Naproxen, a non-steroidal anti-inflammatory drug (NSAID), is one of the most prescribed drugs in the UK used in the management of conditions associated with pain and inflammation. In this post, I discuss the availability of drugs alternative to naproxen. I will briefly explain the following:
- what NSAIDs are used for
- NSAIDs: mechanism of action
- common side effects associated with NSAIDs,
- options for over the counter and prescribed drugs alternative to naproxen
Before diving into the main part of drugs alternative to naproxen, I will firstly discuss the mechanism of action of NSAIDs. Some terminology will is repeated in this post; therefore, it will be much easier if these terms are introduced at the beginning of this post, giving a better understanding of NSAID use.
How does NSAIDs work?
NSAIDs reduce pain and inflammation (swelling), and to produce an antipyretic effect (reduce fever) by stopping the production of chemicals (enzymes) called cyclo-oxygenase COX-1 and COX-2. COX 1 and COX 2 enzymes are responsible for the synthesis of prostaglandins, which are produced in response to injury or infection (BMJ, 2013). Prostaglandins have a prominent role in development of inflammatory response and contribute to signs of inflammation (Ricciotti & FitzGerald, 2012). Drugs such as naproxen or ibuprofen stop COX-1 and COX2 enzymes nonselectively, meaning they inhibit (prevents from working) both enzymes.
It is worth mentioning that there is a ‘newer generation‘ of COX-2 inhibitors, which only stop the COX-2 enzyme (selective just for this enzyme).
Inhibition of COX-1 enzyme is associated with gastrointestinal side effects such as stomach ulcers and bleeding, therefore the use of COX-2 inhibitors has the advantage of causing less of these side effects. A systemic review of different clinical trials suggests that this is the case. Cochrane Collaboration concluded that COX-2 inhibitors are associated with fewer gastric ulcers, ulcer complications and treatment withdrawals due to GI side effects. Furthermore, it is also suggested that COX-2 inhibitors have a “greater upper GI safety and are better tolerated than non-selective NSAIDs” (Rostom et al, 2007). COX-2 inhibitors, however, have limited use in the UK. The main reason for this is increased cardiovascular risk (increased risk of heart attacks and strokes) of COX-2 inhibitors and more narrow licensing for treatment.
When starting treatment with NSAIDs, some patient may be co-prescribed a Proton Pump Inhibitor (PPI) such as Omeprazole or H2-receptor antagonist, such as ranitidine, to ‘protect’ stomach from negative effects of the drug. You can learn more about the use of PPIs with Naproxen in another post: Should I take Naproxen with Omeprazole?
What are NSAIDs used for?
NSAIDs are indicated in the management of conditions characterised by pain and/or inflammation. Common conditions include:
- Acute musculoskeletal disorders for example back pains, muscle strains
- Acute pain, for example, dental pain or headache
- Rheumatoid arthritis
- An acute attack of gout
- Dysmenorrhoea (painful menstruation) and menorrhagia (heavy bleeding)
- Prevention of blood clot formation (antiplatelet effect)
There is not much difference between NSAIDs in terms of their analgesic efficacy – how good they are in reducing pain (Ong et al, 2007), although this is still a debatable subject. The management of certain conditions listed above have preferred first-line NSAID; some NSAIDs are only licensed for specific conditions. For example:
- A low dose of aspirin is the only NSAID used as antiplatelet medication. Read more about ‘baby aspirin‘.
- Mefenamic acid is the only NSAID licensed for the management menorrhagia.
- Naproxen and diclofenac are commonly used as first-line drugs in the management of acute gout attacks for which a high dose of aspirin is not recommended.
- COX-2 inhibitors, such as etoricoxib are mainly used in the management of osteoarthritis and rheumatoid arthritis.
Overall, naproxen is one of the first choices when NSAIDs are considered in prescribing. This is because naproxen is effective and has a low occurrence of side effects, including lower cardiovascular risk (NICE, 2019). Naproxen is the most prescribed NSAID in the UK.
