Drug-food interactions

The aim of this presentation is to highlight the clinical interactions between food and prescribed drugs

Outlines
Definition and incidence of food drug interaction Examples of effect of food on medications absorption, metabolism and excretion Examples of effect of drugs on food absorption, metabolism and excretion Strategies to minimize food-drug interaction

Definition
Any time food changes the effects of a drug, the change is considered a food-drug interaction.
Although some interactions are harmful, others can be beneficial.

Incidence of food-drug interactions is 62.4%, which may cause various complications in therapy.
52.8% were not aware that the timing of drug intake in relation to meals may affect treatment.
Jarosz and Wolnicka (2011): Pol. J. Food Nutn Sei., 2011, Vol. 61, No. 3, pp. 211-218

Historical Perspectives
Clinical problems owing to drug interactions were first recognized in the early 1960s. Hypertensive crises were reported in several patients treated for depression with monoamine oxidase (MAO) inhibitors, after they had eaten certain cheeses (the amino acid tyramine). Tyramine is indirect sympathomimetic, it can cause a significant release of norepinephrine.
beer, avocados ,some processed meats, aged, fermented, overripe or pickled foods, chocolate and yeast-containing foods

F. Sjoqvist & Y. Bo ttiger (2010). Historical perspectives: drug interactions it all began with cheese. Journal of InternalMedicine. 268; 512515

Historical Perspectives
Clinical problems owing to drug interactions were first recognized in the early 1960s. Hypertensive crises were reported in several patients treated for depression with monoamine oxidase (MAO) inhibitors, after they had eaten certain cheeses (the amino acid tyramine). Tyramine is indirect sympathomimetic, it can cause a significant release of norepinephrine.
beer, avocados ,some processed meats, aged, fermented, overripe or pickled foods, chocolate and yeast-containing foods

F. Sjoqvist & Y. Bo ttiger (2010). Historical perspectives: drug interactions it all began with cheese. Journal of InternalMedicine. 268; 512515

Patients at Risk for Food-Nutrient Interactions

Patient with chronic disease Elderly Fetus Infant Pregnant woman Malnourished patient Allergies or intolerances

Figure 4. A working model of drug nutrient interactions.

J Acad Nutr Diet. 2012;112:506-517.

Food-Drug Interactions
Food-Drug interactions falls into the following categories:

1. Drugs that alter food intake

reducing appetite, or increasing appetite leading to weight gain

2- Food that alter drug Pharmacokinetic

Absorption, Metabolism and Excretion of Nutrients, and vice versa

Drugs affecting food intake

Drugs

Nutrients

Nutrients Absorption Nutrients Metabolism

Drugs Absorption Drugs Metabolism

Nutrients Excretion

Drugs Excretion

Interactions

Sites of food-drug interactions

EFFECT OF FOOD/NUTRIENTS ON MEDICATION ABSORPTION

Food changes gastric motility, pH, and provides substances for drug and nutrient chelation and adsorption. An acid environment is necessary for ketoconazole absorption.

Vitamin C in the citrus juice increases the absorption of iron.

Increased amounts of stomach acid results in the destruction of penicillin G, ampicillin and dicloxacillin. The absorption of griseofulvin is increased by fat meal.
Bland, SE (1998): Drug-Food InteractionsJournal of the Pharmacy Society of Wisconsin

Food-Drug Interactions
Calcium or iron components of some foods make complexes with drugs e.g. tetracycline, doxycycline, sodium fluoride and ciprofloxacin, levofloxacin and interfere with absorption,. Fenofibrate, mebendazole, isotretinoin, tamsulosin, labetalol and carbamazepine are examples of drugs that will be better absorbed when taken with food. The absorption of alendronate is impaired by food, calcium, orange juice and coffee. Absorption of ciprofloxacin reduced by concomitant ingestion of the GFJ.

EFFECT OF FOOD/NUTRIENTS ON MEDICATION METABOLISM

High-protein, low carbohydrate diets induce the mixedfunction oxidase system (theophylline).

Indoles in vegetables, such as cabbage and Brussels sprouts, and chemicals in charcoal-broiled meats, smoked and preserved meats induce the mixed-function oxidase system.

