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What is Diclofenac Used For? Uses, Mechanism, and Side Effects

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Diclofenac is a widely prescribed medication categorized as a non-steroidal anti-inflammatory drug (NSAID). It plays a crucial role in managing pain and inflammation across a range of conditions. This article provides a comprehensive overview of diclofenac, detailing its uses, how it works, potential side effects, and important considerations for its use. Understanding these aspects is vital for healthcare professionals and individuals seeking information about this common medication.

Indications: What Diclofenac Treats

Diclofenac is approved by the FDA for treating both acute and chronic pain, particularly when associated with inflammatory conditions affecting the musculoskeletal system. Key uses include:

  • Osteoarthritis: Diclofenac helps manage pain and inflammation in joints affected by osteoarthritis, a degenerative joint disease.
  • Rheumatoid Arthritis: It is used to alleviate symptoms of rheumatoid arthritis, an autoimmune disorder causing chronic inflammation of the joints.
  • Ankylosing Spondylitis: Diclofenac can reduce pain and stiffness associated with ankylosing spondylitis, an inflammatory disease primarily affecting the spine.
  • Actinic Keratosis: Topical diclofenac is FDA-approved to treat actinic keratosis, a skin condition caused by sun exposure that can sometimes lead to skin cancer.
  • Ophthalmic Uses: Diclofenac eye drops are approved for use after cataract surgery, for general eye pain, and for photophobia (light sensitivity).

While diclofenac effectively manages pain and inflammation symptoms, it’s important to note that it does not reverse or prevent the progression of chronic joint damage seen in conditions like osteoarthritis and rheumatoid arthritis.

Beyond its FDA-approved uses, diclofenac has been used off-label to treat other conditions, including:

  • Biliary colic
  • Corneal abrasion
  • Fever
  • Gout
  • Migraines
  • Muscle pain (myalgia)
  • Post-episiotomy pain

In February 2020, diclofenac 1% gel became available over-the-counter for managing arthritic pain, expanding access for patients. However, most other forms of diclofenac require a prescription. Studies have also shown diclofenac’s benefit in post-operative pain management, reducing the need for stronger pain medications after surgery.

Mechanism of Action: How Diclofenac Works

Diclofenac belongs to the phenylacetic acid family of NSAIDs. Its primary mechanism of action involves inhibiting cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are crucial in the body’s production of prostanoids, such as prostaglandins, prostacyclins, and thromboxanes. These prostanoids are key players in inflammatory and pain responses.

By blocking COX-1 and COX-2, diclofenac reduces the synthesis of these inflammatory mediators. While diclofenac inhibits both COX-1 and COX-2, research suggests it has a slightly greater selectivity for COX-2 inhibition in laboratory settings. COX-2 is primarily involved in inflammation and pain, while COX-1 plays a role in maintaining normal bodily functions, such as protecting the stomach lining and supporting kidney function and platelet activity.

This dual inhibition of COX enzymes contributes to diclofenac’s analgesic (pain-relieving), anti-inflammatory, and antipyretic (fever-reducing) properties, similar to other NSAIDs. Diclofenac is considered a potent inhibitor of prostaglandin E2 (PGE2), a primary prostanoid elevated during inflammation.

Furthermore, diclofenac’s peripheral analgesic effects may be due to its ability to reduce the sensitivity of peripheral pain receptors. This is thought to occur through pathways involving nitric oxide and potassium channels. Diclofenac may also reduce levels of substance P, a neuropeptide involved in inflammation and pain, in the synovial fluid of rheumatoid arthritis patients.

The mechanism by which topical diclofenac treats actinic keratosis is thought to involve inhibiting the production of arachidonic acid metabolites. This may reduce the production of epithelial growth factors that promote abnormal cell growth in this condition. However, this specific mechanism is still being researched.

Administration and Dosage

Diclofenac is available in various forms to suit different needs and conditions:

  • Oral: Tablets (immediate-release and extended-release) and suspensions.
  • Topical: Gels, creams, and transdermal patches.
  • Injectable: Intramuscular and intravenous solutions.
  • Rectal: Suppositories.
  • Ophthalmic: Eye drops.

Oral diclofenac is rapidly absorbed and concentrates in synovial fluid, targeting sites of musculoskeletal inflammation. It’s often recommended to take oral diclofenac with food or milk to minimize gastrointestinal upset. Some formulations combine diclofenac with misoprostol to further protect the stomach. Doctors may also prescribe proton pump inhibitors (PPIs) or antacids alongside NSAIDs to reduce the risk of GI side effects.

Dosage varies depending on the formulation, condition being treated, and individual patient factors. It is crucial to use the lowest effective dose for the shortest duration necessary to minimize adverse effects.

