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Review                                                                                                 Harmony with drugs and food
                                                                                                        C. BRIAN TUTTLE,* M SC PHM
There is a growing awareness among professionals who care                                               at mealtime. Another aspect of this topic - the important
for patients' drug and nutritional requirements that constitu-                                          problem of drug-induced nutritional deficiencies - cannot be
ents of foods and beverages can modify the predictable effect                                           adequately dealt with here.
of drugs. Changes in the rate or extent of drug absorption or                                              The following six tables may be used as a guide in selecting
metabolism and occasionally exaggerated clinical responses                                              the most appropriate schedule for drug administration in
may be attributed to the concurrent ingestion of foodstuffs                                             relation to food intake. They are intended to promote the goal
and medications. The absence of food at a critical interval                                             of optimum drug response with minimal gastrointestinal side
may also give rise to untoward effects from certain drugs.                                              effects. The tables are not comprehensive: they are guidelines
   As well as the clinical response, the patient's acceptance of                                        only. Tables I and III in particular should be viewed as
medication can be influenced by the timing of drug adminis-                                             allowing the flexibility necessary to compensate for interpa-
tration in relation to food intake. Attention to the role of food                                       tient variability. For example, while the drugs listed in Table
as a means of preventing "stomach upset" can increase the                                               I should be taken on an empty stomach to achieve optimum
patient's compliance as well as protect the stomach from the                                            blood levels (which may be at the expense of some gastric
persistent onslaught of ulcerogenic drugs, such as acetylsalicy-                                        upset), in many instances the patient can take the medication
lic acid, iron and potassium salts.                                                                     with a light meal if compliance is threatened. The footnotes to
   Nevertheless, for certain drugs the potential benefits of                                            each table help explain this flexibility in interpretation.
reduced gastric upset can be outweighed by the decrease in
bioavailability that results when the drug's absorption is                                                Table 11-Drugs to be taken 1 hour after a meal
significantly impaired by the presence of food. Some drugs
are destroyed in the highly acid environment of the stomach                                               Generic name                                             Trade name(s)
                                                                                                          Antacid preparations'                                    Amphojel, Gelusil, Maalox,
Adapted from an article published in Drugs and Therapeutics for                                                                                                      Mylanta-2 Plain, Riopan,
Maritime Practitioners (1980; 3: no 5)                                                                                                                                Univol
                                                                                                          Antacid-antiflatulent preparations2                      Amphojel 65, Diovol, Duatrol,
*Assistant director of pharmacy, drug information and education,                                                                                                     Maalox Plus, Mylanta, Rioplus
Camp Hill Hospital, Halifax                                                                               1. The buffering effect of food on acid secretion begins to decline after about 1 hour, so
Reprint requests to: Mr. C. Brian Tuttle, Drug information centre,                                        unless symptoms appear earlier this is the optimum time to give an antacid.
Camp Hill Hospital, 1763 Robie St., Halifax, NS B3H 3G2                                                   2. Some are recommended for use between meals.

