Use of NSAIDs can compromise existing renal function especially when Clcr<30 mL/minute. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high-dose situations; however, elderly may demonstrate these adverse effects at lower doses than younger adults. Do not exceed 400 mg/day. Withhold for at least 4-6 half-lives prior to surgical or dental procedures.

>10%:

Central nervous system: Dizziness

Dermatologic: Rash

Gastrointestinal: Abdominal cramps, heartburn, indigestion, nausea

1% to 10%:

Central nervous system: Headache, nervousness

Dermatologic: Itching

Endocrine & metabolic: Fluid retention

Gastrointestinal: Vomiting

Otic: Tinnitus

<1%: CHF, hypertension, arrhythmia, tachycardia, confusion, hallucinations, aseptic meningitis, mental depression, drowsiness, insomnia, urticaria, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, polydipsia, hot flashes, gastritis, GI ulceration, cystitis, polyuria, agranulocytosis, anemia, hemolytic anemia, bone marrow suppression, leukopenia, thrombocytopenia, hepatitis, peripheral neuropathy, toxic amblyopia, blurred vision, conjunctivitis, dry eyes, decreased hearing, acute renal failure, allergic rhinitis, dyspnea, epistaxis

Symptoms of overdose include drowsiness, lethargy, nausea, vomiting, seizures, paresthesia, headache, dizziness, GI bleeding, cerebral edema, cardiac arrest, tinnitus

Management of NSAID intoxication is primarily supportive and symptomatic. Fluid therapy is commonly effective in managing the hypotension that may occur following an acute NSAID overdose, except when this is due to an acute blood loss. Seizures tend to be very short-lived and often do not require drug treatment. Although, recurrent seizures should be treated with I.V. diazepam. Since many of the NSAID undergo enterohepatic cycling, multiple doses of charcoal may be needed to reduce the potential for delayed toxicities.

ACE inhibitors: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure.

Angiotensin II antagonists: Antihypertensive effects may be decreased by concurrent therapy with NSAIDs; monitor blood pressure.

Anticoagulants (warfarin, heparin, LMWHs) in combination with NSAIDs can cause increased risk of bleeding.

Other antiplatelet drugs (ticlopidine, clopidogrel, aspirin, abciximab, dipyridamole, eptifibatide, tirofiban) can cause an increased risk of bleeding.

Corticosteroids may increase the risk of GI ulceration; avoid concurrent use.

Cyclosporine: NSAIDs may increase serum creatinine, potassium, blood pressure, and cyclosporine levels; monitor cyclosporine levels and renal function carefully.

Gentamicin and amikacin serum concentrations are increased by indomethacin in premature infants. Results may apply to other aminoglycosides and NSAIDs.

Hydralazine's antihypertensive effect is decreased; avoid concurrent use.

Lithium levels can be increased; avoid concurrent use if possible or monitor lithium levels and adjust dose. Sulindac may have the least effect. When NSAID is stopped, lithium will need adjustment again.

Loop diuretics efficacy (diuretic and antihypertensive effect) is reduced. Indomethacin reduces this efficacy, however, it may be anticipated with any NSAID.

Methotrexate: Severe bone marrow suppression, aplastic anemia, and GI toxicity have been reported with concomitant NSAID therapy. Avoid use during moderate or high-dose methotrexate (increased and prolonged methotrexate levels). NSAID use during low-dose treatment of rheumatoid arthritis has not been fully evaluated; extreme caution is warranted.

Thiazides antihypertensive effects are decreased; avoid concurrent use.

Verapamil plasma concentration is decreased by diclofenac; avoid concurrent use.

Warfarin's INRs may be increased by piroxicam. Other NSAIDs may have the same effect depending on dose and duration. Monitor INR closely. Use the lowest dose of NSAIDs possible and for the briefest duration.

Duration: 2-4 hours

Distribution: Crosses placenta

Protein binding: 99%

Half-life elimination: 2-3.3 hours

Time to peak, serum: 0.5-1.5 hours

Excretion: Primarily urine and feces (as metabolites)

Mild to moderate pain: 50 mg every 4-6 hours; increases to 100 mg may be required; maximum dose: 400 mg

Rheumatoid arthritis and osteoarthritis: 50 mg every 4-6 hours; increase, over weeks, to 200-400 mg/day in 3-4 divided doses; do not exceed 400 mg/day; maximal benefit for any dose may not be seen for 2-3 weeks

In short-term use, NSAIDs vary considerably in their effect on blood pressure. When NSAIDs are used in patients with hypertension, appropriate monitoring of blood pressure responses should be completed and the duration of therapy, when possible, kept short. The use of NSAIDs in the treatment of patients with congestive heart failure may be associated with an increased risk for fluid accumulation and edema; may precipitate renal failure in dehydrated patients.

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