DICLOFENAC SODIUM tablet, delayed release

Drug Details [pdf]

SPL UNCLASSIFIED SECTION

Rx only

Prescribing information
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 sodium delayed-release tablets are contraindicated for the treatment of perioperative 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 inflammation, 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).
DESCRIPTION

Diclofenac sodium delayed-release tablets are a benzene-acetic acid derivative. Diclofenac sodium delayed-release tablets are available as delayed-release tablets of 75 mg for oral administration. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monosodium salt. The molecular weight is 318.14. Its molecular formula is C14H10Cl2NNaO2, and it has the following structural formula

The inactive ingredients in Diclofenac sodium delayed-release tablets include: lactose (monohydrate), microcrystalline cellulose, croscarmellose sodium, povidone, talc, magnesium stearate, methacrylic acid copolymer, polyethylene glycol, opadry brown (Titanium dioxide, hypromellose, polyethylene glycol, iron oxide red, iron oxide yellow) and purified water.

CLINICAL PHARMACOLOGY

Pharmacodynamics

Diclofenac sodium delayed-release tablets, are a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of diclofenac sodium delayed-release tablets, 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 (see Table 1). Food has no significant effect on the extent of diclofenac absorption. However, there is usually a delay in the onset of absorption of 1 to 4.5 hours and a reduction in peak plasma levels of <20%.

Table 1. Pharmacokinetic Parameters for Diclofenac
	Normal Healthy Adults (20-48 yrs.)
PK Parameter	Mean	Coefficient of Mean Variation (%)
Absolute Bioavailability (%) [N = 7]	55	40
Tmax (hr) [N = 56]	2.3	69
Oral Clearance (CL/F; mL/min) [N = 56]	582	23
Renal Clearance (% unchanged drug in urine) [N = 7]	<1	–
Apparent Volume of Distribution (V/F; L/kg) [N = 56]	1.4	58
Terminal Half-life (hr) [N = 56]	2.3	48

Distribution

The apparent volume of distribution (V/F) of diclofenac sodium is 1.4 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. The major Diclofenac metabolite, 4'-hydroxy-Diclofenac, has very weak pharmacologic activity. The formation of 4’-hydroxy- Diclofenac is primarily mediated by CPY2C9. Both Diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CPY2C8 may also play a role in Diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy- and 3’-hydroxy-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.

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.

Drug Interactions

When co-administered with voriconazole (inhibitor of CYP2C9, 2C19 and 3A4 enzyme), the Cmax and AUC of Diclofenac increased by 114% and 78%, respectively (see PRECAUTIONS, Drug Interactions).

Special Populations

Pediatric: The pharmacokinetics of diclofenac sodium delayed-release tablets 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 sodium delayed-release tablets elimination, so patients with hepatic disease may require reduced doses of diclofenac sodium delayed-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 <30 mL/min; N=6 in each group), AUC values and elimination rate were comparable to those in healthy subjects.

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

Diclofenac sodium delayed-release tablets, are indicated:
- For relief of signs and symptoms of osteoarthritis
- For relief of signs and symptoms of rheumatoid arthritis
- For acute or long-term use in the relief of signs and symptoms of ankylosing spondylitis
CONTRAINDICATIONS

Diclofenac sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to diclofenac.

Diclofenac sodium delayed-release tablets should not be given to 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 (see WARNINGS, Anaphylactoid Reactions, and PRECAUTIONS, Preexisting Asthma).

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

Gastrointestinal (GI) Effects – Risk of GI Ulceration, Bleeding, and Perforation

NSAIDs, including diclofenac sodium delayed-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 sodium delayed-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 NSAID 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 sodium delayed-release tablets in patients with advanced renal disease. Therefore, treatment with diclofenac sodium delayed-release tablets are not recommended in these patients with advanced renal disease. If diclofenac sodium delayed-release tablets therapy must be initiated, close monitoring of the patient’s renal function is advisable.

Hepatic Effects

Elevations of one or more liver tests may occur during therapy with Diclofenac delayed-release tablets. 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 the 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/or AST 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 firth 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 reaction 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 delayed-release tablets 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 delayed-release tablets, the lowest effective dose should be used for the shortest duration possible. Caution should be exercised in prescribing Diclofenac sodium delayed-release tablets with concomitant drugs that are known to be potentially hepatotoxic (e.g., antibiotics, anti-epileptics).

Anaphylactic Reactions

As with other NSAIDs, anaphylactic reactions may occur both in patients with the aspirin traid and in patients without known sensitivity to NSAIDs or known prior exposure to Diclofenac Sodium Delayed-release Tablets. Diclofenac Sodium Delayed-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.) Anaphylaxis-type reactions have been reported with NSAID products, including with Diclofenac products, such as Diclofenac Sodium Delayed-Release Tablet. Emergency help should be sought in cases where an anaphylactoid reaction occurs.

Skin Reactions

NSAIDs, including diclofenac sodium delayed-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 sodium delayed-release tablets should be avoided because it may cause premature closure of the ductus arteriosus.
ADVERSE REACTIONS

In patients taking diclofenac sodium delayed-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, 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
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 a 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 AND ADMINISTRATION

Carefully consider the potential benefits and risks of diclofenac sodium delayed-release tablets and other treatment options before deciding to use diclofenac sodium delayed-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 sodium delayed-release tablets, 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 (diclofenac sodium enteric-coated tablets; diclofenac sodium extended-release tablets, diclofenac potassium immediate-release tablets) are not necessarily bioequivalent even if the milligram strength is the same.
HOW SUPPLIED

35356-714-14

35356-714-20

35356-714-28

35356-714-30

35356-714-60

35356-714-90

35356-725-30

35356-725-60

35356-725-90

MEDICATION GUIDE

MEDICATION GUIDE for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(See the end of this Medication Guide for a list of prescription NSAID medicines.)

