Voltaren Information
Voltaren (Diclofenac) Indications And Usage
Voltaren (Diclofenac) ® Gel is indicated for the relief of the pain of osteoarthritis of joints amenable to topical treatment, such as the knees and those of the hands.
Voltaren (Diclofenac) Dosage And Administration
Apply the gel (2 g) to the affected hand or elbow or wrist, 4 times daily. Voltaren (Diclofenac) ® Gel should be gently massaged into the skin ensuring application to the entire affected hand or elbow or wrist. The entire hand includes the palm, back of the hands, and the fingers. Do not apply more than 8 g daily to any single joint of the upper extremities.
Total dose should not exceed 32 g per day, over all affected joints.
Voltaren (Diclofenac) Contraindications
The use of Voltaren (Diclofenac) ® Gel is contraindicated in patients with a known hypersensitivity to diclofenac.
Voltaren (Diclofenac) ® Gel should not be administered in patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients
Voltaren (Diclofenac) ® Gel is contraindicated in the setting of coronary artery bypass graft (CABG) surgery ).
Voltaren (Diclofenac) Warnings And Precautions
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with NSAIDs, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV toxicity 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 NSAIDs use. The concurrent use of aspirin and NSAIDs such as diclofenac, does increase the risk of serious GI events
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke
NSAIDs, including diclofenac, can cause serious gastrointestinal (GI) events including bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.
NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAIDs therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. Physicians and patients should remain alert for signs and symptoms of GI ulceration and bleeding during diclofenac therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered.
Elevations of one or more liver tests may occur during therapy with diclofenac sodium. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continued therapy. Borderline elevations (i.e. less than 3 times the ULN [ULN = the upper limit of normal range]) or greater elevations of transaminases occurred in about 15% of diclofenac-treated patients. Of the markers of hepatic function, ALT (SGPT) is recommended for the monitoring of liver injury.
In clinical trials, meaningful elevations (i.e., more than 3 times the ULN) of AST (GOT) (ALT was not measured in all studies) occurred in about 2% of approximately 5,700 patients at some time during diclofenac treatment. In a large, open-label, controlled trial of 3,700 patients treated for 2-6 months, patients were monitored first at 8 weeks and 1,200 patients were monitored again at 24 weeks. Meaningful elevations of ALT and/orAST occurred in about 4% of patients and included marked elevations (i.e., more than 8 times the ULN) in about 1% of the 3,700 patients. In that open-label study, a higher incidence of borderline (less than 3 times the ULN), moderate (3-8 times the ULN), and marked (>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 frequently in patients with osteoarthritis than in those with rheumatoid arthritis.
Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations.
In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any 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.
Physicians should measure transaminases 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 be monitored within 4 to 8 weeks after initiating treatment with diclofenac. However, severe hepatic reactions can occur at any time during treatment with diclofenac.
If abnormal liver tests persist or worsen, if clinical signs and/or symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, abdominal pain, diarrhea, dark urine, etc.), diclofenac sodium should be discontinued immediately. To minimize the possibility that hepatic injury will become severe between transaminase measurements, physicians should inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms), and the appropriate action patients should take if these signs and symptoms appear.
To minimize the potential risk for an adverse liver related event in patients treated with diclofenac sodium, the lowest effective dose should be used for the shortest duration possible. Caution should be exercised in prescribing diclofenac sodium with concomitant drugs that are know to be potentially hepatotoxic (e.g., antibiotics, anti-epileptics).
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 role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE-inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of Voltaren (Diclofenac) ® Gel in patients with advanced renal disease. Therefore, treatment with Voltaren (Diclofenac) ® Gel is not recommended in patients with advanced renal disease. If Voltaren (Diclofenac) ® Gel therapy is initiated, close monitoring of the patient's renal function is advisable.
NSAIDs, including Voltaren (Diclofenac) ® Gel, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations, and the use of the drug should be discontinued at the first appearance of skin rash or any other signs of hypersensitivity.
