Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). This medicine works by reducing substances in the body that cause pain and inflammation.
Diclofenac is used to treat mild to moderate pain, or signs and symptoms of osteoarthritis or rheumatoid arthritis. Voltaren is also indicated for the treatment of ankylosing spondylitis. The Cataflam brand of this medicine is also used to treat menstrual cramps.
Diclofenac powder (Cambia) is used to treat a migraine headache attack. Cambia will only treat a headache that has already begun. It will not prevent headaches or reduce the number of attacks.
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Diclofenac is available as Diclofenac sodium or potassium in tablets, capsules, Gel, Powder, and injection formulation.
It is a non-selective COX (cyclo-oxygenase) inhibitor with potent antipyretic, anti-inflammatory, and pain-relieving properties.
It is indicated for acute or long-term use in the relief of signs and symptoms of ankylosing spondylitis.
Dysmenorrhea (immediate-release tablets only):
It is effective in the treatment of primary dysmenorrhea.
Migraine (powder for oral solution only):
Diclofenac is given for 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):
It is helpful in relieving 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 concurrently with opioid analgesics) in adults.
Rheumatoid arthritis (immediate-release, extended-release, and delayed-release tablets; and suppositories [Canadian product] only):
It is effective in relieving the signs and symptoms of rheumatoid arthritis.
Diclofenac dose in adults:
Note: Due to the risk of vascular events such as MI, stroke, the dose should not exceed 100 mg/day.
Note: Dyloject (diclofenac injection) has been discontinued in the United States for more than 1 year.
Diclofenac dose in the treatment of Ankylosing spondylitis:
Delayed-release tablet:
25 mg per oral 4 times daily and 25 mg at bedtime as needed.
Diclofenac dose in the treatment of Migraine:
Powder for oral solution:
50 mg (one packet) as a single dose; safety and efficacy of a second dose have not been established.
Diclofenac dose in the treatment of Osteoarthritis:
Immediate-release tablet:
Oral: 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:
Oral: 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 a final oral daily dose.
maximum combined dose [rectal and oral]: 100 mg/day.
Diclofenac dose in the treatment of mild to moderate Pain:
Immediate-release tablet:
Oral: 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 per oral 4 times daily.
Zorvolex (diclofenac acid): 18 mg or 35 mg per oral 3 times daily.
IV: 37.5 mg every 6 hours as needed; adjust the frequency according to patient response.
maximum: 150 mg/day.
Diclofenac dose in the treatment of primary dysmenorrhea:
Immediate-release tablet:
50 mg 3 times daily; may administer 100 mg as an initial dose, followed by 50 mg 3 times daily.
Diclofenac dose in patients with Rheumatoid arthritis:
Immediate-release tablet:
50 mg per oral 3 to 4 times daily.
Delayed-release tablet:
50 mg per oral 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 the final oral daily dose.
maximum combined dose [rectal and oral]: 100 mg/day.
Diclofenac dose in children:
Note: Different oral formulations are not bioequivalent; do not interchange product.
Diclofenac dose in the treatment of Juvenile idiopathic arthritis:
Children and Adolescents:
Immediate release tablet:
2 to 3 mg/kg/day per oral in divided doses 2 to 4 times/day.
maximum daily dose: 150 mg/day.
Diclofenac dose in the treatment of migraine:
Adolescents ≥18 years:
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.
Pregnancy Risk Factor C/D (≥30 weeks gestation)
Diclofenac can cross the placenta.Some studies have shown that NSAIDs in utero can cause birth defects. However, the data is inconsistent.
Some non-teratogenic effects can be caused by NSAIDs in utero, such as prenatal constriction, persistent pulmonary hypertension, oligohydramnios and necrotizing enterocolitis.
Postnatal resistance to the closure of the ductus Arteriosus may occur.
Diclofenac’s product label clearly states that diclofenac should not be used starting at 30 weeks gestation because of the potential for premature closure of the ductus arteriosus.
Mild rheumatoid-arthritis flares in pregnancy can be treated with NSAIDs. However, they should be avoided during the early and later trimesters.
For migraines that occur during pregnancy, alternative agents to diclofenac may be used.
