Pharmacoeconomic Evaluation of Peramivir versus Oseltamivir in the Treatment of Influenza Complicated with Febrile Seizures for Children / 中国药房

ABSTRACT OBJECTIVE：To compare the effectiveness and economics of peramivir and oseltamivir in the treatment of influenza complicated with febrile seizures in children. METHODS：In retrospective study，152 children with influenza complicated with febrile seizures were collected from our hospital during Dec. 2018 to Mar. 2019.They were divided into peramivir group（81 cases） and oseltamivir group （71 cases）. Fever remission time， medication duration， hospital duration， clinical efficacy （determined by convulsion，cough，nasal obstruction，runny nose，sore throat，etc.），the incidence of rash，the number of children with combined antibiotic and TCM were compared between 2 groups. Cost-effectiveness analysis was used to evaluate cost-effectiveness ratio（CER）and incremental cost-effectiveness ratio（ICER）of medication regimen in 2 groups. The sensitivity analysis of the effect and total cost were carried out with Logistic regression and multiple linear regression respectively through CER and ICER calculated by reducing 15％ drug price. RESULTS：There was no statistical significance in fever remission time， medication duration，hospitalization duration，the incidence of rash and proportion of children with combined antibiotics between 2 groups（P＞0.05）. There was statistical significance in proportion of children with combined TCM and clinical effect，and the proportion of children with combined TCM in peramivir group was significantly lower than oseltamivir group（P＜0.001）. Clinical effect of peramivir group was significantly better than that of oseltamivir group（P＝0.021）. Total cost of peramivir group and oseltamivir group were 5 442.84 yuan/person and 5 571.71 yuan/person（P＝0.795）；CER of them were 54.47 and 56.51；ICER of peramivir group was － 89.38. The results of sensitivity analysis were consistent with those of basic analysis.CONCLUSIONS： Compared with oseltamivir，peramivir is more effective and less costly for children with influenza and febrile seizures.

Antiviral Drugs For Influenza Viruses

Antiviral drugs have significant action against influenza viruses A and B. Virus spread deadly disease in which many people die, and the country economy greatly suffer. Presently, most of the people need to get vaccination, which is depending on the dose limit in humans. It reacts directly or sometimes indirectly in the form of metabolites. However, it is mandatory to know how much drug is absorbed or metabolites concentration after administered. Therefore, pharmacokinetics data is very crucial for all drugs. Our review discusses the mechanism of drugs action and their activity and also describes how antiviral drugs and their metabolites is determined using a highly sensitive instrument such as high-performance liquid chromatography (HPLC), ultra-pressure liquid chromatography (UPLC), mass spectrometry (MS). Therefore, the present review gives brief information about antiviral drugs, their activity, biotransformation and analytical methods for quantification and this information will be helpful for any future studies done by experts in this field and will be beneficial for research scientists and influenza experts of all over the globe.

A randomized controlled study of peramivir, oseltamivir and placebo in patients with mild influenza / 中华内科杂志

Objectives To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza.Methods This was a randomized,double-blind,double-dummy,placebo and positive control,multicenter clinical trial,comparing peramivir trihydrate with oseltamivir and placebo.The inclusive criteria were 15-70 years old,onset within 48 h,positive rapid influenza antigen test,and febrile(＞38℃) accompanied with at least two associated symptoms.The severe cases complicated with chronic pulmonary and cardiac diseases,malignancies,organ transplantation,hemodialysis,uncontrolled diabetes,immunocompromised status,pregnancy and coexistence of bacterium infections were excluded.All patients were randomized 2:2:1 to receive peramivir,oseltamivir and placebo respectively.The primary endpoint was the disease duration,the secondary endpoints included time to normal axillary temperature and normal living activities,viral response,and adverse effects.Results Following informed consent,133 patients were included in this study.Four patients were exclude due to missing medical records,not fitting inclusion or exclusion criteria and poor compliance.A total of 129 patients were finally analyzed,including 49 cases,54 cases and 26 cases in peramivir group,oseltamivir group and placebo group.The median disease duration were 96 (76,120)hours,105(90,124) hours,and 124 (104,172)hours in three groups respectively(P＞0.05).The time to normal axillary temperature,normal living activities and viral response were not significantly different in three groups(P＞0.05).Conclusion The value of antiviral therapy in patients with mild influenza needs to be further determined.

