Is it really OK to take this with food? Old interactions with a new twist.
TL;DR: Revisions of current regulatory guidelines are necessary to take into account this potentially major source of “new” drug interactions.
Abstract: In response to consumers' increased interest in preventive health care, the food industry is producing a variety of foods fortified with calcium, iron, and other minerals and vitamins. This well-meaning idea of food fortification is troubling in the context of clinical pharmacology. The recommended Food and Drug Administration (FDA) meal used in food-drug interaction studies is a high-fat, high-calorie meal with little nutritive value. While some drugs may appear to be safe when taken with food, this may not be true when fortified foods are considered. The mechanisms causing drug-fortified food interactions are the same well-known mechanisms that cause other drug-mineral interactions. Certain drugs may exhibit decreased absorption due to chelation and adsorption. Other drugs may have decreased absorption or increased excretion due to changes in gastric and/or urinary pH. The results of such interactions may be clinically insignificant or severe, including treatment failure, frequent dose changes, antibiotic resistance, and increased morbidity and mortality. Revisions of current regulatory guidelines are necessary to take into account this potentially major source of “new” drug interactions.
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TL;DR: Food‐mediated effects on bioavailability can have significant consequences in drug development, regulatory and clinical settings and the ability to mechanistically understand the causes and predict the occurrence of these effects is a primary focus of research.
Abstract: Objectives Co-ingestion of oral dosage forms with meals can cause substantial changes in bioavailability relative to the fasted state. Food-mediated effects on bioavailability can have significant consequences in drug development, regulatory and clinical settings. To date, the primary focus of research has focused on the ability to mechanistically understand the causes and predict the occurrence of these effects. Key findings The current review describes the mechanisms underpinning the occurrence of food effects, sheds new insights on the relative frequency for newly licensed medicines and describes the various methods by which they can be overcome. Analysis of oral medicines licensed by either the EMA or FDA since 2010 revealed that over 40% display significant food effects. Due to altered bioavailability, these medicines are often required to be dosed, rather restrictively, in either the fed or the fasted state, which can hinder clinical usefulness. Summary There are clinical and commercial advantages to predicting the presence of food effects early in the drug development process, in order to mitigate this risk of variable food effect bioavailability. Formulation approaches aimed at reducing variable food-dependent bioavailability, through the use of bio-enabling formulations, are an essential tool in addressing this challenge and the latest state of the art in this field are summarised here.
70 citations
TL;DR: Prevention of adverse events from food-herb-drug interactions requires clinical monitoring in high-risk regimens and populations as new foods and drugs emerge and more self-medication is promoted.
Abstract: Purpose of the reviewAdverse drug interactions may be the fourth leading cause of death in hospitalized patients. In children and older adults undetected food-drug interactions may lead to serious morbidity and mortality and be misdiagnosed as chronic disease progression. Recent recognition of the e
58 citations
TL;DR: Ingestion of extracts of herbs and berries studied are not expected to markedly change the permeabilities of highly permeable drugs, and Harmful effects at sites of or during absorption are unlikely, however, if high doses of extracts are administered with low permeable drug in vitro, effects on drug permeabilities could not be excluded.
Abstract: Purpose. Extracts made from berries, herbs, and various plant materials, which might possess a range of activities, are used as health promoting products. Because little is known about their effects on the absorption of co-administered drugs, the effects of some food supplements, Finnish berries, and herbs were studied on the permeability of some commonly used drugs.
Methods. The permeabilities of verapamil, metoprolol, ketoprofen, paracetamol, and furosemide were studied across Caco-2 cell monolayers with contemporaneously administered extracts from flax seed, purple loosestrife, and Scots pine bark; bilberries, cowberries, and raspberries; oregano, rosemary, and sage. Toxicological tests were conducted to determine cellular damage.
Results. The effects of extracts on drug permeabilities were generally minor. Flax seed decreased the permeability of all drugs except verapamil. Purple loosestrife and pine decreased verapamil and metoprolol permeability. Changes caused by berries were mainly pH-related. Rosemary and oregano enhanced furosemide permeability.