You can reverse infertility by stopping taking NSAIDs for a prolonged period.
The drug should be stopped by women who are having trouble conceiving and those who are undergoing fertility treatment.
NSAIDs taken close to conception increase the risk of miscarriage.
Diclofenac use during breastfeeding:
Breast milk contains diclofenac.
When diclofenac was calculated from the highest breastmilk concentration, the relative infant dose (RID), is 0.5% to 0.755%. This is compared to an infant therapeutic dosage of 2 to 3 mg/kg/day.
If the RID is less than 10%, breastfeeding is acceptable. However, breastfeeding should not be done if it is more than 25%.
The highest possible milk concentration (100 mg/L) is used to calculate the infant’s daily breast milk dose of 0.015 mg/kg/day.This milk concentration was calculated after maternal administration of oral diclofenac 150mg/day.
Postpartum mothers who want to breastfeed can take NSAIDs. However, alternative agents are possible.
Avoid NSAIDs for breastfeeding women who have platelet dysfunction or thrombocytopenia.
Diclofenac Dose adjustment in renal disease:
Oral Diclofenac:
Mild or moderate impairment:
No dosage adjustment necessary.
Significant impairment or advanced renal disease:
Use is not recommended.
Diclofenac Injections:
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:
In patients with intercurrent disease that increases risk of acute kidney injury, it should be stopped temporarily.
eGFR <30 mL/minute/1.73 m²:
Use should be avoided.
Diclofenac Dose adjustment in liver disease:
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: Lowest effective dose for the shortest duration possible should be used.
Zipsor/Zorvolex: Initial: Treatment should be started at the lowest dose; if efficacy is not achieved with the lowest dose,therapy should be stopped.
Diclofenac Injections:
Mild impairment:
No dosage adjustment necessary.
Moderate to severe impairment:
Use is not recommended (has not been studied).
Side effects of Diclofenac Injections:
Cardiovascular:
Edema
Cerebrovascular Accident
Hypertension
Myocardial Infarction
Significant Cardiovascular Event
Central Nervous System:
Headache
Dizziness
Dermatologic:
Pruritus
Skin Rash
Exfoliative Dermatitis
Stevens-Johnson Syndrome
Toxic Epidermal Necrolysis
Endocrine & Metabolic:
Fluid Retention
Gastrointestinal:
Constipation
Abdominal Pain
Diarrhea
Dyspepsia
Esophageal Perforation
Flatulence
Gastrointestinal Ulcer
Heartburn
Intestinal Perforation
Nausea
Vomiting
Hematologic & Oncologic:
Anemia
Hemorrhage
Prolonged Bleeding Time
Hepatic:
Increased Liver Enzymes
Increased Serum Transaminases
Increased Serum ALT
Increased Serum AST
Hypersensitivity:
Anaphylactoid Reaction
Local:
Infusion Site Reaction
Extravasation
Otic:
Tinnitus
Renal:
Renal Insufficiency
Miscellaneous:
Wound Healing Impairment
Gastrointestinal Inflammation
Side effects of Oral Diclofenac:
Common Side Effects Of Diclofenac:
Cardiovascular:
Edema
Hepatic:
Increased Serum Transaminases
Uncommon Side Effects Of Diclofenac:
Cardiovascular:
Hypertension
Central Nervous System:
Headache
Procedural Pain
Dizziness
Falling
Dermatologic:
Pruritus
Skin Rash
Gastrointestinal:
Constipation
Nausea
Diarrhea
GI Adverse Effects
Abdominal Pain
Vomiting
Dyspepsia
Flatulence
Heartburn
Abdominal Discomfort
Duodenal Ulcer
Genitourinary:
Urinary Tract Infection
Hematologic & Oncologic:
Bruise
Anemia
Prolonged Bleeding Time
Hepatic:
Increased Serum ALT
Increased Serum AST
Infection:
Influenza
Neuromuscular & Skeletal:
Osteoarthritis
Arthralgia
Back Pain
Limb Pain
Renal:
Renal Function Abnormality
Otic:
Tinnitus
Renal:
Increased Serum Creatinine
Renal Function Abnormality
Respiratory:
Upper Respiratory Tract Infection
Nasopharyngitis
Sinusitis
Cough
Bronchitis
Rectal suppository [Canadian product]:
Also refer to adverse reactions associated with oral formulations.
