Merck Manual

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Drug Interactions

By

Shalini S. Lynch

, PharmD, University of California San Francisco School of Pharmacy

Reviewed/Revised Jul 2022 | Modified Sep 2022
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Topic Resources
  • 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 the actions of one or more drugs, resulting in side effects or toxicity

  • Decrease the actions of one or more drugs, resulting in 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.

Duplication

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 Overview of Over-the-Counter Drugs Over-the-counter (OTC) drugs are those available without a prescription. OTC drugs enable people to relieve many annoying symptoms and to cure some diseases simply and without the cost of seeing... read more ) 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 the risk of this kind of duplication 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 Nonsteroidal Anti-Inflammatory Drugs Pain relievers (analgesics) are the main drugs used to treat pain. Doctors choose a pain reliever based on the type and duration of pain and on the drug's likely benefits and risks. Most pain... read more (NSAIDs), 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 Targets in The Body: Cell Receptors Targets in The Body: Cell Receptors Targets in The Body: Cell Receptors )—but one type blocks them, and the other stimulates them.

Alteration

How to Reduce the Risk of Drug-Drug Interactions

  • Consult the doctor or pharmacist before taking any new drugs, including over-the-counter drugs and dietary supplements, such as medicinal herbs.

  • Keep a list of all drugs being taken. Periodically discuss this list with the doctor or pharmacist.

  • Keep a list of all disorders. Periodically discuss this list with the doctor.

  • Select a pharmacy that provides comprehensive services (including checking for possible interactions) and that maintains a complete drug profile for each person. Have all prescriptions dispensed in this pharmacy.

  • Learn about the purpose and actions of all drugs prescribed.

  • Learn about the possible side effects of the drugs.

  • Learn how to take the drugs, what time of day they should be taken, and whether they can be taken during the same time period as other drugs.

  • Review the use of over-the-counter drugs with the pharmacist. Discuss any disorders present and any prescription drugs being taken.

  • Take drugs as instructed.

  • Report to the doctor or pharmacist any symptoms that might be related to the use of a drug.

  • If seeing more than one doctor, make sure each doctor knows all the drugs being taken.

Acid-blocking drugs, such as histamine-2 (H2) 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.

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 1 hour before or 2 hours after eating.

Dietary supplements

Dietary supplements Overview of Dietary Supplements Dietary supplements are used by about 75% of Americans. They are the most common therapies included among integrative medicine and health (IMH) and complementary and alternative medicine (CAM)... read more , including medicinal herbs, are products (besides tobacco) that contain, for example, 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-the-counter drugs. People who take dietary supplements should tell their doctors and pharmacists, so that interactions can be avoided.

Alcohol

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.

