How To Use Voltaren Gel

What is Voltaren Gel and how is it used?

Voltaren Gel is an over the counter and prescription medicine used to care for symptoms of actinic keratosis, osteoarthritis, acute pain and arthritis pain. Voltaren Gel may be used alone or with other medications.

Voltaren Gel belongs to a form of drugs called Topical Skin Products.

It is not known if Voltaren Gel is safe and effective in children younger than 6 years of historic period.

What are the possible side effects of Voltaren Gel?

Voltaren Gel may cause serious side effects including:

chest pain spreading to your jaw or shoulder,
sudden numbness or weakness on i side of the body,
slurred voice communication,
shortness of breath,
skin rash, no affair how mild,
swelling,
rapid weight proceeds,
severe headache,
blurred vision,
pounding in your cervix or ears,
piffling or no urination,
nausea,
diarrhea,
upper correct-side stomach pain,
tiredness,
itching,
night urine,
dirt-colored stools,
yellowing of the peel or eyes,
pale skin,
dizziness,
cold easily and feet,
encarmine or tarry stools,
coughing up blood, and
vomit looking like coffee grounds

Become medical help correct away, if you have any of the symptoms listed above.

The most common side furnishings of Voltaren Gel include:

heartburn,
gas,
tum pain,
nausea,
airsickness,
diarrhea,
constipation,
headache,
dizziness,
drowsiness,
stuffy nose,
itching,
increased sweating,
increased blood pressure, and
skin redness, itching, dryness, scaling or peeling where the medication was applied

Tell the doctor if y'all take any side effect that bothers you lot or that does not get away.

These are not all the possible side furnishings of Voltaren Gel. For more information, ask your doctor or pharmacist.

Call your md for medical advice well-nigh side furnishings. Y'all may report side furnishings to FDA at 1-800-FDA-1088.

Warning

Take chances OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS

Cardiovascular Thrombotic Events

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk ofserious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early on in treatment and may increase with duration of use [see WARNINGS AND PRECAUTIONS].
VOLTAREN® GEL is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [run across CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Gastrointestinal Haemorrhage, Ulceration, and Perforation

NSAIDs crusade an increased gamble of serious gastrointestinal (GI) agin events including bleeding, ulceration, and perforation of the stomach or intestines, whichcan be fatal. These events tin occur at whatever fourth dimension during use and without alert symptoms. Elderly patients and patients with a prior history of peptic ulcerdisease and/or GI haemorrhage are at greater risk for serious GI events [encounter WARNINGS AND PRECAUTIONS].

DESCRIPTION

VOLTAREN® GEL (diclofenac sodium topical gel) is a nonsteroidal anti-inflammatory drug (NSAID) for topical use merely. The chemical name is 2-[(two,six-dichlorophenyl) amino]benzene- acetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is C₁₄H₁₀Cl_iiNNaO_ii, and it has the post-obit chemical structure:

VOLTAREN® GEL (diclofenac sodium) Structural Formula Illustration

It contains the active ingredient, diclofenac sodium, in an opaque, white gel base of operations. Diclofenac sodium is a white to slightly yellow crystalline pulverisation. Diclofenac sodium is a benzeneaceticacid derivative.

The inactive ingredients in VOLTAREN® GEL include: carbomer homopolymer Type C, cocoyl caprylocaprate, fragrance, isopropyl alcohol, mineral oil, polyoxyl twenty cetostearyl ether, propylene glycol, purified water, and strong ammonia solution.

INDICATIONS

VOLTAREN GEL is indicated for the relief of the pain of osteoarthritis of joints amenable to topical handling, such as the knees and those of the hands.

DOSAGE AND ADMINISTRATION

Use the lowest effective dosage for the shortest elapsing consequent with individual patient treatment goals [see WARNINGS AND PRECAUTIONS].

Dosing Menu

[see the patient Instructions for Use]

The dosing card can be found attached to the inside of the carton.

The proper amount of VOLTAREN GEL should be measured using the dosing card supplied in the drug production carton. The dosing card is made of clear plastic. The dosing card should exist used for each application of drug product. The gel should be applied within the rectangular area of the dosing card up to the 2 gram or four gram line (two g for each elbow, wrist, or hand, and 4 g for each genu, ankle, or human foot). The 2 g line is two.25 inches long. The 4 g line is four.5 inches long. The dosing card containing VOLTAREN GEL can be used to utilise the gel. The hands should then be used to gently rub the gel into the skin. Afterwards using the dosing card, concord with fingertips, rinse, and dry. If treatment site is the easily, patients should look at least one (1) hour to wash their hands.

Lower Extremities, Including The Feet, Ankles, Or Knees

Utilize the gel (4 chiliad) to the affected foot, ankle, or articulatio genus 4 times daily. VOLTAREN GEL should be gently massaged into the skin ensuring awarding to the entire afflicted pes, or knee or ankle. The entire pes includes the sole, summit of the foot, and the toes. Exercise not employ more 16 g daily to any single joint of the lower extremities.

Upper Extremities Including The Easily, Wrists, Or Elbows

Apply the gel (2 yard) to the afflicted hand, wrist, or elbow iv times daily. VOLTAREN GEL should be gently massaged into the skin ensuring awarding to the entire afflicted hand, wrist, or elbow. The entire hand includes the palm, back of the hands, and the fingers. Do not apply more than 8 thousand daily to any single joint of the upper extremities.

Total dose should not exceed 32 g per day, over all affected joints.

Special Precautions

Avert showering/bathing for at least 1 hour afterward the application. Inform patient to wash their hands later apply, unless the hands are the treated joint. If VOLTAREN GEL is applied to the hand(s) for treatment; inform patient not to wash the treated manus(southward) for at least one hour after the application.
Exercise not utilize VOLTAREN GEL to open wounds.
Avert contact of VOLTAREN GEL with optics and mucous membranes.
Practice non apply external heat and/or occlusive dressings to treated joints.
Avoid exposure of the treated articulation(s) to natural or artificial sunlight.
Avoid concomitant use of VOLTAREN GEL on the treated skin site with other topical products, including sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medications.
Concomitant employ of VOLTAREN GEL with oral nonsteroidal anti-inflammatory drugs (NSAIDs) has non been evaluated, and may increase adverse NSAIDs furnishings. Do not use combination therapy with VOLTAREN GEL and an oral NSAID unless the do good outweighs the run a risk and bear periodic laboratory evaluations.
Avoid wearing of clothing or gloves for at least x minutes later applying VOLTAREN GEL.

