Safety analysis of Oseltamivir and Baloxavir Marboxil after market approval: a pharmacovigilance study based on the FDA adverse event reporting system.

BACKGROUND AND OBJECTIVES: Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references. METHODS: A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug. RESULTS: Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01-9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74-9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15-32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98-57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43-52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26]. CONCLUSION: Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir's potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.

The type rather than the daily dose or number of antipsychotics affects the incidence of hyperglycemic progression.

There have been concerns that antipsychotics increase the incidence of hyperglycemic progression. Many factors have been suggested to contribute to the risk of antipsychotic-induced hyperglycemic progression, including the type, daily dose, and number of antipsychotics; however, few studies have examined these relationships. This study aimed to examine the affect of antipsychotic treatment-associated factors on hyperglycemic progression, after adjustment for the affect of background factors suggested to be associated with hyperglycemic progression. This was a nationwide, multicenter, prospective cohort study examining the incidence of hyperglycemic progression during a 12 mo period following the initiation of newly prescribed antipsychotic medication. Demographic data, medication history, and blood test values were collected from 631 study participants with normal blood glucose levels at baseline for 12 mo. The primary endpoint (incidence of hyperglycemic progression) was defined as progression from normal to prediabetic or probable diabetic status, and was evaluated based on the Japanese monitoring guidance in patients with schizophrenia. To further examine the affect of antipsychotics on glucose metabolism over time, we examined changes in HbA1c levels 3, 6, and 12 mo after the initiation of treatment with each antipsychotic. We found that treatment with zotepine and clozapine was associated with a significantly high incidence of hyperglycemic progression. Furthermore, changes in HbA1c levels 6 mo after the initiation of zotepine treatment were significantly higher than those following blonanserin and haloperidol treatments. In contrast, there was no significant difference in the change in total cholesterol, triglycerides, HDL cholesterol, and BMI during the same period. Moreover, the "daily dose" and "number" of antipsychotics did not show an association with the incidence of hyperglycemic progression. However, in a post hoc analysis in which the antipsychotics were divided into two groups according to the strength of blockade of H1, M1, M3, and 5-HT2C receptors, the incidence of hyperglycemic progression was higher in the medium- and high-daily dose groups than in the low-daily dose group in the antipsychotic group with strong blockade of these receptors. Our study indicated that the type of antipsychotic had a greater affect on the incidence of hyperglycemic progression than the daily dose of antipsychotics or their number. Among these, zotepine was most likely to increase the incidence of hyperglycemic progression, suggesting the need for caution when these antipsychotics are prescribed.

Early prediction of clinical response in schizophrenia patients receiving the atypical antipsychotic zotepine.

OBJECTIVE: Prior early prediction models for antipsychotic treatment response demonstrate good specificity but poor sensitivity (i.e., high false-negative rates). The purpose of this study was to refine the early prediction model in schizophrenia patients taking an atypical antipsychotic agent, zotepine. METHOD: 135 acutely ill inpatients with DSM-IV-defined schizophrenia received 4 weeks of 150 mg/day zotepine treatment. Psychopathology severity was assessed weekly with the Brief Psychiatric Rating Scale (BPRS) and subscales for positive, negative, and general symptoms. Clinical response was defined as a reduction of 20% or more in the BPRS total score at week 4. A logistic regression model was used to obtain early predictors. The receiver operating characteristic curve was employed to determine the optimal cutoff points of the variables for predicting response. The study was conducted from June 2004 to April 2005. RESULTS: The most significant early predictors for ultimate response at week 4 were BPRS positive subscale score changes at week 1 and, better, at week 2 (p < .001 at both timepoints). At week 1, a BPRS positive score reduction of 4 appeared to be the optimal cutoff point for predicting eventual response, providing a sensitivity of 0.77 and specificity of 0.77. At week 2, a BPRS positive score reduction of 6 was the best for prediction, with a sensitivity of 0.83 and specificity of 0.91. CONCLUSIONS: These findings suggest that using the first 2 weeks' improvement in positive symptoms to predict the fourth week's treatment response is favorable in terms of both specificity and sensitivity. Further studies are needed. Moreover, whether this model could be applied to establish a prediction system for other antipsychotics or other psychotropics also deserves research.

