Drug food interaction

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A change in a drug’s effect on the body when the drug is taken together with certain foods (or beverages). Not all drugs are affected by food, and some drugs are affected by only certain foods. A drug-food interaction can delay, decrease, or enhance absorption of a drug. This can decrease or increase the action of the drug or cause adverse effects. Abstract The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient.

Keywords: Food-drug interaction, Cytochrome P450, Drug, Chelation Go to: Introduction Medicines can treat and cure many health problems. However, they must be taken properly to ensure that they are safe and effective. Medications should be extremely specific in their effects, have the same predictable effect for all patients, never be affected by concomitant food or other medications, exhibit linear potency, be totally non-toxic in any dosage and require only a single dose to affect a permanent cure. However, this ideal drug is still to be discovered.1

Many medicines have powerful ingredients that interact with the human body in different ways. Diet and lifestyle can sometimes have a significant impact on drugs. A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interactions between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs and foods (drug-food interactions), as well as drugs and herbs (drug-herb interactions).

These may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Interactions between food and drugs may inadvertently reduce or increase the drug effect. Some commonly used herbs, fruits as well as alcohol may cause failure of the therapy up a point of to serious alterations of the patient’s health. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug.

Major side-effects of some diet (food) on drugs include alteration in absorption by fatty, high protein and fiber diets.2 Bioavailability is an important pharmacokinetic parameter which is correlated with the clinical effect of most drugs. However, in order to evaluate the clinical relevance of a food-drug interaction the impact of food intake on the clinical effect of the drug has to be quantified as well.

The most important interactions are those associated with a high risk of treatment failure arising from a significantly reduced bioavailability in the fed state. Such interactions are frequently caused by chelation with components in food. In addition, the physiological response to food intake, in particular, gastric acid secretion, may reduce or increase the bioavailability of certain drugs.3,4

Drug interactions can alter the pharmacokinetics and/or pharmacodynamics of a drug. The pharmacodynamic interaction may be additive, synergistic, or antagonistic effects of a drug. Drug interactions (DIs) represent an important and widely under recognized source of medication errors.5 The gastrointestinal absorption of drugs may be affected by the concurrent use of other agents that,1 have a large surface area upon which the drug can be absorbed,2 bind or chelate,3 alter gastric pH,4 alter gastrointestinal motility, or affect transport proteins such as P-glycoprotein. A reduction only in absorption rate of a drug is seldom clinically important, whereas a reduction in the extent of absorption will be clinically important if it results in sub therapeutic serum levels.5

Factors such as nonspecific binding, atypical kinetics, poor effector solubility, and varying ratios of accessory proteins may alter the kinetic behavior of an enzyme and subsequently confound the extrapolation of in vitro data to the human situation.6 Coenzyme Q-10 (CoQ10) is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. It interferes with intestinal efflux transporter P-glycoprotein (P-gp) and as result food-drug interactions arise.7

The interaction of natural products and drugs is a common hidden problem encountered in clinical practice. The interactions between natural products and drugs are based on the same pharmacokinetic and pharmacodynamic principles as drug-drug interactions. Several fruits and berries have recently been shown to contain agents that affect drug-metabolizing enzymes.8 Grapefruit is the most well-known example, but also sevillian orange, pomelo and star fruit contain agents that inhibit cytochrome P450 3A4 (CYP3A4), which is the most important enzyme in drug metabolism.9

The study of drug-drug, food-drug, and herb-drug interactions and of genetic factors affecting pharmacokinetics and pharmacodynamics is expected to improve drug safety and will enable individualized drug therapy. Drugs can show their efficacy only if administered in appropriate quantity with appropriate combination of drugs and foods and at appropriate time.

In contrast to the easy access to information on drug-drug interactions, the information about food-drug interaction is not always available conveniently. It is a difficult and complex problem to accurately determine the effects of food and nutrients on a particular drug. This article aims to help the healthcare professionals specially physicians and pharmacists and patients to become more knowledgeable about drug and food interactions.

Electronic search of literatures was conducted over a period of two months and all original research and review articles were included in this study. No literature was older than 20 years. The drugs were selected and reviewed on the basis of their general utilization pattern and realizing the need for reporting their interaction with different dietary supplements for better therapeutic use of these drugs within the recommended dose regimen.

