Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
Review Article
DRUG-FOOD INTERACTIONS AND ROLE OF PHARMACIST
*MOHAMMAD YAHEYA MOHAMMAD ISMAIL
*Lecturer in Pharmaceutics, Dept. of Pharmacy, Higher College of Technology, P.O. Box 74
PC 133, Sultanate of Oman, E mail: mohammadyaheya@yahoo.com
ABSTRACT
Interaction between foods and drugs can have profound influence on the success of drug treatment and on the side
effect profiles of many drugs. The clinical significance of drug-food interactions can be variable. Drug-food
interactions can lead to a loss of therapeutic efficacy or toxic effects of drug therapy. Generally, the effect of food
on drugs results in a reduction in the drug's bioavailability; however, food can also alter drug clearance. Some
foods greatly affect drug therapy, resulting in serious side effects, toxicity, or therapeutic failure. In some
instances, the interaction may have a beneficial effect by increasing drug efficacy or diminishing potential side
effects. Pharmacists in every practice setting need to be vigilant in monitoring for potential drug-food interactions
and advising patients regarding foods or beverages to avoid when taking certain medications. It is imperative for
pharmacists to keep up-to-date on potential drug-food interactions of medications, especially today’s new drugs,
so that they may counsel properly to the patients.
KEYWORDS Drug-food interactions
INTRODUCTION
Many people have the mistaken
notion that being natural, all herbs and
foods are safe. This is not so. Very often,
herbs and foods may interact with
medications normally taken that result in
serious side reactions. Experts suggest that
natural does not mean it is completely
safe. The medication that is taken by
mouth travels through the digestive system
in the same way as food and herbs taken
orally do. When drugs and certain foods
are taken at the same time, they can
interact in such a way that decrease the
effectiveness of the ingested drug or
reduce the absorption of food nutrients.
Additionally, vitamin and herbal
supplements taken with prescribed
medication can result in adverse reactions.
A drug-food interaction happens when the
food affects the ingredients in a medicine
which the patient is taking affecting the
efficacy of medicine being administered.
High-risk patients, such as the elderly
patients taking three or more medications
for chronic conditions, patients suffering
from diabetes, hypertension, depression,
high cholesterol or congestive heart failure
should be especially monitored for such
drug–food interactions.1
DRUG-FOOD INTERACTIONS
The relationships and interactions
between foods, the nutrients they contain
and drugs are gaining recognition in the
health care and medical fields. Certain
foods and specific nutrients in foods, if
ingested concurrently with some drugs,
may affect the overall bioavailability,
pharmacokinetics, pharmacodynamics and
therapeutic efficacy of the medications.
Furthermore, the therapeutic efficacy of
many drugs depends on the nutritional
status of the individual. In other words, the
presence or absence of some nutrients in
the gastrointestinal tract and/or in the
body’s physiological system, such as in the
blood, can enhance or impair the rate of
drug absorption and metabolism. Drugfood
interactions can happen with both
prescription and over-the-counter
medicines, including antacids, vitamins
and iron pills. Foods containing active
substances that interact against certain
medications can produce unexpected or
adverse effects. Pharmacist can give the
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
information of such interactions to the
patients.2
Nutrients include food,
beverages and dietary supplements.
Consumption of these substances may alter
the effects of drugs the patient takes. For
example:
Food: Like food, drugs taken by mouth
must be absorbed through the lining of the
stomach or the small intestine.
Consequently, the presence of food in the
digestive tract may reduce absorption of a
drug. Often, such interactions can be
avoided by taking the drug one hour before
or two hours after eating. Dietary fiber
also affects drug absorption. Pectin and
other soluble fibers slow down the
absorption of acetaminophen, a popular
painkiller. Bran and other insoluble fibers
have a similar effect on digoxin, a major
heart medication. Certain vitamins and
minerals impact on medications too. Large
amounts of broccoli, spinach and other
green leafy vegetables high in vitamin K,
which promotes the formation of blood
clots, can counteract the effects of heparin,
warfarin and other drugs given to prevent
clotting.3
Dietary Supplements: Dietary
supplements, including medicinal herbs
are products that contain a vitamin,
mineral, herb or amino acid and that are
intended as a supplement to the normal
diet. Supplements are regulated as foods
not as drugs so they are not tested as
comprehensively. However, they may
interact with prescription or over-thecounter
drugs. People who take dietary
supplements should inform their doctors
and pharmacists so that interactions can be
avoided. Some dietary components
increase the risk of side effects.