HOW SUPPLIED

Dosage Form And Forcefulness

VOLTAREN GEL (diclofenac sodium topical gel), 1%

Storage And Handling

VOLTAREN GEL (diclofenac sodium topical gel, 1%) is available in tubes containing 100 grams of the topical gel in each tube. Each tube contains diclofenac sodium in a gel base of operations (10 mg of diclofenac sodium per gram of gel or ane%).

100 grams tubeâ€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦â€¦NDC 63481-684-47

Storage

Store at room temperature 68°F to 77°F (twenty°C to 25°C) [see USP Controlled Room Temperature].

Continue from freezing. Store the dosing card with your VOLTAREN GEL.

Manufactured by: GSK Consumer Healthcare, Warren, NJ 07059. Distributed by: Endo Pharmaceuticals Inc., Malvern, PA 19355. Revised: Sep 2018

SLIDESHOW

Slideshow: Exercises for Knee Osteoarthritis and Joint Hurting See Slideshow

SIDE Furnishings

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]
Centre Failure and Edema [see WARNINGS AND PRECAUTIONS]
Renal Toxicity and Hyperkalemia [run into WARNINGS AND PRECAUTIONS]
Anaphylactic Reactions [run into 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 weather, 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-bullheaded, multicenter, vehicle-controlled, parallel-grouping 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 condom trial in osteoarthritis of the knee. Of these, 355 patients were treated for osteoarthritis of 1 articulatio genus and 228 were treated for osteoarthritis of both knees. Duration of exposure ranged from viii to 12 weeks for the placebo-controlled studies, and upward to 12 months for the open-characterization condom trial.

Brusk-Term Placebo-Controlled Trials

Adverse Reactions Observed In At Least 1% Of Patients Treated With VOLTAREN GEL

Not-serious adverse reactions that were reported during the brusk-term placebocontrolled 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 but adverse reactions that occurred in >1% of treated patients with a greater frequency in the VOLTAREN GEL group (vii%) than the placebo grouping (two%).

Table 1 lists the types of application site reactions reported. Awarding site dermatitis was the most frequent type of awarding site reaction and was reported past four% of patients treated with VOLTAREN GEL, compared to i% of placebo patients.

Table : Non-serious Awarding Site Adverse Reactions (≥1% VOLTAREN GEL Patients) - Brusk-term Controlled Trials

	VOLTAREN GEL N=913	Placebo (Vehicle) Due north=876
Adverse Reaction†	N (%)	N (%)
Any application site reaction	62 (7)	19 (two)
Application site dermatitis	32 (4)	6 (<1)
Application site pruritus	7 (<i)	1 (<1)
Awarding site erythema	vi (<ane)	3 (<one)
Application site paresthesia	5 (<i)	3 (<1)
Application site dryness	4 (<1)	3 (<ane)
Application site vesicles	three (<1)	0
Application site irritation	2 (<1)	0
Application site papules	ane (<ane)	0
†Preferred Term according to MedDRA 9.1

In the placebo-controlled trials, the discontinuation rate due to adverse reactions was v% for patients treated with VOLTAREN GEL, and iii% for patients in the placebo group. Application site reactions, including application site dermatitis, were the most frequent reason for treatment discontinuation.

Long-Term Open-Characterization Safety Trial

In the open-label, long-term condom study, distribution of adverse reactions was like to that in the placebo-controlled studies. In this study, where patients were treated for upwardly to i twelvemonth with VOLTAREN GEL up to 32 g per twenty-four hours, 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 written report was application site dermatitis, which was experienced by vi% of patients.

DRUG INTERACTIONS

Meet Table 2 for clinically significant drug interactions with diclofenac.

Tabular array : Clinically Significant Drug Interactions with Diclofenac

Drugs That Interfere with Hemostasis
Clinical Bear upon:	Diclofenac and anticoagulants such as warfarin have a synergistic consequence on bleeding. The concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone. Serotonin release by platelets plays an of import part in hemostasis. Instance-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of haemorrhage more than an NSAID lonely.
Intervention:	Monitor patients with concomitant utilize of VOLTAREN GEL with anticoagulants (eastward.chiliad., warfarin), antiplatelet agents (e.1000., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of haemorrhage [run across WARNINGS AND PRECAUTIONS].
Aspirin
Clinical Impact:	Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce whatever greater therapeutic effect than the utilize of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI agin reactions every bit compared to use of the NSAID alone [see WARNINGS AND PRECAUTIONS].
Intervention:	Concomitant use of VOLTAREN GEL and analgesic doses of aspirin is non generally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS]. VOLTAREN GEL is non a substitute for depression dose aspirin for cardiovascular protection.
ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers
Clinical Touch on:	NSAIDs may diminish the antihypertensive event of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol). In patients who are elderly, book-depleted (including those on diuretic therapy), or have renal impairment, coadministration 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.
Intervention:	During concomitant use of VOLTAREN GEL and ACE-inhibitors, ARBs, or beta- blockers, monitor blood pressure level to ensure that the desired blood force per unit area is obtained. During concomitant use of VOLTAREN GEL and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal part, monitor for signs of worsening renal function [run across WARNINGS AND PRECAUTIONS]. When these drugs are administered concomitantly, patients should exist adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter.
Diuretics
Clinical Bear on:	Clinical studies, equally well every bit postmarketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.grand., furosemide) and thiazide diuretics in some patients. This event 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 improver to assuring diuretic efficacy including antihypertensive furnishings [see WARNINGS AND PRECAUTIONS].
Digoxin
Clinical Impact:	The concomitant use of diclofenac with digoxin has been reported to increment the serum concentration and prolong the half-life of digoxin.
Intervention:	During concomitant use of VOLTAREN GEL and digoxin, monitor serum digoxin levels.
Lithium
Clinical Bear upon:	NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased fifteen%, and the renal clearance decreased by approximately twenty%. 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.
Methotrexate
Clinical Bear upon:	Concomitant employ of NSAIDs and methotrexate may increment the adventure for methotrexate toxicity (east.m., neutropenia, thrombocytopenia, renal dysfunction).
Intervention:	During concomitant utilise of VOLTAREN GEL and methotrexate, monitor patients for methotrexate toxicity.
Cyclosporine
Clinical Impact:	Concomitant use of VOLTAREN GEL and cyclosporine may increase cyclosporine'southward nephrotoxicity.
Intervention:	During concomitant utilise of VOLTAREN GEL and cyclosporine, monitor patients for signs of worsening renal part.
NSAIDs and Salicylates
Clinical Bear on:	Concomitant use of diclofenac with other NSAIDs or salicylates (due east.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [run into WARNINGS AND PRECAUTIONS].
Intervention:	The concomitant utilize of diclofenac with other NSAIDs or salicylates is not recommended.
Pemetrexed
Clinical Bear on:	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 brusk emptying half-lives (e.1000., diclofenac, indomethacin) should be avoided for a catamenia of ii days before, the day of, and ii days post-obit administration of pemetrexed. In the absenteeism of data regarding potential interaction betwixt pemetrexed and NSAIDs with longer half-lives (east.thousand., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days earlier, the day of, and two days post-obit pemetrexed administration.