Voltaren (Diclofenac) ® Gel should not be applied to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and tolerability of the drug. Voltaren (Diclofenac) ® Gel should not be allowed to come into contact with the eyes or with mucous membranes.
The effect of Voltaren (Diclofenac) ® Gel under occlusive dressings has not been evaluated, and should be avoided.
Anemia is sometimes seen in patients receiving NSAIDs. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoeisis. Patients on long-term treatment with NSAIDs, including Voltaren (Diclofenac) ® Gel, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia or blood loss.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients treated with Voltaren (Diclofenac) ® Gel who may be adversely affected by alteration in platelet function, such as those with coagulation disorders or patients receiving anticoagulants should be carefully monitored.
Voltaren (Diclofenac) Drug Interactions
Voltaren (Diclofenac) Use In Specific Populations
The safety of Voltaren (Diclofenac) ® Gel has not been established during pregnancy. There are no well-controlled studies of diclofenac in pregnant women. Human and animal studies indicate that diclofenac crosses the placenta. In late pregnancy, as with other NSAIDs, Voltaren (Diclofenac) ® Gel should be avoided because it may cause premature closure of the ductus arteriosus.
Teratogenic effects
Pregnancy Category C: Studies in mice, rats, and rabbits in which diclofenac was administered orally throughout gestation revealed no evidence of teratogenicity despite the induction of maternal toxicity and fetal toxicity corresponding to a human equivalent dose approximately 4.5-, 2-, and 9-fold (mouse, rat, rabbit, respectively) of the maximum human topical dose of Voltaren (Diclofenac) ® Gel (based on bioavailability and body surface area comparison).
Nonteratogenic effects
The use of diclofenac, as with other NSAIDs, is associated with the adverse fetal cardiovascular effect of premature closure of the ductus arteriosus.
Of the total number of subjects treated with Voltaren (Diclofenac) ® Gel in clinical studies, 498 were 65 years of age and over. No overall differences in effectiveness or safety were observed between 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 (Diclofenac) ® Gel may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when using Voltaren (Diclofenac) ® Gel in the elderly, and it may be useful to monitor renal function.
Voltaren (Diclofenac) Overdosage
There has been no experience of overdose with Voltaren (Diclofenac) ® Gel.
No events of accidental ingestion have been reported with Voltaren (Diclofenac) Gel. Effects similar to those observed after an overdose of diclofenac tablets can be expected if substantial amounts of Voltaren (Diclofenac) ® Gel are ingested. Symptoms following acute oral NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur after an overdose.
In the event of oral ingestion resulting in significant systemic side effects, it is recommended that the stomach be emptied by vomiting or lavage. Forced diuresis may theoretically be beneficial because the drug is excreted in the urine. The effect of dialysis or hemoperfusion in the elimination of diclofenac (99% protein-bound) remains unproven. In addition to supportive measures, the use of oral activated charcoal may help to reduce the absorption of diclofenac. Supportive and symptomatic treatment should be given for complications such as renal failure, convulsions, gastrointestinal irritation, and respiratory depression.
For additional information about overdose treatment, call a poison control center (1-800-222-1222).
Voltaren (Diclofenac) Description
Voltaren (Diclofenac) ® Gel (diclofenac sodium topical gel) is a nonsteroidal anti-inflammatory drug (NSAID) for topical use only. It contains the active ingredient, diclofenac sodium, in an opaque, white gel base. Diclofenac sodium is a white to slightly yellow crystalline powder. Diclofenac sodium is a benzene–acetic acid derivative. The chemical name is 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is CHCNNaO. It has the following structural formula:
Voltaren (Diclofenac) ® Gel also contains carbomer homopolymer Type C, cocoyl caprylocaprate, fragrance, isopropyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water, and strong ammonia solution.
Voltaren (Diclofenac) Clinical Pharmacology
The pharmacokinetics of Voltaren (Diclofenac) ® Gel were assessed in healthy volunteers following repeated applications during 7 days of Voltaren (Diclofenac) ® 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.
