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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(me kloe fen AM ate)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Use: Labeled Indications
Treatment of inflammatory disorders, arthritis, mild-to-moderate pain, dysmenorrhea
Pregnancy Risk Factor
C/D (3rd trimester)
Pregnancy Considerations
May cause premature closure of the ductus arteriosus in the 3rd trimester of pregnancy.
Lactation
Enters breast milk/not recommended
Contraindications
Hypersensitivity to meclofenamate, aspirin, other NSAIDs, or any component of the formulation; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery
Warnings/Precautions
Boxed warnings:
• Cardiovascular events: See “Concerns related to adverse effects” below.
• Coronary artery bypass graft surgery: See “Disease-related concerns” below.
• Gastrointestinal events: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.
• Cardiovascular events: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. Use caution with fluid retention. Avoid use in heart failure. Concurrent administration of ibuprofen, and potentially other nonselective NSAIDs, may interfere with aspirin's cardioprotective effect. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.
• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Discontinue use with blurred or diminished vision and perform ophthalmologic exam. Periodically evaluate vision in all patients receiving long term therapy.
• Gastrointestinal events: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with ?325 mg of aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt, 2008).
• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.
• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of skin rash or hypersensitivity.
Disease-related concerns:
• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.
• Coronary artery bypass graft surgery: [U.S. Boxed Warning]: Use is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.
• Hepatic impairment: Use with caution in patients with decreased hepatic function. Closely monitor patients with any abnormal LFT. Severe hepatic reactions (eg, fulminant hepatitis, liver failure) have occurred with NSAID use, rarely; discontinue if signs or symptoms of liver disease develop, or if systemic manifestations occur.
• Hypertension: Use with caution; may cause new-onset hypertension or worsening of existing hypertension.
• Renal impairment: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Not recommended for use in patients with advanced renal disease. Long-term NSAID use may result in renal papillary necrosis.
Special populations:
• Elderly: The elderly are at increased risk for adverse effects (especially peptic ulceration, CNS effects, renal toxicity) from NSAIDs even at low doses.
• Pediatrics: Safety and efficacy have not been established in children <14 years of age.
Other warnings/precautions:
• Surgical/dental procedures: Withhold for at least 4-6 half-lives prior to surgical or dental procedures.
Adverse Reactions
>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
Drug Interactions
ACE Inhibitors: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of ACE Inhibitors. Risk C: Monitor therapy
Aminoglycosides: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Risk C: Monitor therapy
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Anticoagulants: Nonsteroidal Anti-Inflammatory Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antidepressants (Tricyclic, Tertiary Amine): May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy
Antiplatelet Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Beta-Blockers: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Nonsteroidal Anti-Inflammatory Agents. Risk D: Consider therapy modification
Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of NSAID (Nonselective). Risk C: Monitor therapy
CycloSPORINE: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of CycloSPORINE. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of CycloSPORINE. Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy
Desmopressin: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification
Eplerenone: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Eplerenone. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Glucosamine: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk D: Consider therapy modification
HydrALAZINE: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of HydrALAZINE. Risk C: Monitor therapy
Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ketorolac: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Risk X: Avoid combination
Lithium: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Lithium. Risk D: Consider therapy modification
Loop Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Methotrexate: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Methotrexate. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Pemetrexed: NSAID (Nonselective) may increase the serum concentration of Pemetrexed. Management: Patients with mild-to-moderate renal insufficiency (CrCl 45-79 mL/minute) may use ibuprofen with caution, but should avoid other NSAIDs for 2-5 days prior to, the day of, and 2 days after pemetrexed. Risk D: Consider therapy modification
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Potassium-Sparing Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Potassium-Sparing Diuretics. Nonsteroidal Anti-Inflammatory Agents may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Risk C: Monitor therapy
Pralatrexate: Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Pralatrexate. More specifically, NSAIDS may decrease the renal excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum levels and/or toxicity if used concomitantly with an NSAID. Monitor for decreased pralatrexate serum levels with NSAID discontinuation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Quinolone Antibiotics: Nonsteroidal Anti-Inflammatory Agents may enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Risk C: Monitor therapy
Salicylates: NSAID (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. NSAID (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of NSAID (Nonselective). Exceptions: Choline Magnesium Trisalicylate. Risk D: Consider therapy modification
Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk D: Consider therapy modification
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the antiplatelet effect of NSAID (Nonselective). Risk C: Monitor therapy
Thiazide Diuretics: Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide Diuretics. Risk C: Monitor therapy
Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thrombolytic Agents: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Risk C: Monitor therapy
Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy
Treprostinil: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Bleeding may occur. Risk C: Monitor therapy
Vancomycin: Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Vancomycin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): NSAID (Nonselective) may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).
Herb/Nutraceutical: Avoid alfalfa, anise, bilberry, bladderwrack, bromelain, cat's claw, celery, chamomile, coleus, cordyceps, dong quai, evening primrose, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginseng (American, Panax, Siberian), grapeseed, green tea, guggul, horse chestnut seed, horseradish, licorice, prickly ash, red clover, reishi, SAMe (S-adenosylmethionine), sweet clover, turmeric, white willow (all have additional antiplatelet activity).