WARNINGS

Included equally part of the PRECAUTIONS section.

PRECAUTIONS

Cardiovascular Thrombotic Events

Clinical trials of several COX-two selective and nonselective NSAIDs of up to three years duration have shown an increased run a risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can exist fatal. Based on bachelor information, it is unclear that the take a chance for CV thrombotic events is similar for all NSAIDs. The relative increment in serious CV thrombotic events over baseline conferred by NSAID employ appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a college absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased run a risk of serious CV thrombotic events began equally early on equally the first weeks of treatment. The increment in CV thrombotic run a risk has been observed most consistently at higher doses.

To minimize the potential chance for an agin CV issue in NSAID-treated patients, apply the lowest constructive dose for the shortest elapsing possible. Physicians and patients should remain alert for the evolution of such events, throughout the entire treatment form, even in the absence of previous CV symptoms. Patients should be informed most the symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as diclofenac, increases the run a risk of serious gastrointestinal (GI) events [run into WARNINGS AND PRECAUTIONS].

Status Post Coronary Artery Bypass Graft (CABG) Surgery

Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the beginning 10-xiv days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG [see CONTRAINDICATIONS].

Post-MI Patients

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI menstruum were at increased risk of reinfarction, CV-related death, and all-cause mortality outset in the start week of treatment. In this same accomplice, the incidence of decease in the showtime twelvemonth postal service-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute charge per unit of death declined somewhat afterwards the get-go year post-MI, the increased relative chance of death in NSAID users persisted over at least the adjacent four years of follow-upward.

Avoid the use of VOLTAREN GEL in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If VOLTAREN GEL is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Gastrointestinal Bleeding, Ulceration, And Perforation

NSAIDs, including diclofenac, crusade serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which tin be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Simply ane in five patients who develop a serious upper GI adverse outcome on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for three-six months, and in virtually 2%-4% of patients treated for 1 year. Nevertheless, even short-term NSAID therapy is not without risk.

Run a risk Factors For GI Bleeding, Ulceration, And Perforation

Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than x-fold increased hazard for developing a GI bleed compared to patients without these chance factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; apply of alcohol; older age; and poor general wellness status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI haemorrhage.

Strategies To Minimize The GI Risks In NSAID-treated Patients

Use the everyman effective dosage for the shortest possible duration.
Avert administration of more than ane NSAID at a time.
Avert use in patients at higher adventure unless benefits are expected to outweigh the increased risk of bleeding. For such patients, too as those with active GI haemorrhage, consider alternating therapies other than NSAIDs.
Remain warning for signs and symptoms of GI ulceration and haemorrhage during NSAID therapy.
If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue VOLTAREN GEL until a serious GI adverse issue is ruled out.
In the setting of concomitant apply of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for prove of GI bleeding [see DRUG INTERACTIONS].

Hepatotoxicity

In clinical trials, of oral diclofenac-containing products, meaningful elevations (i.e. more than three times the ULN) of AST (SGOT) were observed in most 2% of approximately 5,700 patients at some time during diclofenac handling (ALT was non measured in all studies).

In a large, open-label, controlled trial of 3,700 patients treated with oral diclofenac sodium for 2-six months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/or AST occurred in about 4% of 3,700 patients and included marked elevations (greater than 8 times the ULN) in almost 1% of the iii,700 patients. In that open up-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3-eight times the ULN), and marked (greater than 8 times the ULN) elevations of ALT or AST was observed in patients receiving diclofenac when compared to other NSAIDs. Elevations in transaminases were seen more ofttimes in patients with osteoarthritis than in those with rheumatoid arthritis.

Almost all meaningful elevations in transaminases were detected earlier patients became symptomatic. Abnormal tests occurred during the get-go 2 months of therapy with diclofenac in 42 of the 51 patients in all trials who adult marked transaminase elevations.

In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the get-go month, and in some cases, the start 2 months of therapy, but can occur at whatsoever time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.

In a European retrospective population-based, example-controlled study, x cases of diclofenac associated drug-induced liver injury with electric current use compared with non-use of diclofenac were associated with a statistically significant 4-fold adjusted odds ratio of liver injury. In this detail study, based on an overall number of 10 cases of liver injury associated with diclofenac, the adjusted odds ratio increased further with female person gender, doses of 150 mg or more, and duration of use for more than xc days.

Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms. The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should exist monitored inside iv to 8 weeks later initiating treatment with diclofenac. However, severe hepatic reactions can occur at whatsoever time during treatment with diclofenac.

If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consequent with liver disease develop, or if systemic manifestations occur (east.thou., eosinophilia, rash, abdominal hurting, diarrhea, dark urine, etc.), VOLTAREN GEL should be discontinued immediately.

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, languor, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eastward.g., eosinophilia, rash, etc.), discontinue VOLTAREN GEL immediately, and perform a clinical evaluation of the patient.

To minimize the potential risk for an adverse liver related event in patients treated with VOLTAREN GEL, use the lowest effective dose for the shortest duration possible. Exercise caution when prescribing VOLTAREN GEL with concomitant drugs that are known to exist potentially hepatotoxic (east.g., acetaminophen, antibiotics, anti-epileptics).

