OBJECTIVE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity.
OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin.
METHODS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688).
METHODS: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin.
METHODS: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD.
RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]).
CONCLUSIONS: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.

Background: An international consensus list of potentially clinically significant drug-drug interactions (DDIs) in older people has been recently validated. Our objective was to describe the prevalence and characteristics of drug combinations potentially causing clinically significant DDIs identified in the medication history of older patients admitted to the hospital and the prevalence and characteristics of manifest DDIs-DDIs involved in adverse drug events present at hospital admission, DDIs that contributed to ADE-related hospital admissions, and DDIs involved in drug-related laboratory deviations. Methods: The data were obtained from our previous study that examined the drug-relatedness of hospital admissions to University Hospital Hradec Králové via the department of emergency medicine in the Czech Republic. Patients ≥ 65 years old were included. Drug combinations potentially causing clinically significant DDIs were identified using the international consensus list of potentially clinically significant DDIs in older people. Results: Of the 812 older patients admitted to the hospital, 46% were exposed to drug combinations potentially causing clinically significant DDIs. A combination of medications that affect potassium concentrations accounted for 47% of all drug combinations potentially causing clinically significant DDIs. In 27 cases, potentially clinically significant DDIs were associated with drug-related hospital admissions. In 4 cases, potentially clinically significant DDIs were associated with ADEs that were present at admissions. In 4 cases, the potentially clinically significant DDIs were associated with laboratory deviations. Manifest DDIs that contributed to drug-related hospital admissions most frequently involved antithrombotic agents and central nervous system depressants. Conclusion: The results confirm the findings from the European OPERAM trial, which found that drug combinations potentially causing clinically significant DDIs are very common in older patients. Manifest DDIs were present in 4.3% of older patients admitted to the hospital. In 3.3%, manifest DDIs contributed to drug-related hospital admissions. The difference in the rates of potential and manifest DDIs suggests that if a computerized decision support system is used for alerting potentially clinically significant DDIs in older patients, it needs to be contextualized (e.g., take concomitant medications, doses of medications, laboratory values, and patients\' comorbidities into account).

BACKGROUND: Combination metronomic topotecan plus pazopanib is active against preclinical models of gynecological cancer. Both agents are substrates for ATP-binding cassette family transporters so there is an increased likelihood for pharmacokinetic (PK) drug-drug interactions.
METHODS: PK analyses of topotecan were performed during three cycles of a phase I dose-escalation study of metronomic topotecan and pazopanib in consenting adult patients with gynecological cancer. Concentration time data were analyzed using a population PK approach.
RESULTS: Twenty-one patients were evaluable for serial PK studies. Considerable inter- and intra-patient variability was observed in the PK parameters, attributable primarily to highly variable oral bioavailability. No difference in topotecan disposition was detected between administration cycles, nor between the off- versus on-pazopanib studies.
CONCLUSIONS: The lack of a statistically significant drug-drug interaction agrees with preclinical findings suggesting that pazopanib does not influence the PK of metronomic topotecan. No adjustment of low dose metronomic topotecan dosing is merited when used in conjunction with pazopanib.