Voltaren

Voltaren is part of the drug class:

• Acetic acid derivatives and related substances

Cardiovascular Risk

• Nonsteroidal anti-inflammatory drugs (NSAIDs) may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk.
• Voltaren is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Gastrointestinal Risk

• NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events.

This section provides information on the proper use of a number of products that contain diclofenac. It may not be specific to Voltaren. Please read with care.

Keep using this medicine for the full time of treatment. However, do not use this medicine more often or for a longer time than your doctor ordered. This medicine is not for long-term use.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

When used for severe or continuing arthritis, this medicine must be taken every day as ordered by your doctor in order for it to help you. This medicine usually begins to work within one week, but in severe cases up to two weeks or longer may pass before you begin to feel better. Several weeks may pass before you feel the full effects of this medicine.

You may take this medicine with or without food. However, diclofenac capsules should be taken on an empty stomach.

To use the oral solution:

• Open the packet of medicine right before you use it.
• Empty the contents of the packet into a cup with 1 to 2 ounces (30 to 60 milliliters [mL]) of water. Do not use any liquid other than water for mixing the medicine.
• Mix well and drink it immediately on an empty stomach.

Use only the brand of this medicine that your doctor prescribed. Different brands may not work the same way.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For acute pain:
    • Adults—18 or 35 milligrams (mg) three times a day.
    • Children—Use and dose must be determined by your doctor.
  • For osteoarthritis:
    • Adults—35 milligrams (mg) three times a day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage forms (delayed-release tablets, enteric-coated tablets):
  • For ankylosing spondylitis:
    • Adults—25 milligrams (mg) four times a day, with an extra 25 mg dose at bedtime if necessary.
    • Children—Use and dose must be determined by your doctor.
  • For osteoarthritis:
    • Adults—50 milligrams (mg) two or three times a day, or 75 mg two times a day.
    • Children—Use and dose must be determined by your doctor.
  • For rheumatoid arthritis:
    • Adults—50 milligrams (mg) three or four times a day, or 75 mg two times a day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (immediate-release tablets):
  • For osteoarthritis:
    • Adults—50 milligrams (mg) two or three times a day.
    • Children—Use and dose must be determined by your doctor.
  • For pain or menstrual cramps:
    • Adults—50 milligrams (mg) three times a day. Your doctor may direct you to take 100 mg for the first dose only.
    • Children—Use and dose must be determined by your doctor.
  • For rheumatoid arthritis:
    • Adults—50 milligrams (mg) three or four times a day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (solution):
  • For migraine headaches:
    • Adults—One packet (50 milligrams) as a single, one time dose.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

General

Voltaren® (diclofenac sodium enteric-coated tablets) cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

      The pharmacological activity of Voltaren in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Hematological Effects

Anemia is sometimes seen in patients receiving NSAIDs, including Voltaren. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Voltaren, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

      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 receiving Voltaren who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Preexisting Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross-reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Voltaren should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Information for Patients

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

1. Voltaren, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects).
   
2. Voltaren, like other NSAIDs, can cause GI discomfort and, rarely, more serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation).
   
3. Voltaren, 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 the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
   
4. Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
   
5. Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy (see WARNINGS, Hepatic Effects).
   
6. Patients should be informed of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS, Anaphylactic Reactions).
   
7. In late pregnancy, as with other NSAIDs, Voltaren should be avoided because it will cause premature closure of the ductus arteriosus.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. In patients on long-term treatment with NSAIDs, including Voltaren, the CBC and a chemistry profile (including transaminase levels) should be checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Voltaren should be discontinued.

Drug Interactions

Aspirin: When Voltaren is administered with aspirin, its protein binding is reduced. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of diclofenac and aspirin is not generally recommended because of the potential of increased adverse effects.

Methotrexate: NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.

Cyclosporine: Voltaren, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Therefore, concomitant therapy with Voltaren may increase cyclosporine’s nephrotoxicity. Caution should be used when Voltaren is administered concomitantly with cyclosporine.

ACE Inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.

Furosemide: Clinical studies, as well as postmarketing observations, have shown that Voltaren can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.

Lithium: NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.

Warfarin: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.

CYP2C9 Inhibitors or Inducers: Diclofenac is metabolized by cytochrome P450 enzymes, predominantly by CYP2C9. Co-administration of diclofenac with CYP2C9 inhibitors (e.g. voriconazole) may enhance the exposure and toxicity of diclofenac whereas co-administration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac. Use caution when dosing diclofenac with CYP2C9 inhibitors or inducers; a dosage adjustment may be warranted (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Drug Interactions).

Pregnancy

Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women.

Nonteratogenic Effects: Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.

Labor and Delivery

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of Voltaren on labor and delivery in pregnant women are unknown.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Voltaren, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

As with any NSAIDs, caution should be exercised in treating the elderly (65 years and older).

In patients taking Voltaren® (diclofenac sodium enteric-coated tablets), or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1%-10% of patients are:

      Gastrointestinal experiences including: abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, nausea, GI ulcers (gastric/duodenal) and vomiting.

      Abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes and tinnitus.

      Additional adverse experiences reported occasionally include:

Body as a Whole: fever, infection, sepsis

Cardiovascular System: congestive heart failure, hypertension, tachycardia, syncope

Digestive System: dry mouth, esophagitis, gastric/peptic ulcers, gastritis, gastrointestinal bleeding, glossitis, hematemesis, hepatitis, jaundice

Hemic and Lymphatic System: ecchymosis, eosinophilia, leukopenia, melena, purpura, rectal bleeding, stomatitis, thrombocytopenia

Metabolic and Nutritional: weight changes

Nervous System: anxiety, asthenia, confusion, depression, dream abnormalities, drowsiness, insomnia, malaise, nervousness, paresthesia, somnolence, tremors, vertigo

Respiratory System: asthma, dyspnea

Skin and Appendages: alopecia, photosensitivity, sweating increased

Special Senses: blurred vision

Urogenital System: cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria, proteinuria, renal failure

Other adverse reactions, which occur rarely are:

Body as a Whole: anaphylactic reactions, appetite changes, death

Cardiovascular System: arrhythmia, hypotension, myocardial infarction, palpitations, vasculitis

Digestive System: colitis, eructation, fulminant hepatitis with and without jaundice, liver failure, liver necrosis, pancreatitis

Hemic and Lymphatic System: agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia

Metabolic and Nutritional: hyperglycemia

Nervous System: convulsions, coma, hallucinations, meningitis

Respiratory System: respiratory depression, pneumonia

Skin and Appendages: angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria

Special Senses: conjunctivitis, hearing impairment

Carefully consider the potential benefits and risks of Voltaren® (diclofenac sodium enteric-coated tablets) and other treatment options before deciding to use Voltaren. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

      After observing the response to initial therapy with Voltaren, the dose and frequency should be adjusted to suit an individual patient’s needs.

      For the relief of osteoarthritis, the recommended dosage is 100-150 mg/day in divided doses (50 mg b.i.d. or t.i.d., or 75 mg b.i.d.).

      For the relief of rheumatoid arthritis, the recommended dosage is 150-200 mg/day in divided doses (50 mg t.i.d. or q.i.d., or 75 mg b.i.d.).

      For the relief of ankylosing spondylitis, the recommended dosage is 100-125 mg/day, administered as 25 mg q.i.d., with an extra 25-mg dose at bedtime if necessary.

      Different formulations of diclofenac [Voltaren® (diclofenac sodium enteric-coated tablets); Voltaren®-XR (diclofenac sodium extended-release tablets); Cataflam® (diclofenac potassium immediate-release tablets)] are not necessarily bioequivalent even if the milligram strength is the same.

Voltaren (diclofenac) is a nonsteroidal anti-inflammatory drug (NSAID). Diclofenac works by reducing substances in the body that cause pain and inflammation.

Voltaren is used to treat mild to moderate pain, or signs and symptoms of osteoarthritis or rheumatoid arthritis.

Voltaren may also be used for purposes not listed in this medication guide.

Ask your doctor before using Voltaren if you take an antidepressant such as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, or vilazodone. Taking any of these medicines with an NSAID may cause you to bruise or bleed easily.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• cyclosporine;

• lithium;

• methotrexate;

• rifampin;

• antifungal medicine;

• a blood thinner (warfarin, Coumadin, Jantoven);

• heart or blood pressure medication, including a diuretic or "water pill";

• other forms of diclofenac (Flector, Pennsaid, Solaraze, Voltaren Gel);

• other NSAIDs - aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), indomethacin, meloxicam, and others; or

• steroid medicine (prednisone and others).

This list is not complete. Other drugs may interact with diclofenac, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Applies to diclofenac: compounding powder, intravenous solution, oral capsule, oral delayed release tablet, oral powder for reconstitution, oral tablet, oral tablet extended release

Gastrointestinal

Very common (10% or more): Nausea (up to 24%), constipation (up to 13%)
Common (1% to 10%): Abdominal pain, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn, gastric and duodenal ulcers, vomiting
Rare (less than 0.1%): Colitis, eructation, pancreatitis
Frequency not reported: Dry mouth, esophagitis, gastritis, glossitis, hematemesis, stomatitis[Ref]

NSAIDs including this drug, can cause serious gastrointestinal (GI) events which can occur at any time, with or without warning. For patients who develop a serious upper GI event, only about 20% were symptomatic. Upper GI ulcers, gross bleeding, or perforation occurred in approximately 1% of patients treated with NSAIDs for 3 to 6 months and 2% to 4% of patients treated for 1 year. Patients with a prior history of peptic ulcer disease and/or GI bleeding had a greater than 10-fold increased risk for developing a GI bleed than patients with neither of these risk factors.[Ref]

