Real-World Safety and Performance of Saline Nasal Spray Products for Nasal Cleansing and Reducing Obstruction of the Nasal Cavity

Background and Objectives: Three post-marketing clinical follow-up studies were performed in Europe to confirm the safety and performance of four nonprescription, nasal cleansing medical devices: Otrivin Sea Water (OSW) pressurized spray, OSW with aloe vera (OSWAV), Otrisal 0.74% NaCl Metered-Dose Spray (MDS), and Prorhinel spray. Material and Methods: Observational, single-arm, retrospective studies consisting of a single online questionnaire were performed between July 2021 and December 2021. Eligible participants were adults who used the device or supervised use of the device in a participant under 18 years of age within 6 months of completing the questionnaire. Demographics, safety, and device performance were assessed. Results: Based on questionnaires submitted on OSW (n = 556), OSWAV (n = 555), Otrisal MDS (n = 555), and Prorhinel (n = 555), proportions of users who reported safety events were 1.8% for OSW, 2.3% for OSWAV, 1.4% for Otrisal MDS, and 2.0% for Prorhinel. Proportions of users who indicated they were satisfied or very satisfied with device performance ranged from 72.0% - 89.0% across all devices. Device performance for all products was also supported for additional preventative and symptomatic uses through exploratory analyses. Conclusions and Significance: These data confirm device safety and performance of OSW, OSWAV, Otrisal MDS, and Prorhinel for their intended uses.

Post-marketing safety surveillance and reevaluation of Motherwort injection：A clinical study of 10094 cases

OBJECTIVE:To investigate the safety profiles of Motherwort injection(MI).METHODS:A multi-center,prospective and drugderived hospital intensive monitoring method was conducted to assess the safety of MI in real world applications.This study was based on a very large population after the injection was approved and marketed in China.All patients using the injection in participating hospitals were monitored to determine the incidence,pattern,severity and outcome of associated adverse events.RESULTS:The post-marketing surveillance was performed in 10 094 female patients from April to December,2015.The incidence of adverse drug reactions(ADRs) was 0.79‰(8/10 094).Among the 8 patients,the reported adverse events mainly included systemic abnormalities,such as fever,chills and eyelid edema;skin and appendages disorders,such as pruritus and rash;gastrointestinal disorders,such as nausea,abdominal distension and pain;heart rate and rhythm disorders,such as palpitation and increased heart rate.All of these ADRs were mild in severity.CONCLUSION:In this study the ADRs incidence rate of MI is very low,which supports that it is generally safe for use in obstetric and gynecological diseases.However,the total number of 8 ADRs recorded over a relatively short time span seems limited,and the low number of reports could not represent an absolute guarantee of safety.

Postmarketing safety evaluation: depside salt injection made from Danshen(Radix Salviae Miltiorrhizae)

OBJECTIVE: To systematically examine the postmarketing safety of depside salt injection made from Danshen(Radix Salviae Miltiorrhizae),identifythe potential risk factors, and ensure its clinical safety.METHODS: We examined a comprehensive series of studies on the production process, quality standards, pharmacology, population pharmacokinetics, and safety evaluation of depside salt injection made from Danshen(Radix Salviae Miltiorrhizae). Data from Ⅰ-Ⅳ clinical drug trials, hospital information systems(HIS), and spontaneous reporting systems(SRS) were also analyzed.RESULTS: The effective components of salvianolic acid salt content reached almost 100%, and the magnesium lithospermate B content reached morethan 80%. The median lethal dose(LD50) calculated by the Bliss method was 1.49 g/kg, with 95%confidence intervals of 1.29-1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than 80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions(ADRs) included digestive disorders; drug-induced erythrocyte deformation in lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and other tissues; megakaryocytes in lung, liver, and spleen resulting from mild hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other studies indicated no irritative effect of the injection on local tissues and blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis. SRS data showed that the most common ADRs were headache, head distention, dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility of elevated Aspartate transaminase. HIS data indicated no damage to renal function from using depside salt injection made from Danshen(Radix Salviae Miltiorrhizae) at a dosage higher than the recommended dose.CONCLUSION: This study analyzes the clinical characteristics of ADRs from depside salt injection made from Danshen(Radix Salviae Miltiorrhizae),and discusses the factors influencing such reactions. It provides scientific reference and recommendations for clinically safe medication of the Danshen injection.