Mechanism of Action
Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties
Other proposed mechanisms not fully elucidated (and possibly contributing to the anti-inflammatory effect to varying degrees), include inhibiting chemotaxis, altering lymphocyte activity, inhibiting neutrophil aggregation/activation, and decreasing proinflammatory cytokine levels.
Pharmacodynamics/Kinetics
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)
Dosage
Children >14 years and Adults: Oral:
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
Test Interactions
Increased chloride (S), increased sodium (S)
Dietary Considerations
May be taken with food, milk, or antacids.
Geriatric Considerations
Elderly are a high-risk population for adverse effects from NSAIDs. As much as 60% of elderly can develop peptic ulceration and/or hemorrhage asymptomatically. The concomitant use of H2 blockers and sucralfate is not effective as prophylaxis with the exception of NSAID-induced duodenal ulcers which may be prevented by the use of ranitidine. Misoprostol and proton pump inhibitors are the only agents proven to help prevent the development of NSAID-induced ulcers. Also, concomitant disease and drug use contribute to the risk for GI adverse effects. Use lowest effective dose for shortest period possible. Consider renal function decline with age. Use of NSAIDs can compromise existing renal function especially when Clcr is ?30 mL/minute. Tinnitus may be a difficult and unreliable indication of toxicity due to age-related hearing loss or eighth cranial nerve damage. CNS adverse effects such as confusion, agitation, and hallucination are generally seen in overdose or high dose situations, but elderly may demonstrate these adverse effects at lower doses than younger adults.
Anesthesia and Critical Care Concerns/Other Considerations
The 2002 ACCM/SCCM guidelines for analgesia (critically-ill adult) suggest that NSAIDs may be used in combination with opioids in select patients for pain management. Concern about adverse events (increased risk of renal dysfunction, altered platelet function and gastrointestinal irritation) limits its use in patients who have other underlying risks for these events.
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.
Cardiovascular Considerations
Blood Pressure: In short-term use, NSAIDs vary considerably in their effect on blood pressure. A meta-analysis (Pope, 1993) showed that indomethacin and naproxen had the largest effect on blood pressure. Other NSAIDs, including piroxicam, ibuprofen, and sulindac had less of an effect. Ibuprofen combined with captopril or losartan may attenuate the antihypertensive effects of ACE inhibition or receptor blockade on sitting or 24-hour ambulatory diastolic 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.
Heart Failure: The use of NSAIDs in the treatment of patients with heart failure may be associated with an increased risk for fluid accumulation and edema. One study showed that NSAID use in elderly patients had an increased risk of hospitalization for heart failure. This study gives compelling reasons to avoid or limit the use of NSAIDs in patients with heart failure, particularly in the elderly population. The ACC/AHA 2009 heart failure guidelines suggest that NSAIDs be avoided or withdrawn whenever possible in patients with current or prior symptoms of heart failure and reduced LVEF.
Risk of Cardiovascular Events: Patients at increased risk of cardiovascular adverse events include patients immediately postoperative (10-14 days) from CABG surgery, and those with existing CAD, CVD, or history of TIA. Prescribers are encouraged to use the lowest effective dose for the shortest duration of time based on individual patient treatment goals. Available evidence reviewed by the FDA does not suggest an increased risk of serious CV events when NSAIDs are given short term and in the lower doses used OTC.
Drug Interactions: Nonsteroidal anti-inflammatory agents, including ibuprofen and naproxen, may diminish the cardioprotective effect of aspirin (Catella-Lawson F, 2001; Capone ML, 2005). It is surmised that ibuprofen may exhibit greater affinity than aspirin for the COX-1 site or if dosed regularly (or prior to aspirin), it would gain access to the active site first. In either case, aspirin's inhibition of COX (irreversible) would be limited in favor of ibuprofen inhibition (reversible). Avoid regular use of NSAIDs (nonselective) if possible. If used occasionally, take after aspirin (immediate release) ingestion.
Dental Health: Effects on Dental Treatment
The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin®). Recovery of platelet function usually occurs 1-2 days after discontinuation of NSAIDs. See Effects on Bleeding.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; may cause drowsiness, confusion, hallucinations, or depression
Mental Health: Effects on Psychiatric Treatment
May rarely cause agranulocytosis; use caution with clozapine or carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, as sodium: 50 mg, 100 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Meclofenamate Sodium)
50 mg (30): $24.99
100 mg (30): $34.64
References
Bhatt DL, Scheiman J, Abraham NS, et al, “ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risk of Antiplatelet Therapy and NSAID Use. A Report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents,” J Am Coll Cardiol, 2008, 52(18):1502-17.
