• Users Online: 309
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
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


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

Date of Submission24-Apr-2020
Date of Decision19-Nov-2020
Date of Acceptance22-Feb-2021
Date of Web Publication25-Jun-2021

Correspondence Address:
Shekhar Neema
Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_24_20

Rights and Permissions
  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.

Keywords: Drug interactions, food, prescription


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 Sep 25];7:1-6. Available from: https://www.ijdd.in/text.asp?2021/7/1/1/319351




  Introduction Top


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 Top


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 Top


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: Herb- drug interactions

Click here to view


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 Top


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: Positive food drug interactions

Click here to view



  Negative Food–drug Interactions Top


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: Negative food-drug interaction

Click here to view



  Prevention of Food Drug Interactions Top


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 interactions
  • Food list or individualized diet plan for patients
  • Avoidance of herbal remedies concurrently with prescription drugs.



  Conclusion Top


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.



 
  References Top

1.
Btaiche IF, Kraft MD. Nutrients that may optimize drug effects. In: Boullata JI, Armenti VT, editors. Handbook of Drug-Nutrient Interactions. Totowa, New Jersey: Nutrition and Health. Humana Press; 2004.  Back to cited text no. 1
    
2.
Bushra R, Aslam N, Khan AY. Food-drug interactions. Oman Med J 2011;26:77-83.  Back to cited text no. 2
    
3.
Reddy NR, Pierson MD, Sathe SK, Salunkhe DK. Dry bean tannins: A review of nutritional implications. J Am Oil Chem Soc 1985;62:541-9.  Back to cited text no. 3
    
4.
Nomani H, Moghadam AT, Emami SA, Mohammadpour AH, Johnston TP, Sahebkar A. Drug interactions of cola-containing drinks. Clin Nutr 2019;38:2545-51.  Back to cited text no. 4
    
5.
Cederbaum AI. Molecular mechanisms of the microsomal mixed function oxidases and biological and pathological implications. Redox Biol 2015;4:60-73.  Back to cited text no. 5
    
6.
Anderson KE, Conney AH, Kappas A. Nutrition and oxidative drug metabolism in man: Relative influence of dietary lipids, carbohydrate, and protein. Clin Pharmacol Ther 1979;26:493-501.  Back to cited text no. 6
    
7.
Fontana RJ, Lown KS, Paine MF, Fortlage L, Santella RM, Felton JS, et al. Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers. Gastroenterology 1999;117:89-98.  Back to cited text no. 7
    
8.
Steinkellner H, Rabot S, Freywald C, Nobis E, Scharf G, Chabicovsky M, et al. Effects of cruciferous vegetables and their constituents on drug metabolizing enzymes involved in the bioactivation of DNA-reactive dietary carcinogens. Mutat Res 2001;480:285-97.  Back to cited text no. 8
    
9.
Alkhedaide A, Soliman MM, Ibrahim ZS. Carbonated soft drinks alter hepatic cytochrome P450 isoform expression in Wistar rats. Biomed Rep 2016;5:607-12.  Back to cited text no. 9
    
10.
Malaviya A, Baghel S, Verma S, Thakran R, Messi C. Use of coffee for alleviating methotrexate intolerance in rheumatic diseases. Indian J Rheumatol 2019;14:79.  Back to cited text no. 10
  [Full text]  
11.
Chen M, Zhou SY, Fabriaga E, Zhang PH, Zhou Q. Food-drug interactions precipitated by fruit juices other than grapefruit juice: An update review. J Food Drug Anal 2018;26:S61-71.  Back to cited text no. 11
    
12.
Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice–Drug interactions. Br J Clin Pharmacol 1998;46:101-10.  Back to cited text no. 12
    
13.
Rodríguez-Fragoso L, Martínez-Arismendi JL, Orozco-Bustos D, Reyes-Esparza J, Torres E, Burchiel SW. Potential risks resulting from fruit/vegetable-drug interactions: Effects on drug-metabolizing enzymes and drug transporters. J Food Sci 2011;76:R112-24.  Back to cited text no. 13
    
14.
Weathermon R, Crabb DW. Alcohol and medication interactions. Alcohol Res Health 1999;23:40.  Back to cited text no. 14
    
15.
Taylor P, Balsa Criado A, Mongey AB, Avouac J, Marotte H, Mueller RB. How to get the most from methotrexate (MTX) treatment for your rheumatoid arthritis patient?–MTX in the treat-to-target strategy. J Clin Med 2019;8:515.  Back to cited text no. 15
    
16.
Liao HL, Ma TC, Li YC, Chen JT, Chang YS. Concurrent use of corticosteroids with licorice-containing TCM preparations in Taiwan: A National Health Insurance Database study. J Altern Complement Med 2010;16:539-44.  Back to cited text no. 16
    
17.
Izzo AA. Interactions between herbs and conventional drugs: Overview of the clinical data. Med Princ Pract 2012;21:404-28.  Back to cited text no. 17
    
