| Summary: | Abstract Background An inadequate combination of prescription drugs with food or medicinal plants could cause adverse effects in patients or produce negative therapeutic results. Therefore, this generic systematic review protocol aims to identify and synthesize the literature on clinical characteristics and safety issues of these types of pharmacological interactions occurring in children, adolescents, adults, pregnant/lactating women, and older adults. Methods/design This generic protocol follows the stated guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. A literature search will be performed in PubMed, Scopus, and Virtual Health Library (VHL) electronic databases from 1960 till present for studies reporting clinical characteristics and safety issues associated with pharmacological interactions occurring between prescription drugs and food or medicinal plants in participants from birth-age to ≥ 65-year-old, including pregnant/lactating women. Lateral searching will be carried out in PubMed via related citation. Two reviewers will carry out an independent evaluation of eligible studies as well as the corresponding data extraction of the selected ones. Subsequently, the methodological quality evaluation of the selected articles will be completed using the corresponding Joanna Briggs Institute Checklists. Moreover, the quality of evidence will be graded according to the criteria of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group. Quantitative research in humans comprising clinical trials and clinical, comparative and, observational studies will be included. The main outcomes of this protocol involve reported potential food-drug and herb-drug interactions, associated safety issues, and adverse reactions along with the generic name of the prescribed drug and the scientific name of the food and medicinal plants involved in these types of pharmacological interactions. Finally, findings extracted from the selected studies will be summarized in a narrative synthesis. Discussion This generic systematic review protocol seeks to synthesize and critically evaluate current knowledge besides to identify any comprehension gaps in the concurrent administration of prescription drugs with food and herbs. By achieving a better understanding of this topic, this information will allow healthcare professionals to develop useful strategies to recognize, manage, and prevent these types of pharmacological interactions at different age stages, including pregnant/lactating women. Systematic review registration PROSPERO CRD42018117308
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