Diclofenac potassium tablets, USP are a benzeneacetic acid derivative. Diclofenac potassium tablets USP, 50 mg are available as orange, film-coated tablets for oral administration. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monopotassium salt. The structural formula is:

C14H10Cl2KNO2 M.W. 334.24 g/mol

Diclofenac potassium, USP is a faintly yellowish white to light beige, virtually odorless, slightly hygroscopic crystalline powder. It is freely soluble in methanol, soluble in ethanol and water, and practically insoluble in chloroform and in dilute acid. The n-octanol/water partition coefficient is 13.4 at pH 7.4 and 1545 at pH 5.2. It has a single dissociation constant (pKa) of 4.0 ± 0.2 at 25°C in water.

Each tablet, for oral administration, contains 50 mg of diclofenac potassium. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, corn starch, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 4000, povidone, sodium starch glycolate, titanium dioxide, and tricalcium phosphate.

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

Diclofenac potassium 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

Diclofenac is contraindicated in the following patients:

•

Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product (see ).

•

History of asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (see ).

•

In the setting of coronary artery bypass graft (CABG) surgery (see  ).

General

Diclofenac potassium 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 and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

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.

Information for Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with diclofenac and periodically during the course of ongoing therapy.

Cardiovascular Thrombotic Events

Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately (see  ).

Gastrointestinal Bleeding, Ulceration, and Perforation

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, inform patients of the increased risk for the signs and symptoms of GI bleeding (see  ).

Hepatotoxicity

Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, instruct patients to stop diclofenac and seek immediate medical therapy (see  ).

Heart Failure and Edema

Advise patients to be alert for the symptoms of congestive heart failure, including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see  ).

Anaphylactic Reactions

Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur (see  ).

Serious Skin Reactions, Including DRESS

Advise patients to stop diclofenac potassium tablets immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible (see ).

Female Fertility

Advise females of reproductive potential who desire pregnancy that NSAIDs, including diclofenac potassium tablets, may be associated with a reversible delay in ovulation (see  ).

Fetal Toxicity

Inform pregnant women to avoid use of diclofenac potassium tablets and other NSAIDs, starting at 30 weeks gestation because of the risk of the premature closure of the fetal ductus arteriosus. If treatment with diclofenac potassium tablets are needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours (see , ).

Avoid Concomitant Use of NSAIDs

Inform patients that the concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy (see ). Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.

Use of NSAIDS and Low-Dose Aspirin

Inform patients not to use low-dose aspirin concomitantly with diclofenac until they talk to their healthcare provider (see ).

Masking of Inflammation and Fever

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

Laboratory Monitoring

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically (see  ).

Drug Interactions

See Table 2 for clinically significant drug interactions with diclofenac.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term carcinogenicity studies in rats given diclofenac sodium up to 2 mg/kg/day (approximately 0.1 times the maximum recommended human dose (MRHD) of diclofenac, 200 mg/day, based on body surface area (BSA) comparison) have revealed no significant increase in tumor incidence. A 2-year carcinogenicity study conducted in mice employing diclofenac sodium at doses up to 0.3 mg/kg/day (approximately 0.007 times the MRHD based on BSA comparison) in males and 1 mg/kg/day (approximately 0.02 times the MRHD based on BSA comparison) in females did not reveal any oncogenic potential.

Mutagenesis

Diclofenac sodium did not show mutagenic activity in in vitro point mutation assays in mammalian (mouse lymphoma) and microbial (yeast, Ames) test systems and was nonmutagenic in several mammalian in vitro and in vivo tests, including dominant lethal and male germinal epithelial chromosomal studies in mice, and nucleus anomaly and chromosomal aberration studies in Chinese hamsters.

Impairment of Fertility

Diclofenac sodium administered to male and female rats at 4 mg/kg/day (approximately 0.2 times the MRHD based on BSA comparison) did not affect fertility.

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

Pregnancy

Risk Summary

Use of NSAIDs, including diclofenac potassium tablets, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of diclofenac potassium tablets use between about 20 and 30 weeks of gestation, and avoid diclofenac potassium tablets use at about 30 weeks of gestation and later in pregnancy (see ).

Premature Closure of Fetal Ductus Arteriosus

Use of NSAIDs, including diclofenac potassium tablets, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment

Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment.

There are no adequate and well-controlled studies of diclofenac potassium tablets in pregnant women.

Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, no evidence of teratogenicity was observed in mice, rats, or rabbits given diclofenac during the period of organogenesis at doses up to approximately 0.5, 0.5, and 1 times, respectively, the maximum recommended human dose (MRHD) of diclofenac, despite the presence of maternal and fetal toxicity at these doses (see Data). 

Based on published animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors, such as diclofenac, resulted in increased pre- and postimplantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses.

The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Premature Closure of Fetal Ductus Arteriosus:

Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including diclofenac potassium tablets, can cause premature closure of the fetal ductus arteriosus (see ).

