Levothyroxine (l-thyroxine, l-T4) is a drug of choice for treating congenital and primary hypothyroidism. Although clinically significant interactions between l-T4 and food can alter the safety and efficacy of the treatment, they still seem to be generally underestimated by patients, physicians and pharmacists. This review aimed to investigate the effects of meals, beverages, and dietary supplements consumption on l-T4 pharmacokinetics and pharmacodynamics, to identify the most evident interactions, and to perform the recommendations for safe co-administering of l-T4 and food. A total of 121 studies were identified following a systematic literature search adhering to PRISMA guidelines. After full-text evaluation, 63 studies were included. The results proved that l-T4 ingestion in the morning and at bedtime are equally effective, and also that the co-administration of l-T4 with food depends on the drug formulation. We found limited evidence for l-T4 interactions with coffee, soy products, fiber, calcium or iron supplements, and enteral nutrition but interestingly they all resulted in decreased l-T4 absorption. The altered l-T4 efficacy when ingested with milk, juices, papaya, aluminium-containing preparations, and chromium supplements, as well as observed enhancement effect of vitamin C on l-T4 absorption, shall be further investigated in larger, well-designed studies. Novel formulations are likely to solve the problem of coffee, calcium and iron induced malabsorption of l-T4. Maintaining a proper time interval between l-T4 and food intake, especially for coffee and calcium, or iron supplements, provides another effective method of eliminating such interactions.

Bisphosphonates and selective estrogen receptor modulators (SERMs) represent the two most important groups of medications taken orally and employed in osteoporosis treatment. Effectiveness of the therapy may be affected by poor patient adherence, in particular, due to the inconvenient dosing regimen of oral bisphosphonates. With this review we aimed to assess the effects that food, beverages, and dietary supplements consumed during treatment, along with the dosing regimens, may have on pharmacokinetics and pharmacodynamics of oral drugs employed in treating osteoporosis; we also aimed to shape the recommendations valuable for professional patients’ counseling and education, to provide appropriate dosing regimens in order to improve adherence to the therapy. Food, beverages such as coffee, juices, and mineral water, as well as dietary supplements containing multivalent cations, e.g., calcium, magnesium, aluminium, iron, showed to have a deleterious effect on the bioavailability of all the investigated oral bisphosphonates, specifically alendronate, risedronate, ibandronate, minodronate, and etidronate. For risedronate, a delayed-release (DR) tablet was designed to solve the malabsorption problem in the presence of food, hence DR risedronate can be ingested following breakfast. For other oral bisphosphonates, the proper interval between drug and food, beverages, and dietary supplements intake should be maintained to minimize the risk of interactions. The effect of food on pharmacokinetic parameters of selective estrogen receptor modulators (SERMs) was found to be clinically irrelevant.

Proton pump inhibitors (PPIs) are the first-choice drugs used to prevent and treat acid-related diseases. However, a lack of satisfactory response to the standard PPI dose (“PPI failure”) is often reported, especially in patients with gastroesophageal reflux disease. Poor compliance seems to be one of the main causes of PPI failure; hence, it is crucial to gain knowledge on how to properly administer PPIs. In this review, we aimed to evaluate the effect of food, beverages, and dosing regimen on pharmacokinetics and pharmacodynamics of PPIs and to frame recommendations for healthcare professionals to improve both patient’s counseling and compliance to treatment with PPIs. A total of 201 papers were identified following a literature search. After full-text evaluation, 64 studies were included in the review. Co-administration of PPIs with a meal may affect both their bioavailability and effectiveness; however, the influence of food depends on the type of drug and its formulation. Except for pantoprazole, PPIs can be administered in the morning or evening; however, morning intake generally provides better daytime control of gastric acidity. In most cases, the choice of the proper schedule of administration should be based on the patient’s symptoms and individual dosing preferences.

Multiple factors may affect combined antiretroviral therapy (cART). We investigated the impact of food, beverages, dietary supplements, and alcohol on the pharmacokinetic and pharmacodynamic parameters of 33 antiretroviral drugs. Systematic review in adherence to PRISMA guidelines was performed, with 109 reports of 120 studies included. For each drug, meta-analyses or qualitative analyses were conducted. We have found clinically significant interactions with food for more than half of antiretroviral agents. The following drugs should be taken with or immediately after the meal: tenofovir disoproxil, etravirine, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosine, zalcitabine, zidovudine, efavirenz, amprenavir, fosamprenavir, and indinavir should be taken on an empty stomach for maximum patient benefit. Antiretroviral agents not mentioned above can be administered regardless of food. There is insufficient evidence available to make recommendations about consuming juice or alcohol with antiretroviral drugs. Resolving drug-food interactions may contribute to maximized cART effectiveness and safety.

