FDA Approvals: Relenza and Eraxis

FDA Approvals: Relenza and Eraxis  CME/CE

News Author: Yael Waknine
CME Author: Yael Waknine
DisclosuresRelease Date: April 6, 2006; Valid for credit through April 6, 2007

April 6, 2006 — The US Food and Drug Administration (FDA) has approved a new indication for zanamivir oral inhalation, allowing its use for the prophylaxis of influenza in patients aged 5 years and older; and anidulafungin infusion for the treatment of candidemia and other forms of Candida infections (intraabdominal abscess and peritonitis) and esophageal candidiasis.Zanamivir for Inhalation (Relenza) to Prevent Influenza in Adults and Children

On March 29, the FDA approved a new indication for orally inhalable zanamivir (Relenza with Diskhaler, made by GlaxoSmithKline, Inc), allowing its use for the prophylaxis of influenza in patients aged 5 years and older.

The approval was based on a review of data from 4 large-scale, placebo-controlled studies. In 2 studies of postexposure prophylaxis in households with members aged older than 5 years, use of zanamivir within 1.5 days of symptom onset for treatment of the index case and its prophylactic use in other household members were equally effective for significantly reducing the spread of influenza (4.%1 vs 19.0%).

Results from the other 2 trials showed that zanamivir significantly reduced the risk of developing symptoms of influenza in adults aged 18 years and older (mean, 29 years; 86% unvaccinated) and individuals aged 12 to 94 years (mean age, 60 years) during community influenza outbreaks (56% aged older than 65 years; 67% unvaccinated; 2.0% vs 6.1% and 0.2% vs 1.4%, respectively).

According to the FDA, zanamivir has not been proven effective for influenza prophylaxis in the nursing home setting.

Zanamivir should be administered at approximately the same time each day. The recommended dose of zanamivir for household prophylaxis in patients aged 5 years and older is 10 mg (inhalation of two 5-mg blisters) once daily for 10 days, initiated within 1.5 days of symptom onset in the index case.

For the prophylaxis of influenza in a community setting, the recommended regimen for zanamivir in adults and adolescents is 10 mg daily for 28 days, initiated within 5 days of the outbreak being identified. The safety and efficacy of this regimen has not been studied beyond 28 days.

The most frequently reported adverse events related to use of zanamivir in adults and adolescents included headaches, diarrhea, nausea, vomiting, nasal irritation, bronchitis, cough, sinus infections, ear, nose, and throat infections, and dizziness. In children, ear, nose, and throat infections, vomiting, and diarrhea were most common. Less common reported events included rashes and allergic reactions, some of which were severe.

Because of the risk for potentially fatal bronchospasm, zanamivir should not be used in patients with underlying airway disease, such as chronic obstructive pulmonary disease or asthma. Zanamivir should be discontinued in patients who develop bronchospasm or demonstrate a decline in respiratory tract function; immediate treatment and hospitalization may be required.

The FDA notes that some patients without prior pulmonary disease may also have respiratory tract abnormalities from acute infection that could resemble an adverse reaction or increase patient vulnerability to such reactions.

Zanamivir is not intended as a substitute for the yearly flu vaccine, which remains the prophylactic treatment of choice as recommended by the Centers for Disease Control and Prevention's Immunization Practices Advisory Committee.

The drug was previously approved by the FDA for the treatment of uncomplicated acute illness due to influenza A and B virus in patients aged 7 years and older who have been symptomatic for no more than 2 days.Anidulafungin Infusion (Eraxis) for Candidemia and Other Candida Infections

On February 17, the FDA approved anidulafungin intravenous (IV) infusion (Eraxis, made by Pfizer, Inc) for the treatment of candidemia and other forms of Candida infections (intraabdominal abscess and peritonitis) and esophageal candidiasis.

Patients at increased risk for candidemia and systemic candidiasis include those with compromised immune systems, stem-cell and organ-transplant recipients, patients receiving chemotherapy, patients with catheters, critically ill patients in intensive care units, surgical patients, and patients receiving prolonged antibiotic therapy.

