Vestronidase alfavjbk- Sly syndrome- Mepsevii -@-(2017)
Drug Name:Vestronidase alfavjbk- Sly syndrome- Mepsevii -@-(2017)
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Not available
Indication:
U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 39
Name of the Drug- Mepsevii
Active Ingredient- Vestronidase alfavjbk
Pharmacological Classification-
To treat pediatric and adult patients with an inherited metabolic
condition called mucopolysaccharifes type VII (MPS VII) also
known as as Sly syndrome
Date of Approval- 11-15-2017
(Ref- FDA approved List 2017)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
MEPSEVII safely and effectively. See full prescribing information for MEPSEVII.
MEPSEVIITM (vestronidase alfa-vjbk) injection, for intravenous use
Initial U.S. Approval: 2017
INDICATIONS AND USAGE-
MEPSEVII is a recombinant human lysosomal beta glucuronidase indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).
Limitations of Use- The effect of MEPSEVII on the central nervous system manifestations of MPS VII has not been determined.
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (=1 patient) are:
infusion site extravasation, diarrhea, rash, anaphylaxis, infusion site swelling, peripheral swelling and pruritus.
Contra-Indications:
CONTRAINDICATIONS-
None
WARNINGS AND PRECAUTIONS-
Anaphylaxis-
Anaphylaxis to MEPSEVII was reported in 2 of 20 patients in the clinical program
These reactions occurred during MEPSEVII infusion and were observed as early as the first dose of MEPSEVII for one patient.
Manifestations included respiratory distress, cyanosis, decreased oxygen saturation, and hypotension.
The two patients with anaphylaxis to MEPSEVII during the clinical trials had one occurrence each and tolerated subsequent infusions of MEPSEVII, without recurrence.
Anaphylaxis can be life-threatening.
MEPSEVII should be administered under the supervision of a healthcare professional with the capability to manage anaphylaxis.
Patients should be observed for 60 minutes after MEPSEVII administration.
If severe systemic reactions occur, including anaphylaxis, immediately discontinue the MEPSEVII infusion and provide appropriate medical treatment.
Prior to discharge, inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur.
Consider the risks and benefits of re-administering MEPSEVII following anaphylaxis
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE-
MEPSEVII is a recombinant human lysosomal beta glucuronidase indicated in pediatric and adult patients for the treatment of Mucopolysaccharidosis VII (MPS VII, Sly syndrome).
Limitations of Use- The effect of MEPSEVII on the central nervous system manifestations of MPS VII has not been determined.
DOSAGE AND ADMINISTRATION-
• The recommended dosage is 4 mg/kg administered every two weeks as an intravenous infusion.
• Premedication with a non-sedating antihistamine with or without an anti-pyretic is recommended 30 to 60 minutes prior to the start of the infusion.
• Administer the infusion over approximately 4 hours. In the first hour of infusion, infuse 2.5% of the total volume. After the first hour, the rate can be increased to infuse the remainder of the volume over 3 hours as tolerated.
• For additional information on preparation, administration, and storage see the full prescribing information.
DOSAGE FORMS AND STRENGTHS
Injection: 10 mg/5 mL (2 mg/mL) in a single-dose vial
Patient Information:
HOW SUPPLIED/STORAGE AND HANDLING-
MEPSEVII (vestronidase alfa-vjbk) injection is a colorless to slightly yellow liquid supplied as a carton containing one 10 mg/5 mL (2 mg/mL) single-dose vial (NDC 69794-001-01).
Store under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light.
PATIENT COUNSELING INFORMATION-
Anaphylaxis-
Advise patients and caregivers that anaphylaxis has occurred with MEPSEVII administration. Inform patients of the signs and symptoms of anaphylaxis, and have them seek immediate medical care should signs and symptoms occur.
Manufactured by:
Ultragenyx Pharmaceutical Inc. Novato, CA 94949 U.S. License
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
.1. Mechanism of Action-
Mucopolysaccharidosis VII (MPS VII or Sly syndrome) is a lysosomal disorder characterized by the deficiency of GUS that results in GAG accumulation in cells throughout the body leading to multisystem tissue and organ damage.
2. Pharmacodynamics-
In all patients evaluated, MEPSEVII treatment resulted in reduction of urinary excretion of GAGs including chondroitin sulfate and dermatan sulfate, which was sustained with continued treatment.
3. Pharmacokinetics-
The pharmacokinetics of vestronidase alfa-vjbk were evaluated in a total of 19 MPS VII patients including 15 pediatric patients and 4 adults.
After repeated dosing of 4 mg/kg every other week, the mean ± standard deviation of maximal concentration (Cmax) was 20.0 ± 8.1 mcg/mL (range: 6.6 to 34.9 mcg/mL); and the mean ± standard deviation of area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) was 3440 ± 1430 mcg*min/mL (range: 1130 to 5820 mcg*min/mL).
Vestronidase alfa-vjbk concentrations in pediatric patients less than 5 years of age were similar to the concentrations in older children and adults.
Distribution-
After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the total volume of distribution (Vss) was 260 ± 130 mL/kg (range: 97 to 598 mL/kg).
Elimination-
After repeated dosing of 4 mg/kg every other week in MPS VII patients, the mean ± standard deviation of the total clearance (CL) was 1.3 ± 0.7 mL/min/kg (range: 0.6 to 3.3 mL/min/kg); the mean ± standard deviation of the elimination half-life (t1/2) was 155 ± 37 minutes (range: 51 to 213 minutes).
The inter- and intra-subject variability (coefficient of variation) in total clearance (CL) was 59% and 13%, respectively.
Metabolism-
Vestronidase alfa-vjbk is a recombinant human enzyme and is therefore eliminated by proteolytic degradation into small peptides and amino acids.
Excretion-
No excretion studies have been conducted in humans. Vestronidase alfa-vjbk is not expected to be eliminated through renal or fecal excretion.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary
There are no available data on MEPSEVII use in pregnant women to determine a drug-associated risk of adverse developmental outcomes.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
2. Lactation Risk Summary
There are no data on the presence of vestronidase alfa-vjbk in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for MEPSEVII and any potential adverse effects on the breastfed infant from vestronidase alfa-vjbk or from the underlying maternal condition.
3.Pediatric Use-
The safety and effectiveness of MEPSEVII have been established in pediatric patients less than 18 years of age.
4.Geriatric Use-
Clinical trials of MEPSEVII did not include any patients aged 65 and over. It is not known whether elderly patients respond differently from younger patients.