Background: Effective management of drug–food interactions is crucial for enhancing antibiotics’ efficacy/safety. Adhering to PRISMA guidelines, we conducted a systematic review to assess the impact of dietary interventions on the bioavailability of 15 macrolides and 10 tetracyclines. Methods: We included studies examining the influence of food, beverages, antacids, and mineral supplements on the pharmacokinetic parameters of orally administered macrolides and tetracyclines. We searched Medline (via PubMed), Embase and Cochrane Library databases up to December 2022. Risk of bias was assessed using Cochrane and NIH tools. Quantitative analyses were conducted if two or more comparable food-effect studies were available; otherwise, a qualitative summary was provided. Results: We included 120 studies from 97 reports. Meta-analyses were conducted for 8 macrolides and 4 tetracyclines, with qualitative synthesis for 10 and 9, respectively. About 64% of the studies were open-label, crossover designs. Our assessment found that 37% of the studies had a high risk of bias, while only 6% had low risk. Food significantly affected 10 of 13 macrolides (77%) and 6 of 7 tetracyclines (86%). High positive effects on bioavailability were seen with extended-release azithromycin and clarithromycin, and erythromycin estolate. High negative impacts were observed with erythromycin propionate and stearate, azithromycin capsules, demeclocycline and omadacycline. Antacids and mineral supplements significantly decreased tetracyclines absorption. Milk and grapefruit juice showed variable impacts on absorption. Discussion: Interactions depend on antibiotics’ physicochemical characteristics, intervention type, drug formulation and potential patient factors. The quality of evidence was rated low due to outdated studies, methodological diversity and unequal data availability.

Background and Objective Managing drug-food interactions is essential for optimizing the effectiveness and safety profile of quinolones. Following PRISMA guidelines, we systematically reviewed the influence of dietary interventions on the bioavailability of 22 quinolones. Methods All studies describing or investigating the impact of food, beverages, antacids, and mineral supplements on pharmacokinetic parameters or pharmacokinetic/pharmacodynamic indices of orally taken quinolones were considered for inclusion. We excluded reviews, in vitro and in silico studies, studies performed on animals, and those involving alcohol. We performed the search in Medline (via PubMed), Embase, and Cochrane Library, covering reports from database inception to December 2022. We used the following tools to assess the risk of bias: version 2 of the Cochrane risk-of-bias tool for parallel trials, the Cochrane risk-of-bias tool for cross-over studies, and the NIH quality assessment tool for before-after studies. We performed quantitative analyses for each quinolone if two or more food-effect studies with specified and comparable study designs were available. If meta-analyses were not applicable, we qualitatively summarized the results. Results We included 109 studies from 101 reports. Meta-analyses were conducted for 12 antibiotics and qualitative synthesis was employed for the remaining drugs. Of the studies, 60.5% were open-label, cross-over, as recommended by FDA. We judged 46% of studies as having a high risk of bias and only 4% of having a low risk of bias. Among 19 quinolones with available food impact data, 14 (74%) had potentially clinically important interactions. For nalidixic acid, oxolinic acid, and tosufloxacin, food exerted a high positive impact on bioavailability (AUC or C_max increased by > 45%), whereas, for all the remaining drugs, postprandial absorption was lower. The most significant negative influence of food (AUC or C_max decreased by > 40%) occurred for delafloxacin capsules and norfloxacin, whereas the moderate influence (AUC or C_max decreased by 30–40%) occurred for nemonoxacin and rufloxacin. All 14 analysed quinolones showed a substantial reduction in bioavailability when co-administered with antacids and mineral supplements, except for calcium preparations. The impact of beverages was evaluated for 10 quinolones, with 50% experiencing significantly reduced absorption in the presence of milk (the highest negative impact for ciprofloxacin). Moreover, both ciprofloxacin and levofloxacin demonstrated compromised bioavailability when consumed with orange juice, particularly calcium-fortified. Discussion Several factors may influence interactions, including the physicochemical characteristics of quinolones, the type of intervention, drug formulation, and the patient’s health status. We assessed the quality of evidence as low due to the poor actuality of included studies, their methodological diversity, and uneven data availability for individual drugs. Graphical Abstract