DICLOFENAC POTASSIUM tablet, film coated

Drug Details [pdf]

DESCRIPTION

DESCRIPTION
Diclofenac potassium is a benzeneacetic acid derivative. Diclofenac potassium is available as immediate-release tablets of 50 mg (light brown) for oral administration. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monopotassium salt. The molecular weight is 334.25. Its molecular formula is C14H10Cl2NKO2, and it has the following structural formula:

Each diclofenac potassium immediate-release tablet, intended for oral administration, contains 50 mg diclofenac potassium for oral administration. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydroxyethyl cellulose, iron oxides, magnesium stearate, methanol, polyethylene glycol, povidone, sodium bicarbonate and titanium dioxide.
CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY Pharmacodynamics
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of diclofenac, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.
Pharmacokinetics Absorption
Diclofenac is 100% absorbed after oral administration compared to IV administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available. In some fasting volunteers, measurable plasma levels are observed within 10 minutes of dosing with diclofenac potassium immediate-release tablets. Peak plasma levels are achieved approximately 1 hour in fasting normal volunteers, with a range of .33 to 2 hours. Food has no significant effect on the extent of diclofenac absorption. However, there is usually a delay in the onset of absorption and a reduction in peak plasma levels of approximately 30%.
Distribution
The apparent volume of distribution (V/F) of diclofenac potassium is 1.3 L/kg.

Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15-105 µg/mL) achieved with recommended doses.

Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels. It is not known whether diffusion into the joint plays a role in the effectiveness of diclofenac.
Metabolism
Five diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy diclofenac. In patients with renal dysfunction, peak concentrations of metabolites 4'-hydroxy- and 5-hydroxy-diclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects. However, diclofenac metabolites undergo further glucuronidation and sulfation followed by biliary excretion.

One diclofenac metabolite 4’-hydroxy-diclofenac has very weak pharmacologic activity.
Excretion
Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. Because renal elimination is not a significant pathway of elimination for unchanged diclofenac, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary. The terminal half-life of unchanged diclofenac is approximately 2 hours.
Special Populations Pediatric:
The pharmacokinetics of diclofenac has not been investigated in pediatric patients.
Race:
Pharmacokinetics differences due to race have not been identified.
Hepatic Insufficiency:
Hepatic metabolism accounts for almost 100% of diclofenac elimination, so patients with hepatic disease may require reduced doses of diclofenac potassium immediate-release tablets compared to patients with normal hepatic function.
Renal Insufficiency:
Diclofenac pharmacokinetics has been investigated in subjects with renal insufficiency. No differences in the pharmacokinetics of diclofenac have been detected in studies of patients with renal impairment. In patients with renal impairment (inulin clearance 60-90, 30-60, and less than 30 mL/min; N=6 in each group), AUC values and elimination rate were comparable to those in healthy subjects.
INDICATIONS & USAGE
INDICATIONS AND USAGE
Carefully consider the potential benefits and risks of diclofenac potassium immediate-release tablets and other treatment options before deciding to use diclofenac potassium immediate-release tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

Diclofenac potassium immediate-release tablets are indicated:
- For treatment of primary dysmenorrhea
- For relief of mild to moderate pain
- For relief of the signs and symptoms of osteoarthritis
- For relief of the signs and symptoms of rheumatoid arthritis
CONTRAINDICATIONS

CONTRAINDICATIONS
Diclofenac potassium immediate-release tablets are contraindicated in patients with known hypersensitivity to diclofenac. Diclofenac potassium immediate-release tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS, Anaphylactoid Reactions, and PRECAUTIONS, Preexisting Asthma).

Diclofenac potassium immediate-release tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
WARNINGS

WARNINGS CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events
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 an NSAID, 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 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 does increase the risk of serious GI events (see GI WARNINGS).

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 (see CONTRAINDICATIONS).
Hypertension
NSAIDs, including diclofenac potassium immediate-release tablets, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including diclofenac potassium immediate-release tablets, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Congestive Heart Failure and Edema
Fluid retention and edema have been observed in some patients taking NSAIDs. Diclofenac potassium immediate-release tablets should be used with caution in patients with fluid retention or heart failure.
Gastrointestinal Effects- Risk of Ulceration, Bleeding, and Perforation:
NSAIDs, including diclofenac potassium immediate-release tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, 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 those 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 for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID 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 in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
Renal Effects
Caution should be used when initiating treatment with diclofenac potassium immediate-release tablets in patients with considerable dehydration.

