Diclofenac Sodium

Pronunciation

Diclofenac sodium 100mg

Diclofenac sodium 25mg

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Diclofenac Potassium Tablet 50mg		P1S1S3

Mechanism of Action

Non-opioid Analgesic (NSAID) Anti-inflammatory agent, Nonselective COX inhibitor, inhibits COX-1 and COX-2 with relative equipotency

Dosage

Usual oral dose for painful conditions:

Oral: 25 to 50 mg every 6 to 8 hours to a maximum of 150 mg daily.

Deep intramuscular: 75 mg once daily, if required in severe conditions, 75 mg twice daily.

Bolus intravenous: 75 mg may be given over 30 to 120 minutes. The dose may be repeated once after 4 to 6 hours if necessary.

Diclofenac sodium 0.1% eye drops is used in various situations:

• For the prevention of intra-operative miosis during cataract surgery. It is instilled in the appropriate eye 4 times during the 2 hours before surgery
• For the treatment of postoperative inflammation after cataract surgery. It is instilled 4 times daily for up to 28 days starting 24 hours after surgery
• For pain control after accidental trauma, one drop is instilled 4 times daily for up to 2 days
• To relieve symptoms of seasonal allergic conjunctivitis, one drop is instilled 4 times daily as necessary

Topical

Diclofenac dimethylamine is used topically as a gel for the local symptomatic relief of pain and inflammation. It is applied to the affected site 3 or 4 times daily.

Administration in children

In children aged 6 months to 17 years,

for rheumatic disease, Oral: 3 to 5 mg/kg daily in 2 or 3 divided doses.

For soft-tissue disorders, oral: 0.3 to 1 mg/kg (maximum 50 mg) given 3 times daily.

Rectal: those weighing 8 to 11 kg, 12.5 mg twice daily and heavier children 1 mg/kg three times daily. Intravenous infusion or deep intramuscular injection: 0.3 to 1 mg/kg (maximum 50 mg) given 3 times daily, for up to 2 days for postoperative pain.

Regardless of route or indication, a maximum daily dose of 150 mg should not exceeded.

Side Effects

As for NSAIDs in general.

Diclofenac suppositories can cause local irritation.

Transient burning and stinging may occur with diclofenac eye drops.

Topical preparations of diclofenac such as plasters and gel may cause application site reactions.

Common side effects include heartburn, nausea, dyspepsia, diarrhoea, constipation, gastrointestinal ulceration/bleeding, headache, dizziness, rash, salt and fluid retention, and high blood pressure.

Effects on the blood: localized spontaneous bleeding, bruising and prolonged bleeding time have been reported.

It also increases the risk of heart attack, stroke, kidney failure and liver failure.

NSAID can also worsen asthma.

Cardiovascular risk

Chronic ibuprofen use has been found correlated with risk of progression to hypertension and myocardial infarction (heart attack). Both the U.S. Food and Drug Administration (FDA) and The European Medicines Agency (EMA) issues warnings of increased heart attack and stroke risk.

Skin

NSAIDs have been associated with the onset of bullous pemphigoid. It can also cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which can be fatal.

Pharmacokinetics

Diclofenac is rapidly absorbed when given as an oral solution, tablet or rectal suppository, or by intramuscular injection.

It is subject to first-pass metabolism so that about 50% of the drug reaches the systemic circulation in the unchanged form.

Diclofenac is also absorbed percutaneously.

At therapeutic concentrations it is more than 99% bound to plasma proteins.

Diclofenac penetrates synovial fluid where concentrations may persist even when plasma concentrations fall; small amounts are distributed into breast milk.

The terminal plasma half-life is about 1 to 2 hours.

It is excreted mainly in the urine (about 60%) but also in the bile (about 35%); less than 1% is excreted as unchanged diclofenac.

Drug Management

Efficiency:

• Pain and inflammation control

Safety:

• monitor signs of bleeding and bruising, and blood pressure.

Drug Interaction: Interactions involving NSAIDs include

• enhancement of the effects of oral anticoagulants
• increased plasma concentrations of lithium, methotrexate and cardiac glycosides.
• Risk of nephrotoxicity may be increased if given with ACE inhibitors, ciclosporin, tacrolimus or diuretics
• Antihypertensive effects of ACEIs, beta blockers and diuretics may be reduced
• Use of more than one NSAID together (including aspirin) should be avoided because of the increased risk of adverse effects.
• The risk of gastrointestinal bleeding and ulceration is increased when used with steroids, the SSRIs, the SNRI venlafaxaine, the antiplatelet clopidogrel, bisphosphonates or pentoxifylline.

Co-adminstration of

ACE inhibitor can increase risk of kidney problem and increase hypotensive effect. Aspirin.

Caution:

Allergic reaction,

Previous peptic ucler

uncontrolled hypertension,

Impaired renal function

Contraindication:

• Hypersensitivity against diclofenac
• History of allergic reactions (bronchospasm, rhinitis, urticaria) following the use of other NSAIDs such as aspirin
• Third-trimester pregnancy
• Active stomach and/or duodenal ulceration or gastrointestinal bleeding
• Inflammatory bowel disease such as Crohn’s disease or ulcerative colitis
• Severe congestive heart failure (NYHA III/IV)
• Severe liver insufficiency
• Severe chronic kidney disease (creatinine clearance <30 mi/min)
• Caution in patients with pre-existing hepatic porphyria, as diclofenac may trigger attacks
• Caution in patients with severe, active bleeding such as cerebral hemorrhage
• Caution in patients with fluid retention or heart failure
• Can lead to onset of new hypertension or worsening of pre-existing hypertension
• Should not be given intravenously to patients with asthma