Brooks PM and Day RO, “Nonsteroidal Anti-inflammatory Drugs - Differences and Similarities,” N Engl J Med, 1991, 324(24):1716-25.
Capone ML, Sciulli MG, Tacconelli S, et al, “Pharmacodynamic Interaction of Naproxen With Low-Dose Aspirin in Healthy Subjects,” J Am Coll Cardiol, 2005, 45(8):1295-1301.
Catella-Lawson F, Reilly MP, Kapoor SC, et al, “Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin,” N Engl J Med, 2001, 345(25):1809-17.
Clinch D, Banerjee AK, and Ostick G, “Absence of Abdominal Pain in Elderly Patients With Peptic Ulcer,” Age Ageing, 1984, 13(2):120-3.
Clive DM and Stoff JS, “Renal Syndromes Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1984, 310(9):563-72.
Conlin P, Moore T, Swartz S, et al, “Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients,” Hypertension, 2000, 36(3):461-5.
Court H and Volans GN, “Poisoning After Overdose With Nonsteroidal Anti-inflammatory Drugs,” Adverse Drug React Acute Poisoning Rev, 1984, 3(1):1-21.
“Drugs for Pain,” Med Lett Drugs Ther, 1998, 40(1033):79-84.
Glazko AJ, Chang T, Barondy PE, et al, “Metabolic Disposition of Meclofenamic Acid (Meclomen®) in Laboratory Animals and in Man,” Curr Ther Res, 1978, 23:S22-41.
Graham DY, “Prevention of Gastroduodenal Injury Induced by Chronic Nonsteroidal Anti-inflammatory Drug Therapy,” Gastroenterology, 1989, 96(2 Pt 2 Suppl):675-81.
Gurwitz JH, Avorn J, Ross-Degnan D, et al, “Nonsteroidal Anti-inflammatory Drug-Associated Azotemia in the Very Old,” JAMA, 1990, 264(4):471-5.
Hawkey CJ, Karrasch JA, Szczepañski L, et al, “Omeprazole Compared With Misoprostol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1998, 338(11):727-34.
Heerdink ER, Leufkens HG, Herings RM, et al, “NSAIDs Associated With Increased Risk of Congestive Heart Failure in Elderly Patients Taking Diuretics,” Arch Intern Med, 1998, 158(10):1108-12.
Hoppmann RA, Peden JG, and Ober SK, “Central Nervous System Side Effects of Nonsteroidal Anti-inflammatory Drugs. Aseptic Meningitis, Psychosis, and Cognitive Dysfunction,” Arch Intern Med, 1991, 151(7):1309-13.
Hunt SA, Abraham WT, Chin MH, et al, “2009 Focused Update Incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation,” J Am Coll Cardiol, 2009, 53(15):e1-e90.
Jacobi J, Fraser GL, Coursin DB, et al, “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult,” Crit Care Med, 2002, 30(1):119-41. Available at: http://www.sccm.org/pdf/sedatives.pdf. Accessed August 2, 2003.
Knodel LC, “Preventing NSAID-Induced Ulcers: The Role of Misoprostol,” Consult Pharm, 1989, 4:37-41.
Morgan TO, Anderson A, and Bertram D, “Effect of Indomethacin on Blood Pressure in Elderly People With Essential Hypertension Well Controlled on Amlodipine or Enalapril,” Am J Hypertens, 2000, 13(11):1161-7.
Page J and Henry D, “Consumption of NSAIDs and the Development of Congestive Heart Failure in Elderly Patients: An Underrecognized Public Health Problem,” Arch Intern Med, 2000, 160(6):777-84.
Pope JE, Anderson JJ, and Felson DT, “A Meta-analysis of the Effects of Nonsteroidal Anti-inflammatory Drugs on Blood Pressure,” Arch Intern Med, 1993, 153(4):477-84.
Pounder R, “Silent Peptic Ulceration: Deadly Silence or Golden Silence?” Gastroenterology, 1989, 96(2 Pt 2 Suppl):626-31.
Preston SN, “Safety of Sodium Meclofenamate (Meclomen®),” Curr Ther Res, 1978, 23(Suppl 45):5107-12.
Smolinske SC, Hall AH, Vandenberg SA, et al, “Toxic Effects of Nonsteroid Anti-inflammatory Drugs in Overdose. An Overview of Recent Evidence on Clinical Effects and Dose-Response Relationships,” Drug Saf, 1990, 5(4):252-74.
Vale JA and Meredith TJ, “Acute Poisoning Due to Nonsteroidal Anti-inflammatory Drugs,” Med Toxicol, 1986, 1(1):12-31.
Verbeeck RK, “Pharmacokinetic Drug Interactions With Nonsteroidal Anti-inflammatory Drugs,” Clin Pharmacokinet, 1990, 19(1):44-66.
Yeomans ND, Tulassay Z, Juhasz L, et al, “A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,” N Engl J Med, 1998, 338(11):719-26.
International Brand Names
Lexi-Comp.com
Last full review/revision November 2009
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