Conclusions. Ingestion of extracts of herbs and berries studied are not expected to markedly change the permeabilities of highly permeable drugs. Harmful effects at sites of or during absorption are unlikely. However, if high doses of extracts are administered with low permeable drugs in vitro,effects on drug permeabilities could not be excluded. Use of such extracts should therefore be evaluated during continuous medication.
38 citations
Cites background from "Is it really OK to take this with f..."
...Some drugs appear to be safe when taken with food but less so if taken with fortified foods (6)....
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...resistance, and increases in morbidity and mortality (6)....
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TL;DR: The results further confirm the need to adjust regulatory studies to include bioequivalence/bioavailability studies that contain fortified foods more than high‐calorie/high‐fat foods to better reflect current American consumption habits.
Abstract: Chelation interactions between drugs/supplements that contain large amounts of multivalent ions and the fluoroquinolones have been known for quite some time However, there has been a lack of taking this interaction into account when they may be coadministered with foods that have been fortified with amounts of multiple multivalent ions that equal or exceed many supplement products A previous study demonstrated that 12 ounces of calcium-fortified orange juice significantly decreased the bioequivalence of a dose of ciprofloxacin This study examined, in 16 healthy volunteers, whether 12 ounces of orange juice with and without calcium fortification would demonstrate the same chelation interaction with single doses of levofloxacin The results of the study demonstrated that both types of juice decreased levofloxacin Cmax values by 14% to 18% and prolonged tmax values by approximately 50%, with calcium-fortified orange juice decreasing Cmax enough to lose bioequivalence as compared to the control arm (89% [781%, 998%]) Due to the lack of change in overall exposure, it is thought that rather than a chelation interaction, levofloxacin and components of the orange juices competed for intestinal transport mechanisms such as P-glycoprotein and organic anion-transporting polypeptides, which resulted in the discovered interaction These results further confirm the need to adjust regulatory studies to include bioequivalence/bioavailability studies that contain fortified foods more than high-calorie/high-fat foods to better reflect current American consumption habits
36 citations
Cites background or methods from "Is it really OK to take this with f..."
...Sixteen healthy male and female volunteers who met the following inclusion criteria were recruited to this study: (1) at least 18 years old; (2) actual weight no more than ±30% from ideal body weight based on sex, height, and body frame; (3) premenopausal women had to be surgically sterile (ovaries intact; husband had vasectomy allowed) or be using a nonhormonal barrier method of birth control; and (4) free of any drug exposure known to interfere with the pharmacokinetics or assay of levofloxacin for at least 10 days prior to the study....
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...Subjects were excluded if they had any of the following: (1) a clinically significant abnormal physical exam, medical history, electrocardiogram (QTc > 450 msec or any significant conduction disturbances), or laboratory studies; (2) a history of serious intolerance, allergy, or sensitivity to fluoroquinolone antimicrobials or to citrus products; (3) a history of blood dyscrasias; (4) a history of alcohol or drug abuse within the past year; (5) donation of blood during the 8 weeks prior to the study or plans to during or within 8 weeks of completing the study; (6) unable to tolerate venipuncture and multiple blood samplings; (7) cannot follow instructions, in the opinion of the investigator; or (8) used nicotine delivery devices within the past year....
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...Each subject received the following dosage regimens in random order: (1) a single 500-mg tablet of levofloxacin (Levaquin, Ortho-McNeil Corporation, Lot 91P0550, Expiration 04/04) with 12 ounces of water, (2) a single 500-mg tablet of levofloxacin with 12 ounces of commercially available orange juice (Minute Maid Premium Original), and (3) a single 500-mg tablet of levofloxacin with 12 ounces of commercially available calcium-fortified orange juice (Minute Maid Premium Calcium Original)....
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TL;DR: In this paper, a single-dose, open-label, randomized-sequence, crossover study, healthy subjects received 25 mg eltrombopag orally as a tablet fasted and as PfOS fasted or with, 2 hours before, or 2 hours after a high-calcium meal.
34 citations
References
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01 Jan 1994
TL;DR: In this paper, the authors present a list of manufacturers, product categories, and diagnostic product information, including name, product category, and identification of product categories and attributes, with a focus on medical applications.
