FDA

Diclofenac Sodium

Approved 26 Mar 1996OralTablet, delayed release

The FDA lists this product in 60 strengths and forms.

Indications

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; Gastrointestinal Bleeding, Ulceration, and Perforation ) . Diclofenac sodium delayed-release tablets, USP are indicated:

For relief of the signs and symptoms of osteoarthritis
For relief of the 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 the following patients:

Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product (see WARNINGS; Anaphylactic Reactions , Serious Skin Reactions ) .
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (see WARNINGS; Anaphylactic Reactions , Exacerbation of Asthma Related to Aspirin Sensitivity ) .
In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS; Cardiovascular Thrombotic Events ) .

Warnings and precautions

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, including myocardial infarction (MI), and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease.

Indications

For relief of the signs and symptoms of osteoarthritis
For relief of the 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 the following patients:

Known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to diclofenac or any components of the drug product (see WARNINGS; Anaphylactic Reactions , Serious Skin Reactions ) .
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (see WARNINGS; Anaphylactic Reactions , Exacerbation of Asthma Related to Aspirin Sensitivity ) .
In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS; Cardiovascular Thrombotic Events ) .

Warnings and precautions

Interactions

Drug Interactions See Table 2 for clinically significant drug interactions with diclofenac. Table 2: Clinically Significant Drug Interactions with Diclofenac Drugs That Interfere with Hemostasis Clinical Impact:

Diclofenac and anticoagulants such as warfarin have a synergistic effect on bleeding. The concomitant use of diclofenac and anticoagulants have an increased risk of serious bleeding compared to the use of either drug alone.
Serotonin release by platelets plays an important role in hemostasis. Case-control and cohort epidemiological studies showed that concomitant use of drugs that interfere with serotonin reuptake and an NSAID may potentiate the risk of bleeding more than an NSAID alone. Intervention: Monitor patients with concomitant use of diclofenac sodium delayed-release with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding (see PRECAUTIONS; Hematological Toxicity ) . Aspirin Clinical Impact: Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an NSAID and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the NSAID alone (see WARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation ) . Intervention: Concomitant use of diclofenac sodium delayed-release and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding (see PRECAUTIONS; Hematological Toxicity ) . Diclofenac sodium delayed-release is not a substitute for low dose aspirin for cardiovascular protection. ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers Clinical Impact:
NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or beta-blockers (including propranolol).
In patients who are elderly, volume-depleted (including those on diuretic therapy), or have renal impairment, co-administration of an NSAID with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Intervention:
During concomitant use of diclofenac sodium delayed-release and ACE-inhibitors, ARBs, or beta-blockers, monitor blood pressure to ensure that the desired blood pressure is obtained.
During concomitant use of diclofenac sodium delayed-release and ACE-inhibitors or ARBs in patients who are elderly, volume-depleted, or have impaired renal function, monitor for signs of worsening renal function (see WARNINGS; Renal Toxicity and Hyperkalemia ) .
When these drugs are administered concomitantly, patients should be adequately hydrated. Assess renal function at the beginning of the concomitant treatment and periodically thereafter. Diuretics Clinical Impact: Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of diclofenac sodium delayed-release with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects (see WARNINGS; Renal Toxicity and Hyperkalemia ) . Digoxin Clinical Impact: The concomitant use of diclofenac with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Intervention: During concomitant use of diclofenac sodium delayed-release and digoxin, monitor serum digoxin levels. Lithium Clinical Impact: NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis. Intervention: During concomitant use of diclofenac sodium delayed-release and lithium, monitor patients for signs of lithium toxicity. Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of diclofenac sodium delayed-release and methotrexate, monitor patients for methotrexate toxicity. Cyclosporine Clinical Impact: Concomitant use of diclofenac sodium delayed-release and cyclosporine may increase cyclosporine’s nephrotoxicity. Intervention: During concomitant use of diclofenac sodium delayed-release and cyclosporine, monitor patients for signs of worsening renal function. NSAIDs and Salicylates Clinical Impact: Concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy (see WARNINGS; Gastrointestinal Bleeding, Ulceration, and Perforation ) . Intervention: The concomitant use of diclofenac with other NSAIDs or salicylates is not recommended. Pemetrexed Clinical Impact: Concomitant use of diclofenac sodium delayed-release and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information). Intervention: During concomitant use of diclofenac sodium delayed-release and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration. CYP2C9 Inhibitors or Inducers: Clinical Impact: 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 coadministration with CYP2C9 inducers (e.g. rifampin) may lead to compromised efficacy of diclofenac. Intervention: A dosage adjustment may be warranted when diclofenac is administered with CYP2C9 inhibitors or inducers (see CLINICAL PHARMACOLOGY; Pharmacokinetics ) .

Pregnancy and breastfeeding

Pregnancy Risk Summary Use of NSAIDs, including diclofenac sodium delayed-release, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including diclofenac sodium delayed-release, in pregnant women starting at 30 weeks of gestation (third trimester) (see WARNINGS; Premature Closure of Fetal Ductus Arteriosus ) . There are no adequate and well-controlled studies of diclofenac sodium delayed-release 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 the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15% to 20% for pregnancy loss. 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 sodium delayed-release, 200 mg/day, despite the presence of maternal and fetal toxicity at these doses [see Data] .

Based on 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 post-implantation loss. Data 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 sodium delayed-release, 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.

Adverse reactions

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

Cardiovascular Thrombotic Events (see WARNINGS )
GI Bleeding, Ulceration and Perforation (see WARNINGS )
Hepatotoxicity (see WARNINGS )
Hypertension (see WARNINGS )
Heart Failure and Edema (see WARNINGS )
Renal Toxicity and Hyperkalemia (see WARNINGS )
Anaphylactic Reactions (see WARNINGS )
Serious Skin Reactions (see WARNINGS )
Hematologic Toxicity (see WARNINGS ) 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 patients taking diclofenac sodium delayed-release 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, proteinuriarenal 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 To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or http://www.fda.gov/ for voluntary reporting of adverse reactions.

Diclofenac Sodium

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Diclofenac Sodium

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information

At a glance