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Drug Interactions

by Daniel A. Hussar, PhD

The effect a drug has on a person may be different than expected because that drug interacts with

  • Another drug the person is taking (drug-drug interaction)

  • Food, beverages, or supplements the person is consuming (drug-nutrient interaction)

  • Another disease the person has (drug-disease interaction)

The effects of drug interactions are usually unwanted and sometimes harmful. Interactions may increase or decrease the actions of one or more drugs, resulting in side effects or failed treatment.

Drug-Drug Interactions

Drug-drug interactions can involve prescription or nonprescription (over-the-counter) drugs. Types of drug-drug interactions include duplication, opposition (antagonism), and alteration of what the body does to one or both drugs.


When two drugs with the same effect are taken, their side effects may be intensified. Duplication may occur when people inadvertently take two drugs (often at least one is an over-the-counter drug) that have the same active ingredient. For example, people may take a cold remedy and a sleep aid, both of which contain diphenhydramine, or a cold remedy and a pain reliever, both of which contain acetaminophen. This type of duplication is particularly likely with the use of drugs that contain multiple ingredients or that are sold under brand names (thus appearing to be different but actually containing the same ingredients). Awareness of drug ingredients is important, as is checking each new drug to avoid duplication. For example, many prescription-strength pain relievers contain an opioid plus acetaminophen. People taking such a product who do not know its ingredients might take over-the-counter acetaminophen for extra relief, risking toxicity.

Similar problems with duplication can arise when two different drugs with the same effect are taken. This is most likely to occur when people see several doctors, obtain prescriptions at more than one pharmacy, or both. Doctors who are not aware of what others have prescribed may inadvertently prescribe similar drugs. For example, excessive sedation and dizziness can occur when two doctors both prescribe a sleep aid or when one prescribes a sleep aid and the other prescribes another drug (such as an antianxiety drug) that has similar sedative effects. People can reduce this risk by keeping each doctor informed about all drugs being taken and by using one pharmacy to obtain all prescriptions. It is helpful to keep an up-to-date written list of all drugs being taken and to bring the list along on each doctor visit. Also, people should not take previously prescribed drugs (such as a sleeping pill or pain reliever) without checking with the doctor or pharmacist because that drug may duplicate or otherwise interact with one of their current drugs.

Opposition (antagonism)

Two drugs with opposing actions can interact, thereby reducing the effectiveness of one or both. For example, nonsteroidal anti-inflammatory drugs (NSAIDs—see see Nonopioid Analgesics : Nonsteroidal Anti-Inflammatory Drugs), such as ibuprofen, which are taken to relieve pain, may cause the body to retain salt and fluid. Diuretics, such as hydrochlorothiazide and furosemide, help rid the body of excess salt and fluid. If a person takes both types of drug, the NSAID may reduce the diuretic's effectiveness. Certain beta-blockers (such as propranolol), taken to control high blood pressure and heart disease, counteract beta-adrenergic stimulants, such as albuterol, taken to manage asthma. Both types of drugs target the same cell receptors—beta-2 receptors (see Table: )—but one type blocks them, and the other stimulates them.


One drug may alter how the body absorbs, distributes, metabolizes, or excretes another drug.

Acid-blocking drugs, such as histamine-2 (H 2 ) blockers and proton pump inhibitors, raise the pH of the stomach and decrease absorption of some drugs, such as ketoconazole, a drug for fungal infections.

Many drugs are broken down and inactivated (metabolized) by certain enzymes in the liver. Some drugs affect these liver enzymes, either increasing or decreasing their activity, and may cause another drug to be inactivated more quickly or more slowly than usual. For example, by increasing the activity of liver enzymes, barbiturates such as phenobarbital cause the anticoagulant warfarin to be inactivated more quickly and thus to be less effective when taken during the same time period. Conversely, by decreasing the activity of the enzyme system, drugs such as erythromycin and ciprofloxacin can increase the activity of warfarin, risking bleeding. When drugs that affect liver enzymes are used in people taking warfarin, doctors monitor the people more closely and adjust the dose of warfarin to compensate for this effect. The warfarin dose is adjusted again when other drugs are stopped. Many other drugs affect liver enzymes.

Chemicals in cigarette smoke can increase the activity of some liver enzymes. As a result, smoking decreases the effectiveness of some drugs, including theophylline (a drug that widens the airways called a bronchodilator).