Table

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 or 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.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Aid to Sleep, Alka-Seltzer Plus Allergy, Aller-G-Time , Altaryl, Banophen , Benadryl, Benadryl Allergy, Benadryl Allergy Children's , Benadryl Allergy Dye Free, Benadryl Allergy Kapgel, Benadryl Allergy Quick Dissolve, Benadryl Allergy Ultratab, Benadryl Children's Allergy, Benadryl Children's Allergy Fastmelt, Benadryl Children's Perfect Measure, Benadryl Itch Stopping, Ben-Tann , Children's Allergy, Compoz Nighttime Sleep Aid, Diphedryl , DIPHEN, Diphen AF , Diphenhist, DiphenMax , Dytan, ElixSure Allergy, Genahist , Geri-Dryl, Hydramine, Itch Relief , M-Dryl, Nighttime Sleep Aid, Nytol, PediaCare Children's Allergy, PediaCare Nighttime Cough, PediaClear Children's Cough, PHARBEDRYL, Q-Dryl, Quenalin , Siladryl Allergy, Silphen , Simply Sleep , Sleep Tabs, Sleepinal, Sominex, Sominex Maximum Strength, Theraflu Multi-Symptom Strip, Triaminic Allergy Thin Strip, Triaminic Cough and Runny Nose Strip, Tusstat, Unisom, Uni-Tann, Valu-Dryl , Vanamine PD, Vicks Qlearquil Nighttime Allergy Relief, Vicks ZzzQuil Nightime Sleep-Aid
7T Gummy ES, Acephen, Aceta, Actamin, Adult Pain Relief, Anacin Aspirin Free, Aphen, Apra, Children's Acetaminophen, Children's Pain & Fever , Children's Pain Relief, Comtrex Sore Throat Relief, ED-APAP, ElixSure Fever/Pain, Feverall, Genapap, Genebs, Goody's Back & Body Pain, Infantaire, Infants' Acetaminophen, LIQUID PAIN RELIEF, Little Fevers, Little Remedies Infant Fever + Pain Reliever, Mapap, Mapap Arthritis Pain, Mapap Infants, Mapap Junior, M-PAP, Nortemp, Ofirmev, Pain & Fever , Pain and Fever , PAIN RELIEF , PAIN RELIEF Extra Strength, Panadol, PediaCare Children's Fever Reducer/Pain Reliever, PediaCare Children's Smooth Metls Fever Reducer/Pain Reliever, PediaCare Infant's Fever Reducer/Pain Reliever, Pediaphen, PHARBETOL, Plus PHARMA, Q-Pap, Q-Pap Extra Strength, Silapap, Triaminic Fever Reducer and Pain Reliever, Triaminic Infant Fever Reducer and Pain Reliever, Tylenol, Tylenol 8 Hour, Tylenol 8 Hour Arthritis Pain, Tylenol 8 Hour Muscle Aches & Pain, Tylenol Arthritis Pain, Tylenol Children's, Tylenol Children's Pain+Fever, Tylenol CrushableTablet, Tylenol Extra Strength, Tylenol Infants', Tylenol Infants Pain + Fever, Tylenol Junior Strength, Tylenol Pain + Fever, Tylenol Regular Strength, Tylenol Sore Throat, XS No Aspirin, XS Pain Reliever
Advil, Advil Children's, Advil Children's Fever, Advil Infants', Advil Junior Strength, Advil Migraine, Caldolor, Children's Ibuprofen, ElixSure IB, Genpril , Ibren , IBU, Midol, Midol Cramps and Body Aches, Motrin, Motrin Children's, Motrin IB, Motrin Infants', Motrin Junior Strength, Motrin Migraine Pain, PediaCare Children's Pain Reliever/Fever Reducer IB, PediaCare Infants' Pain Reliever/Fever Reducer IB, Samson-8
Esidrix, Ezide, HydroDIURIL, Microzide, Oretic, Zide
Delone , FUROSCIX, Lasix
HEMANGEOL, Inderal, Inderal LA, Inderal XL, InnoPran XL
Accuneb, ProAir digihaler, Proair HFA, ProAir RespiClick, Proventil, Proventil HFA, Proventil Repetabs, Respirol , Ventolin, Ventolin HFA, Ventolin Syrup, Volmax, VoSpire ER
Extina, Ketodan, Kuric, Nizoral, Nizoral A-D, Xolegel
Luminal, Sezaby
Coumadin, Jantoven
A/T/S, Akne-mycin, E.E.S., Emcin Clear , EMGEL, E-Mycin, ERYC, Erycette, Eryderm , Erygel, Erymax, EryPed, Ery-Tab, Erythra Derm , Erythrocin, Erythrocin Lactobionate, Erythrocin Stearate, Ilosone, Ilotycin, My-E, PCE, PCE Dispertab , Romycin, Staticin, T-Stat
Cetraxal , Ciloxan, Cipro, Cipro XR, OTIPRIO, Proquin XR
Elixophyllin, Quibron T, Quibron T/SR, Respbid, Slo-Bid, Slo-Phyllin, Theo X, Theo-24, Theo-Bid Duracap, TheoCap, Theochron, Theo-Dur, Theo-Dur Sprinkle , Theolair, Theolair SR, Theovent LA, T-Phyl, Uni-Dur, Uniphyl
Anacin Adult Low Strength, Aspergum, Aspir-Low, Aspirtab , Aspir-Trin , Bayer Advanced Aspirin, Bayer Aspirin, Bayer Aspirin Extra Strength, Bayer Aspirin Plus, Bayer Aspirin Regimen, Bayer Children's Aspirin, Bayer Extra Strength, Bayer Extra Strength Plus, Bayer Genuine Aspirin, Bayer Low Dose Aspirin Regimen, Bayer Womens Aspirin , BeneHealth Aspirin, Bufferin, Bufferin Extra Strength, Bufferin Low Dose, DURLAZA, Easprin , Ecotrin, Ecotrin Low Strength, Genacote, Halfprin, MiniPrin, St. Joseph Adult Low Strength, St. Joseph Aspirin, VAZALORE, Zero Order Release Aspirin, ZORprin
Contac Cold 12 Hour, Dimetapp Decongestant, Drixoral, ElixSure Cold, ElixSure Congestion, Entex, Genaphed , KidKare , Myfedrine, NASAL Decongestant, Nasofed, Nexafed, PediaCare Infants' Decongestant, Pseudo-Time, Silfedrine, Sudafed, Sudafed 12 Hour, Sudafed 24 Hour, Sudafed Children's Nasal Decongestant, Sudafed Congestion, Sudafed Sinus Congestion, Sudogest, Sudogest 12 Hour, Sudogest Children's , Tylenol Children's Simply Stuffy, Zephrex-D
Flagyl, Flagyl ER, Flagyl RTU, LIKMEZ, MetroCream, MetroGel, MetroGel Vaginal, MetroLotion, Noritate, NUVESSA, Nydamax, Rosadan, Rozex, Vandazole, Vitazol
NOTE: This is the Consumer Version. DOCTORS: VIEW PROFESSIONAL VERSION
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