Fossoli peptide is a C-type natriuretic peptide analogue used for the treatment of pediatric cartilage dysplasia.

1、 Drug name

1. Product Name: VOXZOGO (Voxolitide).

2. Common name: vosoritide.

3. Chinese translation: Voxolitide.

II. Indications

Used for pediatric patients with cartilage dysplasia with unclosed epiphyses to increase linear growth. This indication is granted accelerated approval based on improvement in annualized growth rate, and continued approval may depend on validation and description of clinical benefits in confirmatory trials.

3、 Specifications and characteristics

1. Dosage form: Freeze dried powder injection for injection, subcutaneous injection after reconstitution.

2. Specifications: Three sizes -0.4mg/bottle, 0.56mg/bottle, 1.2mg/bottle. All are white to yellow freeze-dried powders, and after reconstitution, they become clear, colorless to yellow liquids.

4、 Main components

Active ingredient: vosoritide, a 39 amino acid peptide, is a C-type natriuretic peptide analogue produced in Escherichia coli through recombinant DNA technology.

5、 Usage and dosage

1. Administration method: Subcutaneous injection, once a day, try to inject at a fixed time every day.

2. Dose calculation: Based on the actual weight of the patient (see the dose adjustment section below for details).

3. Preparation before injection: Within 1 hour before injection, patients should eat and drink approximately 240-300mL of liquid (water, milk, or juice) to reduce the risk of low blood pressure.

4. Injection site: mid thigh, lower abdomen (at least 5 centimeters away from the navel), upper buttocks or posterior upper arm. The same site should not be used for two consecutive days, and injections should be avoided in areas with redness, swelling, or tenderness.

5. Dissolve and use: Dissolve with sterile injection water provided, gently vortex until the powder is completely dissolved, do not shake. After reconstitution, store at room temperature for up to 3 hours, and discard if exceeded. Each bottle is only used for a single administration, and the remaining portion is discarded.

6、 Dose adjustment

1. Recommended daily dosage based on weight:

Weight 3kg: 0.096mg, injection volume 0.12mL, using 0.4mg specification.

Weight 4kg: 0.12mg, injection volume 0.15mL, using 0.4mg specification.

Weight 5kg: 0.16mg, injection volume 0.2mL, using 0.4mg specification..

Weight 6-7kg: 0.2mg, injection volume 0.25mL, using 0.4mg specification.

Weight 8-11kg: 0.24mg, injection volume 0.3mL, using 0.4mg specification.

Weight 12-16kg: 0.28mg, injection volume 0.35mL, using 0.56mg specification.

Weight 17-21kg: 0.32mg, injection volume 0.4mL, using 0.56mg specification.

Weight 22-32kg: 0.4mg, injection volume 0.5mL, using 0.56mg specification.

Weight 33-43kg: 0.5mg, injection volume 0.25mL, using 1.2mg specification.

Weight 44-59kg: 0.6mg, injection volume 0.3mL, using 1.2mg specification.

Weight 60-89kg: 0.7mg, injection volume 0.35mL, using 1.2mg specification.

Weight ≥ 90kg: 0.8mg, injection volume 0.4mL, using 1.2mg specification.

2. Growth monitoring: Evaluate weight, growth, and physical development every 3-6 months, and adjust dosage based on actual weight. Permanently discontinue medication after epiphyseal closure.

3. Omission treatment: Within 12 hours after a missed dose, it can be replenished; If it exceeds 12 hours, skip the missed dose and administer the next dose at the regular time.

7、 Medication precautions

1. Preparation before injection: Approximately 240-300mL of food and water must be consumed to prevent hypotension and related symptoms such as dizziness, fatigue, and nausea.

2. Injection technique: Injection can only be administered at home after training by medical staff. Use new needles and syringes for each injection.

3. Vomiting treatment: If vomiting occurs after injection, there is no need for additional injection, and the next dose can be administered according to the usual time. If vomiting occurs frequently, the doctor should be informed.

4. Medication discontinuation indication: Medication must be discontinued after epiphyseal closure. Permanently discontinue medication when the doctor confirms no further growth potential.

8、 Medication for special populations

1. Pregnancy period: No human data available. No embryo fetal toxicity or abnormalities were observed in animal studies. The background risk of major birth defects in individuals with chondrodysplasia is higher than that in the general population.

2. Breastfeeding period: Voxolitide can be present in rat milk and is expected to enter human milk. It is necessary to balance the benefits of breastfeeding with the necessity of medication for mothers.

3. Pediatric medication: It has been established to increase the safety and effectiveness of linear growth in children with cartilage dysplasia with unclosed epiphyses. The supporting data comes from a comprehensive controlled study of children aged 5-15 years old, as well as pharmacokinetic data of children aged 4.5 months to 15 years old. Safety data for children under 5 years old have also been obtained.

4. Renal dysfunction: Patients with eGFR ≥ 60mL/min/1.73m ² do not require dose adjustment. EGFR<60mL/min/1.73m ² is not recommended for use.

5. Liver function impairment: The impact on the pharmacokinetics of voxetine is unknown.

9、 Adverse reactions

1. The most common adverse reactions (>10%) are injection site erythema (75%), injection site swelling (62%), rash, vomiting (27%), injection site urticaria (25%), joint pain (15%), decreased blood pressure (13%), and gastroenteritis (13%).

2. Injection site reactions: 85% of patients in the vasopressin group experienced injection site reactions, with an incidence rate of 120.4 times per person per year. Including erythema, swelling, urticaria, pain, bruising, itching, bleeding, discoloration, and induration. Two cases stopped taking medication due to injection pain and anxiety.

3. Blood pressure reduction: 13% of patients experienced transient blood pressure reduction (5% in the placebo group), with a median onset time of 31 minutes and a median relief time of 31 minutes. 3% of patients experience symptomatic hypotension (accompanied by vomiting and/or dizziness).

4. Laboratory abnormalities: 17% of patients in the vasopressin group had elevated alkaline phosphatase levels (compared to 7% in the placebo group).

5. Children under 5 years old: The most common adverse reactions are injection site reactions (86%) and rash (28%), with overall safety similar to older children.

6. Post market experience: hirsutism (including abnormal hair growth and hirsutism).

10、 Contraindications

There are no absolute contraindications.

11、 Drug interactions

1. In vitro study: Fossoli peptide does not inhibit or induce cytochrome P450 enzymes at therapeutic concentrations. Not suppressed OAT1、OAT3、OCT1、OCT2、OATP1B1、OATP1B3、MATE1、MATE2-K、BCRP、P-gp、BSEP Waiting for the carrier.

2. In vivo studies: No clinical studies on drug interactions have been conducted.

12、 Storage method

1. Refrigerated storage: Vosoride bottles and pre filled syringes of diluent should be stored in the refrigerator at 2 ℃ -8 ℃ (36 ℉ -46 ℉). Cannot be frozen.

2. Room temperature storage: Unresolved products can be stored at room temperature of 20 ℃ -25 ℃ (68 ℉ -77 ℉) for up to 90 days, with short-term fluctuations allowed up to 15 ℃ -30 ℃ (59 ℉ -86 ℉). Once placed at room temperature, do not put it back in the refrigerator. Record the starting date of room temperature storage on the packaging.

3. After reconstitution: Store at room temperature for up to 3 hours after reconstitution, discard after exceeding the time limit.

4. Avoid light storage: Store in the original packaging to avoid light.

5. Validity period: It cannot exceed the validity period on the label.

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