliferation and differentiation of bone growth plate chondrocytes, through the STAT-1 pathway, and to a lower production of ECM through the MAPK pathway
Absorption
Peak plasma time: 15 min
Distribution
Vd: 2,880-3,020 mL/kg
Metabolism
Metabolism is expected to occur via catabolic pathways with degradation into small peptide fragments and amino acids
Elimination
Clearance: 79.4-104 mL/min/kg
Half-life: 21-27.9 min
Administration
SC Preparation
Select correct dosage strength and prefilled diluent syringe co-pack based on patient’s ABW
Remove vial and prefilled diluent syringe (sterile water for injection) from refrigerator and allow them to reach room temperature before reconstituting
Attach diluent needle provided with ancillary supplies to diluent prefilled syringe
Inject entire diluent prefilled syringe volume into vial
Gently swirl the diluent in vial until white powder is completely dissolved; do not shake; reconstituted solution is 0.8 mg/mL (0.4-mg or 0.56-mg vial) or 2 mg/mL (1.2-mg vial)
Visually inspect the parenteral drug products for particulate matter and discoloration before administration; reconstituted solution appears as a clear, colorless- to- yellow liquid; discard if discolored or cloudy, or if particles are present
Once reconstituted, vial may be stored at room temperature 20-25ºC (68-77ºF) for up to 3 hr
For administration, extract required dose volume from vial using the supplied administration syringe
Discard any unused portion; do not pool unused portions from vials
Do not administer >1 dose from a vial; do not mix with other medications
SC Administration
Administer SC at approximately the same time each day
Caregivers may inject SC after proper training by a healthcare professional on preparation and administration
Ensure patient has adequate food and fluid (~240-300 mL) intake before administration
Slowly withdraw dosing volume of the reconstituted solution from the single-dose vial into a syringe; refer to prescribing information for specific dosing volumes
Rotate sites for SC injections; recommended injection sites are the front middle of the thighs, lower part of the abdomen at least 2 inches (5 cm) away from navel, top of the buttocks, or the back of the upper arms
Do not use the same injection area on 2 consecutive days
Do not inject into sites that are red, swollen, or tender
Missed dose
- Missed dose <12 hr of scheduled administration: Administer missed dose
- Missed dose >12 hr of scheduled administration: Skip missed dose and administer next dose according to usual dosing schedule
Storage
Unused vials and prefilled diluent syringes
- Refrigerate at 2-8°C (36-46°F); do not freeze
- May store at room temperature 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) for 90 days
- Do not return to refrigerator once stored at room temperature
Reconstituted vials
- Store at room temperature 20-25°C (68-77°F) for up to 3 hr
- Record starting date of room-temperature storage clearly on unopened product carton
- Do not use beyond expiration date on label
- Store in original package to protect from light
Images
Formulary
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