No

Nonsteroidal Anti-Inflammatory Agent (NSAID)

Dental: Management of pain and swelling

Medical: Management of inflammatory disease and rheumatoid disorders (including juvenile rheumatoid arthritis); acute gout; mild to moderate pain; dysmenorrhea; fever, migraine headache

B (D in 3rd trimester or near delivery)

Hypersensitivity to naproxen, aspirin, or other nonsteroidal anti-inflammatory drugs (NSAIDs)

Use with caution in patients with GI disease (bleeding or ulcers), cardiovascular disease (CHF, hypertension), dehydration, renal or hepatic impairment, and patients receiving anticoagulants; perform ophthalmologic evaluation for those who develop eye complaints during therapy (blurred vision, diminished vision, changes in color vision, retinal changes); NSAIDs may mask signs/symptoms of infections; photosensitivity reported; elderly are at especially high-risk for adverse effects

>10%:

Central nervous system: Dizziness

Dermatologic: Pruritus, rash

Gastrointestinal: Abdominal discomfort, nausea, heartburn, constipation, GI bleeding, ulcers, perforation, indigestion

1% to 10%:

Central nervous system: Headache, nervousness

Dermatologic: Itching

Endocrine & metabolic: Fluid retention

Gastrointestinal: Vomiting

Otic: Tinnitus

<1%: Edema, congestive heart failure, arrhythmias, tachycardia, hypertension, confusion, hallucinations, mental depression, fatigue, drowsiness, insomnia, aseptic meningitis, urticaria, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, polydipsia, hot flashes, gastritis, GI ulceration, cystitis, renal dysfunction, polyuria, anemia, hemolytic anemia, bone marrow suppression, leukopenia, thrombocytopenia, inhibits platelet aggregation, prolongs bleeding time, agranulocytosis, hepatitis, peripheral neuropathy, toxic amblyopia, blurred vision, conjunctivitis, dry eyes, decreased hearing, acute renal failure, shortness of breath, epistaxis, allergic rhinitis

Symptoms of overdose include drowsiness, heartburn, vomiting, CNS depression, leukocytosis, renal failure

Management of a nonsteroidal anti-inflammatory drug (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 NSAIDs undergo enterohepatic cycling, multiple doses of charcoal may be needed to reduce the potential for delayed toxicities.

CYP2C8, 2C9, and 2C18 enzyme substrate

Increased toxicity:

Naproxen could displace other highly protein bound drugs, such as oral anticoagulants, hydantoins, salicylates, sulfonamides, and sulfonylureas

Naproxen and warfarin may cause a slight increase in free warfarin

Naproxen and probenecid may cause increased plasma half-life of naproxen

Naproxen and methotrexate may significantly increase and prolong blood methotrexate concentration, which may be severe or fatal

Inhibits prostaglandin synthesis by decreasing the activity of the enzyme, cyclo-oxygenase, which results in decreased formation of prostaglandin precursors

Analgesia: Onset of action: 1 hour; Duration: Up to 7 hours

Anti-inflammatory: Onset of action: Within 2 weeks; Peak: 2-4 weeks

Absorption: Oral: Almost 100%

Time to peak serum concentration: Within 1-2 hours and persisting for up to 12 hours

Protein binding: Highly protein bound (>90%); increased free fraction in elderly

Half-life:

Normal renal function: 12-15 hours

End-stage renal disease: Unchanged

Oral:

Fever: 2.5-10 mg/kg/dose; maximum: 10 mg/kg/day

Juvenile arthritis: 10 mg/kg/day in 2 divided doses

Adults:

Rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis: 500-1000 mg/day in 2 divided doses; may increase to 1.5 g/day of naproxen base for limited time period

Mild to moderate pain or dysmenorrhea: Initial: 500 mg, then 250 mg every 6-8 hours; maximum: 1250 mg/day naproxen base

Dosing adjustment in hepatic impairment: Reduce dose to 50%

Alcohol: Additive impairment of mental alertness and physical coordination, avoid or limit use

Food: Food may decrease the rate but not the extent of oral absorption. Drug may cause GI upset, bleeding, ulceration, perforation; take with food or milk to minimize GI upset.

Occult blood loss, periodic liver function test, CBC, BUN, serum creatinine

Dizziness is common; may cause nervousness; may rarely cause drowsiness, confusion, insomnia, depression, or hallucinations

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; may decrease lithium clearance resulting in an increase in serum lithium levels and potential lithium toxicity; monitor serum lithium levels

No information available to require special precautions

NSAID formulations are known to reversibly decrease platelet aggregation via mechanisms different than observed with aspirin. 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®).

