Diclofenac

OVERVIEW

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) commonly used to relieve pain and reduce inflammation. It is available in various forms, including oral tablets, topical gels, and injectable solutions. It is a powerful NSAID that is effective for managing pain and inflammation, but it also has some risks, especially for gastrointestinal, heart, and kidney health. It should be used under the guidance of a healthcare professional, especially for long-term treatment.

DOSAGE

Oral Tablets

Osteoarthritis/Rheumatoid Arthritis:

Typical Dose: 50 mg two to three times daily.
Maximum Daily Dose: 150 mg, divided into multiple doses.

Acute Pain:

Typical Dose: 100 mg initially, followed by 50 mg every 8 to 12 hours as needed.

Topical Gel or Cream

Application:

Apply a thin layer (usually about 2-4 g) to the affected area, usually 2-3 times daily.

Maximum Daily Dose:

Do not exceed 32 g of gel per day for adults.

Injectable Form

Postoperative Pain:

Typical Dose: 75 mg, administered as a single intramuscular injection, can be followed by oral dosing as needed.

Extended-Release Tablets

Osteoarthritis/Rheumatoid Arthritis:

Typical Dose: 100 mg once daily, or 75 mg twice daily, depending on the product.

MECHANISM OF ACTION

Inhibition of Cyclooxygenase (COX) Enzymes

COX-1: Involved in the production of prostaglandins that protect the gastric mucosa and support normal platelet function.

COX-2: Primarily involved with inflammation and pain; it is induced at sites of inflammation.

Reduction of Prostaglandin Synthesis

• By inhibiting COX enzymes, diclofenac decreases the synthesis of prostaglandins, which are lipid compounds that mediate inflammatory responses, pain signaling, and fever.
• Decreasing prostaglandin levels reduces inflammation, relieves pain, and reduces fever.

Analgesic and Anti-inflammatory Effects

Due to the overall mechanism of action of diclofenac, it has significant analgesic (pain-relieving) and anti-inflammatory properties, making it effective for conditions such as arthritis, muscle pain, and post-surgical pain.

Local Effects

When applied topically, diclofenac penetrates the skin and acts locally at the site of pain, providing targeted relief and minimizing systemic side effects.

ADVERSE DRUG REACTIONS

Gastrointestinal Issues

Nausea and Vomiting: Commonly reported side effects.
Gastric Irritation: May cause dyspepsia, abdominal pain, and indigestion.
Ulcers and Bleeding: Prolonged use may cause peptic ulcers, gastrointestinal bleeding, and perforation, which may be life-threatening.

Cardiovascular Risks

Increased risk of heart attack and stroke: Long-term use, especially at high doses, can increase the risk of serious cardiovascular events.

Renal Effects

Kidney dysfunction: Diclofenac can affect kidney function, especially in individuals who already have kidney problems. It can cause fluid retention and an increase in blood pressure.

Hepatic Effects

Liver disorders: Liver enzyme levels may increase; rare cases of serious liver damage have been reported.

Allergic Reactions

Skin Reactions: Rashes, itching, or more severe skin reactions such as Stevens-Johnson syndrome.
Anaphylaxis: Rare, but serious allergic reactions can occur.

Central Nervous System Effects

Headaches: Some users may experience headaches as a side effect.
Dizziness and Drowsiness: Can occur, affecting the ability to drive or operate machinery.

Respiratory Reactions

Exacerbation of Asthma: In some individuals, particularly those with sensitivity to aspirin or a history of asthma.

CONTRAINDICATION AND WARNING

Contraindications

Allergy to diclofenac or NSAIDs: Patients with hypersensitivity to diclofenac or other nonsteroidal anti-inflammatory drugs should avoid its use.

Active gastrointestinal bleeding: Patients with active peptic ulcer or gastrointestinal bleeding should not take diclofenac due to the increased risk of further bleeding.

Severe kidney problems: Individuals with severe kidney problems should avoid diclofenac, as it can aggravate kidney problems.

Severe Hepatic Impairment: Contraindicated in patients with severe hepatic impairment.

History of NSAID-induced asthma: Patients with a history of asthma aggravated by aspirin or other NSAIDs should avoid diclofenac.

Pregnancy (third trimester): Diclofenac should not be given during the third trimester because of the potential risk to the fetus, including cardiac complications.

Warnings

Cardiovascular risks: Long-term use of diclofenac can increase the risk of heart attack and stroke, especially in individuals who already have cardiovascular problems.

Gastrointestinal risks: The risk of gastrointestinal ulcers and bleeding is increased, particularly in elderly patients or in patients with a history of gastrointestinal problems.

Hepatic Effects: Monitor liver function in patients taking diclofenac, especially if they have pre-existing liver problems.

Effects on the Kidneys: Kidney function should be monitored in patients taking diclofenac, especially in those who already have kidney problems or who are dehydrated.

Elderly patients: The elderly have a higher risk of serious side effects, including gastrointestinal bleeding and kidney failure. Use caution and consider a lower dose.

Drug interactions: Use caution when using diclofenac with other medications, such as anticoagulants, other NSAIDs, and some antihypertensive medications, as interactions may occur.

Surgery and dental procedures: Diclofenac use should be discontinued before elective surgery to reduce the risk of excessive bleeding.

DRUG-DRUG INTERACTIONS

Anticoagulants

Warfarin: The risk of bleeding may increase when diclofenac is used with anticoagulants. Close monitoring of coagulation parameters is necessary.

NSAIDs

Using diclofenac with other NSAIDs (eg, ibuprofen, naproxen) may increase the risk of gastrointestinal bleeding and ulcers. It may also reduce the cardioprotective effects of low-dose aspirin.

Corticosteroids

Combining diclofenac with corticosteroids (e.g., prednisone) may significantly increase the risk of gastrointestinal complications, such as ulcers and bleeding.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs (e.g., fluoxetine, sertraline) may increase the risk of gastrointestinal bleeding when taken with diclofenac.

Antihypertensive Medications

Diclofenac may reduce the effectiveness of certain antihypertensive medications, such as ACE inhibitors, diuretics, and beta-blockers, particularly in some patients.

Methotrexate

Diclofenac may interfere with the elimination of methotrexate, potentially increasing its toxicity, especially at higher doses.

Lithium

Diclofenac may increase levels of lithium in the blood, potentially leading to lithium toxicity.

Uricosurics

Diclofenac may reduce the effectiveness of uricosuric agents (eg, probenecid) used in the treatment of gout, especially at low doses.

Alcohol

The simultaneous use of alcohol and diclofenac may increase the risk of gastrointestinal bleeding.

USE

Osteoarthritis: Relief of pain and inflammation associated with osteoarthritis.

Rheumatoid arthritis: Management of symptoms associated with rheumatoid arthritis.

Acute musculoskeletal pain: Effective for conditions such as sprains, strains and tendinitis.

Back pain: Used for the management of acute and chronic back pain.

Postoperative Pain : Pain relief following surgical procedures, including orthopedic surgery.

Migraine: In some embodiments, diclofenac may be prescribed for the acute treatment of migraine.

Menstrual Pain: Treatment of dysmenorrhea (painful menstruation) to reduce cramps and discomfort.

Localized pain: Available as a gel or patch for topical application, provides targeted relief for conditions such as osteoarthritis in the hands and knees.

Gout attack: It is sometimes used to relieve pain and swelling during an acute gout attack.