Melatonin Interaction Resulting in Severe Sedation.

PURPOSE: Natural health products (NHPs), including melatonin, are widely used products. Despite the widespread assumption that all NHPs are safe, they contain pharmacologically active substances and can therefore have adverse effects and/or interact with pharmaceuticals. OBJECTIVE: To investigate the mechanism underlying NHP interactions identified through the Pharmacy SONAR active surveillance study. METHODS: Active surveillance was undertaken in community pharmacies to identify adverse events in patients who had recently taken NHPs together with conventional pharmaceuticals. For suspected NHP-pharmaceutical interactions, the possible mechanism of action was explored by in vitro analysis of samples of different products to identify cytochrome P450 enzyme (CYP) inhibition potential. RESULTS: Active surveillance identified a 19-year-old male taking citalopram, nortriptyline and oxycodone concomitantly and who experienced severe sedation when melatonin was added to this regimen. In vitro analysis involving several melatonin products showed product-dependent inhibition of CYP1A2, CYP2C19 and CYP3A7. CONCLUSION: The adverse event was likely due to a primary pharmacokinetic interaction between melatonin and citalopram; although mechanistically, interactions affecting cytochrome P450-mediated metabolism may have occurred with all of these health products. A pharmacodynamic interaction may also be possible, but beyond the capacity of this study to establish.

Study of natural health product adverse reactions (SONAR): active surveillance of adverse events following concurrent natural health product and prescription drug use in community pharmacies.

BACKGROUND: Many consumers use natural health products (NHPs) concurrently with prescription medications. As NHP-related harms are under-reported through passive surveillance, the safety of concurrent NHP-drug use remains unknown. To conduct active surveillance in participating community pharmacies to identify adverse events related to concurrent NHP-prescription drug use. METHODOLOGY/PRINCIPAL FINDINGS: Participating pharmacists asked individuals collecting prescription medications about (i) concurrent NHP/drug use in the previous three months and (ii) experiences of adverse events. If an adverse event was identified and if the patient provided written consent, a research pharmacist conducted a guided telephone interview to gather additional information after obtaining additional verbal consent and documenting so within the interview form. Over a total of 112 pharmacy weeks, 2615 patients were screened, of which 1037 (39.7%; 95% CI: 37.8% to 41.5%) reported concurrent NHP and prescription medication use. A total of 77 patients reported a possible AE (2.94%; 95% CI: 2.4% to 3.7%), which represents 7.4% of those using NHPs and prescription medications concurrently (95%CI: 6.0% to 9.2%). Of 15 patients available for an interview, 4 (26.7%: 95% CI: 4.3% to 49.0%) reported an AE that was determined to be "probably" due to NHP use. CONCLUSIONS/SIGNIFICANCE: Active surveillance markedly improves identification and reporting of adverse events associated with concurrent NHP-drug use. Although not without challenges, active surveillance is feasible and can generate adverse event data of sufficient quality to allow for meaningful adjudication to assess potential harms.

Inhibition of human cytochrome p450 metabolism by blended herbal products and vitamins.

PURPOSE: The use of supplements as herbal and micronutrient natural health products with conventional health products has become increasingly popular. It has been reported that some herbal products can inhibit the activity of cytochrome P450-mediated metabolism and drug disposition. This study was designed to investigate a case report of a severe adverse event to determine the potential interactions of femMED, Thyrosense and vitamins on cytochrome P450-mediated drug metabolism. METHODS: The effect of extracts from these commercially available herbal formulations, trans-ß-carotene, multivitamins, and vitamin D3 supplements on cytochrome P450-mediated drug metabolism of marker substrates was determined in vitro. RESULTS: The blended herbal products femMED and Thyrosense had a high potential to affect the safety and efficacy of many health products. Some vitamin and trans-ß-carotene containing products also have the potential to affect drug disposition. The tBC content of various products was analyzed and significant discrepancies were found among them and between values indicated on product labels. Product extracts also exhibited a low to moderate capacity to inhibit cytochrome P450 2C9, 2C19 and 3A4-mediated metabolism. CONCLUSIONS: The findings of this study suggest that these herbal products and most vitamin products may have an inhibitory effect on cytochrome P450 activity that could contribute to development of an adverse event. Further work is warranted to determine how supplementation with these products may affect drug metabolism in an in vivo context.

Pharmacists' participation in research: a case of trying to find the time.

Objective The objective of this case study was to explore how pharmacists involved in the Pharmacy Study Of Natural Health Product Adverse Reactions (SONAR) project perceived the barriers and facilitators to participating in clinical research. Methods A total of 19 semi-structured interviews were completed with pharmacy staff members who had recently completed data collection in the SONAR study which involved asking patients if they had experienced any unwanted effects while taking natural products. Other data sources included detailed field notes and interviews with SONAR researchers. Basic content analysis with multiple coders was used to analyse the data and triangulation was used to highlight areas of consistency and contrasting view points across the data types. Key findings None of the participating pharmacies was able to collect as much data as expected by the SONAR team. Lack of time was stated as the main reason why pharmacy staff had trouble with the data collection. However, observational data and detailed probing in interviews confirmed that data collection itself took very little time (seconds per patient). Lack of time was provided as a socially acceptable excuse that masked deeper issues related to fears associated with challenges modifying established work routines and perceived lack of value associated with research participation. Conclusion To successfully engage pharmacists in practice-based natural health product research it is necessary to establish the direct and indirect benefits of participation because those that believe in the value of the research will make the time for participation.