Generic Name

Diclofenac Sodium; Misoprostol

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Classification

FDA Approved Indications

• Treatment of osteoarthritis of the knee or hand, rheumatoid arthritis, and ankylosing spondylitis in patients at high risk for NSAID-associated gastric ulceration.

Mechanism of Action

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase enzymes (COX-1 and COX-2), reducing prostaglandin synthesis, leading to decreased inflammation and pain. Misoprostol is a prostaglandin E1 analog that replaces protective prostaglandins in the GI tract, reducing ulcer risk and promoting mucous secretion.

Dosage and Administration

Adult: Typically, 50 mg of diclofenac twice daily combined with 200 mcg of misoprostol twice daily. Dosing may vary based on condition and patient response.

Pediatric: Not approved for pediatric use.

Geriatric: Use with caution; consider lower doses due to increased risk of GI and cardiovascular events.

Renal Impairment: Use caution; dose adjustments may be necessary due to potential renal effects.

Hepatic Impairment: Use caution; dose adjustment based on hepatic function is recommended.

Pharmacokinetics

Absorption: Diclofenac is well absorbed with peak plasma concentrations in about 2 hours. Misoprostol is rapidly absorbed and metabolized.

Distribution: Diclofenac binds extensively to plasma proteins (~99%). Misoprostol's active metabolite distributes fairly widely.

Metabolism: Diclofenac is metabolized in the liver mainly via CYP2C9. Misoprostol is rapidly de EMA in the liver.

Excretion: Diclofenac is primarily excreted via the kidneys. Misoprostol metabolites are excreted in urine and feces.

Half Life: Diclofenac: approximately 1-2 hours; misoprostol active metabolites: about 20-40 minutes.

Contraindications

• History of hypersensitivity to diclofenac or misoprostol.
• Active gastrointestinal bleeding or ulcers.
• Pregnancy (category X, due to abortifacient effect).

Precautions

• Use cautiously in patients with renal or hepatic impairment, cardiovascular disease, or history of GI bleeding. Monitor renal function during therapy.

Adverse Reactions - Common

• Gastrointestinal discomfort, diarrhea (Common)
• Nausea, dyspepsia (Common)

Adverse Reactions - Serious

• Gastrointestinal bleeding or ulceration (Uncommon)
• Cardiovascular thrombotic events (e.g., myocardial infarction, stroke) (Rare but serious)
• Hypersensitivity reactions, including anaphylaxis (Rare)

Drug-Drug Interactions

• Other NSAIDs, anticoagulants, corticosteroids (increased GI bleeding risk)
• ACE inhibitors, diuretics (potential nephrotoxicity)

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Take medication with food or as directed to minimize GI irritation.
• Report signs of GI bleeding, such as black stools or vomiting blood.
• Avoid use during pregnancy due to risk of pregnancy loss.
• Report any chest pain, shortness of breath, or signs of allergic reaction.

Special Considerations

Black Box Warnings:

• Cardiovascular thrombotic events, including myocardial infarction and stroke, can occur, especially with long-term use.
• Gastrointestinal bleeding, ulceration, and perforation risk are increased, especially in high doses or at the initiation of therapy.
• Pregnancy: contraindicated in pregnant women, especially after 20 weeks gestation, due to risk to fetus and potential to cause miscarriage.

Genetic Factors: CYP2C9 polymorphisms may affect diclofenac metabolism and risk profile.

Lab Test Interference: May elevate liver enzymes; monitor hepatic function as indicated.

Overdose Management

Signs/Symptoms: Gastrointestinal bleeding, renal failure, hypotension, coma.

Treatment: Supportive care, activated charcoal if ingestion is recent, and symptomatic management. Dialysis may be considered for severe cases.

Storage and Handling

Storage: Store at room temperature away from moisture and heat.

Stability: Stable under normal storage conditions for the duration of the approved shelf life.