Is Naproxen Safe?

Most adults can take naproxen, but the word “safe” needs some context. A short course at the prescribed dose is very different from taking it daily, or adding it to medicines that already affect your kidneys, blood pressure or risk of bleeding.

People get home and read the leaflet inside, see it contains things like Stevens-Johnson syndrome, fatal hepatitis and a long list of who shouldn't be taking it at all and think "oh my god I think I'll just leave this in the cupboard" or "I've been taking this for two weeks! Have I done myself any harm?" and come into the pharmacy in a panic. For most adults, a short course of naproxen at the usual dose is unlikely to cause any of it.

Those warnings are there for a reason, but seeing them in the leaflet does not tell you how likely they are to happen to you. Whether naproxen is suitable depends on your medical history, the other medicines you take, the dose and how long you use it. The more useful distinction is one the leaflet doesn't draw clearly: the difference between a reason you can't take naproxen at all, and a reason your prescriber will keep an eye on you.

The list of people who genuinely can't take it is short. You shouldn't take naproxen if you've had an allergic reaction to it, or if aspirin or ibuprofen has ever brought on wheezing, hives, swelling or nasal symptoms, as the same reaction can happen with naproxen. It's also ruled out with severe heart, liver or kidney failure, with a stomach ulcer now or a history of one, if you've had bleeding or perforation of the gut on an anti-inflammatory before, in the third trimester of pregnancy, and alongside another anti-inflammatory.

Everything else in there is a caution, not a definite no and the benefit and risk need to be considered more carefully. High blood pressure, heart failure, asthma, being over 65, taking an antidepressant, taking a water tablet: none of those stop you having naproxen. They're flags that say this person needs a lower dose, or something to protect their stomach, or a periodic review and monitoring while you take it.

So "is naproxen safe for me" depends on your medical history and how much of it your prescriber knows about, as well as the length of time you intend to take it.

Naproxen and ibuprofen are more alike than many people realise. They both belong to the same group of medicines, called non-steroidal anti-inflammatory drugs or NSAIDs, and both reduce the production of prostaglandins. These are chemicals involved in pain, swelling and inflammation.

The prostaglandins also help maintain the protective lining of your stomach and blood flow through your kidneys. Blocking prostaglandins can therefore reduce your pain, but it also explains why NSAIDs like naproxen and ibuprofen can cause stomach ulcers, affect kidney function and lead to fluid retention in people who are more susceptible.

People often ask whether naproxen is stronger than ibuprofen, usually because ibuprofen has not helped and they have then been prescribed naproxen. You cannot compare the numbers directly, many people assume a 500mg naproxen tablet must be “100mg stronger” than a 400mg ibuprofen tablet. This isn't the case as they are completely different medicines with different doses, so the milligram strength does not tell you which will provide more pain relief.

Pooled trial data puts them close to level on pain relief. In studies of people in real pain after surgery, roughly half got at least half their pain relieved by a single dose, and the figures for naproxen 500mg and ibuprofen 400mg sit almost on top of each other. Nobody has shown one to be the more powerful drug. ^[1]

The biggest difference between the two is how long they remain in the body. Naproxen has a half-life of around 12 to 15 hours, compared with approximately 2 to 2.5 hours for standard ibuprofen, which means they stay in your system for longer and need fewer doses per day. This can make it feel stronger as many find ibuprofen wears off too quickly, but lasting longer is not the same as providing stronger pain relief.

After telling people this, the usual response is "Well why should I not just use ibuprofen?", and this is where it gets a bit "messy". While they work in a similar way, anti-inflammatories aren't interchangeable in practice. Roughly 60% of people respond to any given one, and someone who gets nothing from ibuprofen may do perfectly well on naproxen. It isn't a hierarchy with ibuprofen at the bottom; more that people differ and it isn't fully predictable which one will suit you. If you've tried ibuprofen properly and it didn't touch it, that's a reasonable thing to raise rather than a sign nothing will work. ^[2]

The most suitable option depends on what is causing the pain, the dose being used, how you respond to it and your individual risk of side effects. Some people find one NSAID works better for them than another, even though the medicines work in a broadly similar way.

What you should not do is take naproxen and ibuprofen together to try to create a stronger effect. Because they are both NSAIDs, combining them increases the risk of side effects such as stomach ulcers and bleeding without giving you two completely different types of pain relief.

Most people prescribed naproxen are told two things: take it with food and, if they have also been given omeprazole, take that because it protects the stomach. 

People take this as naproxen sits in your stomach and burns a hole in the lining, and eating food stops this, but the cause of the ulcers is due to shutting down the prostaglandins, so eating food will do nothing to actually stop this. What eating food will do however is reduce the chance of indigestion, nausea and discomfort that are by far the most common complaints when people start taking naproxen, so it is definitely worth doing.