What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.
Contraindications to Diclofenac:
Hypersensitivity to diclofenac (eg anaphylactoid reaction, severe skin reactions) or bovine proteins (Zipsor only), or any component of formulation
History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
Patients with severe to moderate renal impairment during the perioperative period, and those at high risk of volume depletion (injection only)
Use in the CABG setting
Canadian labeling: Additional contraindications not in US labeling
Patients under 16 years old (suppository, tablet), or 18 year of age (packet only).
Third trimester of pregnancy, breastfeeding
Hyperkalemia
Peptic ulcer/ active gastric/ duodenal/ peptic disease
Active GI bleeding or perforation, region ulcer or enteritis or gastritis, gastritis or ulcerative colitis or recurrent or repeated ulceration
Inflammatory bowel disease
Recent history of bleeding or inflammatory lesions in rectum/anus (suppository only).
Other bleeding disorders or cerebrovascular bleeding
Active hepatic disease; severe hepatic impairment
Severe renal impairment (CrCl >30 mL/minute), or deteriorating renal disease
Warnings and precautions
Anaphylactoid reactions
Patients may experience anaphylactoid reactions even if they have not been exposed to it before.
Patients with the “aspirin trifecta” (bronchial asthma and aspirin intolerance, rhinitis) are at greater risk.
It is not recommended to use NSAIDs or aspirin therapy in patients with bronchospasm or asthma.
Cardiovascular events: [US Boxed Warn]
NSAID therapy can cause fatal cardiovascular thrombotic events such as stroke and MI.
This risk can occur during treatment, and it may increase as the duration of use is prolonged.
The relative risk of cardiovascular events seems to be the same for those with and without cardiovascular disease. However, in patients with known risk factors or cardiovascular disease, and those who receive higher doses of medication, the absolute risk is high.
Monitorizing BP is important as it could lead to new-onset hypertension, exacerbation, or worsening of hypertension. NSAIDs can also affect the response to ACE inhibitors, thiazide dialutics, or loop diuretics. This may increase your risk of cardiovascular events.
Patients with edema should not use it due to the possibility of fluid retention and sodium buildup.
Patients with heart failure should avoid using this product.
Patients who have had recent MI should not use the device unless they are comfortable with the risk of developing cardiovascular thrombotic complications.
To minimize cardiovascular events, patients should receive the lowest effective dose over a shorter time period to meet their individual goals.
Patients at high risk should be treated using alternate therapies.
CNS effects
It is possible to experience drowsiness, dizziness and blurred vision as well as other neurologic effects that can lead to impairments in physical or mental abilities.Operating machinery or driving is something patients should be aware of.
Therapy should be stopped if blurred or reduced vision is present. An ophthalmologic exam should also be performed.
Patients who have been using long-term medication should be evaluated periodically.
[US Boxed Warning]: GI events
NSAIDs can cause fatal gastrointestinal inflammation, ulceration and bleeding as well as perforation.
Patients with a history of peptic ulcer disease or GI bleeding are at greater risk.
These events can occur without warning and at any time during therapy.
Patients suffering from active GI bleeding should not take NSAIDs.
Patients with a history or tendency to have acute lower GI bleeding should not receive non-aspirin NSAIDs, especially if they are suffering from angioectasias or diverticulosis.
You should exercise caution when you are over 65, if you smoke, if your liver is calcified, if you have a history of GI problems, advanced hepatic diseases, coagulopathy, coagulopathy, and combination therapy with anticoagulants, corticosteroids, and/or aspirin, or selective serotonin reuptake inhibiters.
To minimize GI side effects, it is important to use the lowest effective dose and for the shortest time. This should be consistent with the individual patient’s goals.
Patients at high risk should consider alternate treatment options.
Due to the possibility of GI ulcers, it is recommended that NSAIDs be used with aspirin.
Hematologic effects
Anemia can result from prolonged NSAID treatment.
Extended bleeding times, decreased platelet adhesion and increased aggregation can be caused by NSAIDs.
