Indian Journal of Drugs in Dermatology

REVIEW ARTICLE
Year
: 2021  |  Volume : 7  |  Issue : 1  |  Page : 1--6

Food and drug interactions in dermatology: Maximizing drug safety and efficacy through intelligent dispensing


Anwita Sinha1, Shekhar Neema2,  
1 Department of Dermatology, Military Hospital Kirkee, Pune, Maharashtra, India
2 Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India

Correspondence Address:
Shekhar Neema
Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra
India

Abstract

Drug interaction is a common phenomenon and awareness about it has increased with the availability of online applications. The optimization of prescription also requires a physician to be aware of interaction of prescription drugs with food and herbs. Patients also commonly pose the question to prescribers about food–drug interactions, especially in our country. The prescriber should be aware of common food–drug interactions in dermatology for safe and effective prescription practices.



How to cite this article:
Sinha A, Neema S. Food and drug interactions in dermatology: Maximizing drug safety and efficacy through intelligent dispensing.Indian J Drugs Dermatol 2021;7:1-6


How to cite this URL:
Sinha A, Neema S. Food and drug interactions in dermatology: Maximizing drug safety and efficacy through intelligent dispensing. Indian J Drugs Dermatol [serial online] 2021 [cited 2021 Dec 2 ];7:1-6
Available from: https://www.ijdd.in/text.asp?2021/7/1/1/319351


Full Text



 Introduction



A common and relevant question often posed by patients to prescribers is whether they should avoid certain foods, beverages, dietary supplements, herbs, and whether the medication should be taken before food, with food, or after food. Food–drug interaction refers to a condition where food affects the activity of a drug or drug affects the nutritious value of food.

Food–drug interactions are often the result of physical and chemical interactions between drugs and food affecting the pharmacokinetic or pharmacodynamic properties of a drug. These interactions can be influenced by factors of a physicochemical nature (e.g., pH, dissolution, disintegration, and binding) or physiological determinants (e.g., absorption, elimination, gastrointestinal (GI) transit time, GI secretions, splanchnic blood flow, liver enzyme inhibition, or induction), formulation (e.g., tablet, capsule, liquid, slow-release reservoir, and enteric-coated tablets), excipients, etc.[1] This article will focus on potential mechanisms of food–drug interactions and their clinical significance, with special reference to dermatological pharmacotherapy.

 Effect of Food/Nutrients on Drug Absorption



The presence of food changes gastric motility, GI pH, and provides substances for drug and nutrient chelation and adsorption. Factors determining absorption of drug concurrently administered with food are given below.

Chelation

Chelation involves the formation of a complex between certain dietary components, especially divalent or trivalent cations (e.g., Ca, Mg, Al, Fe, and Zn) and certain drugs, forming a less soluble substance, thereby decreasing absorption of the drug. Calcium in milk, various traditional antacids (aluminum , magnesium, and calcium containing), and iron-containing products can reduce the absorption of tetracyclines and fluoroquinolone antibiotics.[2] Tannins found in tea, coffee, and some wines form complexes with iron and other heavy metals leading to poor absorption.[3]

Carbohydrate/fat/protein content of meal

A high-carbohydrate meal slows the absorption of many drugs. The absorption of lipophilic drugs is increased when taken with a high-fat meal. High-fat, high-calorie meals also prolong gastric emptying time and may affect drug solubility.

Gastric pH

This is an important variable for absorption of drugs such as ketoconazole and itraconazole which are optimally absorbed in low gastric pH.[4]

 Effect of Food/Nutrients on Drug Metabolism



Most drugs are metabolized by phase I (oxidation reactions) and phase II (conjugation and detoxification reactions). The initial oxidation reactions in phase I are accomplished by various cytochrome (CYP) P450 isoforms, which are largely present in the liver. In the conjugating system, drugs are primarily converted to glucuronides.[5] Blood levels, efficacy, and side effects of a drug may be increased or decreased as a result of induction/inhibition of enzymes due to alteration of dietary constituents. Dietary components of specific foods and beverages which may alter drug metabolism are highlighted below.

Effects of dietary protein, carbohydrate, and fat

Protein content of the diet is important for regulating oxidative drug metabolism and augments hepatic microsomal CYP content. Protein may also increase the rate of blood flow to the liver and therefore increase the metabolism of a drug.[6]

Food preparation

Chemical changes in food induced during cooking at high temperatures influence drug metabolic pathways. For example, charcoal broiling of meats leads to the formation of indoles and polycyclic aromatic hydrocarbons which induces chemical oxidation of drugs.[7] This fact is substantiated by the evidence that polycyclic aromatic hydrocarbons in cigarette smoke account for enhanced drug oxidation rates in smokers. Smoked and preserved meats likely also contain chemicals oxidized by CYP450 isoenzymes.

Cruciferous vegetables

Indoles found in cruciferous vegetables such as cabbage, Brussels sprouts, and alfalfa meal markedly induce chemical oxidations. Variations in Vitamin K intake from foods like cruciferous vegetables can significantly influence anticoagulation with warfarin.[8]

Tea/coffee

Methylxanthines such as caffeine are components of beverages such as coffee and tea and many popular carbonated beverages. Effects on drug metabolism involve saturation and inhibition as well as induction of hepatic enzymes that metabolize methylxanthines and other drugs.[9] These beverages have other relevant effects, such as coffee has recently been studied to relieve the symptoms of methotrexate intolerance and can increase patient compliance.[10] Both green and black tea have been found to reduce folate levels. Coumarins in some herbal teas may enhance the in vivo effects of coumarin anticoagulants.