The main difference between NSAIDs comes from effectiveness linked to anti-inflammatory properties and safety profile in relation to possible side effects. In brief (ibid):
- Ibuprofen (available over the counter without a prescription) is a least effective anti-inflammatory drug as compared to other NSAIDs, but is associated with fewer side effects
- Naproxen has a low occurrence of side effects, but more than ibuprofen.
- Other NSAIDs with similar effectiveness to naproxen include diclofenac, etodolac, indometacin, nabumetone, and piroxicam.
- Piroxicam and ketoprofen have a higher risk of serious gastro-intestinal side effects.
- Naproxen, diclofenac, and indometacin with an intermediate risk of GI side effects.
- COX-2 inhibitors (discussed below) have a lower risk of GI side effects as compared to non-selective NSAIDs.
A patient may not respond to NSAID treatment, switching to another NSAID may improve response. It is recommended that NSAIDs should be used at the lowest dose, which is effective for the shortest possible duration (NICE, 2019).
Drugs alternative to Naproxen: over the counter drugs
NSAIDs available over the counter without a prescription include:
Note: Naproxen is available over the counter as Feminax Ultra for management of period pains and menstrual cramps. I discussed the possible use of Feminax Ultra in an acute gout attack in one of my previous posts.
1. IBUPROFEN as an alternative to naproxen
Ibuprofen is available in tablet, capsule formulations as well as medicated patch and as a liquid formulation for children. Tablet formulation of ibuprofen is available in generic form, with most pharmacies and supermarkets sell their cheap versions of ibuprofen tablets. Ibuprofen tablets are available as:
- Ibuprofen 200mg tablets
- Ibuprofen 400mg tablets
Common capsule formulations of ibuprofen include Nurofen and Anadin brands, available as 200mg and/or 400mg capsules.
Additionally, some products contain ibuprofen lysine (for example Feminax Express Period Pain and Cramps Tablets ), which provides quicker pain relief than the standard formulation of ibuprofen tablets.
A higher strength of ibuprofen exists and can be prescribed by a doctor.
Ibuprofen can be purchased on its own or in combination with paracetamol (Nuromol) or codeine (Nurofen Plus). There is some data suggesting Nuromol is more effective as a pain killer as compared to taking individual drugs alone (paracetamol & ibuprofen).
Over the counter aspirin is available in different forms:
- Aspirin 75mg dispersible tablets
- Aspirin 75mg gastro-resistant tablets
- Aspirin 300mg standard or dispersible tablets
- Aspirin powder (Beechams Powders)
A low dose of aspirin 75mg, commonly known as ‘baby aspirin‘, is used as an antiplatelet medication to prevent clot formation. It is usually taken when recommended by a doctor to prevent heart attacks and strokes in peoples at risk or people who previously suffered from either of the condition. A low dose of aspirin 75mg can also be prescribed and used in pregnancy, as prevention of pre-eclampsia in women at moderate or high risk.
High dose aspirin 300mg is used in pain management when purchased over the counter. Aspirin 300mg can be used in the management of transient ischaemic attacks (mini-stroke) , angina, and heart attacks.
Aspirin can also be purchased as combination products, for example, with paracetamol or with codeine. Some products may contain caffeine.
3. DICLOFENAC over the counter as an alternative to naproxen
Diclofenac (brand: Voltarol Pain-eze) used to be available as pharmacy only medication (P) for the public to buy, however, it was reclassified in 2015 and given the status of prescription-only medication (POM). Diclofenac tablets were recalled from pharmacies as new evidence came into the light about a small increased risk of serious cardiovascular side effects, such as heart attack and stroke. This did not apply to diclofenac available in a topical formulation.
Today, diclofenac can only be purchased without a prescription in the form of gel and medicated patches under the brand name of Voltarol. Vorarol gel is available as:
- Nothing Stronger for all day joint pain relief
- Targeted relief from pain and inflammation in joints
- One application in the morning and evening for all day relief
Strefen Honey and Lemon lozenges contain flurbiprofen. Strefen in the only product available without prescription containing flurbiprofen. Strefen lozenges are used in the management of sore throats in adults and children over the age of 12 years.
