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Pharmacology

What are NSAIDs?

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This Post is adapted from the Canadian Pharmacists Association (CPhA) Drug Monograph: Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Click here to view the Product Summary Table (web image)

Click here to download the Product Summary Table (PDF)

Indications and Clinical Use

  • As anti-inflammatory, analgesic and antipyretic agents, NSAIDs provide symptomatic relief but do not cure the underlying disease.
  • No NSAID has been proven superior for symptom relief.
  • The choice of drug depends on individual risk factors, such as NSAID toxicity, individual patient response, compliance potential, dosage forms, cost and available evidence.
  • For compliance, drugs with a long half-life or available in dosage forms that allow once-daily dosing are preferred (diclofenac, ketoprofen, meloxicam, nabumetone, naproxen, oxaprozin, tenoxicam).

Health Canada-approved Indications 

  • Chronic treatment of inflammatory disorders, including rheumatoid arthritis, osteoarthritis and ankylosing spondylitis.
  • Short-term treatment of mild to moderate pain associated with inflammation, such as musculoskeletal pain, dental pain, post-operative pain, muscle strains and headache.
  • Short-term treatment of fever. 
  • Ketorolac is approved for short-term treatment of severe pain following major surgery. 
  • Pediatrics: Only ibuprofen and naproxen are approved for use in children.

Contraindications

  • Hypersensitivity to the NSAID or to any ingredient in the formulation or component of the container.
  • History of asthma or allergic-type reactions after taking NSAIDs or ASA, including ASA intolerance and the Aspirin Triad (asthma, nasal polyps and ASA intolerance): possible fatal anaphylactoid reactions and cross-reactivity among structurally different NSAIDs.
  • Third trimester of pregnancy: possible premature closure of the ductus arteriosus and possible prolonged parturition.
  • Severe uncontrolled heart failure: possible exacerbations occuring.
  • Active gastric, duodenal or peptic ulcers and inflammatory bowel disease: NSAIDs (including low-dose ASA) can increase the risk of gastrointestinal irritation, bleeding and ulceration.
  • Severe liver impairment: most NSAIDs are metabolized in the liver.
  • Severe renal impairment (ClCr <30 mL/minute or 0.5 mL/second): NSAIDs can cause renal failure, especially in patients who have renal dysfunction.
  • Hyperkalemia: NSAIDs can cause hyperkalemia.
  • Risk of bleeding increases perioperatively; therefore, discontinue prior to surgery. The exception is low-dose ASA when used perioperatively for antithrombotic effects.

Warnings

  • NSAIDs have been associated with an increased risk of potentially fatal thrombotic events including myocardial infarction and stroke [BMJ 2011;342:c7086]. Until further evidence is available use NSAIDs with caution in patients with pre-existing cardiovascular disease (except low-dose ASA).
  • Gastrointestinal perforation, ulceration and bleeding, in some cases fatal, have been reported with all systemic NSAIDs.
  • An anaphylactic-like reaction and aseptic meningitis have been reported with high-dose NSAID use in patients with systemic lupus erythematosus.
Precautions
  • Increased risk of cardiovascular mortality, myocardial infarction and stroke. Risk increases with dose and duration of use.
  • Risk of increasing blood pressure and worsening pre-existing hypertension.
  • Risk of causing sodium and water retention leading to exacerbation of pre-existing heart failure.
  • Risk of gastrointestinal toxicity with any NSAID administered by any route at any time during therapy.The risk increases with dose and duration of therapy.
  • Risk of inhibiting platelet aggregation and increasing bleeding.
  • Increased risk of aseptic meningitis associated with high-dose NSAIDs in patients with autoimmune disorders, such as systemic lupus erythematosus.
  • Risk of acute renal failure, sodium and potassium retention, renal papillary necrosis and interstitial nephritis has been reported with all NSAIDs.

Special Populations

Pediatrics: increased risk of acute kidney injury, even with normal doses. Ensure proper hydration status of children when on NSAID therapy.

Pregnant Women: small risk of spontaneous abortion and cardiac malformations in the first trimester, although newer data suggests otherwise. NSAIDs may be safe for short-term use in the second trimester. However, all NSAIDs are contraindicated in the third trimester because prostaglandin synthesis inhibition can cause premature closure of the ductus arteriosus, resulting in pulmonary hypertension of the newborn. As well, prostaglandin synthesis inhibition close to delivery can delay and prolong labor by inhibiting uterine contractions. Hemorrhage and impaired fetal renal function are other concerns.

Nursing Women: most NSAIDs are known or likely to be excreted in breast milk in small amounts. Preference should be given to NSAIDs considered by the American Academy of Pediatrics and other authorities to be safe for use in lactation: diclofenac (excluding powder for oral solution), flurbiprofen, ibuprofen, indomethacin, ketoprofen, mefenamic acid, naproxen and piroxicam. Agents with a short half-life are preferred.

Geriatrics: Elderly patients are more likely to have risk factors for NSAID toxicity and are less able to tolerate adverse reactions if they occur.

Drug Interactions

Click here for the Drug Interactions Table (web image)

Click here for the Drug Interactions Table (PDF)

Source:
Canadian Pharmacists Association: Compendium of Pharmaceuticals and Specialties, online version (e-CPS), accessed on May 10, 2013
 

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