Proton pump inhibitors, or PPIs, such as omeprazole and lansoprazole work to reduce the amount of acid produced by the stomach. This makes it harder for an ulcer to develop and gives damaged tissue a better chance to heal. This means they offer more meaningful protection from ulcers than food.

A large meta-analysis of randomised NSAID trials found that high-dose naproxen was associated with just over four times the rate of serious upper gastrointestinal complications compared with placebo. Most of these complications were bleeds. Four times sounds scarier than it actually is; almost all the events occurred in trials using high-dose NSAIDs, with naproxen generally taken at 1,000mg per day. The trials lasted for at least four weeks, the average participant was 61 years old and most were being treated for osteoarthritis or rheumatoid arthritis, and four times a very small starting risk is still a small risk.

The likelihood of experiencing a GI side effect increases if you:

1. Have previously had a stomach or duodenal ulcer
2. Have previously had gastrointestinal bleeding, particularly after taking an NSAID
3. Are older than 65+
4. Take a higher dose or use naproxen for longer
5. Take an anticoagulant such as warfarin, apixaban or rivaroxaban
6. Take aspirin, clopidogrel, oral steroids or an SSRI antidepressant
7. Take ibuprofen, diclofenac or another NSAID at the same time

So the answer is food may make naproxen easier on your stomach, while omeprazole can substantially reduce the risk of ulcers. Neither makes naproxen completely safe or cancels out your other risk factors.

Stomach bleeding gets most of the attention with naproxen, but a lesser known caution with naproxen is the kidneys. Your kidneys need a steady supply of blood and enough pressure to filter waste from it. When that blood supply is under strain, prostaglandins help keep the blood vessels supplying your kidneys open. Now in most people with healthy kidneys, this is a non-issue. 

In someone whose kidneys are already under pressure, their kidney function can then fall over a matter of hours or days. This is called an acute kidney injury, usually shortened to AKI.

A 2017 review of 10 community-based studies found that current NSAID use was associated with 73% higher odds of an acute kidney injury. The relative increase was greater in older adults, but the researchers could not calculate one useful absolute risk because people’s starting risk varied so widely. Don't think that this means 73% of people taking naproxen will damage their kidneys; it just means the low risk is higher in those whose kidneys are already under pressure.

Ramipril, losartan and water tablets.

Ramipril belongs to a group called ACE inhibitors. Losartan belongs to a closely related group called angiotensin receptor blockers, or ARBs. Other examples include lisinopril, perindopril, candesartan and valsartan.

These medicines are often prescribed precisely because they protect the heart and kidneys over the longer term. Taking one does not mean it is damaging your kidneys. However, ACE inhibitors and ARBs alter the pressure within the kidney’s filtering system, which can become important when an NSAID is added.

Water tablets, more properly called diuretics, include medicines such as furosemide, indapamide, bendroflumethiazide and spironolactone. They help your body remove excess salt and fluid, but they can also leave less circulating fluid available to the kidneys, particularly if you become unwell or dehydrated.

When you put all three together a diuretic can reduce the amount of fluid reaching the kidneys, ramipril, losartan or another ACE inhibitor or ARB reduces pressure at one side of the kidney’s filter and naproxen can restrict blood flow entering the filter. This combination is commonly known among healthcare professionals as the “triple whammy” because the kidneys are being affected in three different ways at once.

A UK study followed 487,372 people using blood-pressure medicines. Taking an NSAID alongside both a diuretic and an ACE inhibitor or ARB was associated with a 31% higher rate of acute kidney injury. The increase was greatest during the first 30 days, when the rate was 82% higher. ^[4] Again, this was a relative increase. It does not mean that 31% of everyone taking the three medicines developed kidney damage.

Taking ramipril, losartan or a water tablet does not automatically mean naproxen can never be used. The decision depends on your kidney function, age, hydration, medical history, dose and intended length of treatment. People at greater risk may need a blood test before starting naproxen and another after treatment begins. Kidney function is usually assessed using your creatinine level and estimated glomerular filtration rate, or eGFR.

Kidney injury can be difficult to spot because a mild change may cause no obvious symptoms. Possible warning signs include:

1. Passing much less urine than normal
2. Swollen feet or legs
3. Unusual tiredness, dizziness or confusion
4. Nausea or vomiting
5. Breathlessness, particularly when lying down

Stop taking naproxen and seek urgent medical advice if you develop possible symptoms of acute kidney injury, particularly if you are also dehydrated, have existing kidney problems or take an ACE inhibitor, ARB or diuretic.

When people read that naproxen can affect the heart, they usually think of heart attacks and strokes.