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 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)?

Serious side effects include:

heart attack
stroke
high blood pressure
heart failure from body swelling (fluid retention)
kidney problems including kidney failure
bleeding and ulcers in the stomach and intestine
low red blood cells (anemia)
life-threatening skin reactions
life-threatening allergic reactions
liver problems including liver failure
asthma attacks in people who have asthma

Other side effects include:

stomach pain
constipation
diarrhea
gas
heartburn
nausea
vomiting
dizziness

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

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

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

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

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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.

NSAID medicines that need a prescription

Generic Name	Tradename
*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.
Celecoxib	Celebrex®
Diclofenac	Cataflam®, Voltaren®, Arthrotec™ (combined with misoprostol)
Diflunisal	Dolobid®
Etodolac	Lodine®, Lodine® XL
Fenoprofen	Nalfon®, Nalfon ®200
Flurbiprofen	Ansaid®
Ibuprofen	Motrin®, Tab-Profen®, Vicoprofen®* (combined with hydrocodone), Combunox™ (combined with oxycodone)
Indomethacin	Indocin®, Indocin ® SR, Indo-Lemmon™, Indomethagan™
Ketoprofen	Oruvail®
Ketorolac	Toradol®
Mefenamic Acid	Ponstel®
Meloxicam	Mobic®
Nabumetone	Relafen®
Naproxen	Naprosyn®, Anaprox®, Anaprox ®DS, EC-Naproxyn™, Naprelan®, Naprapac® (copackaged with lansoprazole)
Oxaprozin	Daypro®
Piroxicam	Feldene®
Sulindac	Clinoril®
Tolmetin	Tolectin®, Tolectin DS®, Tolectin® 600

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.

Manufactured by:

UNIQUE PHARMACEUTICAL LABORATORIES.
(A Div. of J. B. Chemicals & Pharmaceuticals Ltd.)
Mumbai 400 030, India.

Marketed by:

PACK Pharmaceuticals, LLC
Buffalo Grove, IL 60089

PRINCIPAL DISPLAY PANEL
PRINCIPAL DISPLAY PANEL

INGREDIENTS AND APPEARANCE

DICLOFENAC SODIUM
diclofenac sodium tablet, delayed release

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 35356-714(NDC:16571-201)
Route of Administration	ORAL

Ingredient Name	Basis of Strength	Strength
Active Ingredient/Active Moiety
Diclofenac Sodium (UNII: QTG126297Q) (DICLOFENAC - UNII:144O8QL0L1)	Diclofenac Sodium	75 mg

Ingredient Name	Strength
Inactive Ingredients
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
croscarmellose sodium (UNII: M28OL1HH48)
POVIDONE (UNII: FZ989GH94E)
talc (UNII: 7SEV7J4R1U)
magnesium stearate (UNII: 70097M6I30)
METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A (UNII: NX76LV5T8J)
POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
Titanium dioxide (UNII: 15FIX9V2JP)
hypromelloses (UNII: 3NXW29V3WO)
FERRIC OXIDE RED (UNII: 1K09F3G675)
FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
water (UNII: 059QF0KO0R)

Product Characteristics
Color	brown (Light Brown)	Score	no score
Shape	ROUND (round)	Size	10mm
Flavor		Imprint Code	P;75
Contains

#	Item Code	Package Description	Marketing Start Date	Marketing End Date
Packaging
1	NDC: 35356-714-14	14 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013	06/01/2014
2	NDC: 35356-714-15	15 in 1 BOTTLE; Type 0: Not a Combination Product	04/21/2017	10/11/2019
3	NDC: 35356-714-20	20 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013
4	NDC: 35356-714-28	28 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013	06/01/2014
5	NDC: 35356-714-30	30 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013
6	NDC: 35356-714-60	60 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013
7	NDC: 35356-714-90	90 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013

Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Marketing Information
ANDA	ANDA077863	08/19/2008

DICLOFENAC SODIUM
diclofenac sodium tablet, delayed release

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 35356-725(NDC:16571-202)
Route of Administration	ORAL

Ingredient Name	Basis of Strength	Strength
Active Ingredient/Active Moiety
Diclofenac Sodium (UNII: QTG126297Q) (Diclofenac - UNII:144O8QL0L1)	Diclofenac Sodium	50 mg

Ingredient Name	Strength
Inactive Ingredients
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
croscarmellose sodium (UNII: M28OL1HH48)
POVIDONE (UNII: FZ989GH94E)
talc (UNII: 7SEV7J4R1U)
magnesium stearate (UNII: 70097M6I30)
METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A (UNII: NX76LV5T8J)
POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
Titanium dioxide (UNII: 15FIX9V2JP)
hypromelloses (UNII: 3NXW29V3WO)
FERRIC OXIDE RED (UNII: 1K09F3G675)
FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
water (UNII: 059QF0KO0R)

Product Characteristics
Color	brown (Light Brown)	Score	no score
Shape	ROUND (round)	Size	8mm
Flavor		Imprint Code	P;50
Contains

#	Item Code	Package Description	Marketing Start Date	Marketing End Date
Packaging
1	NDC: 35356-725-30	30 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013	12/31/2019
2	NDC: 35356-725-60	60 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013
3	NDC: 35356-725-90	90 in 1 BOTTLE; Type 0: Not a Combination Product	02/07/2013	10/11/2019

Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
Marketing Information
ANDA	ANDA090066	12/31/2010

Labeler - Lake Erie Medical DBA Quality Care Products LLC (831276758)

Name	Address	ID/FEI	Business Operations
Establishment
Lake Erie Medical DBA Quality Care Products LLC		831276758	repack(35356-714, 35356-725)