Hypertension

NSAIDs, including VOLTAREN GEL, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have dumb response to these therapies when taking NSAIDs [run into DRUG INTERACTIONS].

Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.

Heart Failure And Edema

The Coxib and traditional NSAID Trialistsâ€™ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry written report of patients with centre failure, NSAID use increased the hazard of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of diclofenac may edgeless the CV effects of several therapeutic agents used to care for these medical atmospheric condition (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]) [see DRUG INTERACTIONS].

Avoid the use of VOLTAREN GEL in patients with severe middle failure unless the benefits are expected to outweigh the risk of worsening heart failure. If VOLTAREN GEL is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Renal Toxicity And Hyperkalemia

Renal Toxicity

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.

Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory part in the maintenance of renal perfusion. In these patients, administration of an NSAID may crusade a dose-dependent reduction in prostaglandin formation and, secondarily, in renal claret flow, which may precipitate overt renal decompensation. Patients at greatest gamble of this reaction are those with impaired renal part, dehydration, hypovolemia, center failure, liver dysfunction, those taking diuretics and ACE-inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed past recovery to the pretreatment country.

No information is available from controlled clinical studies regarding the use of VOLTAREN GEL in patients with advanced renal affliction. The renal furnishings of VOLTAREN GEL may hasten the progression of renal dysfunction in patients with preexisting renal disease.

Correct volume condition in dehydrated or hypovolemic patients prior to initiating VOLTAREN GEL. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of VOLTAREN GEL [meet DRUG INTERACTIONS]. Avoid the use of VOLTAREN GEL in patients with advanced renal disease unless the benefits are expected to outweigh the take chances of worsening renal function. If VOLTAREN GEL is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.

Hyperkalemia

Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism land.

Anaphylactoid Reactions

Diclofenac has been associated with anaphylactic reactions in patients with and without known hypersensitivity to diclofenac and in patients with aspirin-sensitive asthma [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Seek emergency help if an anaphylactic reaction occurs.

Exacerbation Of Asthma Related To Aspirin Sensitivity

A subpopulation of patients with asthma may accept aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirinsensitive patients, VOLTAREN GEL is contraindicated in patients with this class of aspirin sensitivity [encounter CONTRAINDICATIONS]. When VOLTAREN GEL is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

Serious Skin Reactions

NSAIDs, including diclofenac, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which tin can be fatal. These serious events may occur without alarm. Inform patients about the signs and symptoms of serious pare reactions, and to discontinue the employ of VOLTAREN GEL at the get-go appearance of peel rash or whatsoever other sign of hypersensitivity. VOLTAREN GEL is contraindicated in patients with previous serious skin reactions to NSAIDs [see CONTRAINDICATIONS].

Premature Closure Of Fetal Ductus Arteriosus

Diclofenac may crusade premature closure of the fetal ductus arteriosus. Avoid utilize of NSAIDs, including VOLTAREN GEL, in pregnant women starting at 30 weeks of gestation (third trimester) [run into Use In Specific Populations].

Hematologic Toxicity

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retentivity, or an incompletely described upshot on erythropoiesis. If a patient treated with VOLTAREN GEL has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including VOLTAREN GEL, may increase the risk of bleeding events. Co-morbid conditions such every bit coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increment this take chances. Monitor these patients for signs of bleeding [encounter DRUG INTERACTIONS].

Masking Of Inflammation And Fever

The pharmacological activity of VOLTAREN GEL in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

Laboratory Monitoring

Because serious GI bleeding, hepatotoxicity, and renal injury tin occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [come across WARNINGS AND PRECAUTIONS].

Sun Exposure

Patients should minimize or avoid exposure to natural or bogus sunlight on treated areas because studies in animals indicated topical diclofenac handling resulted in an before onset of ultraviolet lite induced skin tumors. The potential effects of VOLTAREN GEL on skin response to ultraviolet damage in humans are not known.

Eye Exposure

Contact of VOLTAREN GEL with optics and mucosa, although not studied, should be avoided. Patients should be advised that if eye contact occurs, they should immediately wash out the middle with h2o or saline and consult a physician if irritation persists for more than an hour.

Oral Nonsteroidal Anti-Inflammatory Drugs

Concomitant use of oral and topical NSAIDs may result in a college rate of hemorrhage, more frequent abnormal creatinine, urea, and hemoglobin. Do non employ combination therapy with VOLTAREN GEL and an oral NSAID unless the benefit outweighs the risk.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) that accompanies each prescription dispensed. Patients, families, or their caregivers should be informed of the following information before initiating therapy with VOLTAREN GEL and periodically during the course of ongoing therapy.

Cardiovascular Thrombotic Events

Suggest patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately [see WARNINGS AND PRECAUTIONS].

Gastrointestinal Haemorrhage, Ulceration, And Perforation

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their healthcare provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased chance for and the signs and symptoms of GI bleeding [see WARNINGS AND PRECAUTIONS].

Hepatotoxicity

Inform patients of the alarm signs and symptoms of hepatotoxicity (e.thou., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and "flu-similar" symptoms). If these occur, instruct patients to terminate VOLTAREN GEL and seek immediate medical therapy [see WARNINGS AND PRECAUTIONS].

Middle Failure And Edema

Advise patients to be warning for the symptoms of congestive heart failure including shortness of breath, unexplained weight proceeds, or edema and to contact their healthcare provider if such symptoms occur [see WARNINGS AND PRECAUTIONS].

Anaphylactic Reactions

Inform patients of the signs of an anaphylactic reaction (eastward.1000., difficulty animate, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur [meet CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS].

Serious Peel Reactions

Propose patients to stop VOLTAREN GEL immediately if they develop whatsoever type of rash and to contact their healthcare provider as soon every bit possible [see WARNINGS AND PRECAUTIONS].

Female Fertility

Propose females of reproductive potential who desire pregnancy that NSAIDs, including VOLTAREN GEL, may exist associated with a reversible delay in ovulation [see Use In Specific Populations].

Fetal Toxicity

Inform pregnant women to avoid use of VOLTAREN GEL and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus [meet WARNINGS AND PRECAUTIONS and Utilize In Specific Populations].

Avoid Concomitant Use Of NSAIDs

Inform patients that the concomitant use of VOLTAREN GEL with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased gamble of gastrointestinal toxicity, and piffling or no increment in efficacy [meet WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS]. Alert patients that NSAIDs may be present in "over-the-counter" medications for handling of colds, fever, or insomnia.