Theophylline, a medication administered
to treat asthma contains xanthines, which
are also found in tea, coffee, chocolate and
other sources of caffeine. Consuming large
amounts of these substances while taking
theophylline, increases the risk of drug
toxicity.2
Alcohol: Alcohol affects body processes
and interacts with many drugs. Alcohol is
a drug that interacts with almost every
medication, especially antidepressants and
other drugs that affect the brain and
nervous system. For example, taking
alcohol with metronidazole can cause
flushing, headache, palpitations, nausea
and vomiting.4
Foods containing active
substances that interact against certain
medications can produce unexpected or
adverse effects. Pharmacist can give the
information of such interactions to the
patients.2
Factors Affecting the Extent of
Interaction between Foods and Drugs
The impact of drug-food interactions
depend on a variety of intervening factors
like dosage of the drug, person's age, size
and state of health. Apart from these, the
time foods and the medications are taken
also play an important role. Avoidance of
drug interactions does not necessarily
mean avoiding drugs or foods. In the case
of tetracycline and dairy products, these
should simply be taken at different times;
rather than eliminating one or the other
from the diet. Sufficient information about
the medications and timing of medications
around food intake can help to avoid drug
interaction problems.2, 4
Effect of Drug-Food Interactions
Not all medicines are affected by food, but
many medicines can be affected by the
food and it's time. For example, taking
some medicines at the same time with food
may affect the absorption of the medicine.
The food may delay or decrease the
absorption of the drug. This is why some
medicines should be taken on an
empty stomach. On the other hand,
some medicines are easier to tolerate when
taken with food. It is always advised to ask
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
the doctor or pharmacist whether it's
correct to take the medicine with a snack
or a meal or whether it should be taken on
an empty stomach.5
Table 1: Some examples of drug-food interactions that accelerate the absorption of
drugs (5, 15-17)
CounselingMechanismDrug
Take with food.
Increased bile production,
enhanced dissolution and
absorption.
Carbamazepine
Increased bile flow, delayed
gastric emptying permits
dissolution and absorption.
Dicumerol
Unknown.Erythromycin
Take with high- fat
foods.
Drug is lipid soluble,
enhanced absorption with
high- fat foods.
Griseofulvin
Take with food
Food may reduce first-pass
extraction and metabolism.
Hydralazine, Labetalol and
Metaprolol
Delayed gastric emptying
improves dissolution and
absorption.
Nitrofurantoin, Phenytoin and
Propoxyphene
Food may reduce first-pass
extraction and metabolism.
Propranolol
Delayed gastric emptying
permits dissolution and
absorption, bile may
solubilize the drug.
Spironolactone
MECHANISMS OF DRUG-FOOD
INTERACTIONS
Pharmacokinetic Interactions
Drug Absorption Interactions
Food may affect drug absorption in the GI
tract by altering gastric pH, secretion,
gastrointestinal motility and transit time.
This may result in a change in the rate of
absorption or extent of drug absorption or
both. For example, azithromycin
absorption is decreased when it is taken
with food, resulting in a 43% reduction in
bioavailability. Sustained-release
theophylline products when taken with
high-fat foods may cause a sudden release
(dose dumping) of theophylline, resulting
in increased theophylline concentrations
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
and possible toxicity. Children are more prone to this interaction than adults.
Table 2: Some examples of drug-food interactions that delay the absorption of drugs
CounselingMechanismDrug
Take on empty stomach if not contraindicated.High pectin
foods act as
adsorbant and
protectant.
Acetaminophen
Take drug same time with relation to food, Avoid
taking with high-fiber foods.
High–fiber,
high–pectin
foods bind drug.
Digoxin
Affects blood glucose; more potent when taken half
hour before meals.
Mechanism
unknown.
Glipizide
Take on empty stomach if tolerated.Food raises
gastric pH
preventing
dissolution and
absorption.
Isoniazide
Avoid taking drug with high–protein foods.Drug competes
with amino acids
for absorption
transport.
Levodopa
Avoid taking with high- protein foods.Competitive
absorption.
Methyldopa
Take on empty stomach.Mechanism
unknown.
Nafcillin
Avoid taking with dairy products or iron–rich foods or
supplements.
May form
chelate with
calcium or iron.
Penicillamine
May take with food to prevent gastrointestinal upsetPossibly protein
binding.
Quinidine
Taking with meals may prolong gastric emptying.Mechanism
unknown.
Sulfonamides
Take one hr before or two hr after meals; do not take
with milk.
Binds with
calcium ions or
iron salts
forming
insoluble
chelates.
