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The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Cardiovascular Thrombotic Events [see WARNINGS AND PRECAUTIONS]
- GI Bleeding, Ulceration and Perforation [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Heart Failure and Edema [see WARNINGS AND PRECAUTIONS]
- Renal Toxicity and Hyperkalemia [see WARNINGS AND PRECAUTIONS]
- Anaphylactic Reactions [see WARNINGS AND PRECAUTIONS]
- Serious Skin Reactions [see WARNINGS AND PRECAUTIONS]
- Hematologic Toxicity [see WARNINGS AND PRECAUTIONS]
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 withVOLTAREN® GEL, compared to 1% of placebo patients.
Table 1: Non-serious Application Site Adverse
Reactions ( ≥ 1% VOLTAREN® GEL Patients) – Short-term
|Adverse Reaction†||VOLTAREN® GEL
N=913 N (%)
N=876 N (%)
|Any application site reaction||62 (7)||19 (2)|
|Application site dermatitis||32 (4)||6 ( < 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
See Table 2 for clinically significant drug interactions with diclofenac.
Table 2: Clinically Significant Drug Interactions with
|Drugs That Interfere with Hemostasis|
|Intervention:||Monitor patients with concomitant use of VOLTAREN® GEL with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see WARNINGS AND PRECAUTIONS].|
|Clinical Impact:||Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone [see WARNINGS AND PRECAUTIONS].|
|Intervention:||Concomitant use of VOLTAREN® GEL and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS]. VOLTAREN® GEL is not a substitute for low dose aspirin for cardiovascular protection.|
|ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers|
|Clinical Impact:||NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible.|
|Clinical Impact:||Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis.|
|Intervention:||During concomitant use of VOLTAREN® GEL with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see WARNINGS AND PRECAUTIONS]|
|Clinical Impact:||The concomitant use of diclofenac with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.|
|Intervention:||During concomitant use of VOLTAREN® GEL and digoxin, monitor serum digoxin levels.|
|Clinical Impact:||NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.|
|Intervention:||During concomitant use of VOLTAREN® GEL and lithium, monitor patients for signs of lithium toxicity.|
|Clinical Impact:||Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).|
|Intervention:||During concomitant use of VOLTAREN® GEL and methotrexate, monitor patients for methotrexate toxicity.|
|Clinical Impact:||Concomitant use of VOLTAREN® GEL and cyclosporine may increase cyclosporine's nephrotoxicity.|
|Intervention:||During concomitant use of VOLTAREN® GEL and cyclosporine, monitor patients for signs of worsening renal function.|
|NSAIDs and Salicylates|
|Clinical Impact:||Concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [seeWARNINGS AND PRECAUTIONS].|
|Intervention:||The concomitant use of diclofenac with other NSAIDs or salicylates is not recommended.|
|Clinical Impact:||Concomitant use of VOLTAREN® GEL and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).|
|Intervention:||During concomitant use of VOLTAREN® GEL and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and Gl toxicity.
NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed.
In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.
Last reviewed on RxList: 6/7/2016
Additional Voltaren Gel Information
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