Safety and Effectiveness of Peramivir in Korean Adult Influenza Patients: Prospective Observational Study Based on Post-Marketing Surveillance Data

BACKGROUND: The safety and clinical effectiveness data of peramivir in the real clinical field are limited. A prospective observational study was conducted based on the post-marketing surveillance data to evaluate the post-marketing safety and effectiveness of peramivir in Korean adults with seasonal influenza. METHODS: Among adults aged 20 years or older who were diagnosed with influenza A or B, patients who started peramivir within 48 hours from the initial symptoms of influenza were enrolled. All adverse events (AEs) that occurred within 7 days after administration of peramivir were checked. For the evaluation of effectiveness, changes in the severity of influenza symptoms and daily living performance were examined before and 7 days after the administration of peramivir. The date on which influenza related symptoms disappeared was checked. RESULTS: A total of 3,024 patients were enrolled for safety evaluation and 2,939 patients were for effectiveness evaluation. In the safety evaluation, 42 AEs were observed in 35 (1.16%) patients. The most common AE was fever. AEs were mostly rated as mild in severity. Serious AEs were observed in 10 patients and two of them died. However, both deaths were considered to be less relevant to peramivir. In the effectiveness evaluation, the severity of influenza symptoms decreased by 10.68 ± 4.01 points and daily living performance was improved 5.59 ± 2.16 points. Influenza related symptoms disappeared on average 3.02 ± 2.39 days after peramivir administration. CONCLUSION: Peramivir showed a tolerable safety profile and acceptable effectiveness in Korean adult patients with seasonal influenza.

Characteristics and selection of common drugs for influenza in children / 中华实用儿科临床杂志

Influenza is caused by influenza virus.Neuraminidase inhibitors have produced certain effects for the management of influenza.Among them,Osehamivir has been in extensive use in adults and children,Peramivir and Zanamivir have been used in children.M2 inhibitors and traditional Chinese medicines can also be used in the management of influenza.In clinical practice,the physicians are expected to select anti-influenza drugs based on their mechanism of action and characteristics.

Characteristics and selection of common drugs for influenza in children / 中华实用儿科临床杂志

Influenza is caused by influenza virus.Neuraminidase inhibitors have produced certain effects for the management of influenza.Among them,Osehamivir has been in extensive use in adults and children,Peramivir and Zanamivir have been used in children.M2 inhibitors and traditional Chinese medicines can also be used in the management of influenza.In clinical practice,the physicians are expected to select anti-influenza drugs based on their mechanism of action and characteristics.

Comparison of Efficacy of Intravenous Peramivir and Oral Oseltamivir for the Treatment of Influenza: Systematic Review and Meta-Analysis

PURPOSE: Peramivir is the first intravenously administered neuramidase inhibitor for immediate delivery of an effective single-dose treatment in patients with influenza. However, limited data are available on intravenous (IV) peramivir treatment compared to oral oseltamivir for these patients. MATERIALS AND METHODS: With a systematic review and meta-analysis, we compared the efficacy of IV peramivir with oral oseltamivir for treatment of patients with seasonal influenza. MEDLINE, EMBASE, and Cochrane Central Register were searched for relevant clinical trials. RESULTS: A total of seven trials [two randomized controlled trials (RCTs) and five non-randomized observational trials] involving 1676 patients were finally analyzed. The total number of peramivir- and oseltamivir-treated patients was 956 and 720, respectively. Overall, the time to alleviation of fever was lower in the peramivir-treated group compared with the oseltamivir-treated group [mean difference (MD), −7.17 hours; 95% confidence interval (CI) −11.00 to −3.34]. Especially, pooled analysis of observational studies (n=4) and studies of outpatients (n=4) demonstrated the superiority of the peramivir-treated group (MD, -7.83 hours; 95% CI −11.81 to −3.84 and MD, −7.71 hours; 95% CI −11.61 to −3.80, respectively). Mortality, length of hospital stay, change in virus titer 48 hours after admission, and the incidence of adverse events in these patients were not significantly different between the two groups. CONCLUSION: IV peramivir therapy might reduce the time to alleviation of fever in comparison with oral oseltamivir therapy in patients with influenza; however, we could not draw clear conclusions from a meta-analysis because of the few RCTs available and methodological limitations.

Establishment of Bacterial Endotoxin Test Method for Peramivir Hydrate and Sodium Chloride Injection / 中国药房

OBJECTIVE:To establish a method for bacteria1 endotoxin test for Peramivir hydrate and sodium chloride injec-tion. METHODS:Maximum non-interference concentration of the sample with different batohes were used for interference test. was determined by interference test according to endotoxin gel method stated in Chinese Pharmacopiea (2010 edition)and bacterial en-edotoxintest by tachypleus amebocyte lysate from 2 manufact urers. RESULTS:The interference on bacterial endotoxin test could be excluded when the sample was diluted to 2.5 mg/ml and the limit of bacterial endotoxins was 0.5 EU/ml. CONCLUSIONS:The established method can be used to detect the bacterial endotoxin of Peramivir hydrate and sodium chloride injection.