Drugs alternative to Naproxen: prescription-only medication (POM)
There are over 20 different NSAIDs available as a prescription-only medication. I will summarise the 12 most prescribed drugs, alternative to naproxen in the UK. I excluded aspirin from the list as aspirin is mainly prescribed as an antiplatelet medication rather than for the management of pain and inflammation. Aspirin is one of the most commonly prescribed drugs in the UK. You can read more about the most prescribed drugs in the UK in my separate post.
Despite its availability over the counter, ibuprofen is still commonly prescribed in the UK. There is no difference between ibuprofen prescribed and one that can be purchased over the counter. 400mg ibuprofen (an adult dose) can be purchased from a pharmacy. Ibuprofen exists as prescription-only medication as 600mg tablets and granules and 800mg sustained-release tablets (brand name: Brufen). Overall when looking at prescribing statistics, Brufen is rarely prescribed in the UK.
2. DICLOFENAC SODIUM
Diclofenac sodium is licensed for all grades on pain. Diclofenac sodium is available in a wide range of formulations including:
- Gastro-resistant tablets
- Prolonged-release tablets
- Eye drops
Meloxicam is only licensed and prescribed for the management of osteoarthritis on a short-term basis when a condition is getting worse and long term the management of rheumatoid arthritis or ankylosing spondylitis (a type of arthritis: inflammation of the spine or other joints). Meloxicam comes in the form of 7.5mg and 15mg tablets and orodispersible tablets, which dissolve in the mouth when placed on the tongue.
Etoricoxib (brand name: Arcoxia) is the most prescribed COX-2 inhibitor. Etoricoxib is indicated in the management of:
- Rheumatoid arthritis
- Ankylosing spondylitis and
- Acute gout
Additionally, etoricoxib is also licensed in the management of pain, post-dental surgery, with indicated max 3 days use only. Etoricoxib comes only in the form of tablets ranging from 30mg-120mg of etoricoxib per tablet.
Celecoxib (brand name: Celebrex) is the second COX-2 inhibitor on the list. The indicated use for celecoxib is the same as of etoricoxib. In contrast, celecoxib comes only in for of 100mg and 200mg capsules.
6. MEFENAMIC ACID
In addition to management of pain and inflammation in rheumatoid arthritis, osteoarthritis, and muscular and dental pain, mefenamic acid is licensed for dysmenorrhoea (period pains) and menorrhagia (heavy bleeding during periods). Mefenamic acid is the only NSAID licensed for menorrhagia.
You may ask why mefenamic acid is the only NSAID used in menorrhagia?
Cochrane reviewed the use of NSAIDs I the management of menorrhagia by looking at all clinical trials involving their use. Cochrane concluded that NSAIDs are more effective in reducing heavy period bleeding than a placebo (a dummy pill). There is no difference between individual NSAIDs (naproxen and mefenamic acid) in the reduction of heavy menstrual bleeding (Bofill et al, 2019). The sole management of menorrhagia with mefenamic acid comes from the licensing of this drug. Mefenamic acid comes in the form of capsules under the brand name of Ponstan (250mg of mefenamic acid) and Ponstan Forte (500mg of mefenamic acid).
Indometacin (brand name: Indocid) comes in the form of capsules and suppositories. It is licensed for the treatment of different conditions, including rheumatoid arthritis, osteoarthritis, different musculoskeletal disorders, gout, and dysmenorrhoea. The use of indometacin is associated with a number of side effects, including headaches and dizziness and reversible inhibitory effect on women’s ovulation (eMC, 2019).
Etodolac (brand names: Eccoxolac, Etopan, Lodine) is licensed only in long term management of rheumatoid arthritis and osteoarthritis. All Etodolac brands are available only as tablets.
The last four medicines on the list of alternative naproxen drugs are not commonly prescribed. Nabumetone (brand name: Relifex), similarly to etodolac, is licensed only in the management of osteoarthritis and rheumatoid arthritis. Nabumetone is only available in tablet formulation.
