Topical non-steroidal anti-inflammatory formulations are an effective and useful alternative to oral medication for treatment of local pain. Steve Titmarsh explains... 
 

Topical non-steroidal anti-inflammatory drugs (NSAIDs) are licensed for a variety of soft tissue injuries that result in pain, including muscular and rheumatic pain (see Table 1).1–10 
 
An analysis of 13 Cochrane reviews of topical NSAIDs used for acute and chronic pain (206 studies involving approximately 30,700 participants) found good evidence that some formulations of diclofenac and ketoprofen are ‘useful’ in acute pain caused by sprains and strains, for example. 
 
The authors of the review say that ‘diclofenac Emulgel, ketoprofen gel, piroxicam gel, and diclofenac plaster work reasonably well for strains and sprains.’ The usual measure of efficacy used for these medicines is pain reduced by at least half. The reviewers found that the topical NSAIDs achieved that for strains and sprains in about a week in around 1 in 2 to 1 in 5 people.11

The Cochrane review authors comment that ‘the exact formulation is critically important in acute conditions, and the same may be true for other pain conditions as well’.11 It is not necessarily the concentration of active drug in a formulation that determines the dose that penetrates through the skin.

For example, seven times more diclofenac, calculated as a percentage of applied dose, permeates through human skin from diclofenac diethylamine 1.16 per cent emulsion (0.54 per cent) compared with diclofenac sodium 5 per cent gel (0.077 per cent). That translates to 554ng/cm2 for diclofenac diethylamine 1.16 per cent emulsion compared with 361ng/cm2 for diclofenac sodium 5 per cent gel.12  

Adverse reactions 
The rate of side-effects during acute pain treatment was similar for topical NSAIDs (4.3 per cent) and placebo (4.6 per cent). Indeed, one of the advantages of using topical NSAIDs as opposed to oral formulations is that when applied topically the drug acts locally with little being absorbed systemically: the levels in plasma after topical application are usually less than 5 per cent of those seen after oral administration. That means that side-effects such as gastrointestinal bleeding that can occur with oral NSAIDs are less likely to be associated with topical use. Serious side-effects were uncommon.11 
 
Common side-effects reported for diclofenac use (occurring in between 1/100 and 1/10 people) include rash, eczema, erythema, dermatitis (including dermatitis contact) and pruritus.1  
 
The overall incidence of side-effects reported with felbinac gel is less than 2 per cent. The most common include mild erythema, irritation, dermatitis, pruritis and paraesthesia, which recover spontaneously when treatment is stopped.2  
 
Hypersensitivity reactions such as non-specific allergic reactions and anaphylaxis, respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm, or dyspnoea, or assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema, have been seen rarely with ibuprofen. Treatment should be stopped if they occur.3  
 
Mild-to-moderate local irritation, erythema, pruritus, and dermatitis may be seen where piroxicam gel is applied but the medicine is generally well tolerated. Contact dermatitis, eczema and photosensitivity skin reaction have also been reported. 
 
For ketoprofen gel local skin reactions such as rash, erythema, eczema, pruritus and burning sensation, application site burn have been reported to occur in ≥1/1000 to <1/100 people.5  
 
The amount of product to apply is detailed in patient information leaflets and product monographs; for ketoprofen gel, for example, the instruction is to apply 2–4g, which is equivalent to a 5–10cm strip of gel.5 For diclofenac gel a 2–4g equivalent is described as a cherry- or walnut-sized amount of product.1 
 
Topical NSAIDS should not be used in patients with hypersensitivity to the drugs, particularly people who have a history of asthma, rhinitis or urticaria associated with aspirin or other NSAID use. Other side-effects associated with the use of NSAIDs, such as nasal polyps, angioneurotic oedema in the case of piroxicam and angioedema with diclofenac and ibuprofen, should also preclude the use of topical NSAIDs.  
 
People with dermatosis, eczema or acne, or infected skin lesions or a history of allergic reactions to tiaprofenic acid, fenobrate, UV blocker or perfumes should not use ketoprofen. Ketoprofen is associated with photosensitisation in some individuals so it is advisable to protect treated areas from the sun during use and for two weeks after treatment has finished.1–5 
 
Duration of treatment 
Topical NSAIDs are intended mainly for acute treatment in adults so should be used for the shortest duration possible and applied to intact healthy skin. They should not be used for longer than about a week without medical supervision and advice to do so.  
 
Exceptions include piroxicam where the recommendation is to review treatment after four weeks. For ibuprofen the recommendations vary from two weeks for Ibuleve pain relief 5 per cent spray to ‘a few weeks’ for Ibugel formulations. Ibuprofen plaster should not be used for more than five days.1–10 
 
Table 1. Formulations and indications for topical non-steroidal anti-inflammatory drugs1–10,13 

*There are variations in legal category and indications between different brands/formulations – please see the Summary of Product Characteristics for each medicine 
 

References
1. Thornton & Ross Ltd. Diclofenac 1% gel Summary of Product Characteristics (www.medicines.org.uk/emc/product/12073/smpc; accessed 8 April 2021).
2. Advanz Pharma. Traxam pain relief 3% w/w gel Summary of Product Characteristics (www.medicines.org.uk/emc/product/3422/smpc; accessed 8 April 2021).
3. Dermal Laboratories. Ibugel Summary of Product Characteristics (www.medicines.org.uk/emc/product/3759/smpc; accessed 8 April 2021).
4. Accord UK Ltd. Piroxicam 0.5% gel (www.medicines.org.uk/emc/product/5047; accessed 8 April 2021).
5. Pinewood Healthcare. Ketoprofen 2.5% w/w gel Summary of Product Characteristics www.medicines.org.uk/emc/product/9276/smpc; accessed 8 April 2021).
6. GlaxoSmithKline Consumer Healthcare. Voltarol Back and Muscle Pain Relief 1.16% Gel (www.medicines.org.uk/emc/product/8773/smpc; accessed 9 April 2021).
7. GlaxoSmithKline Consumer Healthcare. Voltarol Back and Muscle Pain Relief 2.32% Gel (www.medicines.org.uk/emc/product/9335/smpc; accessed 9 April 2021).
8. Reckitt Benckiser Healthcare (UK) Ltd. Nurofen Joint & Muscular Pain Relief 200mg Medicated Plaster (www.medicines.org.uk/emc/product/9321/smpc; accessed 9 April 2021).
9. Diomed Developments Limited. Ibuleve Pain Relief 5% Spray (www.medicines.org.uk/emc/product/302/smpc; accessed 9 April 2021).
10. GlaxoSmithKline Consumer Healthcare. Voltarol Medicated Plaster (www.medicines.org.uk/emc/product/6992; accessed 9 April 2021).
11. Derry S, Wiffen PJ, Kalso EA, et al. Topical analgesics for acute and chronic pain in adults – an overview of Cochrane Reviews. Cochrane Database Syst Rev 2017;5:CD008609.
12. Pradal J, Vallet CM, Frappin G, et al. Importance of the formulation in the skin delivery of topical diclofenac: not all topical diclofenac formulations are the same. J Pain Res 2019;12:1149–54.
13. British National Formulary (https://bnf.nice.org.uk/drug; accessed 9 April 2021).