Tetracyclines
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
Table 3: Examples of specific counseling on some drug-food interaction (5, 15-17)
Drugs Effects and Precautions
Antibiotics
Cephalosporins, penicillin Take on an empty stomach to speed absorption of the drugs.
Erythromycin Don't take with fruit juice or wine, which decrease the drug's
effectiveness.
Sulfa drugs Increase the risk of Vitamin B12 deficiency
Tetracycline Dairy products reduce the drug's effectiveness. Lowers Vitamin
C absorption
Anticonvulsants
Dilantin, phenobarbital Increase the risk of anemia and nerve problems due to deficiency
of folalte and other B vitamins.
Antidepressants
Fluoxetine Reduce appetite and can lead to excessive weight loss
Lithium A low-salt diet increases the risk of lithium toxicity; excessive
salt reduces the drug's efficacy
MAO Inhibitors Foods high in tyramine (aged cheese, processed meats, legumes,
wine and beer among others) can produce a hypertensive crisis.
Tricyclics Many foods, especially legumes, meat, fish and foods high in
Vitamin C, reduce absorption of the drugs.
Antihypertensives, Heart Medications
ACE inhibitors Take on an empty stomach to improve the absorption of the
drugs.
Alpha blockers Take with liquid or food to avoid excessive drop in blood
pressure.
Antiarrhythmic drugs Avoid caffeine, which increases the risk of irregular heartbeat.
Beta blockers Take on an empty stomach; food, especially meat, increases the
drug's effects and can cause dizziness and low blood pressure.
Digitalis Avoid taking with milk and high fiber foods, which reduce
absorption, increases potassium loss.
Diuretics Increase the risk of potassium deficiency.
Potassium sparing
diuretics
Unless a doctor advises otherwise, don't take diuretics with
potassium supplements or salt substitutes, which can cause
potassium overload.
Asthma Drugs
Pseudoephedrine Avoid caffeine, which increase feelings of anxiety and
nervousness.
Theophylline High protein diet reduces absorption. Caffeine increases the risk
of drug toxicity.
Cholesterol Lowering Drugs
Cholestyramine Increases the excretion of folate and fat soluble vitamins.
Gemfibrozil Avoid fatty foods, which decrease the drug's efficacy in lowering
cholesterol.
Heartburn and Ulcer Medications
Antacids Interfere with the absorption of many minerals; for maximum
benefit, take medication one hour after eating.
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
Cimetidine, Famotidine,
Sucralfate
Avoid high protein foods, caffeine and other items that increase
stomach acidity.
Hormone Preparations
Oral contraceptives Salty foods increase fluid retention. Drugs reduce the absorption
of folate, vitamin B6 and other nutrients; increase intake of foods
high in these nutrients to avoid deficiencies.
Steroids Salty foods increase fluid retention. Increase intake of foods high
in calcium, vitamin K, potassium and protein to avoid
deficiencies.
Thyroid drugs Iodine-rich foods lower the drug's efficacy.
Laxatives
Mineral Oils Overuse can cause a deficiency of vitamins A, D, E, and K.
Painkillers
Aspirin and stronger
nonsteroidal antiinflammatory
drugs
Always take with food to lower the risk of gastrointestinal
irritation; avoid taking with alcohol, which increases the risk of
bleeding. Frequent use of these drugs lowers the absorption of
folate and vitamin C.
Codeine Increase fiber and water intake to avoid constipation.
Sleeping Pills, Tranquilizers
Benzodiazepines Never take with alcohol. Caffeine increases anxiety and reduce
drug's effectiveness.
In other cases, the components of the food,
such as calcium or iron, may form
complexes with the drug that are less
easily absorbed. Examples include
tetracycline, sodium fluoride and
ciprofloxacin .The absorption of
alendronate is impaired by food, calcium
and almost everything, including orange
juice and coffee. It should be taken with
plain water and nothing else should be
consumed for at least 30 minutes. In many
cases, the actual mechanism by which food
interferes with absorption is not known.
Delayed absorption does not necessarily
reduce the total overall exposure to the
drug; the area under the curve (AUC) may
be equivalent regardless of how the drug is
taken. A reduced rate of absorption may
sometimes be useful in reducing the side
effects of a drug, as in the cases of
ibuprofen, without reducing
bioavailability. The bioavailability of some
drugs may be enhanced by food. For
example, an acid environment is necessary
for the absorption of ketoconazole. The
absorption of griseofulvin is increased by
fat in a meal. Fenofibrate, mebendazole,
isotretinoin, tamsulosin, carbamazpine and
labetalol are examples of drugs that will be
better absorbed when taken with food.