 Table I-Drugs to be taken on an empty stomach
 Generic name                    Trade name(s)                      Generic name                    Trade name(s)                         Generic name                     Trade name(s)
 Acetylsalicylic acid            Ecotrin, Entrophen,                 Glycopyrrolate2                 Robinul                               Pentaerythritol                 Peritrate,
    (enteric-coated) Ic             Triaphen-10                      Iron preparationsid                                                      tetranitratelac                 Peritrate SA
 Ampicillinlab                   Ampicin, Penbritin                     Ferrous fumarate             Palafer, Tolifer                      Phentermine3b                   lonamin
 Atropine2                       In Lomotil, Donnatal                   Ferrous gluconate            Fergon, Fertinic                      Piperazine saltsle              Antepar, Entactyl
 Belladonna2                     In Donnatal                            Ferrous succinate            Cerevon                               Propantheline2                  Pro-Banthine
 Captoprill                      Capoten                                Ferrous sulfate              Fesofor, Ferrosulph                   Pyrvinium's                     Pamovin, Vanquin
 Carbenoxolone3a                 Biogastrone,                        Iron preparations                                                     Quinacrinele                    Atabrine
                                      Duogastrone,                      (slow-release;                                                     Quinidine bisulfatelc           Biquin Durules
 Clidinium2                        In Librax                            coated)l                      Fero-Grad, Slow-Fe                  Rifampinia                       Rimactane
 Cloxacillinia,b                   Orbenin, Tegopen                  lsoniazid"a                      Rimifon                             Sucralfate3a                     Sulcrate
 Dicyclomine2                      Bentylol                          Lincomycinla                    Lincocin                             Tetracyclinesla
 Diethylpropion3b                  Tenuate                           Mazindol3b                      Sanorex                                 Demeclocyline                Declomycin
 Erythromycin                                                        Niclosamidele                   Yomesan                                 Tetracycline                 Achromycin, Tetracyn
     BaselaM                       Erythromid, Robimycin             Penicillaminela                 Cuprimine                               Oxytetracycline              Terramycin
    Stearatela,b                   Erythrocin                        Pencillin Gla,b                  Falapen, Hylenta,                   Theophylline                    Theo-Dur
 Fenfluramine3a                    Pondimin                                                             Megacillin                           (slow-release)
 1. To be taken 1 hour before or 2 hours after a meal:
    a. Gastrointestinal absorption may be significantly impaired when these drugs are taken with a meal. The absorption of most pencillins (exceptions: amoxicillin [Amoxil] and penicillin V [Pen Vee,
 V-Cillin K] ), tetracyclines (exceptions: doxycycline [Vibramycin], minocycline [Minocin]) and erythromycin preparations (exceptions: the estolate [Ilosone] and the ethylsuccinate [EES-200 and
 -400] ) is impaired by the presence of food in the stomach. If stomach upset becomes a problem with a tetracycline the drug can be taken with a light meal but not with milk. Absorption of the
 sulfonamides does not appear to be impaired by food; there may be a delay in absorption with no clinical consequences.
    b. These drugs should be taken with a full glass of water. They are inactivated to various degrees by acid secretions of the stomach and more so if taken at mealtime, when stomach emptying is
 slow and acid output high. Exceptions include amoxicillin (Amoxil), penicillin V (Pen Vee, V-Cillin K), erythromycin estolate (Ilosone) and erythromycin ethylsuccinate (EES-200 and -400), which are
 acid-stable and well absorbed when taken with a meal. The enteric-coated E-Mycin appears to be equally effective when taken with and without food.
    c. Enteric-coated and sustained-release preparations may not release medication as expected when mixed with food.
    d. For optimum absorption iron products are best taken between meals with a full glass of water; however, if stomach upset occurs or is to be avoided, the medication should be taken with or
 after meals but not with milk.
    e. Although not true for all anthelmintics, the action of these drugs (piperazine and pyrvinium for roundworms and niclosamide and quinacrine for tapeworms) is best when they are taken on an
 empty stomach. The surface contact between drug and parasite is diminished in the presence of food.
 2. To be taken half an hour before a meal: Anticholinergic agents are given to inhibit vagal stimuli thought to be responsible for gastric acid hypersecretion and hypermotility in peptic ulcer disease.
 They are more effective against "basal" than against "stimulated" secretion.
 3. To be taken 1 hour before a meal:
    a. Ulcer healing depends upon maximum contact between drug and ulcer base.
    b. For maximum psychologic and pharmacologic effectiveness.