Zotepine-induced catatonia as a precursor in the progression to neuroleptic malignant syndrome.

A 39-year-old man with schizophrenia developed severe catatonia, hyperthermia, muscle rigidity, tachycardia, leukocytosis, and elevated muscle enzyme levels while receiving zotepine therapy. Neuroleptic malignant syndrome (NMS) was diagnosed. After withdrawal of zotepine therapy, transfer to a neurologic intensive care unit, provision of supportive care, and administration of adjunctive bromocriptine therapy, the patient's fever and catatonia subsided. Biochemical irregularities spontaneously returned to normal with no complications. Antipsychotic therapy was restarted with risperidone 12 days after the patient's NMS resolved. After more than 1 year of follow-up, he experienced no adverse events. A recent decrease in mortality from NMS is related to increased awareness of this disorder, but not to treatment with specific agents. Clinicians need to recognize NMS early; although rare, it is a potentially fatal complication of antipsychotic treatment.

Hypothermia caused by antipsychotic drugs in a schizophrenic patient.

In a schizophrenic patient, hypothermia was caused by combined treatment with zotepine, biperiden, and fluphenazine, although combined treatment with zotepine and biperiden had caused no side effects. Other side effects closely resembled those in neuroleptic malignant syndrome.

[The relationship of antihistaminics to cadmium necrosis in rat testes]. / Vztah antihistaminik ke kadmiové nekróze krysích varlat.

Selective necrosis of rat testicles is known to be produced by cadmium in subtoxic doses due to impairment of vessel structures. Classical antihistaminics in the same time in order to exclude that the lesion might have been produced by local release of histamine. Antihistaminics did not prevent necrosis. Instead, Clemastine stressed an interstitial testicular haemorrhage a bit. Methyldosulepine administered with calcium could decrease the vascular permeability because haemorrhage was almost lacking. The finding supports an idea of possible interaction between calcium and cadmium ions.

The anti-inflammatory and analgesic profile of 6,11-dihydrodibenzo-[b.e.]-thiepin-11-one-3-acetic acid (tiopinac).

Tiopinac displayed marked anti-inflammatory activity when given p.o. in rat models of acute and chronic inflammation. It inhibited carrageenan-induced paw edema (40 x phenylbutazone), and cotton-pellet-induced granuloma (0.8 x indomethacin). In an 18-day test, tiopinac prevented the development of adjuvant-induced arthritis (10-15 x naproxen) and had similar activity versus pre-induced arthritis. Tiopinac exhibited antiphlogistic activity in adrenalectomized rats. It did not have corticosteroid activity. Depending upon the type of analgesic test used, the potency of tiopinac varied. When given p.o. it inhibited phenylquinone-induced writhing in the mouse and rat (respectively 16 and 10 x aspirin). In contrast, tiopinac had approximately 10 times the potency of indomethacin in increasing the pain threshold when yeast-inflamed paws were compressed. The pain threshold of the noninflamed paw was not increased. Tiopinac was highly active versus pain induced by flexing the adjuvant arthritic-inflamed paw (greater than or equal to 1000 x aspirin). It was inactive in the mouse hot-plate test in which opiate-like agents are active. Tiopinac, p.o., lowered yeast-induced pyrexia (130 x aspirin). Tiopinac did not have significant cardiovascular or CNS activity. Whereas the Ed50 versus adjuvant arthritis in rats was 0.1 mg/kg/day p.o., rats tolerated up to 20 mg/kg/day p.o. in the 8-day cotton-pellet test. Lack of anorexia and emesis in dogs with up to 30 mg/kg p.o. and mild oral activity in producing gastric erosion in acute and subacute studies in rats suggests that tiopinac may have relatively little gastrointestinal irritating activity.