10. DICLOFENAC POTASSIUM
Diclofenac potassium (brand name: Voltarol Rapid) has wider licensed use. In addition to the treatment of rheumatoid arthritis and Osteoarthrosis, diclofenac potassium can be used for back pains, migraine attacks, acute gout, dental pain, and pain associated with bones and muscles like sprains, frozen shoulder. Diclofenac potassium comes in the form of tablets only, available as 25mg and 50mg tablets.
Piroxicam’s (brand name: Feldene) uncommon use can be simply explained by licensing of this drug, which states that piroxicam should not be used as the first-line option when NSAIDs are considered in the treatment, due to its safety profile (increased risk of GI problems). Piroxicam comes in the form of capsules, gel, and orodispersible tablets (Feldene Melts), which are licensed for the management of osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis.
The list of Naproxen alternative drugs is closed with ketoprofen (brand names: Oruvail, Powergel), which is available in the form of capsules and in a gel formulation. Despite its wide licensed use in the management of different conditions and acute management of the pain, ketoprofen is not commonly prescribed.
Other options in the management of pain and inflammation
Optional management of painful conditions may include:
- Use of alternative drugs such as paracetamol or codeine
- Use of topical NSAIDs
- Use of other drugs such as gabapentin and pregabalin
- Use of heat and cold packs
What medication can replace naproxen?
Naproxen belongs to a group of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). There are over 20 NSAIDs licensed in the UK. Depending on the condition treated, some NSAIDs that could replace naproxen include ibuprofen, diclofenac, meloxicam, etoricoxib, celecoxib, mefenamic acid, and others.
Which is safer ibuprofen or naproxen?
Naproxen is more effective as antiinflammatory drug than ibuprofen, which is the least effective NSAID, however, individuals who take ibuprofen are less likely to experience side effects as compared to naproxen.
What is the best over the counter anti-inflammatory drug?
In the UK, two anti-inflammatory drugs can be purchased over the counter: ibuprofen and naproxen (Feminax Ultra). Although naproxen is more effective as anti-inflammatory drug than ibuprofen, Feminax Ultra is only licensed for the management of pain associated with periods.
Which drug is not an NSAID?
Common drugs which are not classified as NSAIDs and used in pain management include paracetamol; and an opioid group of drugs including codeine, and other morphine-based drugs.
Is naproxen an opioid?
Naproxen is not an opioid. Naproxen belongs to a group of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs have a different mechanism of action compared to opioids.
BMJ (2013; 346:f3195). Non-steroidal anti-inflammatory drugs (NSAIDs). Available at: https://www.bmj.com/content/346/bmj.f3195 Accessed on 14/01/2020
Bofill Rodriguez M, Lethaby A, Farquhar C. Non‐steroidal anti‐inflammatory drugs for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No.: CD000400. DOI: 10.1002/14651858.CD000400.pub4. Available at: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD000400.pub4/full Accessed on 15/01/2020
eMC (2019). SmPC: Indocid capsules 25mg. Available at: https://www.medicines.org.uk/emc/product/5325/smpc Accessed on 16/01/2020
NICE (2019). NSAIDs. Available at: https://bnf.nice.org.uk/treatment-summary/non-steroidal-anti-inflammatory-drugs.html Accessed on 14/01/2020
Ong CK, Lirk P, Tan CH, Seymour RA. An evidence-based update on nonsteroidal anti-inflammatory drugs. Clin Med Res. 2007;5(1):19–34. doi:10.3121/cmr.2007.698 Available at: https://doi.org/10.3121/cmr.2007.698 Accessed on 14/01/2020
OpenPrescribing.net, EBM DataLab, University of Oxford, 2017 Available at: https://openprescribing.net/ Accessed on 16/01/2020
Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986–1000. doi:10.1161/ATVBAHA.110.207449 Available at: https://dx.doi.org/10.1161%2FATVBAHA.110.207449 Accessed on 18/01/2020
Rostom A, Muir K, Dubé C, et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review. Clin Gastroenterol Hepatol. 2007;5(7):818–768. doi:10.1016/j.cgh.2007.03.011 Available at: https://doi.org/10.1016/j.cgh.2007.03.011 Accessed on 16/01/2020