Diclofenac (Systemic) (Lexi-Drugs)

ALERT: US Boxed Warning
  Serious cardiovascular thrombotic events:
  Serious gastrointestinal bleeding, ulceration, and perforation:
Drug Shortages

One or more forms of this drug may be in short supply or unavailable. Refer to the following for additional information:

ASHP: http://www.ashp.org/menu/DrugShortages

Pronunciation

(dye KLOE fen ak)

Brand Names: US

Cambia; Dyloject [DSC]; Voltaren-XR [DSC]; Zipsor; Zorvolex

Brand Names: Canada

APO-Diclo; APO-Diclo Rapide; APO-Diclo SR; Cambia; Diclofenac-50; DOM-Diclofenac; NTP-Diclofenac Sodium SR [DSC]; NTP-Diclofenac Sodium [DSC]; PMS-Diclofenac; PMS-Diclofenac K; PMS-Diclofenac-SR; PRO-Diclo Rapide-50; SANDOZ Diclofenac; SANDOZ Diclofenac Rapide; SANDOZ Diclofenac SR; TEVA-Diclofenac EC; TEVA-Diclofenac SR; TEVA-Diclofenac [DSC]; TEVA-Diclofenac-K; Voltaren; Voltaren Rapide; Voltaren SR

Dosing: Adult

Note: Dyloject (diclofenac injection) has been discontinued in the United States for more than 1 year.

Note: For all indications, it has been recommended to not exceed 100 mg/day based on increased risk of vascular events (eg, stroke, nonfatal MI) (Bhala 2013; Health Canada communication 2014)

Ankylosing spondylitis: Oral: Delayed-release tablet: 25 mg 4 times daily and 25 mg at bedtime as needed

Migraine: Oral: Powder for oral solution: 50 mg (one packet) as a single dose; safety and efficacy of a second dose have not been established.

Osteoarthritis:

Oral:

Immediate-release tablet: 50 mg 2 to 3 times daily; Delayed-release tablet: 50 mg 2 to 3 times daily or 75 mg twice daily; Extended-release tablet: 100 mg once daily

Immediate-release capsule: Zorvolex (diclofenac acid): 35 mg 3 times daily.

Rectal suppository [Canadian product]: Insert 50 mg or 100 mg rectally as single dose to substitute for final oral daily dose (maximum combined dose [rectal and oral]: 100 mg/day)

Pain:

Oral:

Immediate-release tablet: 50 mg 3 times daily; may administer 100 mg as an initial dose, followed by 50 mg 3 times daily

Immediate-release capsule:

Zipsor (diclofenac potassium): 25 mg 4 times daily

Zorvolex (diclofenac acid): 18 mg or 35 mg 3 times daily

IV: 37.5 mg every 6 hours as needed; adjust frequency according to patient response (maximum: 150 mg/day).

Primary dysmenorrhea: Oral: Immediate-release tablet: 50 mg 3 times daily; may administer 100 mg as an initial dose, followed by 50 mg 3 times daily

Rheumatoid arthritis:

Oral: Immediate-release tablet: 50 mg 3 to 4 times daily; Delayed-release tablet: 50 mg 3 to 4 times daily or 75 mg twice daily; Extended-release tablet: 100 mg once daily; may increase to 100 mg twice daily

Rectal suppository [Canadian product]: Insert 50 mg or 100 mg rectally as single dose to substitute for final oral daily dose (maximum combined dose [rectal and oral]: 100 mg/day

Dosing: Geriatric

Refer to adult dosing. Use with caution; initiate using lowest recommended dose and frequency.

Dosing: Renal Impairment: Adult

Oral:

Mild or moderate impairment: No dosage adjustment necessary.

Significant impairment or advanced renal disease: Use is not recommended.

Injection:

Mild impairment: There are no dosage adjustments provided in the manufacturer’s labeling.

Moderate to severe impairment: Use is not recommended; contraindicated in patients in the perioperative period and who are at risk for volume depletion.

KDIGO 2012 guidelines provide the following recommendations for NSAIDs:

eGFR 30 to <60 mL/minute/1.73 m2: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m2: Avoid use.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; however, may require dosage adjustment due to extensive hepatic metabolism. Additional product-specific recommendations:

Cambia: Use the lowest effective dose for the shortest duration possible.

Zipsor/Zorvolex: Initial: Initiate treatment at the lowest dose; if efficacy is not achieved with the lowest dose, discontinue use.

Injection:

Mild impairment: No dosage adjustment necessary.

Moderate to severe impairment: Use is not recommended (has not been studied).

Dosing: Pediatric

Note: Different oral formulations are not bioequivalent; do not interchange products.

Juvenile idiopathic arthritis: Limited data available: Children and Adolescents: Oral: Immediate release tablet: 2 to 3 mg/kg/day in divided doses 2 to 4 times/day; maximum daily dose: 150 mg/day (Haapasaari 1983; Hashkes 2005; Leak 1996; Petty 2016)

Migraine: Adolescents ≥18 years: Oral: Oral solution: 50 mg (one packet) as a single dose at the time of migraine onset; safety and efficacy of a second dose have not been established

Dosing: Renal Impairment: Pediatric

Children and Adolescents: There are no pediatric-specific dosage adjustments provided in the manufacturer’s labeling; some experts have suggested the following:

KDIGO 2012 guidelines provide the following recommendations for NSAIDs (KDIGO 2013):

eGFR 30 to <60 mL/minute/1.73 m2: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury

eGFR <30 mL/minute/1.73 m2: Avoid use.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, may require dosage adjustment due to extensive hepatic metabolism.

Use: Labeled Indications

Ankylosing spondylitis (delayed-release tablets only): Acute or long-term use in the relief of signs and symptoms of ankylosing spondylitis.

Dysmenorrhea (immediate-release tablets only): Treatment of primary dysmenorrhea.

Migraine (powder for oral solution only): Acute treatment of migraine attacks with or without aura in adults.

Osteoarthritis (immediate-release, extended-release, and delayed-release tablets; capsules [Zorvolex]; and suppositories [Canadian product] only): Relief of signs and symptoms of osteoarthritis.

Pain

Capsules/immediate-release tablets only: Relief of mild to moderate acute pain.

Injection only: Management of mild to moderate pain and moderate to severe pain (alone or in combination with opioid analgesics) in adults.

