"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,"...
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
During clinical development, 913 patients were exposed to VOLTAREN® GEL in randomized, double-blind, multicenter, vehicle-controlled, parallel-group studies in osteoarthritis of the superficial joints of the extremities. Of these, 513 patients received VOLTAREN® GEL for osteoarthritis of the knee and 400 were treated for osteoarthritis of the hand. Additionally, 583 patients were exposed to VOLTAREN® GEL in an uncontrolled, open-label, long-term safety trial in osteoarthritis of the knee. Of these, 355 patients were treated for osteoarthritis of 1 knee and 228 were treated for osteoarthritis of both knees. Duration of exposure ranged from 8 to 12 weeks for the placebo-controlled studies, and up to 12 months for the open-label safety trial.
Short-Term Placebo-Controlled Trials
Adverse reactions observed in at least 1% of patients treated with VOLTAREN® GEL: Non-serious adverse reactions that were reported during the short-term placebo-controlled studies comparing VOLTAREN® GEL and placebo (vehicle gel) over study periods of 8 to 12 weeks (16 g per day), were application site reactions. These were the only adverse reactions that occurred in > 1% of treated patients with a greater frequency in the VOLTAREN® GEL group (7%) than the placebo group (2%).
Table 1 lists the types of application site reactions reported. Application site dermatitis was the most frequent type of application site reaction and was reported by 4% of patients treated with VOLTAREN® GEL, compared to 1% of placebo patients.
Table 1: Non-serious Application Site Adverse
Reactions ( ≥ 1% Voltaren® Gel Patients) — Short-term Controlled Trials
|Adverse Reaction†||Voltaren® Gel
N = 913
N = 876
|Any application site reaction||62 (7)||19(2)|
|Application site dermatitis||32 (4)||G ( < 1)|
|Application site pruritus||7 ( < 1)||1 ( < 1)|
|Application site erythema||6 ( < 1)||3 ( < 1)|
|Application site paresthesia||5 ( < 1)||3 ( < 1)|
|Application site dryness||4 < < 1)||3 ( < 1)|
|Application site vesicles||3 ( < 1)||0|
|Application site irritation||2 (< 1)||0|
|Application site papules||1 ( < 1)||0|
|† Preferred Term according to MedDRA 9.1|
In the placebo-controlled trials, the discontinuation rate due to adverse reactions was 5% for patients treated with VOLTAREN® GEL, and 3% for patients in the placebo group. Application site reactions, including application site dermatitis, were the most frequent reason for treatment discontinuation.
Long-Term Open-Label Safety Trial
In the open-label, long-term safety study, distribution of adverse reactions was similar to that in the placebo-controlled studies. In this study, where patients were treated for up to 1 year with VOLTAREN® GEL up to 32 g per day, application site dermatitis was observed in 11% of patients. Adverse reactions that led to the discontinuation of the study drug were experienced in 12% of patients. The most common adverse reaction that led to discontinuation of the study was application site dermatitis, which was experienced by 6% of patients.
Read the Voltaren Gel (diclofenac sodium gel) Side Effects Center for a complete guide to possible side effects
When diclofenac is administered with aspirin, the binding of diclofenac to protein is reduced, although the clearance of free diclofenac is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of diclofenac and aspirin is not generally recommended because of the potential of increased adverse effects.
The effects of anticoagulants such as warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.
Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. The response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure [see WARNINGS AND PRECAUTIONS], as well as to assure diuretic efficacy.
NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs, including diclofenac, and lithium are administered concurrently, patients should be observed carefully for signs of lithium toxicity.
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs, including diclofenac, are administered concomitantly with methotrexate.
Diclofenac, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Therefore concomitant therapy with diclofenac may increase cyclosporine's nephrotoxicity. Caution should be used when diclofenac is administered concomitantly with cyclosporine.
Oral Non-steroidal Anti-inflammatory Drugs
Specific interaction studies of VOLTAREN® GEL and oral NSAIDs were not performed. Also, the clinical trials of VOLTAREN® GEL prohibited concomitant use of oral NSAIDS. There is systemic exposure to diclofenac following normal use of VOLTAREN® GEL, up to 6% of the systemic levels of a single oral dose of diclofenac sodium [see CLINICAL PHARMACOLOGY]. Therefore, concomitant administration of VOLTAREN® GEL with oral NSAIDs or aspirin may result in increased adverse NSAID effects.
Concomitant use of VOLTAREN® GEL with other topical products, including topical medications, sunscreens, lotions, moisturizers, and cosmetics, on the same skin site has not been tested and should be avoided because of the potential to alter local tolerability and absorption.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/28/2015
Additional Voltaren Gel Information
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.
Get the latest treatment options