Patients with coagulation disorders and those taking anticoagulants need to be closely monitored.
Rarely, severe blood dyscrasias can be caused by NSAIDs (e.g., agranulocytosis or thrombocytopenia),
Hepatic effects
Patients with abnormal LFT must be closely monitored due to the possibility of transaminitis.
NSAIDs can cause life-threatening liver reactions (eg, fulminant Hepatitis, severe hepatic disease, or hepatic failure).
Therapy should be stopped if there are any signs or symptoms that indicate liver disease.
Hyperkalemia:
Due to the increased risk for hyperkalemia in older age, DM and renal disease, as well as concomitant use other agents that can cause hyperkalemia (eg ACE inhibitor), it is important to monitor potassium closely.
Effects on the renal system:
NSAIDs can cause decreased renal blood flow and dose-dependent decreases of prostaglandin synthesis, which can lead to renal insufficiency.
Dehydration, hypovolemia and heart failure increase the risk of kidney toxicity in the elderly, as well as those who are taking diuretics or ACE inhibitors.
Patients should be properly hydrated before starting treatment.
Chronic therapy can be used to treat renal papillary necrosis or other injuries.
Reactions to skin:
Exfoliative dermatitis and Stevens-Johnson Syndrome can lead to life-threatening reactions.
The first sign of skin rash or any other hypersensitivity should prompt you to stop therapy.
Aseptic meningitis
Patients with systemic lupus, mixed connective tissue disorders and patients with systemic-lupus erythematosus are at greater risk for aseptic meningitis.
Asthma
Patients with asthma that is aspirin-sensitive should not take diclofenac. If this happens, severe and potentially fatal bronchospasm can occur.
Patients with other forms or asthma should be cautious.
Coronary bypass surgery for coronary artery bypass: [US Boxed Warn]
Therapy is not recommended in the context of (CABG surgery) due to the possibility of MI or stroke.
Hepatic impairment
Patients with hepatic impairment should exercise caution and reduce their dose.
Patients with advanced hepatic diseases are more likely to experience GI bleeding from NSAIDs than those without.
Renal impairment
If the risks of worsening renal function are not outweighed by the benefits, avoid use.
The injection should not be given to patients suffering from moderate or severe renal impairment.
NSAIDs should not be used in patients who have moderate or severe renal impairment during the perioperative period, and are at high risk of volume loss.
What other drugs will affect diclofenac?
Ask your doctor before using diclofenac if you take an antidepressant. Taking certain antidepressants with an NSAID may cause you to bruise or bleed easily.
Tell your doctor about all your other medicines, especially:
heart or blood pressure medication, including a diuretic or "water pill";
other forms of diclofenac (Arthrotec, Flector, Pennsaid, Solaraze, Voltaren Gel);
a blood thinner - warfarin, Coumadin, Jantoven; or
other NSAIDs - aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), indomethacin, meloxicam, and others.
This list is not complete. Other drugs may interact with diclofenac, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.
Monitoring parameters:
BP
CBC
LFTs
RFTs
chemistry profile
weight gain, edema
occult blood loss
GI effects (abdominal pain, bleeding, dyspepsia)
mental confusion, disorientation
Any bleeding, bruising
How to administer Diclofenac?
Injection:
Administer as an intravenous bolus over 15 seconds.
Oral:
Delayed- or extended-release tablets should not be crushed.
Immediate-release formulations can be given with food or milk to avoid gastric distress.
Cambia, Zorvolex:
Administering with food may cause a reduction in effectiveness.
Mechanism of action of Diclofenac (Diclo, Voren):
Diclofenac is an antipyretic, analgesic and anti-inflammatory drug.
It inhibits cyclooxygenase-1 (COX-1) enzymes, which causes decreased formation of prostaglandin precursors.
Others that have been suggested as contributing to the anti-inflammatory effects are decreased proinflammatory cytokine level, chemotaxis inhibition and lymphocyte activity alteration. They also inhibit neutrophil activation.
Absorption: Oral:
50% (systemically available).
Protein binding:
>99% (primarily to albumin).
Metabolism:
Hepatic; undergoes first-pass metabolism; forms several metabolites (1 with weak activity).
