peramivir and Emergencies

In response to the 2009 H1N1 influenza pandemic, the governments of Japan and the United States for the first time authorized the emergency use of unapproved drugs. In this article, we comprehensively review the different regulatory approaches of Japan and the United States, countries with advanced regulatory and healthcare systems, to emergency authorization of the use of medical products as a countermeasure to public health emergencies. We outline the legal system, range of targeted products, requirements for the application dossier, legal stance for authorization, product availability, and termination of the Japanese Emergency Approval (EA), and we compare characteristics with those of the US Emergency Use Authorization (EUA). We also review the actual cases of these 2009 emergency authorizations. The Japanese EA importation of novel H1N1 influenza vaccines with adjuvant is presented, with lessons learned, and contrasted with the US EUA of peramivir.

Topics: Acids, Carbocyclic; Antiviral Agents; Cyclopentanes; Drug Approval; Emergencies; Guanidines; Humans; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Influenza, Human; Japan; Pandemics; United States

A novel H1N1 influenza virus of swine origin has emerged, causing the first pandemic of the 21st century. Infections with 2009 pandemic influenza A (H1N1) are typically moderate. However, in rare cases, respiratory distress, neurological complications and death have been reported. To alleviate complications associated with 2009 H1N1 influenza infection, the neuraminidase (NA) inhibitors oseltamivir (oral) and zanamivir (inhaled) are recommended. Hospitalized patients with severe complications may not respond to these drugs or be able to receive oral antiviral therapy, and therefore, parenteral formulations that would allow rapid delivery at high concentrations are being pursued. Peramivir is a novel potent NA inhibitor currently in clinical trials for intravenous (i.v.) administration. In clinical trials, i.v. peramivir was shown to be safe and well tolerated, with a pharmacokinetic profile that supports once-daily dosing. Based on the safety and efficacy of i.v. peramivir in clinical trials and the need for a parenteral antiviral, the U.S. Food and Drug Administration issued an Emergency Use Authorization (EUA) for the use of peramivir for the treatment of hospitalized patients with known or suspected 2009 H1N1 influenza infection. In Japan, peramivir has been licensed under the name Rapiacta. The development of peramivir leading to the issuance of the EUA and approval in Japan will be discussed.

Topics: Acids, Carbocyclic; Antiviral Agents; Clinical Trials as Topic; Cyclopentanes; Emergencies; Guanidines; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Influenza, Human; Oseltamivir; United States; United States Food and Drug Administration

A 36-year-old man with underlying systemic lupus erythematosus complicated by autoimmune hemolytic anemia underwent immunosuppressive treatment. After showing a low-grade fever for two days, his fever spiked. He was confirmed to have pandemic (H1N1) 2009 by real-time reverse transcription polymerase chain reaction (PCR). His condition deteriorated to acute respiratory distress syndrome (ARDS), and mechanical ventilation became necessary. The lowest PaO(2)/FIO(2) ratio was 77, and he was placed on extracorporeal membrane oxygenation (ECMO). Based on our observation, the emergency use of ECMO in addition to peramivir might be useful. A noteworthy point is that once ARDS deteriorates due to pandemic (H1N1) 2009, intensive supportive care should be started.

Topics: Acids, Carbocyclic; Adult; Anemia, Hemolytic, Autoimmune; Antiviral Agents; Combined Modality Therapy; Cyclopentanes; Disease Outbreaks; Emergencies; Extracorporeal Membrane Oxygenation; Guanidines; Humans; Immunocompromised Host; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza, Human; Lupus Erythematosus, Systemic; Male; Neuraminidase; Oxygen Inhalation Therapy; Prednisolone; Radiography; Respiration, Artificial; Respiratory Distress Syndrome; Viral Proteins

Topics: Acids, Carbocyclic; Antiviral Agents; Cyclopentanes; Drug Approval; Drugs, Investigational; Emergencies; Enzyme Inhibitors; Guanidines; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Injections, Intravenous; Investigational New Drug Application; Neuraminidase; United States; United States Food and Drug Administration