Metronidazole has a benign side effect profile during normal therapeutic use. An 84-year-old woman presented with recurrence of Clostridium difficile infection (CDI). She had received oral vancomycin 5 weeks ago and was prescribed oral metronidazole. There was progressive neutropaenia from day 1 of treatment. Metronidazole was stopped on day 8 and vancomycin was prescribed. Causality assessment via Naranjo algorithm demonstrated a probable adverse effect (8/10) in favour of metronidazole. Very severe neutropaenia on day 16 prompted administration of granulocyte colony stimulating factor (GCSF) for 72 hours. This resulted in transient neutrophilia which confirmed bone marrow integrity and supported a diagnosis of drug-induced myelosuppression. The neutrophil count slowly recovered to normal levels after 4 weeks. To our knowledge, this is the 4th report of metronidazole induced severe neutropenia (levels <1 x10⁹/L). Unlike previous reports, we confirmed bone marrow integrity using GCSF. Unique to our case are the degree of neutrophil suppression and slow recovery of marrow function with a reversed neutrophil/lymphocyte ratio for >21 days.

Fluconazole induced hyponatraemiaAteeba Musaddaq1Fady Zakharious1Amit K J Mandal1Constantinos G Missouris 1, 21Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK2University of Nicosia Medical School, Nicosia, Cyprus

Background and Purpose Polypharmacotherapy is a growing phenomenon associated with adverse effects in older adults. We assessed the potential confounding effects of cumulative anticholinergic burden (ACB) in patients who were hospitalised with falls. Methods A non-interventional, prospective cohort study of unselected, acute admissions aged ≥65 years. Data were derived from electronic patient health records. Results were analysed to determine the frequency of polypharmacotherapy and degree of ACB and their relationship to falls risk. Primary outcomes were polypharmacotherapy, defined by ≥5 medications, and ACB score. Key Results 411 consecutive subjects were included, mean age 83·8 ± 8·0 years: 40·6% male. 38·4% were admitted with fall. Incidence of polypharmacotherapy was 80·8%, (88·0% and 76·3% among those admitted with and without fall respectively). Incidence of ACB score of 0, 1, 2, ≥3 was 38·7%, 20·9%, 14·6% and 25·8% respectively. On multivariate analysis, age (OR=1·03, [1·0 ; 1·05], p= 0·0494), ACB score (OR=1.15, [1.02 ; 1.29], p= 0.0245), polypharmacotherapy (OR=2·14, [1·19 ; 3·87], p= 0·0115) but not Charlson Comorbidity Index (OR=0·92, [0·81 ; 1·04], p= 0·1723) were significantly associated with higher falls rate. Of patients admitted with fall, 29·8% had drug-related orthostatic hypotension, 24·7% had drug-related bradycardia, 37·3% were prescribed centrally acting drugs and 12·0% were taking inappropriate hypoglycaemic agents. Interpretation Polypharmacotherapy results in cumulative ACB and both are significantly associated with falls risk in older adults. The presence of polypharmacotherapy and each unit rise in ACB score have a stronger effect of increasing falls risk compared to age and comorbidities.

COVID-19 and late-onset hypertension with hyporeninaemic hypoaldosteronismAmit K J Manda, MB, FRCP(Ed), FRCP, FACP1Jason Kho MBBCh, BAO1Sofia Metaxa, MD, PhD 1Constantinos G Missouris, MD, FRCP, FACP1,21Wexham Park Hospital, Frimley Health NHS Foundation Trust, UK2University of Cyprus Medical School, Nicosia, Cyprus

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Background and Purpose: The neurocognitive benefits of donepezil are well recognised, but the potential side effects on cardiac conduction remain unclear. Our objectives are to investigate whether long-term donepezil therapy is associated with electrocardiographic (ECG) changes and in particular to assess its effects on the QT interval. Experimental approach: We conducted a single centre retrospective analysis of patients admitted to our institution on donepezil therapy over a 12-month period. 59 patients were identified as suitable for analysis. An admission resting 12-lead ECG was obtained and compared to their ECG prior to commencement of donepezil therapy to assess for any significant difference in ECG parameters. Key Results: Donepezil significantly prolonged the PR (P=0.04), QRS (P=0.04) and QT (P=0.002) intervals. The increase in QT intervals remained significant on correction for heart rate; resulting in 8 (13.6%) patients developing high arrhythmogenic risk based on assessment using QT nomogram plots. Concomitant use of tricyclic antidepressants was associated with significant QT prolongation, while use of rate limiting calcium channel blockers was associated with significant PR prolongation, and beta-blockers with reduction in heart rate. Conclusion and Implications: Our results clearly demonstrate that long-term use of donepezil results in prolongation of the QT interval. We suggest ECG evaluation should take place before and after donepezil initiation, and clinicians should be even more vigilant in those prescribed tricyclic antidepressants.