On the other hand, Grapefruit inhibit CYP450 isoenzymes 1A2 and 3A4.

Grape Fruit
GFJ inhibit the intestinal CYP 3A4 and increase the oral bioavailability of Felodipine, midazolam, cyclosporine, psychotropics by as much as 200%. Grapefruit juice inhibit the P-gp activity, modifying the disposition of drugs that are P-gp substrates such as talinolol, and enhances CoQ10 absorption (5 folds).

GFJ inhibits organic anion-transporting polypeptide (OATP), reduce the oral bioavailability of the OATP substrate fexofenadine
Diaconu CH; Cuciureanu M; Vlase L; Cuciureanu R (2011). Food-drug grapefruit juice. journal Info rmation interactions:

EFFECT OF FOOD/NUTRIENTS ON MEDICATION EXCRETION

At high urinary pH values, weakly acidic drugs largely exist as ionized molecules that cannot be reabsorbed into blood and are lost in the urine. Alkaline urine causes the salicylic acid to be excreted. Patients on low sodium diets will reabsorb more lithium along with sodium; patients on high sodium diets will excrete more lithium and need higher doses

EFFECT OF MEDICATION ON FOOD/NUTRIENT ABSORPTION

Use of antiulcer drugs, decrease the absorption of vitamin B12, thiamin, calcium, magnesium, zinc, and iron. Potassium chloride lowers the pH in the ileum, impairing vitamin B12 absorption. Calcium carbonate increases the rate of absorption of folic acid due to an increased dissolution rate. Aluminum antacids can precipitate bile acids, leading to decreased absorption of vitamin A.

EFFECT OF MEDICATION ON FOOD/NUTRIENT METABOLISM

Anticonvulsants, phenobarbital, and phenytoin increase the metabolism of folic acid and vitamins D and K. The antituberculosis drug, isoniazid, inhibits the conversion of B6 to its active form.

EFFECT OF MEDICATION ON FOOD/NUTRIENT EXCRETION

Laxatives increased excretion of nutrients. Malabsorption of nutrients by the increased gastric motility can lead to significant metabolic imbalances. Loop diuretics increase the excretion of Na, K, Cl, Mg, and Ca. Persons using diuretics are frequently instructed to take the medication with a banana or orange juice.

Examples of Drug Groups and Possible Food Interactions

Cholesterol-Lowering Agent
Lovastatin should be taken with food to enhance GIT absorption and bioavailability. Rosuvastatin absorption was significantly decreased with food (given on an empty stomach) High fiber diets may lower the efficacy of Simvastatin, Ezetimibe, pravastatin and fluvastatin.

Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Warfarin
Leafy and/or dark green vegetables, such as broccoli, Brussels sprouts, kale, parsley, spinach, turnip greens and charbroiled food decrease the anticoagulant activity of warfarin by supplying additional vitamin K.

There is a possible interaction between warfarin and a high protein diet. Dietary protein intake decrease in international normalized ratio (INRs).
Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Warfarin

Warfarin
The opposite can happen with vitamin E, onions, and garlic because they all produce effects that are similar to those of warfarin.

The combination of warfarin administration and cranberry juice ingestion is associated with an elevated INR as cranberry juice may inhibit the activity of CYP2C9.

Oman Medical Journal (2011) Vol. 26, No. 2: 77-83 American Pharmacists Association

Antihypertensive Drugs
Propranolol serum levels increased if taken with diet rich protein Smoking decrease plasma levels of by increasing its metabolism.

Orange juice (Hesperidin), decreased absorption of celiprolol. ACEs inhibitors absorption increased when taken on empty stomach. While GFJ increases the bioavailability of felodipine

Licorice extract (glycyrrhizin and glycyrrhetinic acid) causes sodium retention, interfere with antihypertensive agents.
Bland, SE (1998): Drug-Food InteractionsJournal of the Pharmacy Society of Wisconsin

Analgesics and Antipyretics

Food slows the body absorption of acetaminophen

NSAIDs like ibuprofen, naproxen, ketoprofen can cause stomach irritation and thus they should be taken with food or milk.
The Cmax of ibuprofen increased after Coca-Cola drinking, indicating increased absorption of ibuprofen.