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 a nonsteroidal anti-inflammatory drug 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 nonsteroidal anti-inflammatory drug therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease
No information is available from controlled clinical studies regarding the use of diclofenac potassium immediate-release tablets in patients with advanced renal disease. Therefore, treatment with diclofenac potassium immediate-release tablets is not recommended in these patients with advanced renal disease. If diclofenac potassium immediate-release tablets therapy must be initiated, close monitoring of the patient's renal function is advisable.
Anaphylactoid Reactions
As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to diclofenac potassium immediate-release tablets. Diclofenac potassium immediate-release tablets should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs. (See CONTRAINDICATIONS and PRECAUTIONS, Preexisting Asthma.) Emergency help should be sought in cases where an anaphylactoid reaction occurs.
Skin Reactions
NSAIDs, including diclofenac potassium immediate-release tablets, 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 use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Pregnancy
In late pregnancy, as with other NSAIDs, diclofenac potassium immediate-release tablets should be avoided because it may cause premature closure of the ductus arteriosus.
PRECAUTIONS

PRECAUTIONS General
Diclofenac potassium immediate-release 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 diclofenac in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Hepatic Effects
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including diclofenac potassium immediate-release tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continued therapy. Based on this experience, in patients on chronic treatment with diclofenac potassium immediate-release tablets, periodic monitoring of transaminases is recommended (see PRECAUTIONS, Laboratory Tests). Notable elevations of ALT or AST (three or more times the upper limit of normal) have been reported in approximately 2%-4% of patients, including marked elevations (eight or more times the upper limit of normal) in about 1% of patients in clinical trials with diclofenac. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with diclofenac potassium immediate-release tablets. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), diclofenac potassium immediate-release tablets should be discontinued.
Hematological Effects
Anemia is sometimes seen in patients receiving NSAIDs, including diclofenac potassium immediate-release tablets. This may be due to fluid retention, GI loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including diclofenac potassium immediate-release tablets, 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 diclofenac potassium immediate-release tablets 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, diclofenac potassium immediate-release tablets should not be administered to patients with this form of aspirin sensitivity and should be used with caution in all patients with preexisting asthma.
ADVERSE REACTIONS

ADVERSE REACTIONS
In 718 patients treated for shorter periods, i.e., 2 weeks or less, with diclofenac potassium immediate-release tablets, adverse reactions were reported one-half to one-tenth as frequently as by patients treated for longer periods. In a 6-month, double-blind trial comparing diclofenac potassium immediate-release tablets (N=196) versus diclofenac sodium delayed-release tablets (N=197) versus ibuprofen (N=197), adverse reactions were similar in nature and frequency.

In patients taking diclofenac potassium immediate-release 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, liver failure, 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
OVERDOSAGE

OVERDOSAGE
Symptoms following acute 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, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.

Patients should be managed by symptomatic and supportive care following an NSAID overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 g in adults, 1 to 2 g/kg in children) and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
DOSAGE & ADMINISTRATION

DOSAGE AND ADMINISTRATION
Carefully consider the potential benefits and risks of diclofenac potassium immediate-release tablets and other treatment options before deciding to use diclofenac potassium immediate-release tablets. 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 diclofenac potassium immediate-release tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.

For treatment of pain or primary dysmenorrhea the recommended dosage is 50 mg t.i.d. With experience, physicians may find that in some patients an initial dose of 100 mg of diclofenac potassium immediate-release tablets, followed by 50-mg doses, will provide better relief.

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.

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.

Different formulations of diclofenac, like diclofenac sodium enteric-coated tablets, diclofenac sodium extended-release tablets or diclofenac potassium immediate-release tablets are not necessarily bioequivalent even if the milligram strength is the same.
HOW SUPPLIED

HOW SUPPLIED

Diclofenac Potassium Tablets 50 mg are available for oral administration as light brown, round shaped, unscored, film coated tablets, imprinted “APO” on one side and “DP” over “50” on the other side. They are supplied as follows:

Bottles of 100 NDC: 60505-0135-0

Bottles of 1000 NDC: 60505-0135-1

Store at 20°-25°C (68°-77° F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container [see USP].

