Systemic Bioavailability of Topical Diclofenac Sodium Gel 1% Versus Oral Diclofenac Sodium in Healthy Volunteers

Kienzler, J. L.; Gold, Morris S.; Nollevaux, Fabrice

doi:10.1177/0091270009336234

Cited by 123 publications

(99 citation statements)

References 25 publications

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“…19 However, in other trials, no gastrointestinal bleeding or treatment-related cardiovascular, renal, or serious AEs were reported in patients applying 16 g/d to one or both knees (up to 32 g/d total) for 12 weeks 8 or 16 g/d to both knees and 8 g/d to both hands (48 g/d total) for 1 week. 12 As in this trial, treatment-related gastrointestinal AEs were uncommon and did not result in treatment discontinuation. 8,12 Nonetheless, additional studies would be required in patients receiving DSG 32 g/d for an extended period of time to confirm the tolerability of DSG when administered with drugs known to interact with diclofenac.…”

Section: Discussionmentioning

confidence: 63%

“…12 As in this trial, treatment-related gastrointestinal AEs were uncommon and did not result in treatment discontinuation. 8,12 Nonetheless, additional studies would be required in patients receiving DSG 32 g/d for an extended period of time to confirm the tolerability of DSG when administered with drugs known to interact with diclofenac.…”

Section: Discussionmentioning

confidence: 63%

“…Therapeutic doses of DSG (16 g/day [d]; contains 160 mg of diclofenac sodium) applied to one knee produce peak plasma diclofenac levels approximately 150-fold lower than therapeutic doses of oral diclofenac (150 mg/d). 12 Even at a supratherapeutic dose (48 g/d; contains 480 mg diclofenac sodium), peak plasma diclofenac concentrations were approximately 45-fold lower than those observed with a 150-mg/d dose of oral diclofenac. 12 It has been reported anecdotally that DSG does not cause AEs when used with warfarin or other drugs known to interact with diclofenac.…”

Section: Introductionmentioning

confidence: 94%

“…12 Even at a supratherapeutic dose (48 g/d; contains 480 mg diclofenac sodium), peak plasma diclofenac concentrations were approximately 45-fold lower than those observed with a 150-mg/d dose of oral diclofenac. 12 It has been reported anecdotally that DSG does not cause AEs when used with warfarin or other drugs known to interact with diclofenac. This suggests that minimizing NSAID dose may mitigate the risk of DDIs that could lead to clinically evident AEs.…”

Section: Introductionmentioning

confidence: 94%

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

Wieman¹,

Peniston²,

Gold³

et al. 2012

The Journal of Pain

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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.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

See 2 more Smart Citations

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

Wieman¹,

Peniston²,

Gold³

et al. 2012

The Journal of Pain

View full text Add to dashboard Cite

show abstract

“…Topical NSAIDs produce dramatically lower systemic NSAID concentrations compared with oral NSAIDs (Kienzler et al, 2010) and are recommended as a first-line therapy in patients with osteoarthritis of the knees or hands (Zhang et al, 2007;Zhang et al, 2008), particularly the elderly (American Geriatrics Society, 2009). However, no chronic low back pain guidelines recommend topical NSAIDs and chronic low back pain is not an approved indication for either of the two topical NSAID formulations used in the United States: diclofenac sodium 1% gel (Voltaren ® Gel 1%, 2007) and diclofenac sodium 1.5% in 45.5% dimethyl sulfoxide solution (Pennsaid ® , 2009).…”

Section: Topical Nonsteroidal Anti-inflammatory Drugsmentioning

confidence: 99%

Pharmacotherapy for Chronic Low Back Pain

Peniston¹

2012

Low Back Pain Pathogenesis and Treatment

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Biodistribution of diclofenac following repeated topical applications of two diclofenac sodium formulations to minipigs

Wible

Barrett

Devarakonda

et al. 2013

Biopharm & Drug Disp

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This study evaluated diclofenac concentrations in plasma, selected hind limb tissues and synovial fluid after repeated topical applications of two diclofenac formulations. Group 1 Gottingen minipigs (n = 18) were administered diclofenac sodium 2.0% topical solution twice daily on days 1-6 and once on day 7. Group 2 minipigs (n = 18) were administered diclofenac sodium 1.5% topical solution four times daily on days 1-6 and twice on day 7. Approximately 20 mg of diclofenac was applied daily to a 10 × 15 cm dosing site centered over the patella of the right knee. Plasma and tissue samples were collected throughout and analysed for diclofenac concentrations using liquid chromatography with tandem mass spectrometry. On day 1, diclofenac sodium 2.0% topical solution produced higher plasma concentrations compared with the 1.5% formulation; however, after 24 h and throughout the remainder of the dosing period, plasma concentrations appeared similar, except at the 72 h time point. Twenty-four hours after the final application, skin treated with diclofenac sodium 2.0% topical solution retained a significantly (p < 0.02) greater amount of diclofenac than the 1.5% formulation. Generally, both formulations produced similar diclofenac concentrations in synovial fluid, underlying muscle, tendon and bone 24 h after the last application. The 2.0% diclofenac formulation applied twice daily delivered similar amounts of diclofenac as the 1.5% formulation administered four times daily. The skin retained a significant portion of the applied dose to serve as a depot for continuous diffusion of diclofenac into underlying tissues and systemic circulation.

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Systemic Bioavailability of Topical Diclofenac Sodium Gel 1% Versus Oral Diclofenac Sodium in Healthy Volunteers

Cited by 123 publications

References 25 publications

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

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

Pharmacotherapy for Chronic Low Back Pain

Biodistribution of diclofenac following repeated topical applications of two diclofenac sodium formulations to minipigs

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