Take this medication exactly as directed; do not increase dose without consulting prescriber. Do not crush tablets or break capsules. Take with food or milk to reduce GI distress. Maintain adequate fluid intake (2-3 L/day of fluids unless instructed to restrict fluid intake). Do not use alcohol, aspirin, or aspirin-containing medication, and all other anti-inflammatory medications without consulting prescriber. You may experience drowsiness, dizziness, lightheadedness, or headache (use caution when driving or engaging in tasks requiring alertness until response to drug is known); anorexia, nausea, vomiting, or heartburn (frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may help); fluid retention (weigh yourself weekly and report unusual (3-5 lb/week) weight gain). GI bleeding, ulceration, or perforation can occur with or without pain; discontinue medication and contact prescriber if persistent abdominal pain or cramping, or blood in stool occurs. Report breathlessness, difficulty breathing, or unusual cough; chest pain, rapid heartbeat, palpitations; unusual bruising/bleeding; blood in urine, stool, mouth, or vomitus; swollen extremities; skin rash or itching; acute fatigue; or changes in eyesight (double vision, color changes, blurred vision), hearing, or ringing in ears. Pregnancy/breast-feeding precautions: Notify prescriber if you are or intend to be pregnant. Do not take this drug during last trimester of pregnancy.

Monitor occult blood loss, periodic liver function test, hemoglobin, CBC, BUN, serum creatinine

Suspension, oral: 125 mg/5 mL (15 mL, 30 mL, 480 mL)

Tablet, as sodium:

220 mg (200 mg base)

Anaprox®: 220 mg (200 mg base); 275 mg (250 mg base); 550 mg (500 mg base)

Tablet:

Aleve®: 200 mg

Naprosyn®: 250 mg, 375 mg, 500 mg

Tablet, controlled release (Naprelan®): 375 mg, 500 mg

Alun-Jones E and Williams J, "Hyponatremia and Fluid Retention in a Neonate Associated With Maternal Naproxen Overdosage," J Toxicol Clin Toxicol, 1986, 24(3):257-60.

Berde C, Ablin A, Glazer J, et al, "American Academy of Pediatrics Report of the Subcommittee on Disease-Related Pain in Childhood Cancer," Pediatrics, 1990, 86(5 Pt 2):818-25.

Brooks PM and Day RO, "Nonsteroidal Anti-inflammatory Drugs - Differences and Similarities," N Engl J Med, 1991, 324(24):1716-25.

Clinch D, Banerjee AK, Ostick G, "Absence of Abdominal Pain in Elderly Patients With Peptic Ulcer," Age Ageing, 1984, 13:120-3.

Clive DM, Stoff JS, "Renal Syndromes Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med, 1984, 310(9):563-72.

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.

Forbes JA, Keller CK, Smith JW, et al, "Analgesic Effect of Naproxen Sodium, Codeine, a Naproxen-Codeine Combination and Aspirin on the Postoperative Pain of Oral Surgery," Pharmacotherapy, 1986, 6(5):211-8.

Fredell EW and Strand LJ, "Naproxen Overdose," JAMA, 1977, 238(9):938.

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, Szczepanski L, et al, "Omeprazole Compared With Misoprostrol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs," N Engl J Med, 1998, 338(11):727-34.

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.

Kulling EJ, Beckman EA, and Skagius AS, "Renal Impairment After Acute Diclofenac, Naproxen, and Sulindac Overdoses," J Toxicol Clin Toxicol, 1995, 33(2):173-7.

Lang BA and Finlayson LA, "Naproxen-Induced Pseudoporphyria in Patients With Juvenile Rheumatoid Arthritis," J Pediatr, 1994, 124(4):639-42.

Martinez R, Smith DW, and Frankel LR, "Severe Metabolic Acidosis After Acute Naproxen Sodium Ingestion," Ann Emerg Med, 1989, 18(10):1102-4.

Nader DA and Schillaci RF, "Pulmonary Infiltrates With Eosinophilia Due to Naproxen," Chest, 1983, 83(2):280-2.

Pounder R, "Silent Peptic Ulceration: Deadly Silence or Golden Silence?" Gastroenterology, 1989, 96:(2 Pt 2 Suppl)626-31.

Shaunak S, Brown P, and Morgan-Hughes JA, "Exacerbation of Idiopathic Parkinson's Disease by Naproxen," BMJ, 1995, 311(7002):422.

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.

Wallace CA, Farrow D, and Sherry DD, "Increased Risk of Facial Scars in Children Taking Nonsteroidal Anti-inflammatory Drugs," J Pediatr, 1994, 125(5 Pt 1):819-22.

Wells TG, Mortensen ME, Dietrich A, et al, "Comparison of the Pharmacokinetics of Naproxen Tablets and Suspension in Children," J Clin Pharmacol, 1994, 34(1):30-3.

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.