Improved absorption of a drug may or may
not have a significant effect on the drugs
efficacy.6
Patients taking digoxin should
avoid taking bran fiber, pectin-containing
foods such as apples or pears, or fibercontaining,
bulk-forming laxatives at the
same time, since these agents may bind to
the digoxin, decreasing its absorption. This
interaction could result in decreased serum
concentrations of digoxin and therapeutic
effectiveness. It is advisable to take some
medications with food to reduce
gastrointestinal irritation and possible
nausea. Examples of these medications
include potassium supplements, ferrous
sulfate, nonsteroidal anti-inflammatory
drugs, estrogen, prednisone, tacrine,
terfenadine and nitrofurantoin.
Cholesterol-lowering agent lovastatin
should be taken with food to enhance
gastrointestinal absorption and
bioavailability. Simvastatin, pravastatin
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
and fluvastatin may be taken without
regard to food.2, 4
Examples of some drugfood
interactions which accelerate and
delay the absorption of drugs are shown in
table 1 and table 2 respectively with the
brief counseling.
Drug Metabolism Interactions
Food may alter the hepatic
metabolism of some drugs. It has been
reported that when administered with the
antihypertensive drug felodipine,
concentrated grapefruit juice caused an
increase in the bioavailability of
felodipine. The mean felodipine
bioavailability with grapefruit juice was
284% (range 164%–469%) that of water.
This resulted in lower diastolic blood
pressures and increased heart rate in the
male study volunteers. Adverse effects
such as headaches, facial flushing and
lightheadedness were more common after
ingestion of 250 ml grapefruit juice (125
ml frozen grapefruit concentrate plus 125
ml of water). The bioavailability of
nifedipine with grapefruit juice was 134%
(range 108%–169%) of that with water.
Orange juice did not have these effects. It
is postulated that flavonoid compounds in
grapefruit juice concentrate inhibit
cytochrome P-450 metabolism of
felodipine and nifedipine. This interaction
could increase both the efficacy and
toxicity of these calcium channel blockers.
There is potential clinical significance
because citrus juices are frequently
consumed at breakfast, when many
medications are also taken. Patients should
be advised of this possible interaction.7, 8
First-pass hepatic metabolism of
propranolol and metoprolol may be
decreased when either medication is taken
with food, thereby enhancing
bioavailability. Drug levels and therapeutic
efficacy may be increased due to this
interaction. Monoamine oxidase (MAO)
inhibitors are known to interact with foods
containing tyramine. Tyramine is normally
inactivated by the enzyme monoamine
oxidase and this prevents tyramine from
accumulating in the body. Monoamine
oxidase inhibitors cause increased levels of
tyramine which can lead to a hypertensive
crisis. Patients taking monoamine oxidase
inhibitors should avoid foods high in
tyramine such as aged cheeses, pickled
fish, yeast extracts, red wine, some types
of beer (including nonalcoholic beer), fava
beans and fermented products. Highprotein
foods that have been aged,
fermented, pickled, smoked or bacterially
contaminated are unsafe for patients taking
MAO inhibitors. Foods considered safe
when used fresh and in moderation include
sour cream, yogurt, meat extracts, chopped
liver, dry sausage and alcoholic beverages.
9-12
Drug Excretion Interactions
Foods may alter the urinary pH,
which can affect the activity of certain
drugs. The half-lives of some medications
can be significantly changed by alterations
in urinary pH. Therefore, the half-life of
acidic drugs will be extended in acidic
urine because the drug is in its unionized
form. However, the half-life of an acidic
drug in alkaline urine is reduced because
the drug is in its ionized form. Foods such
as milk, vegetables and citrus fruits can
alkalinize the urine. Meats, fish, cheese
and eggs can acidify the urine. Foods may
alter the renal excretion of some
medications. Lithium and sodium compete
for tubular reabsorption in the kidney. A
high-salt diet causes more lithium to be
excreted, whereas a low-salt diet causes
decreased renal excretion of lithium and an
increase in serum lithium levels.6
Pharmacodynamic Interactions
Foods may interact with medications by
altering their pharmacologic actions. Diets
high in vitamin K may cause antagonism
of warfarin and decreased therapeutic
efficacy of the anticoagulant. Foods rich in
vitamin K include green leafy vegetables
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
(kale, turnip greens, spinach, broccoli and
brussels sprouts), cauliflower, chick peas,
green tea, pork liver and beef liver.