Utilize Of NSAIDs And Low-Dose Aspirin

Inform patients not to employ low-dose aspirin concomitantly with VOLTAREN GEL until they talk to their healthcare provider [encounter DRUG INTERACTIONS].

Centre Exposure

Instruct patients to avoid contact of VOLTAREN GEL with the optics and mucosa, although not studied, should be avoided. Advise patients that if center contact occurs, immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour [encounter WARNINGS AND PRECAUTIONS].

Special Application Instructions

Instruct patients how to use the dosing card to measure the proper dose of VOLTAREN GEL to apply. If the patient loses their dosing card, instruct them that they can call one-855-297-3031 to request a replacement dosing menu or inquire their pharmacist for a new dosing card.

Instruct patients how to correctly mensurate the 2.25 inches (ii g) dose or 4.5 inches (four chiliad) dose while waiting for a replacement dosing card [see DOSAGE AND Administration].

Instruct patients not to apply VOLTAREN GEL to open peel wounds, infections, inflammations, or exfoliative dermatitis, as it may bear upon absorption and tolerability of the drug.

Instruct patients to avoid concomitant utilize of VOLTAREN GEL with other topical products, including sunscreens, cosmetics, lotions, moisturizers, and insect repellants. Concomitant utilise may event in skin reactions or change the absorption of VOLTAREN GEL.

Instruct patients to minimize or avoid exposure of treated areas to natural or artificial sunlight [meet WARNINGS AND PRECAUTIONS and DOSAGE AND ADMINISTRATION].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Carcinogenicity studies in mice and rats administered diclofenac sodium as a dietary constituent for two years at doses upwardly to 2 mg/kg/day (approximately 0.5 and 1 times, respectively, the maximum recommended human topical dose of VOLTAREN GEL based on bioavailability and body surface area (BSA) comparison) resulted in no significant increases in tumor incidence.

In a dermal carcinogenicity study conducted in albino mice, daily topical applications of a diclofenac sodium gel product for two years at concentrations up to 0.035% diclofenac sodium (a 29-fold lower diclofenac sodium concentration than present in VOLTAREN GEL) did not increase neoplasm incidence.

In a photococarcinogenicity study conducted in hairless mice, topical application of a diclofenac sodium gel production at doses up to 0.035% diclofenac sodium (a 29-fold lower diclofenac sodium concentration than nowadays in VOLTAREN GEL) resulted in an before median time of onset of tumors.

Mutagenesis

Diclofenac was not mutagenic or clastogenic in a battery of genotoxicity tests that included the bacterial reverse mutation analysis, in vitro mouse lymphoma point mutation assay, chromosomal aberration studies in Chinese hamster ovarian cells in vitro, and in vivo rat chromosomal aberration analysis of bone marrow cells.

Harm Of Fertility

Diclofenac did not affect male person or female fertility in rats at doses up to 4 mg/kg/day (approximately 2 times than the maximum homo topical dose of VOLTAREN GEL based on bioavailability and BSA comparison).

Use In Specific Populations

Pregnancy

Pregnancy Category C prior to thirty weeks gestation; Category D starting 30 weeks gestation

Risk Summary

Use of NSAIDs, including VOLTAREN GEL, during the third trimester of pregnancy increases the hazard of premature closure of the fetal ductus arteriosus. Avoid utilise of NSAIDs, including VOLTAREN GEL, in pregnant women starting at 30 weeks of gestation (third trimester).

There are no adequate and well-controlled studies of VOLTAREN GEL in pregnant women. Human and animate being studies signal that diclofenac crosses the placenta. Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.South. population, all clinically recognized pregnancies, regardless of drug exposure, have a groundwork rate of 2-4% for major malformations, and 15-xx% for pregnancy loss. In brute reproduction studies, no show of teratogenicity was observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses upwardly to approximately 5, 5, and 10 times, respectively, the maximum recommended topical dose of VOLTAREN GEL, despite the presence of maternal and fetal toxicity at these doses [see Information]. Based on fauna information, prostaglandins have been shown to have an important part in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as diclofenac, resulted in increased pre- and postimplantation loss.

Clinical Considerations

Labor Or Delivery

There are no studies on the furnishings of VOLTAREN GEL during labor or delivery. In fauna studies, NSAIDS, including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increment the incidence of stillbirth.

Data

Brute Data

Reproductive and developmental studies in animals demonstrated that diclofenac sodium assistants during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 5 times the maximum recommended human being dose (MRHD) of VOLTAREN GEL based on bioavailability and torso surface expanse (BSA) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 5 and 10 times the MRHD based on bioavailability and BSA comparison).

In a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (approximately ane and 2 times the MRHD based on bioavailability and BSA comparison) from Gestation Mean solar day 15 through Lactation Twenty-four hour period 21, meaning maternal toxicity (peritonitis, mortality) was noted. These maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival.

Lactation

Risk Summary

Based on bachelor data, diclofenac may be present in human milk. The developmental and health benefits of chest-feeding should exist considered forth with the motherâ€™s clinical need for CATAFLAM and any potential agin furnishings on the breastfed baby from the CATAFLAM or from the underlying maternal condition.

Data

One woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 μg/L, equivalent to an babe dose of well-nigh 0.03 mg/kg/24-hour interval. Diclofenac was not detectable in breast milk in 12 women using diclofenac (afterward either 100 mg/day orally for vii days or a single fifty mg intramuscular dose administered in the firsthand postpartum flow).

Females And Males Of Reproductive Potential

Infertility

Females

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including VOLTAREN GEL, may filibuster or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including VOLTAREN GEL, in women who have difficulties conceiving or who are undergoing investigation of infertility.

Pediatric Utilize

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Elderly patients, compared to younger patients, are at greater hazard for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated do good for the elderly patient outweighs these potential risks, start dosing at the low cease of the dosing range, and monitor patients for agin effects [come across WARNINGS AND PRECAUTIONS].

Of the total number of subjects treated with VOLTAREN GEL in clinical studies, 498 were 65 years of age and over. No overall differences in effectiveness or prophylactic were observed betwixt these subjects and younger subjects, but greater sensitivity to the effect of NSAIDs in some older individuals cannot be ruled out.