Cola-containing drinks

Cola-containing drinks (CCDs) have two main properties which can lead to drug interactions. First, cola drinks contain caffeine. Second, CCD/drug interactions result from the acidic pH of most cola drinks, primarily from their high phosphoric acid content commonly described in case of enhanced absorption of itraconazole in presence of cola drinks. CCDs, by lowering the pH of urine, can affect the renal excretion or precipitation of drugs which are weak acids like methotrexate.[4]

Kava

Kava, a traditional beverage, prepared from the roots and rhizomes of the kava plant (Piper methysticum) is used for its anxiolytic and sedative properties. Kavalactones found in kava inhibit CYP P 450 enzymes, resulting in elevation of the plasma levels of drugs such as alprazolam, antidepressants, and antihistamines. Kava can potentiate hepatotoxicity of many drugs. In March 2002, the Food and Drug Administration issued a warning to health-care providers regarding the potential risk of severe liver injury associated with the use of kava.[11]

Grapefruit Juice and other citrus fruit juices

Grapefruit juice (GFJ) contains furanocoumarins, mainly bergamottin, which inhibit CYP P-450 3A4 and to some extent other CYP isoforms leading to a significant reduction of drug presystemic metabolism and increased bioavailability. Significant GFJ-drug interactions of dermatological interest due to CYP3A4 inhibition are seen with cyclosporine, tacrolimus, sirolimus, erythromycin, albendazole, methylprednisolone, cyclophosphamide, and tadalafil. The risk of torsades de pointes is increased with terfenadine and loratadine. An additional mechanism is the inhibition of P-glycoprotein, a transporter that carries the drug from the enterocyte back to the gut lumen, resulting in a further increase in the fraction of drug and this mechanism may be more important than CYP3A4 inhibition for drugs like cyclosporine. Furanocoumarins and active bioflavonoids present in GFJ are also inhibitors of organic anion transporting polypeptides (OATP) and when ingested concomitantly, they can reduce the oral bioavailability of the OATP substrate, fexofenadine.[12]

Other fruit juices:

Orange juice: Decrease in systemic availability of fexofenadine, clofazimine, itraconazole, and levofloxacin has been observed. The mechanism likely involves inhibition of intestinal OATP1A2[11]Apple juice: Apple juice can also interact with OATP transporter and reduce levels of fexofenadine.[13]

Alcohol

Drugs of dermatological importance causing disulfiram-like reaction on concurrent intake of alcohol include metronidazole, griseofulvin, some cephalosporin antibiotics, and possibly ketoconazole. The unpleasant manifestations of this drug–food interaction include flushing, headache, nausea, vomiting, weakness, vertigo, hypotension, blurred vision, and seizures. Reactions can also occur with the ingestion of foods cooked with wine, wine vinegar, or wine-containing desserts.[14] Alcohol potentiates the sedative action of antihistamines and thalidomide. Consuming alcohol while taking ketoconazole may increase the risk of liver damage. Alcohol consumption, particularly when excessive, has been implicated in the risk of inadequate response to methotrexate and concomitant hepatotoxicity.[15]

Herbal remedies

Herbal products are not subject to consistent standardization and regulation, their content is often variable and uncertain containing a mixture of chemicals. Patients taking prescribed drugs should avoid herbal remedies because of significant drug–herb interactions. Herb–drug interactions of dermatological significance are summarized in [Table 1].{Table 1}

Tyramine and related substances

"Tyramine reactions” or “cheese reactions” are hypertensive reactions which may occur in patients using monoamine oxidase (MAO) inhibitors after ingestion of foods containing tyramine, commonly found in cheeses like cheddar and other high-protein foods that have started to ferment like yeast preparations, broad beans, and certain wines and beer. It manifests as sudden-onset hypertension with palpation, nausea, vomiting, and headache. Dermatological drugs with weak MAO-inhibiting properties such as linezolid, isoniazid, and tricyclic antidepressants may show tyramine reactions.[19]

 Positive Food–drug Interactions



Positive food–drug interactions are those which enhance therapeutic efficacy, reduce drug toxicity, or decrease GI adverse effects. Clinically significant positive food–drug interactions relevant to dermatological drug therapy are summarized in [Table 2].{Table 2}

 Negative Food–drug Interactions



Negative food–drug interactions may result in reduced drug efficacy, therapeutic failure, drug toxicity, or nutrient deficiency. Important negative food–drug interactions relevant to dermatological pharmacotherapy are summarized in [Table 3].{Table 3}

 Prevention of Food Drug Interactions



Drugs can show their efficacy only if administered with appropriate combination of food at appropriate time. Significant food–drug interactions are common in children and the elderly and of utmost importance in drugs with a narrow therapeutic index. Various measures to avoid food–drug interaction are as follows:

Effective counseling by dermatologist, physician, nurse, or pharmacist regarding potential food–drug interactionsFood list or individualized diet plan for patientsAvoidance of herbal remedies concurrently with prescription drugs.

 Conclusion



Food–drug interactions can affect therapeutic response to drugs and these interactions have varying degrees of clinical significance. The interactions in some cases may be advantageous when it lessens side effects or increases therapeutic efficacy, while in some cases, it can result in negative effects like therapeutic failure or drug toxicity. Knowledge of potential food–drug interactions helps clinicians to predict and explain a patient's response to drugs, thereby optimizing drug efficacy and safety.[38]

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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