Hepatic

Borderline elevations of 1 or more liver tests to less than 3 times the upper limit of the normal (3 x ULN) or greater elevations in transaminases occurred in about 15% of patients treated with this drug. Elevations to greater than 3 x ULN of AST occurred in about 2% (n=5700) of patients at some point during treatment. In an open-labeled trial among patients receiving NSAIDs, a higher incidence of transaminase elevations were observed in patients receiving diclofenac (the active ingredient contained in Voltaren) compared with other NSAIDs.[Ref]

Common (1% to 10%): Elevated liver enzymes
Rare (less than 0.1%): Hepatitis, jaundice, liver disorder
Very rare (less than 0.01%): Fulminant hepatitis, hepatic necrosis, hepatic failure
Postmarketing reports: Drug-induced hepatotoxicity[Ref]

Renal

Common (1% to 10%): Abnormal renal function, increased serum creatinine
Rare (less than 0.1%): Nephrotic syndrome, interstitial nephritis, renal papillary necrosis, acute renal failure, urinary frequency, nocturia, proteinuria, and hematuria[Ref]

Dermatologic

Common (1% to 10%): Pruritus, rashes
Rare (less than 0.1%): Angioedema, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria
Very rare (less than 0.01%): Bullous eruptions, eczema, erythema, erythema multiforme, toxic epidermal necrolysis (Lyell's syndrome), dermatitis exfoliative, loss of hair, photosensitivity reaction
Frequency not reported: Increased sweating[Ref]

Hematologic

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, the NSAID effect on platelet function is quantitatively less, of shorter duration, and reversible.[Ref]

Common (1% to 10%): Anemia, increased bleeding time
Rare (less than 0.1%): Agranulocytosis, hemolytic anemia, aplastic anemia, lymphadenopathy, pancytopenia
Very rare (less than 0.01%): Thrombocytopenia, leukopenia, positive Coombs' test
Frequency not reported: Ecchymosis, eosinophilia, melena, purpura, rectal bleeding[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Urticaria, rash, angioedema, bronchospasm
Rare (less than 0.1%): Anaphylactic reactions
Very rare (less than 0.01%): Angioneurotic edema (including facial edema)[Ref]

Metabolic

Rare (less than 0.1%): Changes in appetite, hyperglycemia
Frequency not reported: Weight changes[Ref]

Nervous system

Common (1% to 10%): Dizziness, headaches
Rare (less than 0.1%): Meningitis
Very rare (less than 0.01%): Memory impairment
Frequency not reported: Confusion, drowsiness, insomnia, paresthesia, tremors[Ref]

Cardiovascular

Clinical trials of several cyclooxygenase (COX)-2 selective and nonselective NSAIDs of up to 3 years duration have shown an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs appear to have a similar risk. There is no consistent evidence that concurrent use of aspirin mitigates this increased risk and may be associated with an increased risk of serious gastrointestinal events.

Pharmacoepidemiological data reveal an increased risk of arteriothrombotic events associated with diclofenac (the active ingredient contained in Voltaren) use, particularly at a high dose and during long-term treatment. In a meta-analysis of long-term treatment with diclofenac 150 mg/day, compared with placebo use of this drug resulted in approximately 3 additional major vascular events per 1000 participants.[Ref]

Common (1% to 10%): Edema
Uncommon (0.1% to 1%): Cardiac failure, chest pain
Rare (less than 0.1%): Arrhythmia, hypotension, myocardial infarction, palpitations
Very rare (less than 0.01%): Vasculitis
Frequency not reported: Congestive heart failure, tachycardia, syncope, hypertension[Ref]

Psychiatric

Rare (less than 0.1%): Hallucinations
Very rare (less than 0.01%): Disorientation, depression, nightmare, irritability, psychotic disorder
Frequency not reported: Anxiety, nervousness[Ref]

Other

Common (1% to 10%): Tinnitus,
Rare (less than 0.1%): Hearing impairment
Frequency not reported: Fever, asthenia, vertigo[Ref]

Ocular

Rare (less than 0.1%): Conjunctivitis
Very rare (less than 0.01%): Blurred vision, visual disturbance, diplopia
Frequency not reported: Optic neuritis

General

The most common adverse reactions among patients treated with this drug included; gastrointestinal events of abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding,/perforation, heartburn, nausea, gastric and duodenal ulcers, and vomiting; abnormal renal function, anemia, dizziness, edema, elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, and tinnitus.

Genitourinary

Common (1% to 10%): Urinary tract infection
Frequency not reported: Cystitis, dysuria, hematuria, interstitial nephritis, oliguria/polyuria

Immunologic

Frequency not reported: Infection, sepsis

Local

Common (1% to 10%): Local reactions such as itching, burning, and increased bowel movement with suppository use
Very rare (less than 0.01%): Exacerbation of hemorrhoids with suppository use

Respiratory

Common (1% to 10%): Sinusitis, upper respiratory infection, nasopharyngitis, bronchitis
Rare (less than 0.1%): Pneumonia
Frequency not reported: Asthma, dyspnea

Some side effects of Voltaren may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.