Abstract: Section 1 Manufacturers Index...1
Section 2 Name Index...101
Section 3 Product Category Index...201
Section 4 Product Identification Section...303
Section 5 Product Information...401
Section 6 Diagnostic Product Information...2645
3,228 citations
TL;DR: Simultaneous ingestion of ferrous sulfate and thyroxine causes a variable reduction in thyroxin efficacy that is clinically significant in some patients.
Abstract: ▪Objective:To determine whether simultaneous ingestion of ferrous sulfate and thyroxine reduces the efficacy of thyroid hormone in patients with primary hypothyroidism. ▪Design:Uncontrolle...
203 citations
TL;DR: Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin as the extent of this interaction appears to increase as the time between administration of the two drugs decreases.
Abstract: The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.
175 citations
TL;DR: The decreased cumulative excretion produced by antacids and kaolin-pectin reflected a striking reduction in digoxin absorption associated with these compounds that was not related to alteration of gut transit time or to adsorption of digoxin to these gastrointestinal medications.
Abstract: Employing a Latin-square design and single-dose studies of bioavailability in 10 normal human volunteers, we tested the hypothesis that antacids and kaolin-pectin might interfere with the bioavailability of orally administered digoxin Cumulative six-day urinary digoxin excretion (expressed as the percentage of a 075-mg dose recovered) was: control, 401 ±30 (SE); aluminum hydroxide, 307±29; magnesium hydroxide, 271 ±24; magnesium trisilicate, 291 ±17; and kaolin-pectin 234±20 The differences in means were highly significant (F = 1047, P<0005) Further analysis (multiple comparison test) revealed that control differed significantly from each of the other treatments (α = 005), but there was no such difference between any of the other treatment groups The decreased cumulative excretion produced by antacids and kaolin-pectin reflected a striking reduction in digoxin absorption associated with these compounds that was not related to alteration of gut transit time or to adsorption of
126 citations
"Is it really OK to take this with f..." refers background in this paper
...The authors in this case offer possible theories, including adsorption, alteration in intestinal transit time, decreased dissolution, and/or interference with tablet disintegration, but no solid evidence explaining the interaction.(23,24) And still others report adsorption of digoxin by magnesium in vitro but feel that there is not enough evidence to support a clinical interaction....
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TL;DR: Ciprofloxacin seems to bind to ferric ion in a ratio of 3:1 by interacting with the 4-keto and 3-carboxyl groups on cipro FLXacin, which is probably the cause of the reduction in ciprafloxACin bioavailability in the presence of iron.
Abstract: 1. The effect of ferrous sulphate (300 mg), ferrous gluconate (600 mg), and a combination tablet of iron (10 mg), magnesium (100 mg), zinc (15 mg), calcium (162 mg), copper (2 mg), and manganese (5 mg) (Centrum Forte) co-administration on ciprofloxacin bioavailability was tested in eight healthy subjects. 2. Peak serum ciprofloxacin concentrations and area under the curve (AUC) were significantly reduced when ciprofloxacin was administered with 300 mg ferrous sulphate (3.0 vs 2.0 mg l-1, P less than 0.05 and 12.3 vs 6.7 mg l-1 h, P less than 0.01, respectively). Reductions in peak ciprofloxacin concentrations and AUC also occurred when ciprofloxacin was ingested with 600 mg ferrous gluconate (1.3 mg l-1, P less than 0.01 and 4.1 mg l-1 h, P less than 0.01, respectively) and a Centrum Forte tablet (1.4 mg l-1, P less than 0.01 and 5.4 mg l-1 h, P less than 0.01, respectively). 3. When ferrous ion was mixed with ciprofloxacin, rapid spectral changes occurred (t1/2 = 1.9 min). Additional studies were consistent with oxidation of the ferrous form of iron to its ferric form, which is followed by rapid formation of a Fe(3+)-ciprofloxacin complex. Ciprofloxacin seems to bind to ferric ion in a ratio of 3:1 by interacting with the 4-keto and 3-carboxyl groups on ciprofloxacin. 4. The formation of a ferric ion-ciprofloxacin complex is probably the cause of the reduction in ciprofloxacin bioavailability in the presence of iron.
100 citations