Diclofenac, as with any NSAID, is known to be substantially excreted by the kidney, and the risk of toxic reactions to VOLTAREN GEL may be greater in patients with impaired renal office. Because elderly patients are more than likely to take decreased renal function, care should be taken when using VOLTAREN GEL in the elderly, and it may exist useful to monitor renal function.

OVERDOSE

Symptoms post-obit acute NSAID overdosages take been typically express to languor, drowsiness, nausea, vomiting, and epigastric pain, which accept been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma take occurred, but were rare [see WARNINGS AND PRECAUTIONS].

Manage patients with symptomatic and supportive care post-obit an NSAID overdosage. There are no specific antidotes. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may non be useful due to high protein bounden.

For boosted data almost overdosage handling, contact a poison command centre (one-800222-1222).

CONTRAINDICATIONS

VOLTAREN® GEL is contraindicated in the post-obit patients:

Known hypersensitivity (eastward.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product [see WARNINGS AND PRECAUTIONS]
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or otherNSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs accept been reported in such patients [see WARNINGS AND PRECAUTIONS]
In the setting of coronary avenue bypass graft (CABG) surgery [see WARNINGS AND PRECAUTIONS]

CLINICAL PHARMACOLOGY

Mechanism Of Action

Diclofenac has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of activity of VOLTAREN GEL, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-one and COX-2).

Diclofenac is a strong inhibitor of prostaglandin synthesis in vitro. Diclofenac concentrations reached during therapy take produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in creature models. Prostaglandins are mediators of inflammation. Because diclofenac is an inhibitor of prostaglandin synthesis, its mode of action may exist due to a subtract of prostaglandins in peripheral tissues.

Pharmacokinetics

The pharmacokinetics of VOLTAREN GEL were assessed in good for you volunteers following repeated applications during 7 days of VOLTAREN GEL to 1 knee joint (four 10 4 thou per mean solar day) or to ii knees and 2 hands (four x 12 chiliad per solar day) versus the recommended oral dose of diclofenac sodium for the treatment of osteoarthritis (three x 50 mg per mean solar day). A summary of the pharmacokinetic parameters is presented in Tabular array 3.

Table : Pharmacokinetic Parameters and Comparing of VOLTAREN GEL to Oral Diclofenac Sodium Tablets Later on Repeated Administration

Treatment	Cmax (ng/mL) Hateful ± SD % of Oral (CI)	Tmax (hr) Median Range	AUC0-24 (ng.h/mL) Hateful ± SD % of Oral (CI)
VOLTAREN GEL 4 ten 4 g per day (=160 mg diclofenac sodium per day)	15 ± 7.3 0.6% (0.v-0.7)	14 (0-24)	233 ± 128 five.8% (v-vi.7)
VOLTAREN GEL 4 10 12 chiliad per 24-hour interval (=480 mg diclofenac sodium per twenty-four hours)	53.8 ± 32	14 (0-24)	807 ± 478
	2.2%	10 (0-24)	19.seven%
	(1.ix-two.6)	10 (0-24)	(17-22.eight)
Diclofenac sodium tablets, orally 3 x 50 mg per twenty-four hours (=150 mg diclofenac sodium per day)	2270 ± 778	6.5 (1-14)	3890± 1710
	100%	6.5 (1-14)	100%
Cmax = maximum plasma concentration, tmax = time of Cmax, AUC0-24 = area under the concentration time bend, SD = standard divergence, CI = 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 utilize of VOLTAREN GEL (4 ten iv g per twenty-four hours applied to 1 knee joint) is on boilerplate 17 times lower than with oral handling. (Basis: treatment with VOLTAREN GEL of 1 knee, 4 times a day versus l mg, 3 times a day of oral diclofenac tablets). The amount of diclofenac sodium that is systemically captivated from VOLTAREN GEL is on average 6% of the systemic exposure from an oral form of diclofenac sodium.

The boilerplate height plasma concentration with recommended utilise of VOLTAREN GEL (iv ten 4 g per twenty-four hours applied to 1 knee) is 158 times lower than with the oral handling.

The pharmacokinetics of VOLTAREN GEL has been tested under weather of moderate estrus (application of a heat patch for xv minutes prior to gel application) and of moderate practice (first gel awarding followed by a 20-minute treadmill practice). No clinically relevant differences of systemic absorption and of tolerability were establish betwixt applications of VOLTAREN GEL (4 x 4 yard per solar day on 1 articulatio genus) with and under the conditions tested. Yet, the pharmacokinetics of VOLTAREN GEL were non tested nether the condition of heat awarding following gel application. Therefore, concurrent employ of VOLTAREN GEL and rut is not recommended.

Drug Interaction Studies

Aspirin

When NSAIDs were administered with aspirin, the protein bounden of NSAIDs were reduced, although the clearance of free NSAID was not contradistinct. The clinical significance of this interaction is non known. Come across Table 2 for clinically pregnant drug interactions of NSAIDs with aspirin [encounter DRUG INTERACTIONS].

Clinical Studies

Pivotal Studies In Osteoarthritis Of The Superficial Joints Of The Extremities

Study i evaluated the efficacy of VOLTAREN GEL for the handling of osteoarthritis of the knee in a 12-week, randomized, double-bullheaded, multicenter, placebocontrolled, parallel-group trial. VOLTAREN GEL was administered at a dose of 4 yard, four times daily, on one knee (sixteen g per twenty-four hour period). Pain as assessed past 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 handling of osteoarthritis in subjects with osteoarthritis of the paw in an 8-calendar week, randomized, doubleblind, multicenter, placebo-controlled, parallel-group study. VOLTAREN GEL was administered at a dose of 2 one thousand per paw, iv times daily, on both hands (16 g per solar day). Pain in the target hand as assessed by the patients at Weeks 4 and six on a visual analog scale from 0 to 100 was lower in the VOLTAREN GEL grouping than the placebo group.