Naproxen can contribute to salt and fluid retention. It can also reduce the effect of some medicines used to lower blood pressure and remove excess fluid from the body. That extra fluid can raise blood pressure and make the heart work harder, which is particularly important if someone already has heart failure.

Not everyone who takes naproxen will see their blood pressure rise, and there is no single figure that can predict what will happen to you.

One useful study followed 444 people with osteoarthritis or rheumatoid arthritis who either had cardiovascular disease or were considered at increased risk of it. Their average age was 62, and they took prescription doses of naproxen, ibuprofen or celecoxib for four months.

Average 24-hour systolic blood pressure changed by 1.6mmHg with naproxen, 3.7mmHg with ibuprofen, −0.3mmHg with celecoxib.

Among participants whose blood pressure was normal at the start, 19% of those taking naproxen and 23.2% of those taking ibuprofen met the study’s definition of hypertension after four months. These were mainly elderly patients taking high doses for several months who also had arthritis and existing cardiovascular risks. But it does tell us that it can have an effect on blood pressure.

For heart attacks and strokes caused by blood clots in an artery, the MHRA considers naproxen and low-dose ibuprofen to have the most favourable cardiovascular profiles among traditional non-selective NSAIDs. Diclofenac carries a less favourable risk and is treated more cautiously in people with cardiovascular disease.

A large analysis of randomised trials also found that high-dose naproxen (1,000mg per day) did not produce a statistically significant increase in major vascular events compared with placebo. By contrast, diclofenac increased major vascular events, while high-dose ibuprofen increased major coronary events. ^[3]

Severe heart failure is a reason not to use naproxen. People with milder heart failure, uncontrolled high blood pressure, angina, a previous heart attack or stroke, peripheral arterial disease or several cardiovascular risk factors require a more careful assessment, particularly before higher-dose or long-term treatment.

Medicine interaction checkers have a habit of telling you that two medicines “interact” without explaining what that actually means. With naproxen, one combination may increase your risk of bleeding, another may affect your kidneys and another can cause the level of a completely different medicine to rise in your blood. This does not always mean that the medicines can never be used together. It may mean using naproxen only for a short period or more monitoring.

Anticoagulants and other medicines that increase bleeding

Some of the most important naproxen interactions are with medicines commonly described as blood thinners.

These include anticoagulants such as:

1. Warfarin
2. Apixaban
3. Rivaroxaban
4. Edoxaban
5. Dabigatran
6. Heparin

Naproxen can damage the protective lining of the stomach and affect how platelets help form a clot. Anticoagulants then make it harder for the body to stop any bleeding that begins. Current specialist guidance advises avoiding NSAIDs with direct oral anticoagulants where possible. When an NSAID is necessary, it should generally be used at the lowest effective dose for the shortest possible time, with consideration given to gastroprotection and monitoring for bleeding.

Steroids and some antidepressants

Prednisolone and other corticosteroids do not thin the blood in the same way as anticoagulants. However, using a steroid with naproxen increases the risk of gastrointestinal ulceration and bleeding. Selective serotonin reuptake inhibitor antidepressants, usually shortened to SSRIs, can also increase bleeding risk. Common examples include:

1. Sertraline
2. Citalopram
3. Escitalopram
4. Fluoxetine
5. Paroxetine

SSRIs can affect the way platelets function. When this is combined with the effect of an NSAID on the stomach lining and platelet activity, the risk of an upper gastrointestinal bleed increases. This does not mean they cannot be taken together, as the guidance is currently that a PPI is prescribed alongside naproxen to protect the stomach in those taking an SSRI or corticosteroids.

Lithium and methotrexate: when naproxen affects another medicine

Lithium has a relatively narrow safe range in the blood. Naproxen can reduce its clearance through the kidneys, causing lithium levels to rise and potentially leading to toxicity.

Naproxen can also reduce the removal of methotrexate through the kidneys. This can increase the risk of methotrexate toxicity and kidney damage, particularly with high-dose methotrexate or when kidney function is already reduced.

Lithium and methotrexate can be taken with naproxen as long as the levels of them are monitored and adjusted to any changes. 

Do not accidentally take two NSAIDs

Do not combine naproxen with:

1. Ibuprofen
2. Diclofenac
3. Aspirin for pain relief
4. Celecoxib
5. Etoricoxib
6. Mefenamic acid

Taking two NSAIDs together will do nothing for your pain relief but will increase your risk of side effects.

What about aspirin and clopidogrel?

Low-dose aspirin (75mg) and clopidogrel are antiplatelet medicines. They do not work in exactly the same way as warfarin or apixaban, but they also make it harder for blood clots to form and can increase the risk of bleeding when combined with naproxen.

You should not add pain-relief aspirin (300mg) to naproxen because both are NSAIDs.