C = maximum plasma concentration; t = time of C;AUC = area
under the concentration-time curve; SD = standard deviation; CI = confidence interval.
Systemic exposure (area under the concentration-time curve) and maximum plasma concentrations of diclofenac are significantly lower with Voltaren (Diclofenac) ® Gel than with comparable oral treatment of diclofenac sodium.
Systemic exposure with recommended use of Voltaren (Diclofenac) ® 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 (Diclofenac) ® 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 (Diclofenac) ® 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 (Diclofenac) ® Gel (4 x 4 g per day applied to 1 knee) is 158 times lower than with the oral treatment.
The pharmacokinetics of Voltaren (Diclofenac) ® 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 (Diclofenac) ® Gel (4 x 4 g per day on 1 knee) with and under the conditions tested. However, the pharmacokinetics of Voltaren (Diclofenac) ® Gel were not tested under the condition of heat application following gel application. Therefore, concurrent use of Voltaren (Diclofenac) ® Gel and heat is not recommended.
Voltaren (Diclofenac) How Supplied/storage And Handling
Voltaren (Diclofenac) ® 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%).
20 gram tube (physician’s sample) NDC 63481-684-83
100 gram tube NDC 63481-684-47
3 Carton (3 Tubes containing 100 gram each) NDC 63481-684-03
5 Carton (5 Tubes containing 100 gram each) NDC 63481-684-05
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature]
Keep from freezing.
Voltaren (Diclofenac) Patient Counseling Information
Voltaren (Diclofenac) ® Gel, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms
Patients should be advised to stop Voltaren (Diclofenac) ® Gel immediately if they develop any type of rash and contact their physicians as soon as possible.
Patients should be instructed not to apply Voltaren (Diclofenac) ® Gel to open skin wounds, infections, inflammations, or exfoliative dermatitis, as it may affect absorption and tolerability of the drug.
Patients should be instructed to avoid concomitant use of Voltaren (Diclofenac) ® Gel with other topical products, including sunscreens, cosmetics lotions, moisturizers, insect repellants, on the treated skin site. Concomitant use may result in skin reactions or change the absorption of Voltaren (Diclofenac) ® Gel.
Patients should be instructed to minimize or avoid exposure of treated areas to natural or artificial sunlight.
Patients should be instructed to avoid contact of Voltaren (Diclofenac) ® Gel with the eyes and mucosa, although not studied, should be avoided. Patients should be advised that if eye contact occurs, they should immediately wash out the eye with water or saline and consult a physician if irritation persists for more than an hour.
Comments or Questions?
Call toll-free 1-800-452-0051
©2009 Novartis Consumer Health, Inc., Parsippany, NJ 07054. All Trademarks owned and licensed by Novartis AG
42035D / October 2009
Voltaren (Diclofenac) Medical Guide
NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:
These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.
*Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC) NSAID, and is usually used for less than 10 days to treat pain. The OTC NSAID label warns that long term continuous use may increase the risk of heart attack or stroke.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Revised: June 2008
Voltaren (Diclofenac) Patient Package Insert
Your doctor has prescribed Voltaren (Diclofenac) Gel to help relieve arthritis pain in some of your joints. Voltaren (Diclofenac) Gel may be used to treat arthritis pain:
The dose for your hands, elbows or wrists is 2 grams of Voltaren (Diclofenac) Gel each time you apply it.
The dose for your knees, ankles or feet is 4 grams of Voltaren (Diclofenac) Gel each time you apply it.
Some examples include:
Store Voltaren (Diclofenac) ® Gel at room temperature, 59° F to 86°F (15°C to 30°C).
All registered trademarks in this document are the property of their respective owners.
Comments or Questions?
Call toll-free 1-800-452-0051
©2009 Novartis Consumer Health, Inc., Parsippany, NJ 07054. All Trademarks owned and licensed by Novartis AG
42035D/ October 2009
Voltaren (Diclofenac) Principal Display Panel