A Case of Influenza Associated Fulminant Myocarditis Successfully Treated with Intravenous Peramivir / 감염과화학요법

We report the case of a patient with fulminant myocarditis caused by influenza A virus, who presented with acute-onset heart failure and cardiogenic shock and was treated successfully with single dose of intravenous peramivir and with pharmacologic hemodynamic support. A 45-year-old Korean woman presented to our emergency department (ED) with shortness of breath and an episode of seizure that developed abruptly 5 hours before she arrived in the ED. She had a history of recurrent epileptic seizure 25 years ago, but denied other specific medical illnesses. In the ED, she was hypoxemic (arterial partial pressure of oxygen, 59.8 mmHg on room air) and chest radiography revealed bilateral alveolar infiltrates. A rapid antigen test for influenza A virus was positive, and she was administered a single dose of peramivir (300 mg) intravenously. Five hours later, the patient's dyspnea had worsened and she was hypotensive (blood pressure, 86/53 mmHg), requiring norepinephrine infusion. Further evaluation disclosed an increased cardiac troponin I level of 1.36 ng/mL and a depressed left ventricular ejection fraction of 30%. Under the diagnosis of influenza A-associated myocarditis and cardiogenic shock, she was managed with continuous critical care in the intensive care unit. On day 3, the patient's dyspnea began to resolve and her ventricular function returned to normal. Real-time polymerase chain reaction assays for influenza viruses in serial nasopharyngeal aspirates were positive for influenza A (hH3N2) with a threshold cycle value of 27.39 on day 2, but these became negative by day 4. The patient recovered and was discharged on day 9 after admission. In conclusion, this case indicates that intravenous peramivir might be an effective antiviral agent for the treatment of severe influenza A virus infection.

A Fatal Case in Pregnant Woman Infected by H1N1 2009 in Korea / 감염과화학요법

Pregnant women is known to be at risk of high morbiding and mortality from H1N1 2009. Since the emergence of H1N1 2009 in Korean in April 2009, fatal case has not been reported in the Korean pregnant women yet. This is the first report of fatal case in pregnant women associated with H1N1 2009 infection in Korea. A 29-year-old woman at 32 weeks of gestation presented with pneumonia associated with H1N1 2009 infection, progressed into acute respiratory distress syndrome. On the fourth day of admission fetal distress development. The patient died from refractory critical hypoxemia and multiple organ failure on the 5th hospital day in spite of receiving extracorporeal membrane oxygenation therapy and intravenous peramivir.

A Case of Acute Pulmonary Thromboembolism Complicated Pandemic Influenza (H1N1 2009) / 감염과화학요법

During the pandemic, few patients have suffered from severe pneumonia leading to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction necessitating prolonged intensive care with higher mortality. Although sepsis and ARDS represent hypercoagulable states, acute pulmonary thromboembolism is rarely encountered in influenza infection. Fifty five year old female patient admitted with pneumonia associated with influenza A infection, progressed into ARDS. Pulmonary thromboembolism was detected by CT scan and treated with anticoagulants. This is the first case report of acute pulmonary thromboembolism in a patient with pandemic influenza (H1N1 2009) in Korea.

Quantification of peramivir in rat plasma by liquid chromatography/tandem mass spectrometry employing precolumn derivatization and its application in pharmacokinetics / 军事医学科学院院刊

Objective:To develop a liquid chromatography/tandem mass spectrometry employing precolumn derivatization method for determination of peramivir in rat plasma.Methods: The sample preparation consisted of a protein precipitation extraction followed by derivatization with hydrochloric acid (10 mol/L) methanol (10∶90, v/v) and determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The positive ion SRM mode was performed and the precursor-to-the-product ion transitions of m/z 343→284 and 299→152 were used to measure the derivative of peramivir and Ro 64-0802 (I.S.). The chromatographic separation was achieved using a Zorbax RX-C8 (2.1 mm × 150 mm × 5 μm) analytical column with an isocratic mobile phase composed of acetonitrile-water-formic acid (30∶70∶0.1, v/v/v, 0.2 ml/min). Results:The method was linear over a concentration range of 10 to 10 000 ng/ml. The LLOQ was 10 ng/ml. The average inter-day/intra-day precision values ranged from 5.0% to 7.1%, respectively, while the accuracy values ranged from 89.9% to 106.1%.Conclusion: In this method, retention time is greatly improved, the matrix effects are decreased by chemical derivatization. This method has been successfully applied to the preclinical and clinical research of peramivir.