                                                                                                                        CMA JOURNAL/MAY 15, 1982/VOL. 126                                             1161
  Table 1l-Drugs to be taken with food
  Generic name                     Trade name(s)                     Generic name                    Trade name(s)                         Generic name                     Trade name(s)
  Acetylsalicylic acid'            Various                           Hydralazine4                     Apresoline                              Phenytoinl4a                   Dilantin
  Allopurinoll                     Zyloprim                          Hydrochlorothiazidel,4a          Hydrodiuril, Dyazide                    Piroxicam'                      Feldene
  Aminophyllinel                   Corophyllin                       Hydrocortisonel                  Cortef                                  Potassium salts'               Kaochlor, Kaon,
  Betamethasone'                   Betnesol, Betnelan                Ibuprofen'                       Motrin, Amersol                                                           Kay Ciel, K-Lyte
  Biperidin'                       Akineton                          Indomethacini                    Indocid                                 Prednisolonel                  Delta-Cortef
  Bromocriptinel                   Parlodel                          Iron preparationsia                                                      Prednisonel                    Colisone, Deltasone
  Carbamazepine4a                  Tegretol                             Ferrous fumarate              Palafer, Tolifer                        Probucol4s                     Lorelco
  Chlorothiazidel                  Diuril                               Ferrous gluconate             Fergon, Fertinic                        Procyclidinel                  Kemadrine
  Chlorpromazinel                  Largactil                            Ferrous succinate             Cerevon                                 Promethazinel                  Phenergan
  Chlorpropamidel                  Diabinese                            Ferrous sulfate               Fesofor, Ferrosulph                     Propranolol4b                  Inderal
  Chlorthalidonel                  Hygroton                          Isosorbide dinitrate2            Coronex, Isordil                        Propoxyphene4a                 Darvon
  Cholestyramine3a                 Questran                          Ketoprofeni                      Orudis                                  Reserpinel                     Serpasil
  Cimetidine3a                    Tagamet                            Levodopal                        Larodopa, Sinemet                       Spironolactone4a               Aldactone
  Clofibrate'                     Atromid-S                          Methotrexatel                          _                                 Sulfasalazinel                 Salazopyrin
  Dexamethasone'                  Decadron                           Metoclopramide3b                 Maxeran                                 Sulfinpyrazone'                Anturan
  Diclofenac'                     Voltaren                           Metoprolol4b                     Betaloc, Lopressor                      Sulindaci                      Clinoril
  Dicoumarol4                     Dufalone                           Metronidazolel                   Flagyl                                  Thioridazinel                  Mellaril
  Digestants and                  Accelerase,  Donnazyme,            Minocyclinelb                    Minocin                                 Theophyllinel                  Elixophylline, Theolair
     enzyme preparations2            Entozyme, Fermentol,            Nalidixic acidi                  NegGram                                 Tolbutamidel                   Mobenol, Orinase
                                     Ultrase, Viokase                Naproxen'                        Naprosyn                                Tolmetini                      Tolectin
  Doxycyclinelb                   Vibramycin                         Nitrofurantoin4a                 Furanex, Macrodantin                    Triamterenel                   Dyrenium, Dyazide
  Ethacrynic acid,                Edecrin                            Oxtriphyllinel                   Choledyl                                Trihexyphenidyll               Artane
  Fenoprofeni                     Nalfon                             Oxyphenbutazonel                 Tandearil                               Trimeprazinel                  Panectyl
  Glyburide2                      Diabeta                            Pancrelipase3a                   Cotrazym                                Zomepirac'                     Zomax
  Griseofulvin4a                  Fulvicin, Grisovin                 Phenylbutazonel                  Butazolidin
 1. To be taken immediately before, with or after a meal, or with food or milk to prevent or minimize stomach upset. Depending upon the amount and type of food taken, the absorption of these drugs
 may be delayed, but their total bioavailability will not be significantly affected. There is considerable variation among patients in the amount of gastric distress experienced with these drugs. Some
 need only to take their medication with milk or a light snack, while others, because of marked epigastric or abdominal distress, or for other medical reasons, should take their medication with food to
 protect the stomach.
    a. If stomach upset develops when taken on an empty stomach, iron preparations can be taken with food.
    b. The absorption of doxycycline, and minocycline, unlike that of other tetracyclines, is not significantly impaired by food; in fact, these two drugs may be better tolerated when taken with food.
 2. To be taken with a meal to prevent systemic side effects.
 3. To be taken with a meal (a, immediately before; b, before or just after, in motility disorders) to provide a clinical effect.
 4. May be taken with a meal for enhanced bioavailability.
    a. Gastrointestinal absorption is enhanced.
    b. Metabolism of the drug during its first passage through the liver is reduced; this does not mean that these drugs are less effective when taken on an empty stomach, but only that somewhat
 higher blood levels can be expected when they are taken with a meal.

