"The U.S. Food and Drug Administration yesterday approved Ruconest, the first recombinant C1-Esterase Inhibitor product for the treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE).
Hypersensitivity Reactions Including Anaphylaxis
Hypersensitivity reactions, including anaphylaxis, occurred in clinical studies and postmarketing experience. [see ADVERSE REACTIONS]. Hypersensitivity reactions were the most commonly observed adverse reactions in patients treated with VPRIV in clinical studies. Patients were not routinely pre-medicated prior to infusion of VPRIV during clinical studies. The most commonly observed symptoms of hypersensitivity reactions were: headache, dizziness, hypotension, hypertension, nausea, fatigue/asthenia, and pyrexia/body temperature increased. Generally the reactions were mild and, in treatment-na´ve patients, onset occurred mostly during the first 6 months of treatment and tended to occur less frequently with time. Additional hypersensitivity reactions of chest discomfort, dyspnea, and pruritus have been reported in post-marketing experience.
As with any intravenous protein product, hypersensitivity reactions are possible, therefore appropriate medical support including personnel adequately trained in cardiopulmonary resuscitative measures and access to emergency measures should be readily available when VPRIV is administered. If anaphylactic or other acute reactions occur, immediately discontinue the infusion of VPRIV and initiate appropriate medical treatment.
The management of hypersensitivity reactions should be based on the severity of the reaction, e.g., slowing the infusion rate, treatment with medications such as antihistamines, antipyretics and/or corticosteroids, and/or stopping and resuming treatment with increased infusion time. In cases where patients have exhibited symptoms of hypersensitivity to the active ingredient or excipients in the drug product or to other enzyme replacement therapy, pre-treatment with antihistamines and/or corticosteroids may prevent subsequent reactions.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate carcinogenic potential or studies to evaluate mutagenic potential have not been performed with velaglucerase alfa.
In a male and female fertility study in rats, velaglucerase alfa did not cause any significant adverse effect on male or female fertility parameters up to a maximum dose of 17 mg/kg/day (102 mg/m²/day, about 1.8 times the recommended human dose of 60 Units/kg/day based on the body surface area).
Use In Specific Populations
Pregnancy Category B
There are no adequate and well controlled studies with VPRIV in pregnant women and there is limited experience in pregnant women. However, animal reproduction studies have been conducted for VPRIV. In these 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, VPRIV should be used during pregnancy only if clearly needed.
Disease-Associated Maternal and Embryo/Fetal Risk
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.
Reproduction studies with velaglucerase alfa have been performed in pregnant rats at intravenous doses up to 17 mg/kg/day (102 mg/m²/day, about 1.8 times greater than the recommended human dose of 60 Units/kg/day or 1.5 mg/kg/day or 55.5 mg/m²/day based on the body surface area). Reproduction studies have been performed in pregnant rabbits at intravenous doses up to 20 mg/kg/day (240 mg/m²/day, about 4.3 times the recommended human dose of 60 Units/kg/day based on the body surface area). These studies did not reveal any evidence of impaired fertility or harm to the fetus due to velaglucerase alfa.
A pre-and postnatal development study in rats showed no evidence of any adverse effect on pre-and postnatal development at doses up to 17 mg/kg/day (102 mg/m²/day, about 1.8 times greater than the recommended human dose of 60 Units/kg/day based on the body surface area).
It is not known whether VPRIV is present in human milk. The developmental and health benefits of breastfeeding should be considered along with any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. Exercise caution when VPRIV is administered to a nursing woman.
The safety and effectiveness of VPRIV have been established for enzyme replacement therapy (ERT) in patients between 4 and 17 years of age with type 1 Gaucher disease. Use of VPRIV in this age group is supported by evidence from adequate and well-controlled studies of VPRIV in 74 adult patients and 20 pediatric patients. The safety and efficacy profiles were similar between pediatric and adult patients [see ADVERSE REACTIONS and Clinical Studies]. The efficacy and safety of VPRIV has not been established in pediatric patients younger than 4 years of age.
In clinical studies of VPRIV in Gaucher's disease, a total of 56 VPRIV-treated patients were 65 years of age or older including 10 patients who were 75 years of age or older. Among 205 patients who switched from imiglucerase to VPRIV, 52 patients were 65 years of age or older of which 10 were 75 years and older. The adverse reaction profile in elderly patients was consistent with that previously observed across pediatric and adult patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be approached cautiously, considering potential comorbid conditions.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/21/2015
Additional VPRIV Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.