Rheumatoid arthritis (immediate-release, extended-release, and delayed-release tablets; and suppositories [Canadian product] only): Relief of signs and symptoms of rheumatoid arthritis.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Ankylosing Spondylitis:

ACR/SAA/SPARTAN, “Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis,” 2016

Drug-Induced Liver Injury:

American College of Gastroenterology (ACG), “2014 ACG Guideline for Idiosyncratic Drug-induced Liver Injury,” July 2014

Heart Failure:

ACCF/AHA, “2013 ACCF/AHA Guideline for the Management of Heart Failure,” June 2013

Juvenile idiopathic arthritis:

American College of Rheumatology, “2013 Update of the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis” 2013

Osteoarthritis:

American College of Rheumatology, “Recommendations for the Use of Nonpharmacologic and Pharmacologic Therapies in Osteoarthritis of the Hand, Hip, and Knee,” 2012

Other:

“The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines,” 2011

Administration: IV

Administer as an IV bolus over 15 seconds.

Administration: Oral

Do not crush delayed- or extended-release tablets. May administer immediate-release formulations with food or milk to avoid gastric distress.

Cambia, Zorvolex: Administering with food may cause a reduction in effectiveness.

Administration: Pediatric

Oral:

Immediate release: Administer with milk or food to decrease GI upset; take with full glass of water to enhance absorption

Oral solution: Empty contents of packet into 1 to 2 ounces (30 to 60 mL) of water (do not use other liquids); mix well and administer right away. Food may reduce effectiveness.

Dietary Considerations

Oral immediate-release formulations may be taken with food to decrease GI distress. However, food may reduce effectiveness of oral solution and diclofenac acid (capsule). Some products may contain phenylalanine.

Storage/Stability

Capsule, tablet: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.

Injection: Store at 20°C to 25°C (68°F to 77°F). Do not freeze. Protect from light.

Powder for oral solution: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Suppository [Canadian product]: Store at 15°C to 30°C (59°F to 86°F); protect from heat.

Preparation for Administration: Adult

Powder for oral solution: Empty contents of one packet into 30 to 60 mL of water (do not use other liquids); mix well and administer immediately.

Preparation for Administration: Pediatric

Oral solution: Empty contents of packet into 1 to 2 ounces (30 to 60 mL) of water (do not use other liquids); mix well and administer immediately.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience, nausea, constipation, heartburn, vomiting, diarrhea, flatulence, fatigue, injection site pain, or sweating a lot. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of abdominal ulcers (severe abdominal or back pain; black, tarry, or bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or abnormal swelling), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), shortness of breath, severe dizziness, passing out, excessive weight gain, swelling of arm or leg, angina, tachycardia, severe headache, vision changes, severe loss of strength and energy, severe abdominal pain, signs of DVT (edema, warmth, numbness, change in color, or pain in the extremities), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
  Geriatric Patients: High-Risk Medication:
  International issues:
Medication Guide and/or Vaccine Information Statement (VIS)
Contraindications

Hypersensitivity to diclofenac (eg, anaphylactoid reactions, serious skin reactions) or bovine protein (Zipsor only) or any component of the formulation; history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs; use in the setting of CABG surgery; patients with moderate to severe renal impairment in the perioperative period and who are at risk for volume depletion (injection only).

Canadian labeling: Additional contraindications (not in US labeling): Severe uncontrolled heart failure; active gastric/duodenal/peptic ulcer; active GI bleed or perforation, regional ulcer or enteritis, gastritis, ulcerative colitis, or recurrent ulceration; cerebrovascular bleeding or other bleeding disorders; inflammatory bowel disease; severe hepatic impairment; active hepatic disease; severe renal impairment (CrCl <30 mL/minute) or deteriorating renal disease; known hyperkalemia; patients <16 years of age (suppository, tablet) or <18 years of age (packet only); breastfeeding; pregnancy (third trimester); recent history of bleeding or inflammatory lesions of rectum/anus (suppository only)

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with “aspirin triad” (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.

• Cardiovascular events: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may occur early during treatment and may increase with duration of use. Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses. New onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure (ACCF/AHA [Yancy 2013]). Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long term therapy.

• GI events: [US Boxed Warning]: NSAIDs cause an increased risk of serious gastrointestinal inflammation, ulceration, bleeding, and perforation (may be fata); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis (Strate 2016). Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt 2008).

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare, sometimes fatal severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if clinical signs or symptoms of liver disease develop or if systemic manifestations occur.

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE inhibitors). Monitor potassium closely.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and elderly patients are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first sign of skin rash (or any other hypersensitivity).

Disease-related concerns:

• Aseptic meningitis: May increase the risk of aseptic meningitis (rarely), especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders.

• Asthma: Contraindicated in patients with aspirin-sensitive asthma; severe, potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.

• Coronary artery bypass graft surgery: [US Boxed Warning]: Use is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.

• Hepatic impairment: Use with caution in patients with hepatic impairment; reduced doses may be required due to extensive hepatic metabolism. Patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs.

• Renal impairment: Avoid use in patients with advanced renal disease unless benefits are expected to outweigh risk of worsening renal function; monitor closely if therapy must be initiated. Injection is not recommended in patients with moderate to severe renal impairment and is contraindicated in patients with moderate to severe renal impairment in the perioperative period and who are at risk for volume depletion.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Elderly patients are at greater risk for serious GI, cardiovascular, and/or renal adverse events.

Dosage form specific issues:

• Injection: Not indicated for long-term use.

• Oral solution: May contain phenylalanine.

• Zipsor: Contains gelatin; use is contraindicated in patients with history of hypersensitivity to bovine protein.

Other warnings/precautions:

• Appropriate use: Oral solution: Indicated only for the acute treatment of migraine (not indicated for migraine prophylaxis or cluster headache). Acute migraine agents (eg, NSAIDs, triptans, opioids, ergotamine, or a combination of the agents) used for 10 or more days per month may lead to worsening of headaches (medication overuse headache); withdrawal treatment may be necessary in the setting of overuse.

• Bioequivalence: Different formulations of oral diclofenac are not bioequivalent, even if the milligram strength is the same; do not interchange products.

• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.

Geriatric Considerations

Elderly patients are at high-risk for adverse effects from NSAIDs. Up to 60% of elderly patients can develop an asymptomatic peptic ulcer and/or hemorrhage. Using the lowest effective dose for the shortest period possible is recommended. Use of NSAIDs can compromise existing renal function especially when CrCl is <30 mL/minute. CNS adverse effects such as confusion, agitation, and hallucination may occur even with lower doses in elderly patients.

