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Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such as hypotension, acute kidney injury (AKI), or hypoglycemia. We sought to achieve consensus among clinical experts on recommendations for SDMG that could be studied in future intervention studies.A modified Delphi process following the Conducting and Reporting Delphi Studies reporting guidelines.An international group of clinicians with expertise relevant to SDMG was recruited through purposive and snowball sampling. A scoping review of the literature was presented, followed by three sequential rounds of development, refinement, and voting on recommendations. Meetings were held virtually and structured to allow participants to provide their input and rapidly prioritize and refine ideas.Opinions of participants were measured as the percentage who agreed with each recommendation, whereas consensus was defined as75% agreement.Quantitative data were summarized using counts and percentages. A qualitative content analysis was performed to capture the context of the discussion around recommendations and any additional considerations brought forward by participants.The final panel included 26 clinician participants from four countries and 10 clinical disciplines. Participants reached a consensus on 42 specific recommendations: five regarding the signs and symptoms accompanying volume depletion that should trigger SDMG; six regarding signs that should prompt urgent contact with a health care provider including a reduced level of consciousness, severe vomiting, low blood pressure, presence of ketones, tachycardia, and fever; and 14 related to scenarios and strategies for patient self-management, including frequent glucose monitoring, checking ketones, fluid intake, and consumption of food to prevent low blood sugars. There was consensus that renin-angiotensin system inhibitors, diuretics, non-steroidal anti-inflammatory drugs, sodium-glucose cotransporter-2 inhibitors, and metformin should be temporarily stopped. Participants recommended that insulin, sulfonylureas, and meglitinides be held only if blood glucose was low and that basal and bolus insulin be increased by 10-20% if blood glucose was elevated. There was consensus on six recommendations related to the resumption of medications within 24-48 hours of the resolution of symptoms and the presence of normal patterns of eating and drinking.Participants were from high-income countries, predominantly Canada. Findings may not be generalizable to implementation in other settings.A multidisciplinary panel of clinicians reached a consensus on recommendations for SDMG in the presence of signs and symptoms of volume depletion, as well as self-management strategies and medication instructions in this setting. These recommendations may inform the design of future trials of SDMG strategies.

Objective: To explore whether CYP3A inhibition by metronidazole is the primary mechanism by which metronidazole interacts with coadministered CYP3A substrates. Data Sources: Literature was accessed using the MEDLINE database (1966–February 2007). Search terms included metronidazole, cytochrome P450, CYP3A4, CYP3A5, drug interactions, and P-glycoprotein. References from pertinent articles, as well as from tertiary sources, were also considered. Study Selection and Data Extraction: All articles identified from the data sources that were published in English were evaluated. Case reports and pharmacokinetic evaluations were included. Data Synthesis: Elevated plasma concentrations and toxicities have been reported for a number of CYP3A substrates including amiodarone, carbamazepine, quinidine, tacrolimus, and cyclosporine when administered with metronidazole. This has led to the widespread belief that metronidazole is a significant inhibitor of CYP3A4. However, 4 pharmacokinetic studies conducted in humans showed that metronidazole did not increase plasma concentrations of the CYP3A substrates midazolam, erythromycin, cyclosporine, and alprazolam, thereby refuting the suggestion that metronidazole is a CYP3A4/5 inhibitor. Conclusions: Drug interactions between metronidazole and certain CYP3A substrates do not appear to result from CYP3A4/5 inhibition by metronidazole. Until any mechanism is identified by which metronidazole alters the disposition of certain CYP3A substrates, drug interactions with this agent should be assessed on a case-by-case basis, taking into account the safety index of the coadministered drug and the availability of equally effective substitutes for either metronidazole or the drug with which it putatively interacts.