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Drug Interactions With Three Commonly Used Over-the-Counter Pain Medications 
by Robbi Erickson August 18, 2005

This article explores the possible negative interactions that over-the-counter pain medications Acetaminophen, Aspirin, and Ibuprofen can have with prescription drugs and other substances. It also presents some health warnings and common uses of all three OTC pain medications.

One of the most dangerous misconceptions that consumers can make is to assume that they don’t have to worry about their safety or the possible interactions between their over-the-counter pain medicine with their prescription drugs. However, these pain medications can impact the effectiveness, strength, and safety of prescriptions drugs, and in some cases they can cause a serious or even life threatening reaction. In order to avoid these negative interactions consumers should know what drugs and substances will negatively react to, or be effected by acetaminophen, aspirin, and ibuprofen.


Acetaminophen is used as a pain reliever and as a fever reducer. If taken in amounts greater than what is directed this drug can cause serious damage to your hepatic system and can even cause renal failure. If you have type 1 diabetes you should also be aware that acetaminophen can impact the accuracy of home blood glucose readings. You may want to consult with your doctor over how to avoid this problem. In general, acetaminophen has a tendency to interact with the following drugs:

1. Alcohol and Ethyl

Acetaminophen could have a negative reaction in people who consume large quantities of alcohol in conjunction with high doses of acetaminophen. The threat of developing a condition known as hepatotoxicty is also possible. (Hepatotoxicty is the official medical term applied to liver damage caused by medications or chemicals.)

2. Charcoal

Charcoal has a neutralizing effect on acetaminophen and should be administered in cases of acetaminophen overdoses.

3. Isoniazid

Isoniazid, which is used as a antimycobacterial, may lead to severe acetaminophen hepatoxicity. If you are taking an Isoniazid and also have a tendency to take large doses of acetaminophen, your hepatic functions should be monitored.

4. Oral contraceptive agents

Oral contraceptive agents have a tendency to increase the body’s ability to metabolize acetaminophen. A larger dose of acetaminophen may be needed to be effective. However, be careful not to overdose. Ask your doctor for proper dosing to compensate for the effects of your oral contraceptive agent.

5. Phenobarbital

Phenobarbital, used to control epilepsy or used as a sedative for insomniacs, also seems to increase the body’s ability to metabolize acetaminophen. In some cases this acceleration has led to increased hepatic damage due to the loss of the enzymes that function as neutralizers of toxic metabolites.

6. Phenytoin

Phenytoin, an anticonvulsant used to treat epilepsy, potentially could lead to acetaminophen toxicity if the patient overdoses on acetaminophen.

7. Propranolol

Propranolol is a beta-blocker used for a variety of treatments for: high blood pressure, prophylaxis of migraine, hyperthyroidism, portal hypertension, and even for anxiety and panic disorders. In regards to its interaction with acetaminophen, Propranolol decreases the body’s ability to metabolize acetaminophen. This may inadvertently cause an overdose even when the patient follows the recommended dosage schedule. If your hepatic system does not function properly, you should be vary careful, avoid using acetaminophen, or be monitored while taking both of these drugs together. Other beta-blocker substances could have a similar reaction with acetaminophen and similar precautions should be taken.

8. Sulfinpyrozone

Sulfinpyrozone is used for preventing gout and gout related arthritis. It has a significant chance of increasing the toxic effects of acetaminophen, especially in the liver. Chances of organ damage increase when an overdose of acetaminophen is taken.

9. Terfenadine

Terfenadine, used for the treatment of allergy symptoms, can lead to cariotoxicity and an increase in terfenadine levels, especially if the patient is taking large doses of acetaminophen.


Aspirin is used as a pain reliever, a fever reducer, and as a blood thinner. If you have had an allergic reatction to any other pain medications or fever reducers you do not want to take aspirin as it could trigger an allergic reaction. Also, children and teenagers should not take aspirin when they have the chickenpox as this could lead to brain and liver damage also known as Reye’s Syndrome. Pregnant women should also be careful when taking aspirin, as it has been shown to cause birth defects and fetal death. It is especially important for pregnant women not to take aspirin during their last trimester, unless specifically advised by their doctor to do so. Aspirin can also interact with the following drugs:

1. Acetazolamide

Acetazolamide, used as a glaucoma treatment, can lead to the development of both acetazolamide and salicylate toxicity.

2. Charcoal

Charcoal acts as a neutralizing agent for aspirin and should be administered immediately after an overdose of aspirin.

3. Dipyridamole

Dipyridamole is normally used in conjunction with aspirin to help prevent blood clots form forming in the blood stream. Dipyridamole has a tendency to decrease the body’s ability to metabolize aspirin, which in turn can lead to higher aspirin levels in the person’s blood.

4. Ginko biloboa

Ginko biloboa is an over-the-counter substance used for memory and concentration improvement. It has a tendency to impair the clotting ability of a person who also takes aspirin, and it could possibly lead to hemorrhagic problems.

5. Griseofulvin

Griseofulvin, used for the treatment of skin infections like jock itch, will reduce plasma salicylate levels when taken in conjunction with aspirin.

6. Methylprednisolone

Methylprednisolone, a corticosteroid, may reduce your salicylate levels and increase your glomerular filtration rates. This fluctuation in body mechanisms may cause aspirin to remain in the blood longer causing patients to overdose accidentally even when following the directed dose schedule.

7. Nitroglycerin

The effectiveness of Nitroglycerin, used to widen blood vessels to allow for blood to flow through them more easily, may be impaired by the use of aspirin.

8. Oral contraception agents

Oral contraception agents may also reduce the effectiveness of aspirin.


Ibuprofen is used for pain management. It should be noted that severe allergic reactions can occur with the use of Ibuprofen, so if you have had an allergic reaction to any other pain medication you should ask your doctor before taking a product with Ibuprofen in it. Warning signs for an allergic reaction to Ibuprofen included blurred vision and changes in color vision. If you have a cardiac condition, Ibuprofen may also increase your chances of edema and water retention. Ibuprofen also impacts a person’s ability to clot, and therefore if you have any type of bleeding problem such as ulcerations or lesions, Ibuprofen should not be taken unless specified by your doctor. Women who are pregnant should also not use Ibuprofen during their last trimester as it may impair the development of their baby. In addition to these warnings, Ibuprofen also has a tendency to interact with the following drug:

1. Baclofen

Baclofen, used as a muscle relaxant an antispastic agent, could lead to baclofen toxicity problems.

General Precautions

If you take any of these drugs, consult your doctor for the proper dosages and the proper selection of over-the counter pain medications. Your doctor will be able to recommend the correct type of medication for your situation


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