Table : Efficacy outcomes of VOLTAREN GEL in Studies 1 and 2

		VOLTAREN GEL	Placebo (Vehicle)	Adapted Divergence (Placebo — VOLTAREN GEL)
Study 1 (Knee) WOMAC Pain *# at Week 12	Sample Size	127	119
	Mean Result	28	37	Δ=7†
	95% Confidence Interval			(1, 12)
Study 2 (Paw) Pain Intensity# at Week 4	Sample Size	198	187
	Hateful Consequence	43	50	Δ=vii‡
	95% Confidence Interval			(two, 12)
Study ii (Hand) Hurting Intensity# at Calendar week half dozen	Sample Size	198	187
	Hateful Effect	40	47	Δ=7‡
	95% Confidence Interval			(1, 13)
* WOMAC = Western Ontario McMaster Osteoarthritis Index # Calibration from 0 (best) to 100 (worst) † Departure is adjusted using an assay of covariance (ANCOVA) model with primary effects of treatment and center and baseline covariate. ‡ Difference is adapted 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-i strata.

PATIENT INFORMATION

Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

What is the almost important data I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?

NSAIDs can cause serious side furnishings, including:

Increased take chances of a center attack or stroke that can lead to death. This chance may happen early in treatment and may increase:
- with increasing doses of NSAIDs
- with longer employ of NSAIDs

Do not have NSAIDs right before or after a heart surgery chosen a "coronary artery bypass graft (CABG)."

Avoid taking NSAIDs after a recent heart assault, unless your healthcare provider tells you to. Y'all may have an increased take chances of some other heart attack if y'all accept NSAIDs afterward a recent heart assail.

Increased risk of bleeding, ulcers, and tears (perforation) of the esophagus (tube leading from the mouth to the breadbasket), stomach and intestines:
- anytime during employ
- without alert symptoms
- that may cause death

The run a risk of getting an ulcer or bleeding increases with:

past history of breadbasket ulcers, or breadbasket or intestinal bleeding with utilize of NSAIDs
taking medicines called "corticosteroids", "anticoagulants", "SSRIs", or "SNRIs"
increasing doses of NSAIDs
longer use of NSAIDs
smoking
drinking booze
older age
poor wellness
advanced liver disease
bleeding problems

NSAIDs should only be used:

exactly every bit prescribed
at the lowest dose possible for your treatment
for the shortest time needed

What are NSAIDs?

NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as dissimilar types of arthritis, menstrual cramps, and other types of short-term pain.

Who should not take NSAIDs?

Practice non take NSAIDS:

if y'all accept had an asthma set on, hives, or other allergic reaction with aspirin or any other NSAIDs.
correct earlier or later center bypass surgery.

Before taking NSAIDs, tell your health care provider about all of your medical conditions, including if you:

have liver or kidney problems
have high blood pressure level
take asthma
are pregnant or plan to become significant. Talk to your health care provider if you are considering taking NSAIDs during pregnancy. You should not accept NSAIDs after 29 weeks of pregnancy.
are breastfeeding or plan to breast feed.

Tell your wellness intendance provider about all of the medicines you take, including prescription or overthe-counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines tin collaborate with each other and cause serious side effects. Do not commencement taking new medicine without talking to your health intendance provider starting time.

What are the possible side effects of NSAIDs?

NSAIDs tin can cause serious side effects, including:

See "What is the near important information I should know about medicines chosen Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?"

new or worse loftier blood pressure
heart failure
liver problems including liver failure
kidney problems including kidney failure
low red blood cells (anemia)
life-threatening skin reactions
life-threatening allergic reactions

Other side effects of NSAIDs include: stomach hurting, constipation, diarrhea, gas, heartburn, nausea, airsickness and dizziness.

Get emergency help right away if you go whatever of the following symptoms:

shortness of jiff or problem breathing
chest pain
weakness in one part or side of your body
slurred speech
swelling of the face or throat

Stop taking your NSAID and phone call your wellness care provider right away if you become any of the following symptoms:

nausea
more than tired or weaker than usual
diarrhea
itching
your skin or eyes look yellow
indigestion or stomach pain
flu-like symptoms
vomit blood
there is blood in your bowel movement or it is blackness and viscid like tar
unusual weight proceeds
skin rash or blisters with fever
swelling of the arms, legs, hands, and feet

If you take too much of your NSAID, call your health intendance provider or become medical help right away. These are not all the possible side effects of NSAIDs. For more information, ask your wellness care provider or pharmacist near NSAIDs.

Telephone call your doctor for medical advice well-nigh side furnishings. Y'all may report side effects to FDA at 1-800-FDA1088.

Other information most NSAIDs

Aspirin is an NSAID but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, breadbasket, and intestines. Aspirin tin can too crusade ulcers in the breadbasket and intestines.
Some NSAIDs are sold in lower doses without a prescription (over-the-counter). Talk to your health care provider earlier using over-the-counter NSAIDs for more than 10 days.

Full general data about the safe and effective employ of NSAIDs

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not utilise NSAIDs for a condition for which it was not prescribed. Do not requite NSAIDs to other people, even if they have the aforementioned symptoms that y'all have. It may damage them.

If you would like more information about NSAIDs, talk with your health care provider. You lot can ask your chemist or health care provider for data about NSAIDs that is written for health professionals.

Manufactured past: Novartis Pharma Produktions GmbH, Wehr, Germany for Sandoz Inc., Princeton, NJ 08540For more data, become to www.XXXXXX.com or call one-800-398-5876. Revised May2016

Instructions for Utilize

VOLTAREN® GEL
(diclofenac sodium)

Important: Use the dosing card that is inside the VOLTAREN® GEL carton to correctly measure each dose. The dosing carte du jour is re-usable. Do not throw the dosing card away. Before you utilise VOLTAREN® GEL for the starting time time, your healthcare provider orpharmacist should show y'all how to correctly measure your dose using the dosing card.

Read this Instructions for Apply before yous showtime using VOLTAREN® GEL and each fourth dimension you get a refill. In that location may exist new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Your healthcare provider has prescribed VOLTAREN® GEL to help relieve arthritis pain in some of your joints. VOLTAREN® GEL may be used to treat arthritis pain in the arms (hands, wrists, and elbows) and in the legs (feet, ankles, and knees). It is non known if VOLTAREN® GEL is safe and constructive if used on your spine, hips, or shoulders.

Use VOLTAREN® GEL exactly how your healthcare provider prescribes it for you lot. Do not use VOLTAREN® GEL anywhere other than where your healthcare provider tells you to.
Do not use more than a full of 32 grams of VOLTAREN® GEL each twenty-four hours. If you add up the amount of VOLTAREN® GEL equally directed by your healthcare provider, it should not be more 32 grams in ane mean solar day.