Postmarketing evaluation on the safety and effectiveness of Dengzhanxixin injection made from Dengzhanxixin(Herba Erigerontis Breviscapi)

OBJECTIVE: To assess the safety and effectiveness of Dengzhanxixin injection(DZI) extracted from Dengzhanxixin(Herba Erigerontis Breviscapi) and identify its potential risks.METHODS: A series of studies were conducted on the production process, quality standards, and pharmacology. Postmarketing clinical studies and literature reviews including adverse reactions(ADR),adverse events(ADE), case analysis and systematic reviews were also conducted. Data from the hospital information system and spontaneous reporting system were analyzed.RESULTS: The acute toxicity test indicated that the Lethal Dose 50 test( LD 50) dosage was 250 times more than the clinical maximum daily dosage(6mg/kg). In long-term toxicity tests, rats experi-enced renal tubular damage at 480 mg/kg. However, the dose of 120 mg/kg is safe and non-toxic,which is 40 times above the clinical daily maximum. Beagles had increased serum creatinine at160 mg/kg. In a prospective study, 15 962 cases experienced 16 ADR/ADE. The rate of ADR/ADE was0.1002%. ADR symptoms included rash(16.00%),chills(16.00%), and fever(16.00%).CONCLUSION: There is significant evidence that DZI is safe and effective in a clinical setting.

Establishment of safety evidence for Xingxue~ Shuxuening injection

OBJECTIVE: To systematically investigate the safety of Xingxue~ Shuxuening injection(SXN) in preand post-marketing, and to ensure clinical drug safety.METHODS: Strict quality control in raw herb selection and production processes was adopted and pharmacology research on SXN was performed by the drug manufacturing company, Heilongjiang ZBD Pharmaceutical Co., Ltd. We systematically reviewed the safety literature of Xingxue~ SXN. Adverse drug reaction(ADR) data of the drug, extracted from Spontaneous Reporting System(SRS), and clinical characters based on 20 hospital information systems(HIS) in China, were analyzed. Large-scale prospective safety monitoring and Risk Minimization Action Plans(Risk MAPs) of Xingxue~SXN were carried out.RESULTS: The quality of SXN was stable and controllable when it was produced. Drug toxicology studies found no effect on rabbits with hemolytic or condensed, local stimulation and muscle stimulation, and no allergic reactions in guinea pigs. The ADRs of Xingxue~ SXN were dizziness, phlebitis,and vomiting based on SRS data. The injection did not conform to instructions in clinical practice when we analyzed HIS database, and patient’s abnormal blood urea nitrogen levels may be related to the drug, when analyzed using the propensity score method. A nested case-control study was designed and performed to analyze the influencing factors of suspected allergic reactions to SXN. The study showed that patients with an allergy history were more prone to allergic reactions(P<0.001),and some medicine combinations could cause allergic reactions.CONCLUSION: These studies have established a body of evidence on Xingxue~ SXN safety, and provide a good model for Chinese medicine injection for clinical safety. The Xingxue~ SXN production process and toxicology research indicate the safety of the injection. However, the use of the injection is not consistent with instructed clinical practice.Xingxue~ SXN causes ADRs perhaps from inappropriate usage or its pharmacological action. This injection needs better Risk MAPs to ensure its clinical safety.

Postmarketing studies on safety of Dengfeng~ shenmai injection

OBJECTIVE: To systematically research the postmarketing safety of Dengfeng shenmai injection, identify potential risk factors, and ensure its clinical safety. METHODS: We investigated a comprehensive series of studies on the production process, quality standards, pharmacology, postmarketing clinical studies, and safety evaluation of Shenmai injection, including literature analysis of adverse drug reaction(ADR) case analysis and systematic review. Data from the hospital information system(HIS) and spontaneous reporting system(SRS) were also analyzed. RESULTS: The approximate dosage leading to death in dogs is 45.0-67.5 g raw drug/kg and the toxic reactions are restlessness, skin irritation, salivation, and vomiting. The results of chronic toxicity tests in mice and dogs, and the other tests such as 6-month toxicity, drug safety, genetic toxicity, and reproductive toxicity of rats and dogs, were positive or qualified. Patient ADR history and ADR family history were closely associated with itching based on the data analysis from SRS. There was no damage to renal function from Shenmai injection use at a dosage and a treatment course outside the recommended dosage and treatment course as specified based on data analysis from HIS. The most common ADR from Shenmai injection are difficulty breathing, facial flushing, nausea, vomiting, chest tightness, skin itching, rash, and back pain. CONCLUSION: This study includes complete information on Shenmai injection ADR incidence rate. We found that Shenmai injection is safe and this study can provide clinical, research, and production institutions with an objective, reliable, and scientific basis for use of Shenmai injection.