Food intake did not affect the absorption of oral Diclofenac.

Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Antihistamines
Fexofenadine, loratadine, rupatadine, cimetidine cetirizine, are all antihistamines. It is best to take prescription antihistamines on an empty stomach to increase their effectiveness.

Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Bronchiodilators
High-fat meals increase the amount of theophylline in the body, while high carbohydrate meals may decrease it. Caffeine (chocolate, colas, coffee, and tea) contains xanthine that increases the risk of drug toxicity when taken with xanthine derivative, theophylline. GFJ increases the bioavailability of theophylline.

Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Antitubercular Drugs
Isoniazid is associated with tyramine and histamine interactions as it inhibits monoamine oxidase and histaminase. Food greatly decreases isoniazid bioavailability. Oleanolic acid has antimycobacterial activity against the Mycobacterium tuberculosis, when administered with isoniazid, it exerts synergistic effect.

High fat meals decrease the serum concentration of cycloserine, a bacteriostatic anti-tubercular drug and results in incomplete eradication of bacteria.
Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Antidiabetics
Glimepiride administered with breakfast or the first main meal of the day. (absence of food interaction). Immediate release glipizide taken 30 minutes before meals. However, extended release tablets taken with breakfast. Acarbose, is taken immediately at the start of each meal because it delays the carbohydrate absorption by inhibiting the enzyme alpha-glucosidase.

Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Thyroxine
Thyroxine better absorbed on empty stomach. Iron and Ca++ supplements delay absorption of Thyroxin.

Grapefruit juice delay the absorption of levothyroxine, but it seems to have only a minor effect on its bioavailability.

Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Antitumor Drugs
Mercaptopurine is inactivated by xanthine oxidase (XO), Cows milk contains a high level of XO, So, concurrent intake reduces bioavailability of mercaptopurine. Sesame seeds, negatively interferes with tamoxifen in inducing regression of established tumor size but beneficially interacts with tamoxifen on bone in ovariectomized athymic mice.

Immunomodulatory diet containing glutamine and n-3 fatty acids is useful adjuncts with antitumor treatment.
Oman Medical Journal (2011) Vol. 26, No. 2: 77-83

Benefits of Minimizing Food Drug Interactions

Medications achieve their intended effects Improved compliance with medications

Less need for additional medication or higher dosages

Fewer caloric or nutrient supplements are required Adverse side effects are avoided

Measures to avoid food drug interactions

The clinician should become more proactive in anticipating potential food drug interactions. Educating patients, physicians, dieticians and nurses on the impact of food on the effects of drugs is necessary to avoid pharmacotherapy complications. Medication orders are reviewed for existing or potential interactions between the medication ordered and food and medications the patient is currently taking

Conclusion
Food-drug interactions can produce negative effects in safety and efficacy of drug therapy, as well in the nutritional status of the patient. Interactions can be avoided by properly timing the drug intake with food. It is suggested that patients should tell their doctors and pharmacists about their food intake and dietary supplements so that interactions can be avoided.

limitation
Lack of database for hospitalization from food drug interactions Lack of researches on food drug interactions

Take Home Message

Diet has a significant impact on proper and safe treatment

References
Miroslaw Jarosz*, Katarzyna Wolnicka Relations Between Oecurrence of the Risk of Food-Drug Interaetions and Patients' Soeio-Demographic Characteristics and Selected Nutrition Habits. Pol. J. Food Nutn Sei., 2011, Vol. 61, No. 3, pp. 211-218 Oman Medical Journal (2011) Vol. 26, No. 2: 77-83 Bland, SE (1998): Drug-Food InteractionsJournal of the Pharmacy Society of Wisconsin Diaconu CH; Cuciureanu M; Vlase L; Cuciureanu R (2011). Food-drug interactions: grapefruit juice. journal Information J Acad Nutr Diet. 2012;112:506-517. F. Sjoqvist & Y. Bo ttiger (2010). Historical perspectives: drug interactions it all began with cheese Journal of InternalMedicine. 268; 512515