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

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.

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.

CYP2C8/9 substrates: Piroxicam may increase the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, and warfarin.

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.

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.

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.

Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).

Food: Onset of effect may be delayed if piroxicam is taken with food.

Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, red clover, horse chestnut, green tea, ginseng, ginkgo (all have additional antiplatelet activity).

Onset of action: Analgesic: ~1 hour

Peak effect: 3-5 hours

Protein binding: 99%

Metabolism: Hepatic

Half-life elimination: 45-50 hours

Excretion: Primarily urine and feces (small amounts) as unchanged drug (5%) and metabolites

Children: 0.2-0.3 mg/kg/day once daily; maximum dose: 15 mg/day

Adults: 10-20 mg/day once daily; although associated with increase in GI adverse effects, doses >20 mg/day have been used (ie, 30-40 mg/day)

Dosing adjustment in hepatic impairment: Reduction of dosage is necessary

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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