Tolerability of diclofenac sodium 1% gel with concomitant medications known to interact with diclofenac

Abstract

Background

Topical diclofenac sodium 1% gel (DSG) has demonstrated efficacy and tolerability in patients with osteoarthritis (OA) of the knees or hands, including elderly patients and those with an increased risk of gastrointestinal, cardiovascular, and renal adverse events (AEs). Medications known to interact with diclofenac were disallowed in a clinical trial of DSG for knee OA; however, patients were not to be discontinued for intake of disallowed treatment, unless there was a safety issue. This post hoc analysis examined the frequency and type of AEs in patients who received DSG concomitantly with drugs known to have potential interactions with diclofenac.

Materials and methods

This was a post hoc analysis of a randomized controlled trial of DSG for knee OA pain. Patients (n = 254) aged ≥ 35 years with OA in one or both knees, but with clinical OA symptoms in only one knee, administered DSG topically to the target knee four times daily (total dose, 16 g/d) for 12 weeks. Drugs with the potential for major or moderate drug–drug interactions (DDIs) were identified via Drugs.com. AE rates were compared in patients with versus those without ≥1 potential DDI.

Results

At least one AE was experienced by 62.6% (107/171) of patients with ≥1 DDI and by 55.4% (46/83) of patients with no DDIs. Gastrointestinal AEs (upper and lower) were reported in 5.3% (9/171) and 7.2% (6/83), cardiovascular AEs in 4.7% (8/171) and 1.2% (1/83), renal AEs in 1.2% (2/171) and 0%, and hepatic AEs in 0% and 1.2% (1/83) of patients with ≥1 DDI compared with patients with no DDIs, respectively.

Conclusion

Concurrent use of DSG with medications that had potential for major to moderate DDIs had little impact on the frequency of AEs in this population. Further research is needed to consider how factors such as dose, duration, and timing of concomitant drug administration may affect the likelihood of clinically evident AEs resulting from a potential DDI.

Keywords:

• drug interactions
• nonsteroidal anti-inflammatory drugs
• topical administration
• knee osteoarthritis

Acknowledgments

The original study and present post hoc analysis were both supported by Novartis Consumer Healthcare, (Parsippany, NJ, USA) the post hoc analysis also was supported by Endo Pharmaceuticals Inc, (Malvern, PA, USA). Editorial support (medical writing, literature search, document retrieval, and copyediting) for the preparation of this manuscript was provided by Jeffrey Coleman and Robert Gatley of Complete Healthcare Communications, Inc (Chadds Ford, PA, USA), with financial support from Endo Pharmaceuticals Inc.

Disclosure

MG is an employee of Novartis Consumer Healthcare and MW is an employee of Endo Pharmaceuticals. JP and LA received financial support as clinical trial investigators and presented research at scientific congresses with reimbursement of associated expenses by Endo Pharmaceuticals Inc. The authors report no other conflicts of interest in this work.