Pregnancy Risk Factor

C/D (≥30 weeks gestation)

Pregnancy Considerations

Diclofenac crosses the placenta. Birth defects have been observed following in utero NSAID exposure in some studies; however, data is conflicting (Bloor 2013). Nonteratogenic effects, including prenatal constriction of the ductus arteriosus, persistent pulmonary hypertension of the newborn, oligohydramnios, necrotizing enterocolitis, renal dysfunction or failure, and intracranial hemorrhage have been observed in the fetus/neonate following in utero NSAID exposure. In addition, nonclosure of the ductus arteriosus postnatally may occur and be resistant to medical management (Bermas 2014; Bloor 2013). Because they may cause premature closure of the ductus arteriosus, product labeling for diclofenac specifically states use should be avoided starting at 30-weeks gestation.

Use of NSAIDs can be considered for the treatment of mild rheumatoid arthritis flares in pregnant women; however, use should be minimized or avoided early and late in pregnancy (Bermas 2014; Saavedra Salinas 2015). If treatment of migraine is needed in pregnant women, agents other than diclofenac are preferred (Amundsen 2015).

The chronic use of NSAIDs, including diclofenac, in women of reproductive age may be associated with infertility that is reversible upon discontinuation of the medication. Consider discontinuing use in women having difficulty conceiving or those undergoing investigation of fertility. The use of NSAIDs close to conception may be associated with an increased risk of miscarriage (Bermas 2014; Bloor 2013).

Breast-Feeding Considerations

Diclofenac is present in breast milk.

The relative infant dose (RID) of diclofenac is 0.5% to 0.75% when calculated using the highest breast milk concentration located and compared to an infant therapeutic dose of 2 to 3 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is <10%; when an RID is >25%, breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Using the highest milk concentration (100 mcg/L), the estimated daily infant dose via breast milk is 0.015 mg/kg/day. This milk concentration was obtained following maternal administration of oral diclofenac 150 mg/day.

In general, NSAIDs may be used in postpartum women who wish to breastfeed; however, agents other than diclofenac may be preferred (Amundsen 2015; Montgomery 2012) and use should be avoided in women breastfeeding infants with platelet dysfunction or thrombocytopenia (Bloor 2013; Sammaritano 2014).

Lexicomp Pregnancy & Lactation, In-Depth
Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

Injection: Frequency not always defined.

Cardiovascular: Edema (≤10%), cerebrovascular accident, hypertension, myocardial infarction, significant cardiovascular event

Central nervous system: Headache (≤10%), dizziness (8%)

Dermatologic: Pruritus (≤10%), skin rash (≤10%), exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Endocrine & metabolic: Fluid retention

Gastrointestinal: Constipation (13%), abdominal pain (≤10%), diarrhea (≤10%), dyspepsia (≤10%), esophageal perforation (≤10%), flatulence (≤10%), gastrointestinal ulcer (≤10%; including gastric/duodenal), heartburn (≤10%), intestinal perforation (≤10%), nausea (≤10%), vomiting (≤10%)

Hematologic & oncologic: Anemia (≤10%), hemorrhage (≤10%), prolonged bleeding time (≤10%)

Hepatic: Increased liver enzymes (≤10%), increased serum transaminases (15%), increased serum ALT (≤4%; >8X ULN: ≤1%), increased serum AST (2% to ≤4%; >8X ULN: ≤1%)

Hypersensitivity: Anaphylactoid reaction

Local: Infusion site reaction (10%), extravasation (3%)

Otic: Tinnitus (≤10%)

Renal: Renal insufficiency (≤10%)

Miscellaneous: Wound healing impairment (8%), gastrointestinal inflammation

<1%, postmarketing, and/or case reports : Abnormal Dreams, agranulocytosis, alopecia, anaphylaxis, angioedema, anxiety, aplastic anemia, asthma, auditory impairment, blurred vision, cardiac arrhythmia, cardiac failure, change in appetite, colitis, coma, confusion, conjunctivitis, convulsions, cystitis, depression, diaphoresis, drowsiness, dyspnea, dysuria, ecchymoses, eosinophilia, eructation, erythema multiforme, esophagitis, exfoliative dermatitis, fever, fulminant hepatitis, gastritis, gastrointestinal hemorrhage, glossitis, hallucination, hematemesis, hematuria, hemolytic anemia, hepatic failure, hepatic necrosis, hepatitis, hepatotoxicity, hyperglycemia, hypertension, hypotension, infection, insomnia, interstitial nephritis, jaundice, leukopenia, lymphadenopathy, malaise, melena, meningitis, nervousness, oliguria, palpitations, pancreatitis, pancytopenia, paresthesia, pneumonia, polyuria, proteinuria, purpura, rectal hemorrhage, renal failure, respiratory depression, sepsis, skin photosensitivity, stomatitis, syncope, tachycardia, thrombocytopenia, toxic epidermal necrolysis, tremor, urticaria, vasculitis, vertigo, weakness, weight changes

Oral: Frequency not always defined.

>10%:

Cardiovascular: Edema (33%)

Hepatic: Increased serum transaminases (≤3 x ULN; 15%)

1% to 10%:

Cardiovascular: Hypertension (2% to 3%)

Central nervous system: Headache (4% to 8%), procedural pain (3%), dizziness (2%), falling (2%)

Dermatologic: Pruritus (7%), skin rash

Gastrointestinal: Constipation (5% to 8%), nausea (6% to 7%), diarrhea (6%), GI adverse effects (gastric ulcer, hemorrhage, and perforation; ≤4%, risk increases with therapy duration), abdominal pain (2% to 3%), vomiting (3%), dyspepsia (2% to 3%), flatulence (2% to 3%), heartburn, abdominal discomfort (2%), duodenal ulcer

Genitourinary: Urinary tract infection (7%)

Hematologic & oncologic: Bruise (3%), anemia, prolonged bleeding time

Hepatic: Increased serum ALT (>3 x ULN: ≤4%; >8 x ULN: ≤1%), increased serum AST (>3 x ULN; ≤4%; >8 x ULN: ≤1%)

Infection: Influenza (3%)

Neuromuscular & skeletal: Osteoarthritis (5%), arthralgia (3%), back pain (3%), limb pain (3%)

Renal: Renal function abnormality

Otic: Tinnitus

Renal: Increased serum creatinine (2%), renal function abnormality

Respiratory: Upper respiratory tract infection (8%), nasopharyngitis (6%), sinusitis (3% to 5%), cough (4%), bronchitis (3%)