The approval was based in part on data from a double-blind, double-dummy, randomized phase 3 study (n = 245), showing that IV anidulafungin was more effective than fluconazole for successfully treating candidemia and other forms of Candida infections by the end of therapy (median duration, 14 vs 11 days; 75.6% vs 60.2%). Also, success rates remained higher in the anidulafungin group at 2- and 6-week follow-ups (64.6% vs 49.2% and 55.9% vs 44.1%, respectively).

Results of a similar study of patients with esophageal candidiasis (n = 442; 84.6% HIV+) revealed that cure-improvement rates were similar for patients treated with anidulafungin or fluconazole (97.4% vs 98.7%). However, the relapse rate at 2 weeks was higher in the anidulafungin group (53.3% vs 19.3%).

The recommended regimen for anidulafungin in the treatment of candidemia and other Candida infections is a 200-mg loading dose on day 1, followed by a 100-mg daily dose thereafter. Therapy duration should be based on clinical response; in general, antifungals should be continued for at least 14 days after the last positive culture.

Patients with esophageal candidiasis should receive a 100-mg loading dose of anidulafungin on day 1, followed by a 50-mg daily dose thereafter. Treatment should continue for a minimum of 14 days and for at least 7 days following resolution of symptoms. Because of the risk for relapse in patients with HIV infection, suppressive therapy may be considered after a course of treatment.

The FDA notes that the drug's safety and efficacy has not been determined for pediatric patients. Anidulafungin should not be administered to patients with hypersensitivity to the drug, product excipients, or other echinocandin agents.

In clinical studies, anidulafungin and fluconazole therapy were similarly well-tolerated, with comparable rates for adverse events. Adverse events most commonly reported in the anidulafungin group included hypokalemia (3.1%), diarrhea (3.1%), and increased alanine aminotransferase levels (2.3%). In the esophageal candidiasis study, headache (1.3%) and increased gamma glutamyl transpeptidase levels (1.3%) occurred most frequently.

Anidulafungin has not been linked to a risk for renal toxicity and has no clinically relevant drug-drug interactions. Furthermore, there are no requirements for dosage adjustments based on race, age, HIV status, hepatic insufficiency, or renal insufficiency.

Some cases of clinically significant hepatic abnormalities have been reported with use of anidulafungin in patients with serious underlying medical conditions. Possible histamine-mediated symptoms have also been reported infrequently, including rash, urticaria, flushing, pruritus, dyspnea, and hypotension.

http://www.fda.gov/cder/foi/label/2006/021036s008lbl.pdf

http://www.fda.gov/cder/foi/label/2006/021632s000,021948s000lbl.pdf

Pearls for Practice

The FDA has approved a new indication for zanamivir for inhalation, allowing its use for the prophylaxis of influenza in patients aged 5 years and older. It should not be used in patients with underlying airway disease because of the risk for potentially fatal bronchospasm. Zanamivir is not intended as a substitute for annual influenza vaccinations.The recommended dose of zanamivir for prophylaxis of influenza in a household setting of patients aged 5 years and older is 10 mg (inhalation of two 5-mg blisters) once daily for 10 days, initiated within 1.5 days of symptom onset in the index case. In the community setting, prophylactic therapy should be initiated within 5 days of outbreak identification; the recommended regimen for adults and adolescents is 10 mg daily for 28 days. Doses should be taken at approximately the same time each day.According to clinical study data, intravenous anidulafungin is more effective than fluconazole for successfully treating candidemia and other forms of Candida infections. In patients with esophageal candidiasis, the majority of whom were HIV+, anidulafungin was similarly effective compared with fluconazole and associated with an increased relapse rate at 2 weeks posttherapy.

Medscape Medical News 2006. ©2006 Medscape

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This is a part of article FDA Approvals: Relenza and Eraxis Taken from "Buy Diflucan Fluconazole" Information Blog