People often want a clean cut-off: three days is safe, but on day four naproxen suddenly becomes dangerous. It does not work like that. The risk of serious side effects generally increases with higher doses and longer treatment.

Long-term is also not inherently unsafe. Some people take it for years without it causing them any issues. 

The length of time you can stay on naproxen for, comes down to your current medical history, medicines and past experiences with NSAIDs. Even then your clinician will usually take this into account and provide ongoing checks and monitoring periodically if you are at an increased risk of an adverse effect. NHS Specialist Pharmacy Service guidance advises considering kidney function and a full blood count within two weeks of starting an NSAID or changing the dose, and blood pressure within four weeks particularly in the elderly and higher-risk patients.

This monitoring does not make naproxen harmless, but it will identify if any changes are happening that need to be looked at or if naproxen is causing you any issues.

In pharmacy the ones that become a worry are people who started on naproxen for a short-term problem that then turned quietly into a repeat prescription daily and they haven't been reviewed since. If this sounds like you, I'm not telling you to immediately stop naproxen, but 

Naproxen should generally be avoided during pregnancy unless a doctor or pharmacist has specifically advised you to take it. Paracetamol is normally the first painkiller considered during pregnancy, although there may be circumstances where a clinician decides that naproxen is necessary. After 20 weeks, naproxen can affect the baby’s kidney function. This may reduce the amount of urine the baby produces and lead to a lower volume of amniotic fluid around them, known as oligohydramnios. BUMPS advises that taking naproxen before 20 weeks would not normally require additional monitoring for birth defects beyond the detailed scan routinely offered at around 20 weeks.

Small amounts of naproxen can pass into breast milk. NHS guidance says it is not normally used during breastfeeding, and ibuprofen or diclofenac are generally preferred when an anti-inflammatory painkiller is needed.

Naproxen reduces prostaglandin production, and prostaglandins are involved in the release of an egg from the ovary. NSAIDs may therefore interfere with ovulation in some women while they are being taken.

By this point, naproxen may sound like a medicine that nobody should ever take. That is not the point. Most adults can take it, and for many people a short course will be straightforward.

When we review a naproxen request, we are not looking for every rare side effect listed in the leaflet. We are mainly looking for the smaller number of things that materially change the risk or suggest that another course of painkillers is not the right answer.

A very common message we get after rejecting some is "I've taken naproxen before and I was absolutely fine, you're just being awkward". This may well be the case, but something may have changed since then, or it cannot be prescribed without additional monitoring for you, which we cannot do via an online setting. This is why we will usually not supply it to you if you have previously developed asthma, wheezing, nasal symptoms, hives or another serious allergic reaction after taking naproxen, aspirin, ibuprofen or another NSAID. We will also not supply if you have an active or recurrent stomach ulcer or gastrointestinal bleed, suffered from a previous gastrointestinal bleed or perforation caused by an NSAID, have severe kidney, liver or heart failure, pregnant or over 65. This doesn't mean a GP cannot prescribe this for you, but they can perform the additional monitoring needed to make it safe to do so. We are not being awkward and it does cost us when we reject someone, it's done for your safety.

Reading the leaflet, it is easy to be on edge but most side effects aren't a reason to worry.

Call 999 or go to A&E

1. Swelling of your face, lips, tongue or throat, difficulty breathing or swallowing, or a widespread rash coming on fast
2. Vomiting blood, or something that looks like coffee grounds
3. Black, tarry or sticky stools, or blood in your stools
4. Sudden severe pain in your abdomen
5. Chest pain, weakness or numbness down one side, difficulty speaking, or a sudden severe headache

Stop and get advice the same day

1. Any new rash. This is the one people ignore. The prescribing information is unusually blunt about it: stop at the first appearance of a rash, mouth ulcers or sores, or anything else that looks like an allergic reaction. Serious skin reactions to anti-inflammatories are very rare, but they're most likely in the first month and they can start looking like an ordinary rash. If you develop one on naproxen, stop and get it looked at rather than waiting to see what it does. If it does turn out to be one of the serious ones, naproxen can never be restarted.
2. Blistering or peeling skin, or sores in your mouth, eyes or genitals
3. Yellowing of your skin or the whites of your eyes, or dark urine
4. Wheezing or breathlessness that's new, particularly if you have asthma
5. Passing much less urine than usual
6. A severe headache with a stiff neck and fever

Stop and get advice within a few days

1. Persistent indigestion, heartburn or upper abdominal pain that's new or getting worse
2. Swelling of your ankles, feet or legs
3. Unexplained bruising or bleeding, including nosebleeds that won't settle
4. Feeling unusually tired, sick or generally unwell in a way that isn't like you
5. Ringing in your ears or blurred vision