<1%, postmarketing, and/or case reports: Abnormal dreams, agranulocytosis, alopecia, anaphylactoid reaction, anaphylaxis, angioedema, anxiety, aplastic anemia, aseptic meningitis, asthma, auditory impairment, azotemia (Gurwitz, 1990), blurred vision, cardiac arrhythmia, cardiac failure, cerebrovascular accident, change in appetite, chest pain, colitis, coma, confusion, conjunctivitis, cystitis, decreased hemoglobin (Goldstein, 2011), depression, diaphoresis, diplopia, disorientation, drowsiness, dyspnea, dysuria, ecchymoses, eosinophilia, eructation, erythema multiforme, esophageal ulcer, esophagitis, exfoliative dermatitis, fever, fluid retention, fulminant hepatitis, gastritis, glossitis, hallucination, hearing loss, hematemesis, hematuria, hemolytic anemia, hepatic failure, hepatic necrosis, hepatitis, hepatotoxicity, hyperglycemia, hypotension, infection, insomnia, interstitial nephritis, intestinal perforation, jaundice, leukopenia, lymphadenopathy, malaise, melena, memory impairment, meningitis, myocardial infarction, nephrotic syndrome, nervousness, oliguria, palpitations, pancreatitis, pancytopenia, paresthesia, peptic ulcer, pneumonia, polyuria, proteinuria, psychotic reaction, purpura, rectal hemorrhage, renal failure, renal papillary necrosis, respiratory depression, seizure, sepsis, skin photosensitivity, Stevens-Johnson syndrome, stomatitis, syncope, tachycardia, taste disorder, thrombocytopenia, toxic epidermal necrolysis, tremor, urticaria, vasculitis, vertigo, weakness, weight changes, xerostomia

Rectal suppository [Canadian product]:

Also refer to adverse reactions associated with oral formulations.

<1%, postmarketing, and/or case reports: Hemorrhoids (exacerbation), local hemorrhage, proctitis, rectal irritation

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C8 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (minor);Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits UGT1A6

Drug Interactions 

5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. Risk C: Monitor therapy

Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination. Risk C: Monitor therapy

Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren. Management: Monitor renal function periodically in patients receiving aliskiren and any nonsteroidal anti-inflammatory agent. Patients at elevated risk of renal dysfunction include those who are elderly, are volume depleted, or have pre-existing renal dysfunction. Risk C: Monitor therapy

Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Apixaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of apixaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: Consider therapy modification

Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

CycloSPORINE (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE (Systemic). Management: Consider alternatives to nonsteroidal anti-inflammatory agents (NSAIDs). Monitor for evidence of nephrotoxicity, as well as increased serum cyclosporine concentrations and systemic effects (eg, hypertension) during concomitant therapy with NSAIDs. Risk D: Consider therapy modification

CYP2C9 Inducers (Moderate): May decrease the serum concentration of Diclofenac (Systemic). Risk C: Monitor therapy

CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Diclofenac (Systemic). Management: Consider using a reduced dose of diclofenac when used together with moderate CYP2C9 inhibitors. Arthrotec (diclofenac and misoprostol) prescribing information recommends a maximum dose of 50 mg twice daily. Risk D: Consider therapy modification

Dabigatran Etexilate: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of dabigatran and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Deferasirox: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Risk C: Monitor therapy

Deferiprone: UGT1A6 Inhibitors may increase the serum concentration of Deferiprone. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy

Dexibuprofen: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Dexibuprofen. Risk X: Avoid combination

Dexketoprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Digoxin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Drospirenone: Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Drospirenone. Risk C: Monitor therapy

Edoxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of edoxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Felbinac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Floctafenine: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Haloperidol: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Haloperidol. Specifically including drowsiness and confusion. Risk C: Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk D: Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Management: Concomitant treatment with these agents should generally be avoided. If used concomitantly, increased diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds) must be employed. Risk D: Consider therapy modification

HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Ketorolac (Nasal): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Ketorolac (Systemic): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Risk D: Consider therapy modification

Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Risk D: Consider therapy modification

Macimorelin: Nonsteroidal Anti-Inflammatory Agents may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

Methotrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Methotrexate. Management: Alternative anti-inflammatory therapy should be considered whenever possible, especially if the patient is receiving higher, antineoplastic doses of methotrexate. Risk D: Consider therapy modification

Mifamurtide: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Mifamurtide. Risk X: Avoid combination

Morniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Nalmefene: Diclofenac (Systemic) may increase the serum concentration of Nalmefene. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Diclofenac (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Seek alternatives to the combined use of diclofenac with other nonsteroidal anti-inflammatory agents (NSAIDs). Avoid the use of diclofenac/misoprostol with other NSAIDs. Risk D: Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Risk X: Avoid combination

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.Risk C: Monitor therapy

Omacetaxine: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of nonsteroidal antiinflammatory drugs (NSAIDs) with omacetaxine in patients with a platelet count of less than 50,000/uL. Risk X: Avoid combination

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pelubiprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Phenylbutazone: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy

PRALAtrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of PRALAtrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Prostaglandins (Ophthalmic): Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Prostaglandins (Ophthalmic). Nonsteroidal Anti-Inflammatory Agents may also enhance the therapeutic effects of Prostaglandins (Ophthalmic). Risk C: Monitor therapy

Quinolones: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy

Resveratrol: May increase the serum concentration of Diclofenac (Systemic). Risk C: Monitor therapy

Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding. Risk D: Consider therapy modification

Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Risk D: Consider therapy modification

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Risk D: Consider therapy modification

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Sodium Phosphates: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with NSAIDs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Risk D: Consider therapy modification

Tacrolimus (Systemic): Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy

Talniflumate: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Tenofovir Products: Diclofenac (Systemic) may enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Risk D: Consider therapy modification

Tenoxicam: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Tolperisone: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Tolperisone. Specifically, the risk of hypersensitivity reactions may be increased. Tolperisone may enhance the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy

Tricyclic Antidepressants (Tertiary Amine): May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Risk C: Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vancomycin: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Vancomycin. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification

Voriconazole: May increase the serum concentration of Diclofenac (Systemic). Management: Consider using a lower dose of diclofenac when used with voriconazole. Arthrotec (diclofenac and misoprostol) labeling recommends limiting the total daily dose to a maximum of 50 mg twice daily. Risk D: Consider therapy modification

Zaltoprofen: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination

Test Interactions

May lead to false-positive aldosterone/renin ratio (ARR) (Funder 2016).

