Nonsteroidal anti-inflammatory drugs (
NSAIDs) are among the most commonly prescribed drugs worldwide and are responsible for approximately one-quarter of all
adverse drug reaction reports.
NSAIDs are widely prescribed for patients with
rheumatic disease--a population at increased risk for serious gastrointestinal (GI) complications.
Topical administration of
NSAIDs offers the advantage of local, enhanced
drug delivery to affected tissues with a reduced incidence of systemic adverse effects, such as
peptic ulcer disease and GI haemorrhage.
NSAIDs administered topically penetrate slowly and in small quantities into the systemic circulation; bioavailability and maximal plasma
NSAID concentration after topical application are generally less than 5 and 15%, respectively, compared with equivalent
oral administration. Product formulation may have a dramatic impact, not only on absorption rates but also on penetration depth. Compared with
oral administration, topical application leads to relatively high
NSAID concentrations in the dermis. Concentrations achieved in the muscle tissue below the site of application are variable, but are at least equivalent to that obtained with
oral administration.
NSAIDs applied topically do reach the synovial fluid, but the extent and mechanism (topical penetration versus distribution via the systemic circulation) remain to be determined. In addition, marked interindividual variability was noted in all studies; percutaneous absorption may be strongly influenced by individual skin properties. In general, interpretation of clinical studies measuring efficacy of topical
NSAIDs in
rheumatic disease states is difficult because of a remarkably high placebo response rate, use of rescue
paracetamol (
acetaminophen), and significant variability in percutaneous absorption and response rates between patients. Overall efficacy rates attributable to topical
NSAIDs in patients with rheumatic disorders ranged from 18 to 92% of treated patients. Topically applied
NSAIDs have a superior safety profile to oral formulations. Adverse effects secondary to topical
NSAID application occur in approximately 10 to 15% of patients and are primarily cutaneous in nature (
rash and
pruritus at site of application). GI
adverse drug reactions are rare with topically applied
NSAIDs, compared with a 15% incidence reported for oral
NSAIDs. Available clinical studies suggest, but do not document, equivalent efficacy of topical over oral
NSAIDs in
rheumatic diseases.