Angiotensin II receptor blockers (ARBs) and manufacturing contamination: A retrospective National Register Study into suspected associated adverse drug reactions

Abstract

The aim of this study was to determine if any suspected adverse drug reactions (ADRs) observed with the use of angiotensin II receptor blockers (ARBs) could be linked to either (a) their unique respective physicochemical and pharmacological profiles and (b) the recently disclosed suspected carcinogenic manufacturing contaminants found in certain sartan drug class batches. Methods:The pharmacology profiles of ARBs were data-mined from the Chemical Database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL). Suspected ADR data (from 01/2016-10/2022, inclusive) and prescribing rates of ARBs over a 5-year prescribing window (from 09/2016 to 08/2021, inclusive) were obtained via analysis of the United Kingdom Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card drug analysis profile and Open prescribing databases, respectively. Results:The overall suspected ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied were found to be different between the sartan drug class members (chi-squared test, P < .05). There is a greater relative rate of reports for valsartan across all investigated organ classes of ADRs, than other ARBs, despite valsartan's more limited pharmacological profile and similar physicochemical properties to other sartans. The disparity in ADR reporting rates with valsartan vs other ARBs could be due to the dissimilarity in formulation excipients, patient factors and publicity surrounding batch contaminations, amongst others. Cancer-related ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied are not statistically significant (chi-squared test, P > .05) based on the datasets used over the 5-year period. Conclusion:No connection between ARB pharmacology and their suspected ADRs could be found. No conclusion between sartan batch contaminations and increased suspected cancer-related ADRs was found.

The Medical Impact of Emergent Banning of N-nitrosodimethylamine (NDMA)- contaminated Antihypertensive Drug: A nationwide longitudinal cohort study

“…In contrast, there was no evidence that the risks of all-cause and cardiovascular deaths were increased and after emergent banning. Although NDMA-contaminated valsartan is no longer on the market, the issue of impurities in antihypertensive drugs continues, including recent azide (azidomethyl-biphenyl-tetrazole) issue associated with the angiotensin type 1 receptor antagonist class, namely “sartan’, 12 and the results of this study can offer valuable evidence for determining future health policy stance.…”

A General Method to Access Underexplored Ylideneamino Sulfates as Interrupted Beckmann-Type Rearrangement Intermediates

“…The O-sulfation of ketoximes (Chart 2) all showed good to excellent conversions as measured by 1 H NMR spectroscopy and isolated yields (typically 67-98%) after an extractive purification protocol (Supplementary materials). These results also showed that mono-substituted aromatic oximes were not influenced by the attached groups from highly electron-donating methoxy groups (2e) to highly electron-withdrawing nitro groups (2f).…”

“…The amide functional group is one of the most important and widely encountered structural units in organic chemistry and biochemistry. The amide bond is commonly found in bioactive drug molecules including valsartan, an angiotensin receptor blocker (ARB) [1]; sitagliptin, an anti-diabetic medicine used to treat type-2 diabetes [2]; olaparib, a PARP inhibitor used to treat BRCA-mutated advanced ovarian cancer [3]; and apixaban, an anti-coagulant used to prevent stroke in nonvalvular atrial fibrillation via the inhibition of Factor Xa (Figure 1) [4].…”

Use of National Database of Health Insurance Claims and Specific Health Checkups for examining practical utilization and safety signal of a drug to support regulatory assessment on postmarketing drug safety in Japan

“…risk and carcinogenic contaminant during valsartan prescription have been reported (11), but there was little safety information available at the time of this study in Japan. This study aimed to elucidate the prescribing patterns and cumulative dose per patient of valsartan-containing drugs to provide information related to the assessment of patient health effects caused by NDMA.…”