"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
Serious hypersensitivity reactions, including anaphylaxis, have occurred in some patients treated with ELELYSO. In clinical trials, 2 of 72 (3%) patients treated with ELELYSO experienced signs and symptoms consistent with anaphylaxis. Signs and symptoms of these patients included urticaria, hypotension, flushing, wheezing, chest tightness, nausea, vomiting, and dizziness. These reactions occurred during ELELYSO infusion.
In clinical trials with ELELYSO, 21 of 72 (29%) patients experienced hypersensitivity reactions, including anaphylaxis. Signs and symptoms of hypersensitivity reactions included pruritus, angioedema, flushing, erythema, rash, nausea, vomiting, cough, chest tightness, and throat irritation. These reactions have occurred up to 3 hours after the start of infusion [see ADVERSE REACTIONS].
Due to the potential for anaphylaxis, appropriate medical support should be readily available when ELELYSO is administered. Observe patients closely for an appropriate period of time after administration of ELELYSO, taking into account the time to onset of anaphylaxis seen in clinical trials. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur. If anaphylaxis occurs, ELELYSO should be immediately discontinued, and appropriate medical treatment should be initiated.
Management of hypersensitivity reactions should be based on the severity of the reaction and include slowing or temporary interruption of the infusion and/or administration of antihistamines, antipyretics, and/or corticosteroids for mild reactions. Pretreatment with antihistamines and/or corticosteroids may prevent subsequent hypersensitivity reactions. Patients were not routinely premedicated prior to infusion of ELELYSO during clinical studies. If severe hypersensitivity reactions occur, immediately stop the infusion of ELELYSO and initiate appropriate treatment.
Consider the risks and benefits of re-administering ELELYSO in patients who have experienced a severe reaction associated with ELELYSO. Caution should be exercised upon rechallenge, and appropriate medical support should be readily available [see ADVERSE 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 taliglucerase alfa. In a male and female fertility study in rats, taliglucerase alfa did not cause any significant adverse effect on male or female fertility parameters up to a maximum dose of 55 mg/kg/day (about 5 times the recommended human dose of 60 units/kg based on the body surface area).
Use In Specific Populations
The limited available data on ELELYSO use in pregnant women are not sufficient to inform a drug-associated risk. However, there are clinical considerations [see Clinical Considerations]. In animal reproduction studies when pregnant rats and rabbits were administered taliglucerase alfa at intravenous doses up to 5 times the recommended human dose (RHD),there was no evidence of embryofetal toxicity [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. 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.
Disease-Associated Maternal and/or Embryo/Fetal Risk
Women with Type 1 Gaucher disease have an increased risk of spontaneous abortion 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 fetus and thrombocytopenia which can lead to increased bleeding and possible postpartum hemorrhage requiring transfusion.
Reproduction studies have been performed with taliglucerase alfa administered during the period of organogenesis in rats and rabbits. In rats, intravenous doses up to 55 mg/kg/day (about 5 times the RHD of 60 units/kg based on the body surface area) did not cause any adverse effects on embryofetal development. In rabbits, intravenous doses up to 27.8 mg/kg/day (about 5 times the RHD of 60 units/kg based on the body surface area) did not show any embryofetal toxicity.
There are no data on the presence of taliglucerase in human milk, the effects on the breast fed 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 ELELYSO and any potential adverse effects on the breastfed child from ELELYSO or from the underlying maternal condition.
The use of ELELYSO for treatment of pediatric patients with Type 1 Gaucher disease is supported by evidence of effectiveness from adequate and well-controlled trials of ELELYSO in adults, with additional pharmacodynamic data from 5 pediatric patients and pharmacokinetic data from 9 pediatric patients who participated in clinical trials [see Clinical Studies, CLINICAL PHARMACOLOGY]. Data from 14 pediatric patients were included in the safety evaluation [see ADVERSE REACTIONS]. There are insufficient data to inform dosing in patients less than 4 years of age.
Pediatric patients experienced a higher frequency of vomiting during ELELYSO treatment (4 of 9 treatment-na´ve patients) than adult patients, and this may be a symptom of hypersensitivity reaction. The frequencies of other adverse reactions were similar between pediatric and adult patients [see ADVERSE REACTIONS].
During clinical trials, 8 patients aged 65 or older were treated with ELELYSO. Clinical trials of ELELYSO did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/11/2015
Additional Elelyso Information
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