The safe use of over-the-counter painkillers

The largest group of over-the-counter painkillers are non-steroidal anti-inflammatory drugs (NSAIDs). As their name suggests, they also reduce inflammation but – unlike other anti-inflammatory medicine – do not contain steroids. Over-the-counter NSAIDs are used in the treatment of many different kinds of pain, including headaches, period pain and toothache. NSAIDs also reduce inflammation and lower fever.

There are more than ten different NSAIDs, but not all of them are available without a prescription. Sometimes only lower doses are available without a prescription. Higher doses have to be prescribed by a doctor. In Germany and other countries, the following NSAIDs are available over the counter without a prescription from a doctor:

• Acetylsalicylic acid (the drug in medicines like “Aspirin”) (in doses of up to 500 mg per tablet)
• Diclofenac (up to 25 mg per tablet)
• Ibuprofen (up to 400 mg per tablet)
• Naproxen (up to 250 mg per tablet)

These medications are also the most commonly used NSAIDs.

Acetaminophen (paracetamol) is another very widely used painkiller that is available without a prescription. While also relieving pain and lowering fever, it doesn’t reduce inflammation (unlike NSAIDs).

In some medications acetaminophen is combined with an NSAID – for instance, with acetylsalicylic acid. Caffeine is sometimes added too. It isn’t clear whether these kinds of combinations have any advantages or disadvantages over using the different drugs separately. There are no good-quality studies comparing combination medications with individual drugs.

NSAIDs inhibit the action of certain enzymes known as cyclooxygenases or COX enzymes. For this reason, NSAIDs are sometimes also referred to as COX inhibitors. COX enzymes play an important role in the production of certain hormone-like substances, such as the prostaglandins. These have various jobs, including triggering and regulating the reactions in an inflammation. Other processes in our bodies, including blood clotting and the production of stomach acid, are also influenced by these substances. There are two different COX enzymes:

• COX-1 is mainly found in the stomach, kidneys and blood platelets. It is responsible for maintaining a natural balance of the processes it influences.
• COX-2 is mostly made in the parts of the body where inflammations occur. It increases reactions such as pain, swelling and fever.

By inhibiting the action of both COX enzymes, over-the-counter NSAIDs can reduce pain, fever and inflammation. But other processes that are regulated by the COX enzymes are also slowed down. That can cause side effects, especially stomach problems.

Not all painkillers have the same side effects, though: Acetylsalicylic acid (the drug in medicines like Aspirin) has a stronger effect on the COX-1 enzyme, for instance, while diclofenac mostly inhibits COX-2.

It is still not clear exactly how acetaminophen (paracetamol) works. There are various potential explanations – for instance, that it may affect hormone-like substances too.

The risk of side effects can be reduced by using the lowest dose of painkillers possible. It is generally important not to exceed the maximum single dose or the maximum daily dose. The information in the following table applies to Germany but may be very similar in other countries.

So if someone has a packet of 400 mg ibuprofen tablets, for instance, they should not take more than three tablets per day (24 hours).

This information applies when the medications are used without a prescription. It may be possible to take some of the drugs at a higher dose when prescribed by a doctor.

Different NSAIDs shouldn’t be combined with each other. But an NSAID can be combined with acetaminophen if one medication alone isn’t effective enough.

Depending on their age and weight, (sometimes much) lower doses are recommended for children. Some of the medicines mentioned here should only be given to children after you have checked with your doctor.

When used in the right dose and only temporarily, over-the-counter NSAIDs are generally well tolerated. It is important that there are no reasons not to take them, like having kidney disease.

The most common side effects of NSAIDs affect the stomach. These are usually minor problems like indigestion and stomach ache. More serious side effects like gastritis ( inflammation of the stomach lining), ulcers, or bleeding in the stomach or bowel (gastrointestinal bleeding) are less common. You may have gastrointestinal bleeding if you notice any of the following:

• Black-colored stool (poo)
• Anemia symptoms such as exhaustion, feeling short of breath during physical activity, and pale skin.

In rare cases an ulcer damages a larger blood vessel, which causes major bleeding. Vomiting blood (red or black-colored vomit) is a sign of this complication. Another rare serious side effect known as a perforation can occur if a stomach ulcer results in a hole in the wall of the stomach. This causes sudden severe stomach pain. Heavy bleeding in the stomach and perforation of the stomach are life-threatening conditions. If you recognize signs of these or other serious complications, it’s important to immediately make an emergency call (112 in Germany and many other countries, 911 in the U.S.)