Alcoholic beverages may increase the
central nervous system depressant effects
of medications such as benzodiazepines,
antihistamines,antidepressants,
antipsychotic, muscle relaxants, narcotics
or any drug with sedative actions.3
An example of a food potentiating the
effect of a medication is coffee, as caffeine
has additive effects on theophylline. It has
been reported that caffeine increased
serum theophylline levels by 20%–30%
and increased the half-life of theophylline
by decreasing clearance. Patients may
complain of nervousness, tremor or
insomnia. Caffeine has some
bronchodilatory effects, which may
enhance the effects of theophylline. A
lower dosage of theophylline may be
necessary for those patients who consume
excessive quantities of coffee (more than 6
cups daily).
ROLE OF PHARMACIST IN
PREVENTION OF DRUG-FOOD
INTERACTIONS
Pharmacists in every practice setting need
to be vigilant in monitoring for potential
drug-food interactions and advising
patients regarding foods or beverages to
avoid when taking certain medications. It
is imperative for pharmacists to keep upto-date
on potential drug-food interactions
of medications, especially today’s new
drugs, so that they may counsel properly.
In providing drug information to patients,
pharmacists often discuss potential side
effects and how the medication should be
taken. It is important to provide
information to patients on when to take
their medications in relation to food intake.
Consequences of drug-food interactions
may include delayed, decreased or
enhanced absorption of the drug. Food
may also affect the bioavailability,
metabolism and excretion of certain
medications. The patient may experience
an adverse side effect or toxicity or may
not receive the full therapeutic benefit of
the medication. The Joint Commission on
the Accreditation of Healthcare
Organizations (JCAHO) requires that a
patient’s medication profile include
potential drug-food interactions, that the
pharmacist call the prescriber whenever
the potential for a medication-food
interaction exists and document the
communication and follow-up action on
the prescription or order form, and that
patients be given instructions and
counseling regarding the potential for
drug-food interactions before their hospital
discharge. Elderly patients may be at a
greater risk for drug-food interactions
because they typically consume more
medications for their chronic medical
conditions. A study of drug-nutrient
interactions in long-term care facilities
found a significant relationship between
the number of medications a resident
consumed and the number of drug-nutrient
interactions for which a resident was at
risk.13
Counseling and Guidance about DrugFood
Interactions
The following information can be given to
the patients while dispensing the
medicine.13-14
• Read the prescription label on the
container. If you do not understand
something or think you need more
information, ask your physician or
pharmacist.
• Read directions, warnings and
interaction precautions printed on all
medication labels and package inserts.
Even over-the-counter medications can
cause problems.
• Take medication with a full glass of
water.
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
• Do not stir medication into your food
or take capsules apart (unless directed
by your physician). This may affect the
efficacy of medication.
• Do not take vitamin pills at the same
time you take medication. Vitamins
and minerals can interact with some
drugs.
• Do not mix medication into hot drinks
because the heat from the drink may
destroy the effectiveness of the drug.
• Never take medication with alcoholic
drinks.
• Be sure to tell your physician and
pharmacist about all medications you
are taking, both prescription and non-
prescription.
• Check with the pharmacist on how
food can affect specific medications
taken with the food.
Examples of specific counseling on some
drug-food interaction are summarized in
TABLE 3.
Precautions to be taken
• Medications need to be taken at
different times relative to meals.
• Consult a physician when health
problems persist.
• During pregnancy and nursing always
consult a physician or pharmacist
before taking any medication. Drugs
taken by the mother may affect the
infant.
• Check with a doctor or pharmacist for
the proper way and time to take
medication.
CONCLUSION
Interaction between foods and
drugs can have profound influence on the
success of drug treatment and on the side
effect profiles of many drugs. The clinical
significance of drug-food interactions can
be variable. Some foods greatly affect drug
therapy, resulting in serious side effects,
toxicity or therapeutic failure. In some
instances, the interaction may have a
beneficial effect by increasing drug
efficacy or diminishing potential side
effects.
The interactions are not always detrimental
to therapy, but can in some cases be used
to improve drug absorption or to minimize
adverse effects. These interactions have
received more attention recently,
especially drug interactions with grapefruit
juice. As new drug approvals occur with
ever increasing speed, there is less
information available about their adverse
effects and interactions when the drugs
reach the market. Pharmacists in every
practice setting need to be vigilant in
monitoring for potential drug-food
interactions and advising patients
regarding foods or beverages to avoid
when taking certain medications. It is
imperative for pharmacists to keep up-todate
on potential drug-food interactions of
medications, especially today’s new drugs,
so that they may counsel properly to the
patients.
Asian Journal of Pharmaceutical and Clinical Research
Vol.2 Issue 4, October.-December. 2009
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