Apotex Inc.
Diclofenac Potassium Tablets 50 mg

Manufactured by:         Manufactured for:
Apotex Inc.                 Apotex Corp.
Toronto, Ontario          Weston, Florida
Canada, M9L 1T9        33326

Revised: January 2006

Rev. 03
INFORMATION FOR PATIENTS

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. Diclofenac potassium immediate-release tablets, 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. Diclofenac potassium immediate-release tablets, 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. Diclofenac potassium immediate-release tablets, 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.

6. Patients should be informed of the signs of an anaphylactoid 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).

7. In late pregnancy, as with other NSAIDs, diclofenac potassium immediate-release tablets should be avoided because it may 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 diclofenac potassium immediate-release tablets, 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, diclofenac potassium immediate-release tablets should be discontinued.
Drug Interactions Aspirin:
When diclofenac potassium immediate-release tablets are 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:
Diclofenac potassium immediate-release tablets, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Therefore, concomitant therapy with diclofenac potassium immediate-release tablets may increase cyclosporine’s nephrotoxicity. Caution should be used when diclofenac potassium immediate-release tablets are 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.
Diuretics:
Clinical studies, as well as post-marketing observations, have shown that diclofenac 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 PRECAUTIONS – 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.
Pregnancy Teratogenic Effects: Pregnancy Category C
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. Diclofenac potassium immediate-release tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
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 diclofenac 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 diclofenac potassium immediate-release tablets, 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).
BOXED WARNING (What is this?)

Cardiovascular Risk

      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. (See WARNINGS).

      Diclofenac potassium immediate-release tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

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. (See WARNINGS).
MEDICATION GUIDE
Medication Guide

for

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:
- with longer use of NSAID medicines
- in people who have heart disease
NSAID medicines should never be used right before or after a heart surgery called a “coronary artery bypass graft (CABG).”

NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:
- can happen without warning symptoms
- may cause death
The chance of a person getting an ulcer or bleeding increases with:
- taking medicines called “corticosteroids” and “anticoagulants”
- longer use
- smoking
- drinking alcohol
- older age
- having poor health
NSAID medicines should only be used:
- exactly as prescribed
- at the lowest dose possible for your treatment
- for the shortest time needed
What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:
- different types of arthritis
- menstrual cramps and other types of short-term pain
Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?

Do not take an NSAID medicine:
- if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
- for pain right before or after heart bypass surgery
Tell your healthcare provider:
- about all of your medical conditions.
- about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist.
- if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
- if you are breastfeeding. Talk to your doctor.
What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Get emergency help right away if you have any of the following symptoms:

Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.
Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs):
- Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
- Some of these NSAID medicines are sold in lower doses without a prescription (over-the-counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.
*Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC) NSAIDs, 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.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

All registered trademarks in this document are the property of their respective owners.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: September 2008
PRINCIPAL DISPLAY PANEL

Label Image

INGREDIENTS AND APPEARANCE

DICLOFENAC POTASSIUM
diclofenac potassium tablet, film coated

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 16590-072(NDC: 60505-0135)
Route of Administration	ORAL

Ingredient Name	Basis of Strength	Strength
Active Ingredient/Active Moiety
diclofenac potassium (UNII: L4D5UA6CB4) (diclofenac - UNII:144O8QL0L1)	diclofenac potassium	50 mg

Product Characteristics
Color	brown	Score	no score
Shape	ROUND	Size	6mm
Flavor		Imprint Code	APO;DP;50
Contains

#	Item Code	Package Description
Packaging
1	NDC: 16590-072-30	30 in 1 BOTTLE
2	NDC: 16590-072-60	60 in 1 BOTTLE
3	NDC: 16590-072-90	90 in 1 BOTTLE

Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Marketing Information
ANDA	ANDA076561	03/18/2004

Labeler - Stat Rx USA (786036330)

DICLOFENAC POTASSIUM tablet, film coated

Diclofenac Potassium by

Drug Labeling and Warnings

Drug Details [pdf]