Genes of Interest
Monitoring Parameters

Monitor CBC, chemistry profile, weight gain, edema, liver function tests (baseline and periodically during chronic therapy), renal function (serum BUN, serum creatinine, urine output); occult blood loss; blood pressure; observe for bleeding, bruising; GI effects (abdominal pain, bleeding, dyspepsia); mental confusion, disorientation

Advanced Practitioners Physical Assessment/Monitoring

Evaluate cardiac risk and potential for GI bleeding prior to prescribing this medication. Monitor blood pressure at the beginning of therapy and periodically during use. Schedule ophthalmic evaluations for patients who develop eye complaints during long-term NSAID therapy.

Nursing Physical Assessment/Monitoring

Monitor blood pressure at the beginning of therapy and periodically during use. Schedule ophthalmic evaluations for patients who develop eye complaints during long-term NSAID therapy.

Product Availability

Dyloject (diclofenac injection) has been discontinued in the United States for more than 1 year.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as base:

Zorvolex: 18 mg, 35 mg [contains brilliant blue fcf (fd&c blue #1), fd&c blue #2 (indigotine)]

Capsule, Oral, as potassium:

Zipsor: 25 mg [contains gelatin (bovine)]

Packet, Oral, as potassium:

Cambia: 50 mg (1 ea, 9 ea) [anise-mint flavor]

Cambia: 50 mg (1 ea [DSC], 9 ea [DSC]) [contains aspartame, saccharin sodium; anise-mint flavor]

Solution, Intravenous, as sodium:

Dyloject: 37.5 mg/mL (1 mL [DSC])

Tablet, Oral, as potassium:

Generic: 50 mg

Tablet Delayed Release, Oral, as sodium:

Generic: 25 mg, 50 mg, 75 mg

Tablet Extended Release 24 Hour, Oral, as sodium:

Voltaren-XR: 100 mg [DSC]

Generic: 100 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Packet, Oral, as potassium:

Cambia: 50 mg (1ea, 3ea, 9ea) [contains ASPARTAME, SACCHARIN SODIUM]

Suppository, Rectal:

Voltaren: 50 mg (30ea); 100 mg (30ea)

Generic: 50 mg (30ea, 500ea[DSC]); 100 mg (30ea)

Tablet, Oral, as potassium:

Voltaren Rapide: 50 mg

Generic: 50 mg

Tablet Delayed Release, Oral, as sodium:

Voltaren: 50 mg [contains CORN STARCH]

Generic: 25 mg, 50 mg

Tablet Extended Release 24 Hour, Oral:

Voltaren SR: 75 mg [contains POLYSORBATE 80]

Generic: 75 mg

Tablet Extended Release 24 Hour, Oral, as sodium:

Voltaren SR: 100 mg

Generic: 100 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • M01AB05
Generic Available (US)

May be product dependent

Pricing: US

Capsules (Zipsor Oral)

25 mg (per each): $9.36

Capsules (Zorvolex Oral)

18 mg (per each): $8.67

35 mg (per each): $8.67

Pack (Cambia Oral)

50 mg (per each): $90.74

Tablet, 24-hour (Diclofenac Sodium ER Oral)

100 mg (per each): $2.70 – $2.81

Tablet, EC (Diclofenac Sodium Oral)

25 mg (per each): $1.42

50 mg (per each): $0.95 – $1.47

75 mg (per each): $1.14 – $1.77

Tablets (Diclofenac Potassium Oral)

50 mg (per each): $1.55 – $2.76

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties

Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.

Pharmacodynamics/Kinetics

Absorption: Oral: ~50% (systemically available)

Distribution: Oral: ~1.3 to 1.4 L/kg

Protein binding: >99%, primarily to albumin

Metabolism: Hepatic; undergoes first-pass metabolism; forms several metabolites (1 with weak activity)

Bioavailability: 55%

Half-life elimination: Oral: ~2 hours; ~1 hour (liquid filled capsule [Zipsor]); Injection: ~1.4 hours

Time to peak, serum: Note: Fasted values reported for oral products; may be delayed with food

Cambia: ~0.25 hours

Cataflam, Zorvolex: ~1 hour

Zipsor: ~0.47 ± 0.17 hour

Injection: ~5 minutes

Tablet, delayed release (diclofenac sodium): 2.3 hours

Tablet, extended release (diclofenac sodium): 5.3 hours

Excretion: Urine (~65%); bile (~35%)

Pharmacodynamics/Kinetics: Additional Considerations

Body weight: Injection: Increased volume of distribution and clearance with increased body weight (>95 kg).

Dental Use

Immediate-release tablets: Acute treatment of mild-to-moderate pain

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin®). See Effects on Bleeding.

Effects on Bleeding

Nonselective NSAIDs such as diclofenac (systemic) inhibit platelet aggregation and prolong bleeding time in some patients. Unlike aspirin, the NSAID effect on platelet function is quantitatively less, of shorter duration, and reversible. Normal platelet function should occur in ~5 elimination half-lives or in <10 hours after discontinuation of diclofenac (systemic). Concomitant use of other NSAIDs should be avoided.

Dental Usual Dosing

Pain: Adults: Oral: Starting dose: 50 mg 3 times/day; maximum dose: 150 mg/day

Index Terms

Cataflam; Diclofenac Potassium; Diclofenac Sodium; Voltaren; Zorvolex

FDA Approval Date
July 28, 1988
References

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Jacobi J, Fraser GL, Coursin DB, et al, “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult,” Crit Care Med, 2002, 30(1):119-41. Available at http://www.sccm.org/pdf/sedatives.pdf. Accessed August 2, 2003.[PubMed 11902253]

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3(suppl):1-150.

Kulling EJ, Beckman EA, and Skagius AS, “Renal Impairment After Acute Diclofenac, Naproxen, and Sulindac Overdoses,” J Toxicol Clin Toxicol, 1995, 33(2):173-7.[PubMed 7897758]

Montgomery A, Hale TW; Academy of Breastfeeding Medicine. ABM clinical protocol #15: analgesia and anesthesia for the breastfeeding mother, revised 2012. Breastfeed Med. 2012;7(6):547-553.[PubMed 23215911]

Morgan TO, Anderson A, and Bertram D, “Effect of Indomethacin on Blood Pressure in Elderly People With Essential Hypertension Well Controlled on Amlodipine or Enalapril,” Am J Hypertens, 2000, 13(11):1161-7.[PubMed 11078175]

Page J and Henry D, “Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients: An Underrecognized Public Health Problem,” Arch Intern Med, 2000, 160(6):777-84.[PubMed 10737277]

Pillans PI and O’Connor N, “Tissue Necrosis and Necrotizing Fasciitis After Intramuscular Administration of Diclofenac,” Ann Pharmacother, 1995, 29(3):264-6.[PubMed 7606072]