The risk of serious side effects is higher when NSAIDs are taken at high prescription-only doses and over a longer period of time. Then about 1 to 2 out of 100 people experience these kinds of serious problems in the gastrointestinal tract.

The short-term use of over-the-counter painkillers very rarely leads to such serious side effects. But your risk is higher if you

• are over the age of 65,
• currently have a stomach ulcer or gastritis, or had one of them in the past,
• have chronic inflammatory bowel disease like Crohn’s disease or ulcerative colitis,
• take several different NSAIDs at once,
• are already taking low-dose acetylsalicylic acid for the prevention of complications following a heart attack or stroke, or
• are taking anticoagulant (anti-clotting) medication, steroid medication or SSRI antidepressants too.

The other possible serious side effects of NSAIDs mainly affect the cardiovascular system. The drugs can, for example, increase the risk of heart attacks. The situation here is similar to that of the stomach problems: The risk is higher especially if you take higher doses of NSAIDs such as diclofenac or ibuprofen as prescribed by a doctor. It is also greater with prescription-only NSAIDs like COX-2 inhibitors (also known as coxibs).

Over-the-counter use is different: Low doses of ibuprofen, for example, don’t increase the risk of cardiovascular disease. Diclofenac still has a risk, but it is low. People who already have a cardiovascular disease such as high blood pressure or have already had a heart attack or stroke are at a higher risk.

Your risk of a serious side effect of an NSAID is generally higher if you have another medical condition. The medication can interfere with the functioning of the kidney, for instance – this can become a problem if you already have weakened kidneys. NSAIDs such as acetylsalicylic acid can also trigger asthma-like coughing attacks. This can worsen breathing problems in people who have asthma.

One rare complication is Reye’s syndrome. It can occur when children who have a viral infection with a fever take acetylsalicylic acid. Reye’s syndrome can lead to life-threatening liver and brain damage.

Acetaminophen is generally well tolerated, but as is the case with all NSAIDs: It is important to take the medication at the correct dose and only for a short period of time to prevent side effects. You should read the package insert beforehand to see if there are any reasons you shouldn’t be taking it

In studies, mild side effects such as nausea or dizziness were observed, but they were rare. Acetaminophen can have serious side effects if the dose is too high. That can lead to toxicity. If left untreated, an overdose can become fatal because of severe damage to the liver.

Having certain medical conditions is a reason not to take NSAIDs or acetaminophen. It is a good idea to ask your pharmacist or doctor about this.

NSAIDs aren’t suitable for people with advanced kidney disease, for instance. People who have a stomach ulcer or severe cardiac insufficiency (heart failure) shouldn’t take NSAIDs either. Pregnant women are only allowed to take certain NSAIDs during certain weeks of pregnancy. People who have asthma may experience breathing problems with NSAIDs.

Acetaminophen is not suitable for people who have liver disease. This is because it is broken down by the liver and can cause severe liver damage. It is also not suitable for people who have problems with alcohol abuse. Anyone with advanced kidney disease needs to wait eight hours between taking the tablets.

Acetylsalicylic acid is not suitable for children under the age of twelve who have a viral infection with a fever because of the risk of Reye’s syndrome.

You can lower the risk of painkiller-related side effects by paying attention to the package insert and

• always taking “as little as possible, as much as necessary,”
• only taking painkillers for as long as really needed,
• watching out for possible interactions with other medications, and
• checking whether you have any risks or medical conditions that make certain painkillers unsuitable for you.

Over-the-counter painkillers can also interact with other medications. It is called a “drug-drug interaction” if two medications influence each other – for instance, if they increase, weaken or cancel out their effects. As a result, the medications may no longer work properly or the risk of side effects might increase.

NSAIDs can interact with various medications:

• For instance, taking them together with certain medications that suppress the immune system (cyclosporine and tacrolimus) increases the risk of kidney damage. This is also true if you take NSAIDs together with diuretics or certain blood-pressure-lowering drugs known as ACE inhibitors and angiotensin II antagonists (sartans). NSAIDs can increase the effect of anti-clotting medications (anticoagulants) such as clopidogrel and Marcumar, which may lead to bleeding.
• NSAIDs can increase the effect of anti-clotting medications (anticoagulants) such as clopidogrel and Marcumar, which may lead to bleeding.

Alcohol and various medications, as well as malnutrition, can affect the breakdown of acetaminophen in the body and lead to an overdose of this painkiller. That is why taking acetaminophen together with certain medications or alcohol can lead to liver damage. So you should not drink alcohol when using acetaminophen.