Fruit Juices Among all fruit juices, grape fruit juice (GFJ) possesses high interaction with almost all types of drugs. The juice modifies the body’s way of metabolizing the medication, affecting the liver’s ability to work the drug through a person’s system. Taniguchi in 2007 reported a case of purpura associated with concomitant ingestion of cilostazol, aspirin and grapefruit juice in 79 years old man. His purpura disappeared upon cessation of grapefruit juice, although his medication was not altered. The most probable cause of his purpura is an increase in the blood level of cilostazol because of the inhibition of cilostazol metabolism by components of grapefruit juice; Taniguch.9

Numerous reports have documented drug interactions with GFJ that occur via inhibition of CYP3A enzymes.10 Furanocoumarins present in GFJ inhibit the intestinal CYP 3A4 and have been shown to increase the oral bioavailability of medications that are CYP 3A4 substrates like Felodipine, midazolam, cyclosporine and raise their concentrations above toxic levels.11

GFJ is generally contraindicated to patients taking psychotropics and it is advised to inform patients about described interaction.12 The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol.13 The overall exposure of some drugs can be increased by more than fivefold when taken with GFJ and increase the risk of adverse effects.14

With new anticonvulsants, serum iron and sodium need to be monitored. Additionally, users are advised to avoid drinking grape fruit juice within 1-2 hr(s) of taking these anticonvulsants.15 Furanocoumarines and active bioflavonoids present in GFJ are also inhibitors of OATP and when ingested concomitantly, can reduce the oral bioavailability of the OATP substrate, fexofenadine.16 Overall, a series of flavonoids present in GFJ are identified as esterase inhibitors, of which kaempferol and naringenin are shown to mediate pharmacokinetic drug interaction with most of the calcium channel antagonist and the statin groups of drugs such as enalapril and lovastatin due to their capability of esterase inhibition.17

Cholesterol-lowering agent lovastatin should be taken with food to enhance gastrointestinal absorption and bioavailability. The absorption of rosuvastatin, another anti-hyper lipidemic agent, was significantly decreased in the fed state compared with the fasting state, which suggests that rosuvastatin should be administered on an empty stomach.18

Simvastatin, Ezetimibe, pravastatin and fluvastatin may be taken without regards to food. However, high fiber diets may lower the efficacy of these drugs.19 Concomitant administration of statins with food may alter statin pharmacokinetics or pharmacodynamics, increasing the risk of adverse reactions such as myopathy or rhabdomyolysis or reducing their pharmacological action. Consumption of pectin or oat bran together with Lovastatin reduces absorption of the drug, while alcohol intake does not appear to affect the efficacy and safety of Fluvastatin treatment.20

Warfarin Warfarin is commonly used to treat or prevent thromboembolic events.21 Patients taking warfarin are at particular risk of interactions with dietary supplements, yet approximately 30% use herbal or natural product supplements on a regular basis.22 There is a possible interaction between warfarin and a high-protein diet. The potential for increased dietary protein intake to raise serum albumin levels and/or cytochrome P450 activity has been postulated as mechanisms for the resulting decrease in international normalized ratio (INRs).23

Some vegetables (broccoli, Brussels sprouts, kale, parsley, spinach, and others) are high in vitamin K. Eating large quantities or making sudden changes in the amounts eaten of these vegetables, interferes with the effectiveness and safety of warfarin therapy.24

Eating charbroiled food may decrease warfarin activity, while eating cooked onions may increase warfarin activity.25 Soy foods have been reported both to increase and to decrease warfarin activity.25 The significance of these last three interactions remains unclear. The combination of warfarin administration and cranberry juice ingestion appeared to be associated with an elevated INR without bleeding in elderly patient.

A number of studies have been documented on the interaction of warfarin and cranberry juice.26-30 Cranberry juice is a flavonoid, which has been shown to induce, inhibit, or act as a substrate for the biosynthesis of several cytochrome P-450 (CYP) isoenzymes. Specifically, cranberry juice may inhibit the activity of CYP2C9, the primary isoenzyme involved in the metabolism of S-warfarin. It was suggested that cranberry juice increased the International Normalized Ratio (INR) of patients taking warfarin, but neither clearly identified cranberry juice as the sole cause of INR elevation.31 If warfarin sodium is ingested with leafy green vegetables, the hypoprothrombinemic effect of warfarin may be decreased and thromboembolic complications may develop.32

Monoamnine Oxidases Antidepressant activity of monoamine oxidase inhibitors (MAOIs) was initially noted in the 1950s. Although older monoamine oxidase inhibitors (MAOIs) are effective in the treatment of depressive disorders, they are under-utilized in clinical practice due to main concerns about interaction with tyramine-containing food (matured cheese, red vine, ripped bananas, yogurt, shrimp paste and salami) or so called cheese reaction, since they are capable of producing hypertensive crisis in patients taking MAOIs.33

The first-generation MAOIs such as phenelzine and isocarboxazid were largely nonselective inhibitors of both subtypes of MAO, MAO (A) and MAO (B). These medications carried with them dietary restrictions.34 Tyramine is an indirectly acting sympathomimetic agent, is degraded by MAO but in the presence of MAOIs, it escapes degradation and reaches the systemic circulation where it is taken up by the adrenergic neuron, leading to a hypertensive crisis.35 However, MAOIs have been well established as an effective intervention for people with treatment-resistant depression, and transdermal formulations may provide a valuable therapeutic option and eliminate the drug-food interaction.

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