July 4, 2015
Recommended Topic Related To:

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 non-steroidal 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 has anti-inflammatory, anti-nociception, and anti-pyretic effects.

Pharmacokinetics

The pharmacokinetics of VOLTAREN® GEL were assessed in healthy volunteers following repeated applications during 7 days of VOLTAREN® 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.

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

Treatment Cmax (ng/mL) Mean ± SD % of Oral (Cl) tmax(hr) Median (range) AUC0-24(ng•h/mL) Mean ± SD % of Oral (Cl)
Voltaren® Gel
4 x 4 g per day
(=160 mg diclofenac sodium per day)
15 ±7.3
0.6%
(0.5-0.7)
14
(0-24)
233 + 128
5.8%
(5-6.7)
Voltaren® Gel
4 x 12 g per day
(=480 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; AUC0-24 = area under the concentration-time curve; SD = standard deviation; Cl = confidence interval.

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.

Systemic exposure with recommended use of VOLTAREN® 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 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 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 (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 (4 x 4 g per day on 1 knee) with and under the conditions tested. However, the pharmacokinetics of VOLTAREN® GEL were not tested under the condition of heat application following gel application. Therefore, concurrent use of VOLTAREN® 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 for the treatment of osteoarthritis of the knee in a 12-week, randomized, double-blind, multicenter, placebo-controlled, parallel-group trial. VOLTAREN® 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 group than the placebo group.

Study 2 evaluated the efficacy of VOLTAREN® 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 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 group than the placebo group.

Table 3: Efficacy Outcomes of Voltaren® 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 28 37 Δ=7†
95% Confidence Interval     (1,12)
Study 2 (Hand) Pain Intensity# at Week 4 Sample Size 198 187  
Mean Outcome 43 50 A=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 baseline covariate.
++ Difference is adjusted using an analysis of covariance (ANCOVA) model with main effects of treatment, center, indicator of 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: 5/28/2015
This monograph has been modified to include the generic and brand name in many instances.

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Arthritis

Get the latest treatment options