Pope JE, Anderson JJ, and Felson DT, “A Meta-analysis of the Effects of Nonsteroidal Anti-inflammatory Drugs on Blood Pressure,” Arch Intern Med, 1993, 153(4):477-84.[PubMed 8435027]

Riad LE, Sawchuk RJ, McAlary MM, et al, “Effect of Food on the Multiple-Peak Behavior After a Single Oral Dose of Diclofenac Sodium Slow-Release Tablet in Humans,” Am J Ther, 1995, 2(4):237-42.[PubMed 11850655]

Ringold S, Weiss PF, Beukelman T, et al; American College of Rheumatology. 2013 update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013;65(10):2499-2512.[PubMed 24092554]

Robinson MH, Wheatley T, and Leach IH, “Nonsteroidal Anti-inflammatory Drug-Induced Colonic Stricture; an Unusual Cause of Large Bowel Obstruction and Perforation,” Dig Dis Sci, 1995, 40(2):315-9.[PubMed 7851196]

Robinson PM and Ahmed I, “Diclofenac and Post-tonsillectomy Haemorrhage,” Clin Otolaryngol, 1994, 19(4):344-5.[PubMed 7994893]

Saavedra Salinas MÁ, Barrera Cruz A, Cabral Castañeda AR, et al. Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II. Reumatol Clin. 2015;11(5):305-315.[PubMed 25776823]

Sammaritano LR, Bermas BL. Rheumatoid arthritis medications and lactation. Curr Opin Rheumatol. 2014;26(3):354-360.[PubMed 24614280]

Smolinske SC, Hall AH, Vandenberg SA, et al, “Toxic Effects of Nonsteroid Anti-inflammatory Drugs in Overdose. An Overview of Recent Evidence on Clinical Effects and Dose-Response Relationships,” Drug Saf, 1990, 5(4):252-74.[PubMed 2198051]

Strate LL, Gralnek IM. ACG clinical guideline: management of patients with acute lower gastrointestinal bleeding. Am J Gastroenterol. 2016;111(4):459-474. doi: 10.1038/ajg.2016.41.[PubMed 26925883]

Vale JA and Meredith TJ, “Acute Poisoning Due to Nonsteroidal Anti-inflammatory Drugs,” Med Toxicol, 1986, 1(1):12-31.[PubMed 3537613]

Verbeeck RK, “Pharmacokinetic Drug Interactions With Nonsteroidal Anti-inflammatory Drugs,” Clin Pharmacokinet, 1990, 19(1):44-66.[PubMed 2199127]

Voltaren (diclofenac) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; June 2016.

Voltaren Rapide (diclofenac) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; July 2018.

Voltaren SR (diclofenac) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; July 2018.

Voltaren-XR extended-release tablets (diclofenac) [prescribing information]. East Hanover, NJ: Novartis; May 2016.

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Willkens RF, “Worldwide Clinical Safety Experience With Diclofenac,” Semin Arthritis Rheum, 1985, 15(2 Suppl 1):105-10.[PubMed 3909410]

Yancy CW, Jessup M, Bozkurt B, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):e240-e327.[PubMed 23741058]

Yeomans ND, Tulassay Z, Juhasz L, et al, “A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1998, 338(11):719-26.[PubMed 9494148]

Zipsor (diclofenac) [prescribing information]. Newark, CA: Depomed, Inc; October 2016.

Zorvolex (diclofenac) [prescribing information]. Philadelphia, PA: Iroko Pharmaceuticals; May 2016.

Brand Names: International

Abitren (IL); Actifen CR (PH); Acuflam (PH); Adiflam (ET); Allvoran (DE); Almiral (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TW, TZ, UG, YE, ZM, ZW); Anterin (TW); Anuva (ID); Arcanafenac (ZA); Artimed (ET); Artrites (CO); Berifen (CR, DO, GT, HN, NI, PA, SV); Betaren (IL); Bi Su Fu (CN); Bioran (ZW); Catafast (SA); Catafen (PH); Cataflam (AE, BE, BH, CL, CY, EC, EE, EG, ET, HK, ID, IL, IQ, IR, JO, KW, LB, LK, LT, LU, LV, LY, MT, NL, NO, OM, PE, PT, QA, SA, SY, TR, TW, UY, VE, VN, YE, ZW); Cataflam D (ID); Cataflam Drops (MY); Catanac (TH); Catas (KR); Cencenac (TH); Clofec (TH); Clofen (AE, JO, KW, LB, QA, SA); Clofen Retard (AE, KW); Clofenex-50 (HK); Clonac (AU); Cordralan (PE); Curafen (PH); D-Fiam (TH); Declophen (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Depain (KR); Diclac (CN, IE); Diclax SR (NZ); Dicloas (ET); Diclobene (AT); Diclofen (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, TW, YE); Diclofen Cremogel (BH); Diclofenac (CO); Dicloflam (ZA); Diclomax (IN, ZW); Diclon (DK, MY); Diclosan SR (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Diclosian (TH); Diclowal (CR, DO, GT, HN, NI, PA, SV); Dicofen (PH); Difelene (VN); Difena (TW); Difene (IE); Diflosid (PH); Dioxaflex (DO, GT, HN, NI, PA, SV); Dioxaflox (CR); Disflam (EC); Divoltar (ID); Divon CR (LK); Doflex (IN); Dolotren (CR, DO, ES, GT, HN, NI, PA, SV); Dolpasse (AT); Dosanac (SG); E (GR); Ecofenac (CH); Epifenac (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Eurofenac (HK); Fenac (AU); Flamquit (TW); Flector (FR, LB); Flexagen (ZA); Flogozan (CR, DO, GT, HN, NI, PA, SV); Fortfen SR (ZA); Inac (SG); Inflamac (CH); Inflanac (HK, LK, MY, TH); Joflam (QA); Kadiflam (ID); Lesflam (SG); Maxit (LK); Merflam (ID); Mioclof (PH); Mobifen (BD); Monoflam (CZ, DE); Neodolpasse (AT); Nepenthe (PH); Novarin (BD); Ofenac (KR); Olfen (AE, BB, BM, BS, BZ, GY, HK, JM, JO, LB, MY, PR, QA, SR, TT); Olfen-75 SR (MY); Osteoflam (IN); Panamor (ZA, ZW); Potaflam (ID); Profenac (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Raost (ID); Remafen (MY); Remethan (DE, ET, HK, MY, SG, ZW); Ren (HK); Rewodina (DE, MY, RU); Rhemofenax (MY); Sefnac (TH); Soproxen (TH); Swiss Relief Dual Release (IL); Taks (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Troflam (ID); Tromax (ET); Ultrafen (SG); Vartelon (HK); Vesconac (TH); Vivian (ZW); Volcan (BD); Voldic (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Voldick-K (ET); Volna-K (TW); Volta (TH); Voltaflam (PK); Voltaflex (BR); Voltaren (AE, AR, AT, BB, BE, BF, BG, BH, BJ, BR, CH, CI, CL, CO, CY, CZ, DE, DK, EE, EG, ET, FI, GH, GM, GN, HK, HR, HU, ID, IL, IQ, IR, IS, IT, JO, KE, KW, LB, LR, LT, LU, LV, LY, MA, ML, MR, MU, MW, MY, NE, NG, NL, NO, NZ, OM, PH, PL, PT, PY, QA, RO, RU, SA, SC, SD, SE, SI, SK, SL, SN, SY, TH, TN, TR, TW, TZ, UA, UG, UY, VE, VN, YE, ZA, ZM, ZW); Voltaren Acti-Go (IL); Voltaren Dolo (FR); Voltaren Rapid (AU, NZ, UA); Voltaren SR (BH, CY, EG, HK, LB, MT, NZ, PH, SA); Voltarene (FR, GR); Voltarol (IE); Voltfast (ET, SG, TH); Voltine (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, SA, SY, YE); Volton-CR (HK); Voren (PH, TW); Votalin (CN); Votan (PH); Votan SR (PH); Votrex (AE); Voveran (IN); Vurdon (AE, BF, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, OM, SA, SC, SD, SL, SN, SY, TN, TZ, UG, YE, ZM, ZW); Yingtaiqing (CN); Yuren (TW); Zobid (MY); Zobid D (LK); Zolterol (MY); Zolterol SR (LK, SG)

