VPRIV

Gauchers Disease Agents

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Administer via intravenous infusion only.
Vials are single-use only.
 
Reconstitution:
Determine the number of vials to be reconstituted based on the individual patient's weight and prescribed dose.
Reconstitute each 400 unit vial with 4.3 ml of Sterile water for injection, USP. This results in a final concentration of 100 units/ml and a withdrawal volume of 4 ml.
Once reconstituted, mix vials gently; do not shake.
The product should be used immediately; however, if immediate use is not possible, vials may be stored for up to 24 hours at 2—8 degrees C (36—46 degrees F). Do not freeze. Protect from light.
 
Dilution:
The reconstituted vials must be diluted further prior to infusion.
Visually inspect the vial solution; it should be clear to slightly opalescent and colorless.
With a single syringe withdraw the calculated volume of drug from the appropriate number of vials.
Using a separate syringe, withdraw air from a bag of 100 ml of 0.9% sodium chloride (NS). Then dilute the calculated dose directly into the sodium chloride.
Mix gently. Do not shake. Slight flocculation (described as white irregular shaped particles) may occasionally occur. Diluted solution with slight flocculation is acceptable for administration.
Diluted infusion may be stored for up to 24 hours at 2—8 degrees C (36—46 degrees F). Do not freeze. Protect from light.
 
IV infusion:
Infuse over 60 minutes.
Do not infuse with other products in the same infusion tubing.
Filter the diluted solution through an in-line, low protein-binding 0.2 micrometer filter during administration.
The infusion should be completed within 24 hours of reconstitution of the vials.

anaphylactoid reactions / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known

infusion-related reactions / Rapid / 23.0-52.0
prolonged bleeding time / Delayed / 5.0-11.0
antibody formation / Delayed / 2.0-2.0
bone pain / Delayed / 2.0
hypotension / Rapid / 2.0
hypertension / Early / 2.0
sinus tachycardia / Rapid / 2.0
dyspnea / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known

headache / Early / 30.0-35.0
dizziness / Early / 8.0-22.0
fever / Early / 13.0-22.0
abdominal pain / Early / 15.0-19.0
back pain / Delayed / 17.0-18.0
fatigue / Early / 13.0-15.0
asthenia / Delayed / 13.0-15.0
nausea / Early / 6.0-10.0
rash / Early / 2.0
urticaria / Rapid / 2.0
flushing / Rapid / 2.0
vomiting / Early / Incidence not known

VPRIV

Rx

IV enzyme used for type 1 Gaucher disease
Replaces endogenous enzyme beta-glucocerebrosidase
Indicated for adults, adolescents, and children 4 years and older

60 units/kg IV administered as a 60-minute infusion every other week for treatment naive patients. Dosage adjustments may be made based on achievement and maintenance of therapeutic goals. Clinical studies evaluated doses ranging from 15 to 60 units/kg IV every other week. Patients currently treated with a stable dose imiglucerase may be switched to the same dose of velaglucerase alfa (i.e. same number of units per dose as imiglucerase dose) 2 weeks after the last imiglucerase dose. In a 12-month, open-label study of 40 patients (aged 9 years and older) who had received at least 30 months of imiglucerase therapy, patients switched to velaglucerase alfa at the same dose and had stable hemoglobin and platelet counts during the 12 months after the switch. No patient required dosage adjustment.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Velaglucerase Alfa products.

VPRIV Intravenous Inj Pwd F/Sol: 400U

A specific maximum dosage is not available, but at the time of approval, the maximum dosage studied was 60 units/kg IV every other week. Dosage is based on disease severity and patient response.

A specific maximum dosage is not available, but at the time of approval, the maximum dosage studied was 60 units/kg IV every other week. Dosage is based on disease severity and patient response.

A specific maximum dosage is not available, but at the time of approval, the maximum dosage studied was 60 units/kg IV every other week. Dosage is based on disease severity and patient response.