Some drugs affect the rate at which the kidneys excrete another drug. For example, large doses of vitamin C increase the urine's acidity and thus may change the rate of excretion and activity of certain drugs. For example, the rate of excretion may be decreased for acidic drugs such as aspirin but may be increased for basic drugs such as pseudoephedrine.

Because there are so many drug interactions, many doctors and pharmacists reduce the risk of problems by checking reference books and computer software programs when prescribing or dispensing prescriptions for additional drugs. In most pharmacies, drug orders and prescriptions are reviewed using a computer system that automatically checks for drug interactions.

Drug-Nutrient Interactions

Nutrients include food, beverages (including alcohol), and dietary supplements. Consumption of these substances may alter the effects of drugs the person takes.


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 1 hour before or 2 hours after eating.

Dietary supplements

Dietary supplements, including medicinal herbs, are products (besides tobacco) that contain a vitamin, mineral, herb, or amino acid and that are intended as a supplement to the normal diet (see Overview of Medicinal Herbs and Nutraceuticals). Supplements are regulated as foods, not as drugs, so they are not tested as comprehensively. However, they may interact with prescription or over-the-counter drugs. People who take dietary supplements should tell their doctors and pharmacists, so that interactions can be avoided.


Although many people do not consider alcohol a nutrient, it affects body processes and interacts with many drugs. For example, taking alcohol with the antibiotic metronidazole can cause flushing, headache, palpitations, and nausea and vomiting. Doctors or pharmacists can answer questions about possible alcohol and drug interactions.

Some Drug-Food Interactions

Affected Drug

Interacting Food


Bisphosphonates (such as alendronate, ibandronate, and risedronate)

Any food

Food, even orange juice, coffee, or mineral water, may markedly reduce the absorption and effectiveness of these drugs. Alendronate and risedronate must be taken with plain water at least 30 minutes before the first food, beverage, or drug of the day is taken, and ibandronate must be taken at least 1 hour before.

  • Certain benzodiazepines (such as triazolam)

  • Calcium channel blockers (such as felodipine, nifedipine, and nisoldipine)

  • Cyclosporine

  • Estrogen and oral contraceptives

  • Certain statins (such as atorvastatin, lovastatin, and simvastatin)

Grapefruit juice

Grapefruit juice inhibits enzymes involved in drug metabolism and thereby intensifies the effect of certain drugs, including many that are not listed here.



The fiber in oatmeal and other cereals, when consumed in large amounts, can interfere with the absorption of digoxin.

MAO inhibitors (such as phenelzine and tranylcypromine)

Foods high in tyramine, including many cheeses (such as American processed, cheddar, blue, brie, mozzarella, and Parmesan), yogurt, sour cream, cured meats (such as sausage and salami), liver, dried fish, caviar, avocados, bananas, yeast extracts, raisins, sauerkraut, soy sauce, fava beans, red wine, and certain beers

Severe headache and a potentially fatal increase in blood pressure (hypertensive crisis) can occur if people taking an MAO inhibitor (used most often to treat depression) consume these foods. These foods must be avoided.


Calcium or foods containing calcium, such as milk and other dairy products

These foods can reduce the absorption of tetracycline, which should be taken 1 hour before or 2 hours after eating.

Warfarin (an anticoagulant)

Foods high in vitamin K (such as broccoli, Brussels sprouts, spinach, and kale)

Such foods may reduce the effectiveness of warfarin, increasing the risk of clotting. Intake of such foods should be limited, and the amount consumed daily should remain constant.

MAO = monoamine oxidase.

Drug-Disease Interactions

Sometimes, drugs that are helpful in one disease are harmful in another disorder. For example, some beta-blockers taken for heart disease or high blood pressure can worsen asthma and make it hard for people with diabetes to tell when their blood sugar is too low. Some drugs taken to treat a cold may worsen glaucoma. People should tell their doctor all of the diseases they have before the doctor prescribes a new drug. Diabetes, high or low blood pressure, an ulcer, glaucoma, an enlarged prostate, poor bladder control, and insomnia are particularly important, because people with such diseases are more likely to have a drug-disease interaction.

Drug-disease interactions can occur in any age group but are common among older people, who tend to have more diseases (see Aging and Drugs).

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