Diclofenac (Systemic) (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(dye KLOE fen ak)

Brand Names: US

Cambia; Dyloject [DSC]; Voltaren-XR [DSC]; Zipsor; Zorvolex

Brand Names: Canada

Cambia; Diclofenac K; Voltaren; Voltaren Rapide; Voltaren SR

Warning
  • This drug may raise the chance of heart and blood vessel side effects like heart attack and stroke. If these happen, they can be deadly. The risk of these side effects may be greater if you have heart disease or risks for heart disease. However, the risk may also be raised in people who do not have heart disease or risks for heart disease. The risk of these health problems can happen as soon as the first weeks of using this drug and may be greater with higher doses or with long-term use. Do not use this drug right before or after bypass heart surgery.
  • This drug may raise the chance of very bad and sometimes deadly stomach or bowel side effects like ulcers or bleeding. The risk is greater in older people. The risk is also greater in people who have had stomach or bowel ulcers or bleeding before. These problems may occur without warning signs. Talk with the doctor.
What is this drug used for?
  • It is used to ease pain.
  • It is used to treat arthritis.
  • It is used to treat ankylosing spondylitis.
  • It is used to ease painful period (menstrual) cycles.
  • It is used to treat migraine headaches.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to diclofenac or any other part of this drug.
  • If you have an allergy to aspirin or NSAIDs.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have ever had asthma caused by a salicylate drug like aspirin or a drug like this one like NSAIDs.
  • If you have any of these health problems: GI (gastrointestinal) bleeding or kidney problems.
  • If you have had a recent heart attack.
  • If you are having trouble getting pregnant or you are having your fertility checked.
  • If you are pregnant or may be pregnant. Do not take this drug if you are in the third trimester of pregnancy. You may also need to avoid this drug at other times during pregnancy. Talk with your doctor to see when you need to avoid taking this drug during pregnancy.
  • If you are breast-feeding or plan to breast-feed.
  • If you are taking any other NSAID.
  • If you are taking a salicylate drug like aspirin.
  • If you are taking pemetrexed.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • All products:
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • Have your blood work checked if you are on this drug for a long time. Talk with your doctor.
  • High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
  • Talk with your doctor before you drink alcohol.
  • If you smoke, talk with your doctor.
  • If you have asthma, talk with your doctor. You may be more sensitive to this drug.
  • Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
  • Do not take this drug for longer than you were told by your doctor.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • The chance of heart failure is raised with the use of drugs like this one. In people who already have heart failure, the chance of heart attack, having to go to the hospital for heart failure, and death is raised. Talk with the doctor.
  • The chance of heart attack and heart-related death is raised in people taking drugs like this one after a recent heart attack. People taking drugs like this one after a first heart attack were also more likely to die in the year after the heart attack compared with people not taking drugs like this one. Talk with the doctor.
  • If you are taking aspirin to help prevent a heart attack, talk with your doctor.
  • This drug may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this drug with your other drugs.
  • Liver problems have happened with drugs like this one. Sometimes, this has been deadly. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • If you are 65 or older, use this drug with care. You could have more side effects.
  • NSAIDs like this drug may affect egg release (ovulation) in women. This may cause you to not be able to get pregnant. This goes back to normal when this drug is stopped. Talk with your doctor.
  • This drug may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking this drug, call your doctor right away.
  • All oral products:
  • Do not switch brands or types of this drug (like tablets, liquid) unless you talk with the doctor. They may not work the same.
  • Packets:
  • If you have phenylketonuria (PKU), talk with your doctor. Some products have phenylalanine.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of high potassium levels like a heartbeat that does not feel normal; feeling confused; feeling weak, lightheaded, or dizzy; feeling like passing out; numbness or tingling; or shortness of breath.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Chest pain or pressure or a fast heartbeat.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Feeling very tired or weak.
  • Very bad belly pain.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if you have signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in your mouth, throat, nose, or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • All products:
  • Headache.
  • Upset stomach.
  • Constipation.
  • Dizziness.
  • All oral products:
  • Belly pain or heartburn.
  • Throwing up.
  • Diarrhea.
  • Gas.
  • Feeling sleepy.
  • Sweating a lot.
  • Injection:
  • Pain where the shot was given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • Tablets and capsules:
  • Take with or without food. Take with food if it causes an upset stomach.
  • Take with a full glass of water.
  • Long-acting products:
  • Swallow whole. Do not chew, break, or crush.
  • Packets:
  • If you take this drug with food, it may not work as well. Talk with your doctor.
  • Empty contents of packet into 2 to 4 tablespoons (30 to 60 mL) of water, mix well, and drink it right away.
  • Injection:
  • It is given as a shot into a vein.
What do I do if I miss a dose?
  • Tablets and capsules:
  • If you take this drug on a regular basis, take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • Many times this drug is taken on an as needed basis. Do not take more often than told by the doctor.
  • Packets:
  • Only 1 dose of this drug is needed. If you miss your dose, take it as soon as you think about it.
  • Injection:
  • Call your doctor to find out what to do.
How do I store and/or throw out this drug?
  • All oral products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Tablets and capsules:
  • Protect from light.
  • Injection:
  • If you need to store this drug at home, talk with your doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Diclofenac (Systemic) (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(dye KLOE fen ak)

