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Voltaren Gel

"Jan. 12, 2011 -- A new study weighs in on the debate over the relative safety of nonsteroidal anti-inflammatory medications (NSAIDs), commonly used to treat joint and muscle aches and pain.

The study, published online in the BMJ,"...

Voltaren Gel

CLINICAL PHARMACOLOGY

Mechanism of Action

The mechanism of action of diclofenac is similar to that of other nonsteroidal anti-inflammatory drugs. Diclofenac inhibits the enzyme, cyclooxygenase (COX), an early component of the arachidonic acid cascade, resulting in the reduced formation of prostaglandins, thromboxanes and prostacylin. It is not completely understood how reduced synthesis of these compounds results in therapeutic efficacy.

Pharmacodynamics

Diclofenac, the active component of Voltaren® Gel (diclofenac sodium gel) has anti-inflammatory, anti-nociception, and antipyretic effects.

Pharmacokinetics

The pharmacokinetics of Voltaren® Gel were assessed in healthy volunteers following repeated applications during 7 days of Voltaren® Gel (diclofenac sodium gel) to 1 knee (4 x 4 g per day) or to 2 knees and 2 hands (4 x 12 g per day) versus the recommended oral dose of diclofenac sodium for the treatment of osteoarthritis (3 x 50 mg per day). A summary of the pharmacokinetic parameters is presented in Table 2. Systemic exposure (area under the concentration-time curve) and maximum plasma concentrations of diclofenac are significantly lower with Voltaren® Gel than with comparable oral treatment of diclofenac sodium.

Table 2 : Pharmacokinetic Parameters and Comparison of Voltaren® Gel to Oral Diclofenac Sodium Tables After Repeated Administration

Treatment (ng/mL)
Mean ± SD
% of Oral (CI)
tmax (hr)
Median
(range)
AUC0-24 (ng*h/mL)
Mean ± SD
% of Oral (CI)
Voltaren® Gel 4 x 4 g per day (=160 mg diclofenac sodium per day) 15=7.30.6
% (0.5-0.7)
14 (0-24) 233 ± 1285.5
% (5-6.7)
Voltaren® Gel 4 x 12 g per day (=430 mg diclofenac sodium per day) 53.8 ± 32
2.2%
(1.9-2.6)
10
(0-24)
807 ± 478
19.7%
(17-22.8)
Diclofenac sodium tablets orally 3 x 50 mg per day (=150 mg diclofenac sodium per day) 2270 ± 778
100%
6.5 (1-14) 3890= 1710
100%
Cmax=maximum plasma concentration; tmax=time of Cmax; AUC 0-24=area under the concentration-time curve; SD= standard deviaion; CI=confidence interval

Systemic exposure with recommended use of Voltaren® Gel (diclofenac sodium gel) (4 x 4 g per day applied to 1 knee) is on average 17 times lower than with oral treatment. (Basis: treatment with Voltaren® Gel (diclofenac sodium gel) of 1 knee, 4 times a day versus 50 mg, 3 times a day of oral diclofenac tablets). The amount of diclofenac sodium that is systemically absorbed from Voltaren® Gel (diclofenac sodium gel) is on average 6% of the systemic exposure from an oral form of diclofenac sodium.

The average peak plasma concentration with recommended use of Voltaren® Gel (diclofenac sodium gel) (4 x 4 g per day applied to 1 knee) is 158 times lower than with the oral treatment.

The pharmacokinetics of Voltaren® Gel has been tested under conditions of moderate heat (application of a heat patch for 15 minutes prior to gel application) and of moderate exercise (first gel application followed by a 20-minute treadmill exercise). No clinically relevant differences of systemic absorption and of tolerability were found between applications of Voltaren® Gel (diclofenac sodium gel) (4 x 4 g per day on 1 knee) with and under the conditions tested. However, the pharmacokinetics of Voltaren® Gel (diclofenac sodium gel) were not tested under the condition of heat application following gel application. Therefore, concurrent use of Voltaren® Gel (diclofenac sodium gel) and heat is not recommended.

Clinical Studies

Pivotal Studies in Osteoarthritis of the Superficial Joints of the Extremities

Study 1 evaluated the efficacy of Voltaren® Gel (diclofenac sodium gel) for the treatment of osteoarthritis of the knee in a 12week, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial. Voltaren® Gel (diclofenac sodium gel) was administered at a dose of 4 g, 4 times daily, on 1 knee (16 g per day). Pain as assessed by the patients at Week 12 using the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) Pain Subindex was lower in the Voltaren® Gel (diclofenac sodium gel) group than the placebo group.

Study 2 evaluated the efficacy of Voltaren® Gel (diclofenac sodium gel) for the treatment of osteoarthritis in subjects with osteoarthritis of the hand in an 8-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group study. Voltaren® Gel (diclofenac sodium gel) was administered at a dose of 2 g per hand, 4 times daily, on both hands (16 g per day). Pain in the target hand as assessed by the patients at Weeks 4 and 6 on a visual analog scale from 0 to 100 was lower in the Voltaren® Gel (diclofenac sodium gel) group than the placebo group. 16 HOW SUPPLIED/STORAGE AND HANDLING Voltaren® Gel (diclofenac sodium gel) is available in tubes containing 100 g of the topical gel in each tube. Physician samples are packaged in 20 g tubes. Each tube contains diclofenac sodium in a gel base (10 mg of diclofenac sodium per gram of gel or 1%).

Table 3 : Efficacy outcomes of Voltaren® Gel (diclofenac sodium gel) in Studies 1 and 2

    Voltaren® Gel Placebo (Vehicle) Adjusted Difference [Placebo - Voltaren Gel)
Study 1 (Knee) WOMAC Pain at Week 12 Sample Size 127 119  
Mean outcome 2S 37 Δ = 7†
95% confidence interval     (1,12)
Study 2 (Hand) Pain Intensity at Week 4 Sample size 198 187  
Mean outcome 43 50 Δ = 7† †
95% confidence interval     (2,12)
Study 2 (Hand) Pain Intensity at Week 6 Sample size 198 187  
Mean outcome 40 47 Δ = 7††
95% confidence interval     (1, 13)
* WOMAC=Western Ontario McMaster Osteoarthritis Index.
# Scale from 0 (best) to 100 (Worst)
† Difference is adjusted using an analysis of covariance (ANCOVA) model with main effects of treatment and center and baselin covariate.
†† Diddference is adjusted using an analysis of covariance (ANCOVA) model with main effects of treatment, center, indicator for pain in the CMC-1 joint, and baseline as a covariate, and the treatment-by-CMC-1 indicator interaction. Difference is weighted by size of CMC-1 strata

Last reviewed on RxList: 10/15/2009
This monograph has been modified to include the generic and brand name in many instances.

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