The dose for your easily, wrists, or elbows is 2 grams of VOLTAREN® GEL each time you use it.

Apply VOLTAREN® GEL 4 times a day (a total of 8 grams each day). Exercise not apply more than viii grams each twenty-four hours to whatsoever one of your afflicted easily, wrists, or elbows.

The dose for your feet, ankles, or knees is 4 grams of VOLTAREN® GEL each time you apply it.

Apply VOLTAREN® GEL iv times a day (a total of 16 grams each day). Practise non apply more than 16 grams each day to any ane of your affected feet, ankles, or knees.

Some examples of VOLTAREN® GEL application include:

If yous utilize 2 grams of VOLTAREN® GEL on one manus, 4 times a mean solar day, your total dose for 1 24-hour interval is viii grams.
If yous use 4 grams of VOLTAREN® GEL on one knee, four times a day, your full dose for one day is sixteen grams.
Your total dose for one 24-hour interval, treating ane paw and one articulatio genus, is 8 grams plus 16 grams, which equals 24 grams of VOLTAREN® GEL.

Effigy A

VOLTAREN® GEL (diclofenac sodium topical gel) Figure A Illustration

Before you use a new tube of VOLTAREN® GEL for the first time, open up the foil seal that covers the tube opening by using the spiked meridian of the cap. Call back to remove the dosing card from the carton to measure your dose (encounter Figure A).
Use VOLTAREN® GEL to make clean, dry skin that does not have any cuts, open wounds, infections, or rashes.
Do not employ heating pads or apply bandages to where you take practical VOLTAREN® GEL.
Avoid exposing peel where you apply VOLTAREN® GEL to sunlight and artificial low-cal, such as tanning booths.
Do not utilize sunscreens, cosmetics, lotions, moisturizers, insect repellants, or other topical medicines on the same pare areas where you have practical VOLTAREN® GEL.
Do not get VOLTAREN® GEL in your eyes, nose, or rima oris. VOLTAREN® GEL is only to be used on your skin (topical use). If you get VOLTAREN® GEL in your eyes, rinse your optics right away with water or saline. Talk with your healthcare provider if eye irritation lasts for more than one hour.

What if I miss a dose?

If you miss a dose of VOLTAREN® GEL, go on with your side by side scheduled dose using theprescribed amount of VOLTAREN® GEL. Practice not double the dose.

Applying 2 grams (2 yard) of VOLTAREN® GEL to hands, wrists, or elbows:

Step ane. Remove the dosing carte that is attached inside the VOLTAREN® GEL carton. Use the dosing card to correctly measure each dose of VOLTAREN® GEL. To measure the correct corporeality of VOLTAREN® GEL, identify the dosing card on a flat surface so that you can read the impress. If the impress is backwards, flip dosing card over (see Effigy A). If y'all lose or misplace your dosing card, you lot can inquire your chemist for a new one or call 1-800-452-0051. Ask yourhealthcare provider or chemist to testify you how to correctly measure your dose of VOLTAREN® GEL while you lot are waiting to receive your new dosing card.

Figure B, C and Figure D

VOLTAREN® GEL (diclofenac sodium topical gel) Figure B, C and Figure D Illustration

Pace two. Squeeze VOLTAREN® GEL onto the dosing card evenly, up to the 2 g line (a 2.25 inch length of gel). Make sure that the gel covers the 2 g area of the dosing card (come across Figure B). Put the cap back on the tube of VOLTAREN® GEL. Enquire your healthcare provider or pharmacist if you are not sure how to correctly measure out your dose of VOLTAREN® GEL.

Footstep 3. Apply the gel to your manus, wrist, or elbow. You can use the dosing card to apply the gel (run across Figure C). So, use your hands to gently rub the gel into the pare (see Figure D). Do not share your dosing carte with some other person. Make sure to cover the unabridged affected hand, wrist, or elbow with the gel. Recollect that the hand includes the palm of your manus, the peak of yourhand, and your fingers.

Pace 4. After using the dosing carte du jour, hold end with fingertips, rinse and dry. Store the dosing card until side by side utilize. Do non shower or bathe for at least 1 hour after applying VOLTAREN® GEL. Do non wash your treated hands for at least 1 hr later applying the VOLTAREN® GEL.

Pace 5. Later on applying VOLTAREN® GEL, wait 10 minutes earlier roofing the treated skin with gloves or clothing.

Applying iv grams (four thousand) of VOLTAREN® GEL to anxiety, ankles, or knees:

Step 1. Refer to Step one in a higher place.

Step 2. Squeeze VOLTAREN® GEL onto the dosing card evenly upwardly to the iv yard line (a 4.5 inchlength of gel), making sure the gel covers the 4 1000 area of the dosing card (see Figure E). Put thecap back on the tube of VOLTAREN® GEL. Enquire your healthcare provider or chemist if you are not sure how to correctly measure your dose of VOLTAREN® GEL.

Step three. Apply VOLTAREN® GEL to your pes, ankle, or human knee. You tin can use the dosing carte toapply the gel (see Figure F). Then, utilise your hands to gently rub the gel into the peel (see Figure Thou). Practice non share your dosing menu with another person. Make certain to cover your entire foot, talocrural joint, or knee expanse with the gel. For example, cover the peel higher up, below, inside and outside theknee cap. Remember that the foot includes the sole of your human foot, the peak of your foot, and your toes.

Figure Eastward, F and Effigy Thousand

VOLTAREN® GEL (diclofenac sodium topical gel) Figure E, F and Figure G Illustration

Refer to Steps 4 and 5 above. Wash your hands later on applying VOLTAREN® GEL to your foot,ankle, or knee.

What are the ingredients in VOLTAREN® GEL?

Active ingredient: diclofenac sodium

Inactive ingredients: carbomer homopolymer Blazon C, cocoyl caprylocaprate, fragrance, isopropyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water, and strong ammonia solution.

How should I shop VOLTAREN® GEL? Store at 20°C to 25°C (68°F to 77°F). Exercise not freezeVOLTAREN® GEL. Store the dosing menu with your VOLTAREN® GEL.

Go on VOLTAREN® GEL, the dosing card, and all medicines out of the attain of children.

This Medication Guide and Instructions for Use accept been canonical past the U.Due south. Nutrient and Drug Administration.