Brand Names: US

Cambia; Dyloject [DSC]; Voltaren-XR [DSC]; Zipsor; Zorvolex

Brand Names: Canada

Cambia; Diclofenac K; Voltaren; Voltaren Rapide; Voltaren SR

Warning
  • This drug may raise the chance of heart and blood vessel side effects like heart attack and stroke. If these happen, they can be deadly. The risk of these side effects may be greater if your child has heart disease or risks for heart disease. However, the risk may also be raised in people who do not have heart disease or risks for heart disease. The risk of these health problems can happen as soon as the first weeks of using this drug and may be greater with higher doses or with long-term use. Do not give this drug to your child right before or after bypass heart surgery.
  • This drug may raise the chance of very bad and sometimes deadly stomach or bowel side effects like ulcers or bleeding. The risk is greater in older people. The risk is also greater in people who have had stomach or bowel ulcers or bleeding before. These problems may occur without warning signs. Talk with the doctor.
What is this drug used for?
  • It is used to ease pain.
  • It is used to treat arthritis.
  • It is used to treat migraine headaches.
  • It may be given to your child for other reasons. Talk with the doctor.
  • If your child has menstrual periods:
  • It is used to ease painful period (menstrual) cycles.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child has an allergy to aspirin or NSAIDs.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child has ever had asthma caused by a salicylate drug like aspirin or a drug like this one like NSAIDs.
  • If your child has kidney disease.
  • If your child has GI (gastrointestinal) bleeding.
  • If your child has had a recent heart attack.
  • If your child is having her fertility checked.
  • If your child is taking any other NSAID.
  • If your child is taking a salicylate drug like aspirin.
  • If your child is taking pemetrexed.
  • If your child is pregnant:
  • Do not give this drug to your child if she is in the third trimester of pregnancy. You may also need to avoid giving this drug to your child at other times during pregnancy. Talk with your child’s doctor to see when you need to avoid giving this drug to your child during pregnancy.
  • If your child is breast-feeding a baby:
  • Talk with the doctor if your child is breast-feeding a baby or plans to breast-feed a baby.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • All products:
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists.
  • Have your child’s blood work checked if he/she is on this drug for a long time. Talk with your child’s doctor.
  • High blood pressure has happened with drugs like this one. Have your child’s blood pressure checked as you have been told by the doctor.
  • Alcohol may interact with this drug. Be sure your child does not drink alcohol.
  • If your child smokes, talk with the doctor.
  • If your child has asthma, talk with the doctor. He/she may be more sensitive to this drug.
  • Do not give your child more of this drug than what the doctor told you to give. Giving more of this drug than you are told may raise the chance of very bad side effects.
  • Do not have your child use longer than you have been told by your child’s doctor.
  • Your child may bleed more easily. Make sure your child is careful and avoids injury. Be sure your child has a soft toothbrush.
  • The chance of heart failure is raised with the use of drugs like this one. In people who already have heart failure, the chance of heart attack, having to go to the hospital for heart failure, and death is raised. Talk with the doctor.
  • The chance of heart attack and heart-related death is raised in people taking drugs like this one after a recent heart attack. People taking drugs like this one after a first heart attack were also more likely to die in the year after the heart attack compared with people not taking drugs like this one. Talk with the doctor.
  • If your child is taking aspirin to help prevent a heart attack, talk with the doctor.
  • This drug may affect how much of some other drugs are in the body. If your child is taking other drugs, talk with the doctor. Your child may need to have blood work checked more closely while taking this drug with other drugs.
  • If your child is or may be sexually active:
  • NSAIDs like this drug may affect egg release (ovulation) in females. This may affect being able to get pregnant. This goes back to normal when this drug is stopped. Talk with the doctor.
  • If your child is pregnant:
  • This drug may cause harm to the unborn baby if your child takes it during pregnancy. If your child is pregnant or gets pregnant while taking this drug, call the doctor right away.
  • All oral products:
  • Do not switch brands or types of this drug (like tablets, liquid) unless you talk with the doctor. They may not work the same.
  • Packets:
  • If your child has phenylketonuria (PKU), talk with your child’s doctor. Some products have phenylalanine.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
  • Signs of high potassium levels like a heartbeat that does not feel normal; feeling confused; feeling weak, lightheaded, or dizzy; feeling like passing out; numbness or tingling; or shortness of breath.
  • Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Chest pain or pressure or a fast heartbeat.
  • Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
  • Feeling very tired or weak.
  • Very bad belly pain.
  • Liver problems have happened with drugs like this one. Sometimes, this has been deadly. Call the doctor right away if your child has signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
  • A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if your child has signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away:
  • All products:
  • Headache.
  • Upset stomach.
  • Constipation.
  • Dizziness.
  • All oral products:
  • Belly pain or heartburn.
  • Throwing up.
  • Diarrhea.
  • Gas.
  • Feeling sleepy.
  • Sweating a lot.
  • Injection:
  • Pain where the shot was given.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • Tablets and capsules:
  • Give this drug with or without food. Give with food if it causes an upset stomach.
  • Give this drug with a full glass of water.
  • Long-acting products:
  • Have your child swallow whole. Do not let your child chew, break, or crush.
  • Packets:
  • If you give this drug with food, it may not work as well. Talk with the doctor.
  • Empty contents of packet into 2 to 4 tablespoons (30 to 60 mL) of water, mix well, and have your child drink it right away.
  • Injection:
  • It is given as a shot into a vein.
What do I do if my child misses a dose?
  • Tablets and capsules:
  • If your child takes this drug on a regular basis, give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses.
  • Many times this drug is given on an as needed basis. Do not give to your child more often than told by the doctor.
  • Packets:
  • Only 1 dose of this drug is needed. If your child missed the dose, give it as soon as you think about it.
  • Injection:
  • Call your child’s doctor to find out what to do.
How do I store and/or throw out this drug?
  • All oral products:
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Tablets and capsules:
  • Protect from light.
  • Injection:
  • If you need to store this drug at home, talk with your child’s doctor, nurse, or pharmacist about how to store it.
  • All products:
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.