>= 4 years: A specific maximum dosage is not available, but at the time of approval, the maximum dosage studied was 60 units/kg IV every other week. Dosage is based on disease severity and patient response.
< 4 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Velaglucerase alfa substitutes for the deficient enzyme glucocerebrosidase in patients with Gaucher's disease. Gaucher's disease is an autosomal recessive congenital disorder of lipid metabolism and is categorized as a lysosomal storage disorder. The disease is characterized by a deficiency of the lysosomal enzyme glucocerebrosidase, a necessary catalyst for the hydrolysis of glucocerebroside, an endogenous, very insoluble glycolipid. Patients with this condition have a build-up of glucocerebroside in lysosomes of phagocytic cells, which are found in storage cells of the liver, spleen, bone marrow, and other organs. Clinically, this build-up is associated with splenomegaly, hepatomegaly, increased skin pigmentation, painful bone lesions, and blood dyscrasias..
 
Velaglucerase alfa is designed to be preferentially taken up by macrophages, the drug's site of action. Treatment with velaglucerase alfa results in hydrolysis of the accumulated glucocerebroside within macrophages and improvement in hemoglobin, hematocrit, and platelet counts, and a decrease in hepatomegaly and splenomegaly. Reductions in size of an enlarged liver and spleen correspond to hematological improvement and patients' subjective improvement. Treatment with velaglucerase alfa does not cure the underlying condition, but it does reverse the disease process and provide symptomatic improvement. Continued use is required to maintain suppression of symptoms.

Velaglucerase alfa is administered by intravenous infusion. A multicenter pharmacokinetic study was conducted in pediatric patients (n = 7, 4—17 years old) and adults (n = 15, 19—62 years old) with type 1 Gaucher's disease. After administration (60 units/kg via infusion), serum concentrations of velaglucerase alfa declined rapidly with a mean half-life of 11—12 minutes. The mean clearance ranged from 6.72—7.56 ml/min/kg. The mean volume of distribution at steady state ranged from 82—108 ml/kg (8.2—10.8% of body weight). No accumulation or change in velaglucerase alfa pharmacokinetics over time from weeks 1 to 37 was observed. Due to an inadequately validated analytical assay used in the evaluations, the accurate and definitive pharmacokinetic parameters are not available. The effect of anti-drug antibody formation on the pharmacokinetic parameters of velaglucerase alfa is unknown.

There are no adequate and well controlled studies with the use of velaglucerase alfa in human pregnancy; there is limited clinical experience in pregnant women. More than 300 pregnancies have been reported from the pharmacovigilance database and published observational cohort studies, including the international Gaucher Disease registry. Available data has not identified an association between velaglucerase use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, no fetal harm was observed in rats or rabbits when velaglucerase alfa was administered intravenously during organogenesis at doses with exposures up to 1.8 times and 4.3 times greater than, respectively, the recommended human daily dose. Because animal reproduction studies are not always predictive of human response, use the drug during pregnancy only if clearly needed. Pregnant women with Type 1 Gaucher disease have an increased risk of spontaneous abortion, especially if disease symptoms are not treated and controlled pre-conception and during a pregnancy. Pregnancy may exacerbate existing Type 1 Gaucher disease symptoms or result in new disease manifestations. Type 1 Gaucher disease manifestations may lead to adverse pregnancy outcomes including hepatosplenomegaly, which can interfere with the normal growth of a pregnancy, and thrombocytopenia, which can lead to increased bleeding and possible hemorrhage. Imiglucerase has been suggested as an enzyme-replacement treatment option during pregnancy, based on limited data from case studies.

There are no data on the presence of velaglucerase alfa in human breast milk. Reported cases from the pharmacovigilance database are insufficient to determine any effects on the breast-feeding infant or on milk production. Enzymes such as velaglucerase are likely to be degraded by the infant's digestive sytem and unlikely to reach the systemic circulation of a nursing infant. Limited data in a report from a panel of clinicians that treat Gaucher's disease indicated that breast-feeding complications were reduced in women treated with alglucerase or imiglucerase postpartum. No adverse effects on the nursing infants were reported secondary to enzyme replacement therapy. Consider reducing the duration of breast-feeding to avoid excessive bone loss in the mother. Imiglucerase has been suggested as an enzyme-replacement treatment option, based on limited data from case studies and breast milk concentration data. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.