Version May 2024
(For additional information see "Vosoritide: Pediatric drug information")
Note: Adjust dose based on actual body weight as patient grows; vial strength and resultant concentration varies based on patient weight. Permanently discontinue upon closure of epiphyses.
Achondroplasia: Note: Ensure patient is well hydrated and has adequate food intake 1 hour prior to dose to reduce the risk of low blood pressure and related symptoms (eg, dizziness, fatigue, nausea).
Children ≥5 years and Adolescents: SUBQ:
|
Actual Body Weight |
Dose |
Injection Volume |
Frequency of Dosing |
Vial Strength Needed for Reconstitution |
Reconstituted Concentration |
|---|---|---|---|---|---|
|
10 to <12 kg |
0.24 mg |
0.3 mL |
Once daily |
0.4 mg/vial |
0.8 mg/mL |
|
12 to <17 kg |
0.28 mg |
0.35 mL |
Once daily |
0.56 mg/vial |
0.8 mg/mL |
|
17 to <22 kg |
0.32 mg |
0.4 mL |
Once daily | ||
|
22 to <33 kg |
0.4 mg |
0.5 mL |
Once daily | ||
|
33 to <44 kg |
0.5 mg |
0.25 mL |
Once daily |
1.2 mg/vial |
2 mg/mL |
|
44 to <60 kg |
0.6 mg |
0.3 mL |
Once daily | ||
|
60 to <90 kg |
0.7 mg |
0.35 mL |
Once daily | ||
|
≥90 kg |
0.8 mg |
0.4 mL |
Once daily |
Altered kidney function: Children ≥5 years and Adolescents: SUBQ:
eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <60 mL/minute/1.73 m2: Use not recommended.
There are no dosage adjustments provided in the manufacturer's labeling.
Mild, transient decreased blood pressure was commonly observed in clinical trials and may be associated with dizziness, fatigue, and/or nausea (all cases were deemed inconsequential and were self-limiting) (Savarirayan 2020). Resolution occurred within a median of 31 minutes (range: 5 to 90 minutes). Patients with significant cardiac/vascular disease or taking antihypertensive medications were excluded from clinical trials.
Mechanism: Dose-related; related to the pharmacologic action. Vosoritide is structurally similar to atrial natriuretic peptide and may result in vascular side effects (Duggan 2021; Savarirayan 2020).
Onset: Rapid; median onset 31 minutes (range: 18 to 120 minutes).
Risk factors:
• Inadequate food and/or fluid intake prior to administration
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children and adolescents.
>10%:
Cardiovascular: Decreased blood pressure (13%) (table 1)
|
Drug (Vosoritide) |
Placebo |
Number of Patients (Vosoritide) |
Number of Patients (Placebo) |
|---|---|---|---|
|
13% |
5% |
60 |
61 |
Dermatologic: Urticaria at injection site (25%)
Gastrointestinal: Gastroenteritis (13%), vomiting (27%)
Immunologic: Antibody development (35%)
Local: Erythema at injection site (75%), injection site reaction (85%; including bleeding at injection site, bruising at injection site, induration at injection site, injection site pruritus, pain at injection site, skin discoloration at injection site), swelling at injection site (62%)
Neuromuscular & skeletal: Arthralgia (15%)
1% to 10%:
Dermatologic: Xeroderma (5%)
Gastrointestinal: Diarrhea (10%)
Hypersensitivity: Seasonal allergy (7%)
Infection: Influenza (10%)
Nervous system: Dizziness (10%) (table 2), fatigue (8%) (table 3)
|
Drug (Vosoritide) |
Placebo |
Number of Patients (Vosoritide) |
Number of Patients (Placebo) |
|---|---|---|---|
|
10% |
3% |
60 |
61 |
|
Drug (Vosoritide) |
Placebo |
Number of Patients (Vosoritide) |
Number of Patients (Placebo) |
|---|---|---|---|
|
8% |
3% |
60 |
61 |
Otic: Otalgia (10%)
There are no contraindications listed in the manufacturer's labeling.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Subcutaneous [preservative free]:
Voxzogo: 0.4 mg (1 ea); 0.56 mg (1 ea); 1.2 mg (1 ea) [contains polysorbate 80]
No
Solution (reconstituted) (Voxzogo Subcutaneous)
0.4 mg (per each): $1,186.56
0.56 mg (per each): $1,186.56
1.2 mg (per each): $1,186.56
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Parenteral: SUBQ: Ensure patient has adequate food and liquid intake (240 to 300 mL [8 to 10 ounces]) within 1 hour prior to administration (to reduce the risk of low blood pressure and associated symptoms). Administer SUBQ into the thigh (front middle part), lower abdomen (≥2 inches from navel), back of upper arm, or top of the buttocks. Rotate injection sites; the same injection area should not be used on 2 consecutive days. Administer at the same time each day. Do not inject into sites that are red, swollen, or tender.
Missed doses: Administer dose as soon as possible; if the next scheduled dose is due in <12 hours, skip the missed dose and resume the regular dosing schedule.
Achondroplasia: To increase linear growth in pediatric patients with achondroplasia who are ≥5 years of age with open epiphyses.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
A phase 2 dose-finding study of vosoritide did not include patients of reproductive potential (Savarirayan 2019).
Adverse events were not observed in animal reproduction studies.
It is not known if vosoritide is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Monitor body weight, growth, and physical development every 3 to 6 months; monitor for epiphyseal closure. Signs and symptoms of low BP (eg, dizziness, fatigue, nausea); BP (as clinically appropriate).
Vosoritide is a C-type natriuretic peptide analog that binds to natriuretic peptide receptor-B and indirectly antagonizes downstream signaling from mutant fibroblast growth factor receptor 3 (FGFR3) via inhibition of extracellular signal-regulated kinases 1 and 2 in the mitogen-activated protein kinase pathway at the level of rapidly accelerating fibrosarcoma serin/threonine protein kinase. Antagonism of the mutant form of FGFR3 (which negatively regulates endochondral bone growth in achondroplasia) results in positive regulation/promotion of chondrocyte proliferation and differentiation.
Distribution: Vd: Children ≥5 years and Adolescents ≤13 years: Mean range: 2.88 ± 2.45 to 3.02 ± 1.98 L/kg.
Metabolism: Degrades into small peptide fragments and amino acids via catabolic pathways.
Half-life elimination: Children ≥5 years and Adolescents ≤13 years: Mean range: 21 ± 4.7 to 27.9 ± 9.9 minutes.
Time to peak: Children ≥5 years and Adolescents ≤13 years: SUBQ: Median: 15 minutes.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
