"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).
Anaphylaxis And Hypersensitivity Reactions
Anaphylaxis and hypersensitivity reactions have been reported in patients treated with Vimizim. In premarketing clinical trials, 18 of 235 (7.7%) patients treated with Vimizim experienced signs and symptoms consistent with anaphylaxis. These 18 patients experienced 26 anaphylactic reactions during infusion with signs and symptoms including cough, erythema, throat tightness, urticaria, flushing, cyanosis, hypotension, rash, dyspnea, chest discomfort, and gastrointestinal symptoms (e.g., nausea, abdominal pain, retching, and vomiting) in conjunction with urticaria. These cases of anaphylaxis occurred as early as 30 minutes from the start of infusion and up to three hours after infusion. Anaphylaxis occurred as late into treatment as the 47th infusion.
In clinical trials with Vimizim, 44 of 235 (18.7%) patients experienced hypersensitivity reactions, including anaphylaxis. Hypersensitivity reactions have occurred as early as 30 minutes from the start of infusion but as late as six days after infusion. Frequent symptoms of hypersensitivity reactions (occurring in more than 2 patients) included anaphylactic reactions, urticaria, peripheral edema, cough, dyspnea, and flushing.
Due to the potential for anaphylaxis, appropriate medical support should be readily available when Vimizim is administered. Observe patients closely for an appropriate period of time after administration of Vimizim, taking into account the time to onset of anaphylaxis seen in premarketing clinical trials. Inform patients of the signs and symptoms of anaphylaxis, and instruct them to seek immediate medical care should signs and symptoms occur.
Because of the potential for hypersensitivity reactions, administer antihistamines with or without antipyretics prior to infusion. 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 additional antihistamines, antipyretics, and/or corticosteroids for mild reactions. However, if severe hypersensitivity reactions occur, immediately stop the infusion of Vimizim and initiate appropriate treatment.
Consider the risks and benefits of re-administering Vimizim following a severe reaction.
Risk Of Acute Respiratory Complications
Patients with acute febrile or respiratory illness at the time of Vimizim infusion may be at higher risk of life-threatening complications from hypersensitivity reactions. Careful consideration should be given to the patient's clinical status prior to administration of Vimizim and consider delaying the Vimizim infusion.
Sleep apnea is common in MPS IVA patients. Evaluation of airway patency should be considered prior to initiation of treatment with Vimizim. Patients using supplemental oxygen or continuous positive airway pressure (CPAP) during sleep should have these treatments readily available during infusion in the event of an acute reaction, or extreme drowsiness/sleep induced by antihistamine use.
Spinal Or Cervical Cord Compression
Spinal or cervical cord compression (SCC) is a known and serious complication of MPS IVA and may occur as part of the natural history of the disease. In clinical trials, SCC was observed both in patients receiving Vimizim and patients receiving placebo. Patients with MPS IVA should be monitored for signs and symptoms of SCC (including back pain, paralysis of limbs below the level of compression, urinary and fecal incontinence) and given appropriate clinical care.
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 elosulfase alfa. Based on the mechanism of action, elosulfase alfa is not expected to be tumorigenic. Daily intravenous administration of elosulfase alfa in rats at doses up to 20 mg/kg (55 times the human steady-state AUC in male rats and 33 times the human steady-state AUC in female rats at the recommended human weekly dose) had no effects on fertility or reproductive performance.
Use In Specific Populations
Pregnancy Category C
There is a Morquio A Registry that collects data on pregnant women with MPS IVA who are treated with Vimizim. Contact MARS@bmrn.com or call 1-800-983-4587 for information and enrollment [see PATIENT INFORMATION].
There are no adequate and well-controlled studies with Vimizim in pregnant women. However, animal reproduction studies have been conducted for elosulfase alfa. In these studies, no effects on embryo-fetal development were observed in rats given daily administration of elosulfase alfa up to 33 times the human steady-state AUC (area under the curve) at the recommended human weekly dose pre-mating and through the period of organogenesis. No effects on embryo-fetal development were observed in rabbits given daily administration of elosulfase alfa at doses up to 8 times the human steady-state AUC at the recommended weekly dose during organogenesis, which produced maternal toxicity. A dose-dependent increase in stillbirths was observed when elosulfase alfa was administered daily in rats during organogenesis through lactation at doses 5 times the human steady-state AUC at the recommended human weekly dose. An increase in pup mortality was observed at doses producing maternal toxicity. Vimizim should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Disease-associated maternal and embryo/fetal risk
Pregnancy can adversely affect the health of females affected with MPS IVA and lead to adverse pregnancy outcomes for both mother and fetus.
All reproductive studies with rats included pre-treatment with diphenhydramine to prevent or minimize hypersensitivity reactions. The effects of elosulfase alfa were evaluated based on comparison to a control group treated with diphenhydramine alone. Daily intravenous (IV) administration of up to 20 mg/kg elosulfase alfa in rats (33 times the human steady-state AUC at the recommended weekly dose of 2 mg/kg) during a 15-day pre-mating period, mating, and the period of organogenesis, produced no maternal toxicity or effects on embryo-fetal development. Daily intravenous administration of up to 10 mg/kg in rabbits (8 times the human steady-state AUC at the recommended weekly dose) during the period of organogenesis had no effects on embryo-fetal development. However, maternal toxicity (gross changes in liver) was observed in rabbits given doses of 1 mg/kg/day and higher (0.1 times the human steady-state AUC at the recommended weekly dose). Elosulfase alfa produced an increase in the percentage of stillbirths when administered daily to rats at doses of 6 mg/kg IV and higher (5 times the human steady-state AUC at the recommended weekly dose) during the period of organogenesis through lactation. Daily administration of 20 mg/kg IV (33 times the human steady-state AUC at the recommended weekly dose) produced maternal toxicity and an increase in mortality of offspring during the lactation period. This study lacked a full evaluation of neurodevelopmental milestones; however, no effects of elosulfase alfa were noted in tests for learning and memory.
It is not known if Vimizim is present in human milk. Elosulfase alfa is present in milk from treated rats [see Use in Specific Populations]. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Vimizim and any potential adverse effects on the breastfed child from the drug or from MPS IVA. Exercise caution when administering Vimizim to a nursing mother. There is a Morquio A Registry that also collects data on breastfeeding women with MPS IVA who are treated with Vimizim. Contact MARS@bmrn.com or call 1-800-983-4587 for information and enrollment [see PATIENT INFORMATION].
Safety and effectiveness of Vimizim have been established in pediatric patients 5 years of age and older. Use of Vimizim in patients 5 years of age and older is supported by an adequate and well-controlled trial in pediatric and adult patients. Clinical trials with Vimizim were conducted in 176 patients (median age 12 years, range 5 to 57 years old) with the majority of patients in the pediatric age group (53% aged 5 to 11 years, 27% aged 12 to 17 years) [see Clinical Studies]. Safety and effectiveness in pediatric patients below 5 years of age have not been established.
Clinical studies of Vimizim did not include any patients aged 65 and over. It is not known whether they respond differently from younger patients.
Last reviewed on RxList: 2/27/2014
This monograph has been modified to include the generic and brand name in many instances.
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