Real-World Evidence on Levetiracetam-Induced Hypokalemia: An Active Comparator Cohort Study.

BACKGROUND: Levetiracetam is an anti-seizure medication (ASM) with an established safety profile. However, a potential safety signal of hypokalemia following levetiracetam use was published in the World Health Organization newsletter. OBJECTIVE: To investigate the possible causal association between the use of levetiracetam and the development of hypokalemia. METHOD: This was a new-user, active-comparator retrospective cohort study using Real-world Evidence Research Network data at the Saudi Food and Drug Authority from 2016 to 2022. Adults (≥ 18 years old) with an incident prescription for either levetiracetam or carbamazepine were followed for up to 6 months from the prescription date. Hypokalemia was ascertained by using diagnostic code (i.e., E87.6) or by serum potassium level below 3.5 mmol/L. A Cox proportional hazards model, adjusted with stabilized inverse probability of treatment weight, was fitted to compare the hazard of hypokalemia between levetiracetam and carbamazepine exposed patients. RESULTS: A total of 8,982 patients entered the study cohort. The incidence rate of hypokalemia was 303 cases per 10,000 patient-years in the levetiracetam-exposed cohort compared to 57 cases per 10,000 patient-years among carbamazepine users. Compared to carbamazepine users, patients exposed to levetiracetam had an adjusted hazard ratio related to induced hypokalemia of 1.99 (95% confidence interval, 0.88-4.49). Results of sensitivity analyses were comparable to the main analysis. CONCLUSION: The hazard ratio for hypokalemia with the use of levetiracetam versus carbamazepine was statistically comparable. However, the potential association between levetiracetam use and hypokalemia cannot be ruled out given the elevated hazard ratios from the main and sensitivity analyses. Further studies may provide a more precise assessment of this association.

Bioequivalence trials for the approval of generic drugs in Saudi Arabia: a descriptive analysis of design aspects.

BACKGROUND: This retrospective analysis aimed to comprehensively review the design and regulatory aspects of bioequivalence trials submitted to the Saudi Food and Drug Authority (SFDA) since 2017. METHODS: This was a retrospective, comprehensive analysis study. The Data extracted from the SFDA bioequivalence assessment reports were analyzed for reviewing the overall design and regulatory aspects of the successful bioequivalence trials, exploring the impact of the coefficient of variation of within-subject variability (CVw) on some design aspects, and providing an in-depth assessment of bioequivalence trial submissions that were deemed insufficient in demonstrating bioequivalence. RESULTS: A total of 590 bioequivalence trials were included of which 521 demonstrated bioequivalence (440 single active pharmaceutical ingredients [APIs] and 81 fixed combinations). Most of the successful trials were for cardiovascular drugs (84 out of 521 [16.1%]), and the 2 × 2 crossover design was used in 455 (87.3%) trials. The sample size tended to increase with the increase in the CVw in trials of single APIs. Biopharmaceutics Classification System Class II and IV drugs accounted for the majority of highly variable drugs (58 out of 82 [70.7%]) in the study. Most of the 51 rejected trials were rejected due to concerns related to the study center (n = 21 [41.2%]). CONCLUSION: This comprehensive analysis provides valuable insights into the regulatory and design aspects of bioequivalence trials and can inform future research and assist in identifying opportunities for improvement in conducting bioequivalence trials in Saudi Arabia.

Recording type 2 diabetes mellitus in a standardised central Saudi database: a retrospective validation study.

OBJECTIVES: This study was conducted to assess the validity of recording (and the original diagnostic practice) of type 2 diabetes mellitus at a hospital whose records were integrated to a centralised database (the standardised common data model (CDM) of the Saudi National Pharmacoepidemiologic Database (NPED)). DESIGN: A retrospective single-centre validation study. SETTINGS: Data of the study participants were extracted from the CDM of the NPED (only records of one tertiary care hospital were integrated at the time of the study) between 1 January 2013 and 1 July 2018. PARTICIPANTS: A random sample of patients with type 2 diabetes mellitus (≥18 years old and with a code of type 2 diabetes mellitus) matched with a control group (patients without diabetes) based on age and sex. OUTCOME MEASURES: The standardised coding of type 2 diabetes in the CDM was validated by comparing the presence of diabetes in the CDM versus the original electronic records at the hospital, the recording in paper-based medical records, and the physician re-assessment of diabetes in the included cases and controls, respectively. Sensitivity, specificity, positive predictive value and negative predictive value were estimated for each pairwise comparison using RStudio V.1.4.1103. RESULTS: A total of 437 random sample of patients with type 2 diabetes mellitus was identified and matched with 437 controls. Only 190 of 437 (43.0%) had paper-based medical records. All estimates were above 90% except for sensitivity and specificity of CDM versus paper-based records (54%; 95% CI 47% to 61% and 68%; 95% CI 62% to 73%, respectively). CONCLUSIONS: This study provided an assessment to the extent of which only type 2 diabetes mellitus code can be used to identify patients with this disease at a Saudi centralised database. A future multi-centre study would help adding more emphasis to the study findings.

Association between prehypertension and psychological distress among adults in Saudi Arabia: A population-based survey.

BACKGROUND: Prehypertension is a precursor to hypertension status. Psychological distress has been identified earlier among hypertensives; however, there is little evidence for the presumptive relationship between prehypertension and psychological distress. OBJECTIVE: The study aimed to assess the psychological wellbeing of the Al-Kharj, Saudi Arabia population, using the General Health Questionnaire (GHQ-12) and correlating it with prehypertensive patients in the same population. METHODS: A cross-sectional analysis of the population of Al-Kharj, Saudi Arabia, was carried out between January and June of 2016. With an 85 percent response rate, a total of 1016 participants participated in the study. A multiple linear regression analysis was performed to assess the relationship between prehypertension and psychological distress. RESULTS: The findings of the adjusted analysis demonstrated that, on average prehypertensive patients were more distressed psychologically than non-hypertensive patients (unstandardized Beta regression coefficient = 3.600; P-value 0.025). Similarly, on average women were found to be more psychologically distressed than men (unstandardized Beta = 1.511, P-value 0.002). Civil workers and unemployed individuals were more psychologically distressed than employed individuals (unstandardized Beta = 1.326, P-value 0.041) while adjusting for the sociodemographic and other variables such as BMI, diabetes status, cholesterol, and smoking status. CONCLUSION: The current study shows that as compared to normotensive patients, self-rated mental wellbeing and psychological wellbeing are all considerably poorer among prehypertensive patients. To prevent individuals from having negative psychological outcomes and their long-term complications, the Government of Saudi Arabia needs to concentrate on prehypertensive, female, and unemployed individuals. Well-designed longitudinal studies, primarily in Saudi Arabia, are needed in the future to research the cause and impact of poor mental health and prehypertension.