18.
Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P. St John's wort (Hypericum perforatum): Drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56.  Back to cited text no. 18
    
19.
Rao TS, Yeragani VK. Hypertensive crisis and cheese. Indian J Psychiatry 2009;51:65.  Back to cited text no. 19
    
20.
Negroni R, Arechavala AI. Itraconazole: Pharmacokinetics and indications. Arch Med Res 1993;24:387-93.  Back to cited text no. 20
    
21.
Kersemaekers WM, Dogterom P, Xu J, Marcantonio EE, de Greef R, Waskin H, et al. Effect of a high-fat meal on the pharmacokinetics of 300-milligram posaconazole in a solid oral tablet formulation. Antimicrob Agents Chemother 2015;59:3385-9.  Back to cited text no. 21
    
22.
Ogunbona FA, Smith IF, Olawoye OS. Fat contents of meals and bioavailability of griseofulvin in man. J Pharm Pharmacol 1985;37:283-4.  Back to cited text no. 22
    
23.
Frey BM, Frey FJ. Clinical pharmacokinetics of prednisone and prednisolone. Clin Pharmacokinet 1990;19:126-46.  Back to cited text no. 23
    
24.
Gautam M, Tahiliani H, Nadkarni N, Patil S, Godse K. Acitretin in pediatric dermatoses. Indian J Paediatr Dermatol 2016;17:87.  Back to cited text no. 24
  [Full text]  
25.
Grønhøj Larsen F, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff PB, Nielsen-Kudsk F. Acitretin is converted to etretinate only during concomitant alcohol intake. Br J Dermatol 2000;143:1164-9.  Back to cited text no. 25
    
26.
Lange H, Eggers R, Bircher J. Increased systemic availability of albendazole when taken with a fatty meal. Eur J Clin Pharmacol 1988;34:315-7.  Back to cited text no. 26
    
27.
Welling PG. Effects of food on drug absorption. Annu Rev Nutr 1996;16:383-415.  Back to cited text no. 27
    
28.
Shenoi SD, Prabhu S. Photochemotherapy (PUVA) in psoriasis and vitiligo. Indian J Dermatol Venereol Leprol 2014;80:497.  Back to cited text no. 28
[PUBMED]  [Full text]  
29.
Fu PP, Xia Q, Zhao Y, Wang S, Yu H, Chiang H-M. Phototoxicity of herbal plants and herbal products. J Environ Sci Health Part C 2013;31:213-55.  Back to cited text no. 29
    
30.
Gupta SK, Manfro RC, Tomlanovich SJ, Gambertoglio JG, Garovoy MR, Benet LZ. Effect of food on the pharmacokinetics of cyclosporine in healthy subjects following oral and intravenous administration. J Clin Pharmacol 1990;30:643-53.  Back to cited text no. 30
    
31.
Kovarik JM, Barilla D, McMahon L, Wang Y, Kisicki J, Schmouder R. Administration diluents differentiate Neoral from a generic cyclosporine oral solution. Clin Transplant 2002;16:306-9.  Back to cited text no. 31
    
32.
Mudge DW, Atcheson B, Taylor PJ, Sturtevant JM, Hawley CM, Campbell SB, et al. The effect of oral iron admiinistration on mycophenolate mofetil absorption in renal transplant recipients: A randomized, controlled trial. Transplantation 2004;77:206-9.  Back to cited text no. 32
    
33.
Nix DE, Adam RD, Auclair B, Krueger TS, Godo PG, Peloquin CA. Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid. Tuberculosis 2004;84:365-73.  Back to cited text no. 33
    
34.
Zent C, Smith P. Study of the effect of concomitant food on the bioavailability of rifampicin, isoniazid and pyrazinamide. Tuber Lung Dis 1995;76:109-13.  Back to cited text no. 34
    
35.
Leyden JJ, Del Rosso JQ. Oral antibiotic therapy for acne vulgaris: Pharmacokinetic and pharmacodynamic perspectives. J Clin Aesthetic Dermatol 2011;4:40.  Back to cited text no. 35
    
36.
Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. Drug Saf. 1995;12:314-33.  Back to cited text no. 36
    
37.
Segal EM, Flood MR, Mancini RS, Whiteman RT, Friedt GA, Kramer AR, et al. Oral chemotherapy food and drug interactions: A comprehensive review of the literature. J Oncol Pract 2014;10:e255-68.  Back to cited text no. 37
    
38.
Sinigaglia L, Varenna M, Casari S. Pharmacokinetic profile of bisphosphonates in the treatment of metabolic bone disorders. Clin Cases Miner Bone Metab 2007;4:30.  Back to cited text no. 38
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Effect of Food/N...
Effect of Food/N...
Positive Food...
Negative Food...
Prevention of Fo...
Conclusion
References
Article Tables

 Article Access Statistics
    Viewed851    
    Printed14    
    Emailed0    
    PDF Downloaded61    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]