Oligohydramnios/Neonatal Renal Impairment:

If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If diclofenac potassium tablets treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue diclofenac potassium tablets and follow up according to clinical practice (see ).

Data

Human Data

Premature Closure of Fetal Ductus Arteriosus:

Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus.

Oligohydramnios/Neonatal Renal Impairment:

Published studies and postmarketing reports describe maternal NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis.

Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain.

Animal Data

Reproductive and developmental studies in animals demonstrated that diclofenac sodium administration during organogenesis did not produce teratogenicity despite the induction of maternal toxicity and fetal toxicity in mice at oral doses up to 20 mg/kg/day (approximately 0.5 times the maximum recommended human dose [MRHD] of diclofenac, 200 mg/day, based on body surface area (BSA) comparison), and in rats and rabbits at oral doses up to 10 mg/kg/day (approximately 0.5 and 1 times, respectively, the MRHD based on BSA comparison). In a study in which pregnant rats were orally administered 2 or 4 mg/kg diclofenac (0.1 and 0.2 times the MRHD based on BSA) from Gestation Day 15 through Lactation Day 21, significant maternal toxicity (peritonitis, mortality) was noted. These maternally toxic doses were associated with dystocia, prolonged gestation, reduced fetal weights and growth, and reduced fetal survival. Diclofenac has been shown to cross the placental barrier in mice, rats, and humans.

Labor or Delivery

There are no studies on the effects of diclofenac during labor or delivery. In animal studies, NSAIDS, including diclofenac, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.

Nursing Mothers

Risk Summary

Based on available data, diclofenac may be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for diclofenac and any potential adverse effects on the breastfed infant from the diclofenac or from the underlying maternal condition.

Data

One woman treated orally with a diclofenac salt, 150 mg/day, had a milk diclofenac level of 100 mcg/L, equivalent to an infant dose of about 0.03 mg/kg/day. Diclofenac was not detectable in breast milk in 12 women using diclofenac (after either 100 mg/day orally for 7 days or a single 50 mg intramuscular dose administered in the immediate postpartum period).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects (see  ,  ,  ).

Diclofenac is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see , ).

The following adverse reactions are discussed in greater detail in other sections of the labeling:

•

Cardiovascular Thrombotic Events (see )

•

GI Bleeding, Ulceration and Perforation (see )

•

Hepatotoxicity (see )

•

Hypertension (see )

•

Heart Failure and Edema (see )

•

Renal Toxicity and Hyperkalemia (see )

•

Anaphylactic Reactions (see )

•

Serious Skin Reactions (see )

•

Hematologic Toxicity (see )

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In 718 patients treated for shorter periods, i.e., 2 weeks or less, with diclofenac potassium 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 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 tablets or other NSAIDs, the most frequently reported adverse experiences occurring in approximately 1% to 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, fixed drug eruption (FDE), urticaria

Special Senses: conjunctivitis, hearing impairment

To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which have been generally reversible with supportive care. Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression and coma have occurred, but were rare (see  ,  ).

Manage patients with symptomatic and supportive care following an NSAID overdosage. There are no specific antidotes. Consider emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 grams per kg of body weight in pediatric patients) and/or osmotic cathartic in symptomatic patients seen within four hours of ingestion in patients with a large overdose (5 to 10 times the recommended dosage). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.

For additional information about overdosage treatment, contact a poison control center (1-800-222-1222).

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

After observing the response to initial therapy with diclofenac potassium 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 three times a day. With experience, physicians may find that in some patients an initial dose of 100 mg of diclofenac potassium tablets, followed by 50-mg doses, will provide better relief.

For the relief of osteoarthritis the recommended dosage is 100 to 150 mg/day in divided doses, 50 mg twice a day or three times a day.

For the relief of rheumatoid arthritis the recommended dosage is 150 to 200 mg/day in divided doses, 50 mg three times a day or four times a day.

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

Diclofenac potassium tablets USP, 50 mg are available as orange, round, biconvex, film-coated tablets debossed with the numbers “93” and “948” on one face of the tablet and plain on the other.

Bottles of 30 NDC 68788-8411-3

Bottles of 60 NDC 68788-8411-6

Bottles of 90 NDC 68788-8411-9

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from moisture.

Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Brands listed are the trademarks of their respective owners.

Dispense with Medication Guide available at: www.tevausa.com/medguides

Manufactured In Israel By:
Teva Pharmaceutical Ind. Ltd.
Kfar Saba, 4410202, Israel

Manufactured For:
Teva Pharmaceuticals
Parsippany, NJ 07054

Rev. R 12/2024

Repackaged By: Preferred Pharmaceuticals Inc.

Dispense with Medication Guide available at: www.tevausa.com/medguides

Repackaged By: Preferred Pharmaceuticals Inc.

NDC 68788-8411

Diclofenac Potassium Tablets, USP

50 mg

PHARMACIST: Dispense the accompanying Medication Guide to each patient.

Rx only