  Table IV-Drugs to be taken with liberal amounts of fluid
  Generic name                    Trade name (s)                     Generic name                    Trade name (s)                        Generic name                    Trade name (s)
  Acetylsalicylic acid            Various                            Iron preparationslc              Various                               Probenecid2a                    Benemid
     (plain)ibMc                                                     Methotrexate2                       _                                  Psyllium hydrophilic
  Allopurinol2a                   Zyloprim                           Methylcellulose2b                                                        mucilloid2a                   Metamucil
  Ampicillinld                    Ampicin, Penbritin                 Penicillamine2c                  Cuprimine                             Sulfinpyrazone2a                Anturan
  Cloxacillinid                   Orbenin, Tegopen                   Penicillin Gid                   Falapen, Hylenta,                    Sulfonamidesza                   Various
  Cyclophosphamide3               Procytox                                                               Megacillin                        Tetracyclinel                    Various
  Erythromycin                                                       Potassium chloride               Kaochlor, Kaon,
    Baseld                        Erythromid, Robimycin                 (liquid)ilac                     Kay-Ceil, K-Lyte
    Stearateld                    Erythrocin
 1. To be taken with a full glass of water (240 ml [8 oz0) to promote dispersion and dissolution of the drug and thus reduce the risk of esophageal or peptic ulceration, or to minimize acid
 degradation in the stomach and enhance bioavailability.
    a. Liquid potassium preparations must be diluted with water to avoid gastrointestinal injury. Doses of 20 mmol of potassium should be taken with at least 90 or 120 ml (3 or 4 oz) of cool water,
 fruit juice or a carbonated beverage. Higher doses (e.g., 40 mmol) should be taken with 240 ml (8 oz) of water or other fluid.
     b. When there is a danger of gastrointestinal bleeding, plain acetylsalicylic acid can be taken with milk or dispersed in 30 ml of an antacid to enhance dissolution in the stomach.
    c. Should generally not be taken within 1 hour of bedfime.
    d. When these acid-labile drugs are taken on an empty stomach with a full glass of water the fluid volume enhances stomach emptying and dilutes the gastric contents.
 2. To be taken with at least 240 ml (8 oz) of water:
    a. Patients should try to drink 8 to 10 glasses of water a day to prevent crystalluria or the formation of urinary calculi.
    b. Patients should drink a generous quantity of fluid for the bulk-forming effect of these laxatives and to prevent obstruction.
    c. It is especially important that patients treated for cysteinuria drink about 500 ml (a pint) of water at bedtime and again during the night, when the urine is more acid.
 3. To be followed by 2000 to 3000 ml of fluid to ensure prompt excretion of toxic active metabolites.

  Table V-Drugs not to be taken with milk

 Acetylsalicylic acid (enteric-coated)2&              Ecotrin, Entrophen, Triphen-10                       Table VI-Drugs not to be taken with fruit juices or carbonated beverages
 Bisacodyl2a                                          Dulcolax
 Erythromycin                                         E-Mycin, Erythrocin
    (coated)2b                                           Filmtab                                           Generic name                                            Trade name(s)
 Ferrous sulfate (liquid, drops)                      Fer-ln-Sol                                                                                                   Ampicin, Penbritin
 Tetracyclines'                                       Various                                              Ampicillin
                                                                                                           Cloxacillin                                             Orbenin, Tegopen
 1. To be taken at least 1 hour before or 1 hour after milk or other dairy products, which                 Erythromycin
 contain sufficient calcium to complex with and render unabsorbable a significant proportion
                                                                                                              Base                                                  Erythromid, Robimycin
 of the dose.                                                                                                 Stearate                                              Erythrocin
                                                                                                           Penicillin G                                             Falapen, Hylenta, Megacillin
 2. To be taken at least 1 hour before or 1 hour after milk.
    a. Milk may enhance the dissolution of the enteric coating, which is designed to protect
 the stomach from irritation by the drug.
    b. Milk may enhance the dissolution of the protective coating, which is designed to protect            *Fruit juices and most carbonated beverages are quite         acidic    and can   inactivate   many
 the acid-labile drug from degradation in the stomach.                                                     acid-labile drugs.

1162     CMA          JOURNAL/MAY                   15, 1982/VOL. 126

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