Naproxen is classified as a non-steroidal anti-inflammatory drug (NSAID). Naproxen is commonly prescribed in the UK for the management of pain and inflammation. This post is a review of naproxen alternative drugs which are available in the UK. Additionally, I will discuss NSAIDs use, their mechanism of action and common side effects.
How do NSAIDs work?
NSAIDs reduce pain, and inflammation, and produce an antipyretic effect (reduce fever) by stopping the production of chemicals (enzymes) called cyclo-oxygenase-1 (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). Drugs such as naproxen or ibuprofen (a common NSAID available without a prescription) stop COX-1 and COX2 enzymes nonselectively, meaning they inhibit (prevent 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 the COX-1 enzyme is associated with gastrointestinal (GI) side effects such as stomach ulcers and bleeding, therefore the use of COX-2 inhibitors has the advantage of possible reduction of GI 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 the increased cardiovascular risk (increased risk of heart attacks and strokes) of COX-2 inhibitors and more narrow licensing for treatment (what drug(s) can be prescribed for).
When starting treatment with NSAIDs, some patients may be co-prescribed a Proton Pump Inhibitor (PPI), such as omeprazole, to ‘protect’ the stomach from the negative effects of NSAIDs.
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 at reducing pain (Ong et al, 2007), although this is still a debatable subject. The management of some conditions from the above list has preferred first-line NSAIDs; some NSAIDs are only licensed for specific conditions. For example:
- A low dose of aspirin (baby aspirin) is the only NSAID used as an antiplatelet medication.
- Mefenamic acid is the only NSAID licensed for the management of 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.
Naproxen is one of the preferred choices when NSAIDs are considered in prescribing. This is because naproxen is effective and has a low rate 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 the 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 the 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. Naproxen is more effective 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 gastrointestinal 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.
Patients may be switched to a different NSAID when treatment with one NSAID is not satisfactory. It is recommended that NSAIDs should be used at the lowest dose, which is effective for the shortest possible duration (NICE, 2019).
Naproxen alternative drugs: over-the-counter options
NSAIDs available over the counter without a prescription include:
Note: Naproxen used to be available over the counter as a branded product called Feminax Ultra. Feminax Ultra was licensed for the management of period pains and menstrual cramps.
1. Ibuprofen as an alternative to naproxen
Ibuprofen is available in a variety of formulations including:
- medicated patch and as a
- liquid formulation for children.
Ibuprofen tablets are available in various generic forms. Most pharmacies and supermarkets sell their cheap versions of ibuprofen tablets. Independent pharmacies may offer different generic ibuprofen tablets to provide the best price and availability for customers. Most common ibuprofen tablets come in two strengths:
- Ibuprofen 200mg tablets
- Ibuprofen 400mg tablets
Common capsule formulations of ibuprofen include Nurofen and Anadin brands, available as 200mg and/or 400mg capsules. Some cheaper generic options for ibuprofen capsules may be sold in pharmacies.
Some products contain ibuprofen lysine, which provides quicker pain relief than the standard formulation of ibuprofen tablets. Products containing ibuprofen lysine are usually marketed for quick relief of symptoms, for example for controlling the pain associated with migraines and period pains.
A higher strength of ibuprofen can be prescribed by a doctor, although it is not a common practice.
2. Combination products containing ibuprofen
Ibuprofen can be purchased on its own or in combination with other drugs. Common ibuprofen containing combination medicines:
- Ibuprofen with paracetamol (Nuromol)
- Ibuprofen with codeine, for example, Nurofen Plus or a generic Almus Ibuprofen and Codeine tablets.
Some data suggest Nuromol is more effective as a pain killer as compared to taking individual drugs alone (paracetamol & ibuprofen).
Combination products containing codeine are usually recommended for the treatment of pain which is not controlled by other analgesics including paracetamol and ibuprofen. In practice, however many patients choose products containing codeine due to its drowsiness and possibly better control of pain compared to other simple painkillers.
3. Naproxen alternative: aspirin
Over the counter aspirin is available in different forms and strengths:
- Aspirin 75mg dispersible tablets
- Aspirin 75mg gastro-resistant tablets
- Aspirin 300mg standard or dispersible tablets
- Aspirin powder (Beechams Powders)
Although low-dose aspirin is classified as NSAID, its use is different to naproxen. A low dose of aspirin 75mg, commonly known as ‘baby aspirin’, is used as an antiplatelet medication to prevent clot formation. Low-dose aspirin is usually taken by recommendation from a doctor to prevent heart attacks and strokes in people 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, for the 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 (emergency situations).
Aspirin can also be purchased as a combination product, for example, with paracetamol or with codeine. Some products may contain caffeine.
4. Diclofenac over the counter as an alternative to naproxen
Can you buy diclofenac tablets over the counter?
Diclofenac tablets (brand: Voltarol Pain-eze) used to be available as pharmacy-only medication (P) for the public to buy. In 2015 over the counter diclofenac tablets were reclassified to prescription-only medication (POM) and consequently removed from pharmacy shelves
Over the counter diclofenac tablets were discontinued as new evidence came into the light about a small increased risk of serious cardiovascular side effects, such as heart attack and stroke.
It is still possible to get diclofenac over the counter, however only in topical forms including gels and medicated patches. Diclofenac gel is sold under the brand name called Voltarol. Recently also a new gel called Motusol became available.
Vorarol and Motusol gels are available as 1.16% and 2.32% (12-hour) preparations.
Strefen Honey and Lemon lozenges contain flurbiprofen. Strefen is the only product available without a prescription containing flurbiprofen. Strefen lozenges are used in the management of sore throats in adults and children over the age of 12 years.
Naproxen alternative drugs: prescription-only medication (POM)
Over 20 different NSAIDs are available as prescription-only medication in the UK. Below is a summary of the most prescribed naproxen alternatives. Aspirin is not included in the list as it is mainly prescribed as an antiplatelet medication rather than medication used for the management of pain and inflammation.
Despite its wide availability over the counter, ibuprofen is still commonly prescribed in the UK. There is no difference between ibuprofen which is prescribed and one that can be purchased over the counter. 400mg ibuprofen tablets or capsules (an adult dose) can be purchased from pharmacies only. Ibuprofen exists as a prescription-only medication as 600mg tablets and granules and 800mg sustained-release tablets (brand name: Brufen). A higher strength of ibuprofen tablets or granules is not commonly prescribed in the UK.
7. Diclofenac sodium
Diclofenac sodium is licensed for different grades of pain caused by various conditions. 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 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, and post-dental surgery, with indicated max 3 days of 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.
11. Mefenamic acid
In addition to the 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.
Why mefenamic acid is the only NSAID used in menorrhagia?
Cochrane reviewed the use of NSAIDs in 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 and tablets.
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 indomethacin is associated with a number of side effects, including headaches and dizziness and a reversible inhibitory effect on women’s ovulation (eMC, 2019).
Etodolac (brand names: Eccoxolac, Etopan, Lodine) is licensed only in the 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.
15. 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, and 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 pain, oral ketoprofen is not commonly prescribed. Ketoprofen is usually prescribed in a form of a gel.
Other options in the management of pain and inflammation?
Various drugs can be used/prescribed in the management of painful conditions. These may include:
- Use of alternative drugs such as paracetamol or codeine
- Use of topical NSAIDs
- Use of other drugs such as gabapentin and pregabalin (usually for neuropathic pain)
- Use of heat and cold packs
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eMC (2019). SmPC: Indocid capsules 25mg. Available at: https://www.medicines.org.uk/emc/product/5325/smpc Accessed on 22/10/2022
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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 22/10/2022
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 22/10/2022