Typical dosage ranges include:

  • Oral Diclofenac Sodium: 100-150 mg daily in divided doses for osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.
  • Topical Diclofenac Sodium Gel (1-2%): Up to 16g per day for single joint osteoarthritis, up to 32g per day for multiple joint osteoarthritis.
  • Topical Diclofenac Sodium Gel (3%): Twice daily application for actinic keratosis.
  • Intravenous Diclofenac Sodium: 37.5 mg every 6 hours for acute moderate to severe pain.
  • Intramuscular Diclofenac Solution: 75 mg as needed for moderate to severe pain.
  • Ophthalmic Diclofenac: 1-2 drops in the affected eye(s) four times daily.
  • Oral Diclofenac Potassium: 50-200 mg daily in divided doses for migraines, osteoarthritis, general pain, and rheumatoid arthritis.
  • Diclofenac Epolamine Transdermal Patch (1.3%): Applied twice daily to the affected area.

Adverse Effects of Diclofenac

Like all NSAIDs, diclofenac carries a risk of side effects, primarily due to COX enzyme inhibition. While diclofenac may have a slightly lower risk of gastrointestinal issues compared to some non-selective NSAIDs, it’s associated with an increased risk of cardiovascular events.

Potential side effects include:

  • Cardiovascular: Increased risk of myocardial infarction (heart attack), heart failure, stroke, and death, especially in patients with pre-existing cardiovascular risk factors and with higher doses. This risk is linked to the COX-2 inhibition, which can reduce production of cardioprotective prostaglandin-I2 (PGI2).
  • Gastrointestinal (GI): Although potentially less than non-selective NSAIDs, diclofenac can still cause GI issues due to COX-1 inhibition, leading to reduced protective prostaglandins in the stomach. This can result in stomach upset, erosion, ulcers, and bleeding.
  • Renal: NSAIDs can impair kidney function, potentially leading to acute kidney injury, particularly in those with pre-existing kidney problems. This is due to reduced prostaglandin synthesis affecting kidney blood flow.
  • Hepatic: Liver damage and elevated liver enzymes are possible, though usually transient and reversible. Rarely, serious liver problems like hepatitis can occur, especially with long-term use.
  • Anaphylaxis: Allergic reactions, including anaphylaxis, are rare but possible. Symptoms can include hives, flushing, rapid heart rate, bronchospasm, swelling, and low blood pressure.
  • Hematologic: Increased bleeding risk due to COX-1 inhibition affecting platelet function. Rarely, low white blood cell counts (neutropenia) and aplastic anemia can occur.
  • Dermatologic: Topical diclofenac may cause skin irritation at the application site.

Contraindications and Precautions

Diclofenac is contraindicated in certain situations due to potential risks:

  • Cardiovascular Disease: Patients with a history of heart attack or stroke should avoid diclofenac due to increased cardiovascular risk. It is also contraindicated after coronary artery bypass graft surgery.
  • Elderly Patients: Diclofenac is on the Beers list of medications to avoid in the elderly due to increased risk of cardiovascular and gastrointestinal side effects.
  • NSAID Allergy: Individuals with a known allergy to diclofenac or other NSAIDs should not use it.
  • Renal Insufficiency: Diclofenac is generally contraindicated in patients with significant kidney problems.
  • Gastrointestinal Bleeding/Ulcers: Patients with a history of GI bleeding or ulcers should avoid diclofenac.
  • Pregnancy: Diclofenac formulations with misoprostol are contraindicated in pregnancy due to the risk of miscarriage associated with misoprostol.

Caution and monitoring are advised in patients with:

  • Helicobacter pylori infection
  • Mild to moderate renal impairment

Monitoring and Toxicity

Patients taking diclofenac should be regularly monitored for:

  • Symptom relief: To ensure the lowest effective dose is used.
  • Blood pressure: To detect hypertension.
  • Gastrointestinal symptoms: Such as GERD or bleeding.
  • Renal function: Due to potential kidney effects.
  • Complete blood count (CBC): To monitor for bleeding risk and blood cell abnormalities.
  • Liver function tests: To assess liver health.

Diclofenac overdose can cause mild symptoms like nausea and dizziness, but severe overdose can lead to seizures, coma, cardiovascular events, and metabolic acidosis. There is no specific antidote for diclofenac overdose. Treatment is supportive, focusing on maintaining vital functions and managing symptoms. Activated charcoal may be used in cases of recent ingestion to limit absorption.

Enhancing Healthcare Team Outcomes

Effective and safe diclofenac therapy relies on appropriate prescribing, patient education, and monitoring. An interprofessional healthcare team approach is crucial, involving physicians, pharmacists, nurses, and other professionals. Patients should be educated about the risks and benefits of diclofenac to ensure informed decision-making and optimal outcomes while minimizing potential adverse events.

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