Brands, Medical Use, Clinical Data
Drug Category
- Anti-Inflammatory Agents, Non-Steroidal
- Cyclooxygenase Inhibitors
- Gout Suppressants
Dosage Forms
- Suppository
- Suspension
- Tablet
- Tablet (enteric-coated)
- Tablet (extended-release)
Brands / Synonyms
Aleve; Anaprox; Bonyl; Diocodal; DL Naproxen; DL-Naproxen; Dysmenalgit; Ec-naprosyn; Equiproxen; Floginax; Laraflex; Laser; Mnpa; Naixan; Naprelan; Napren; Naprium; Naprius; Naprosine; Naprosyn; Naprosyne; Naproxen; Naproxen Sodium; Naprux; Naxen; Naxyn; Niaxan; Nycopren; Opipramol; Panoxen; Pranoxen; Prevacid Naprapac; Prexan; Proxen; Proxine; Reuxen; Treximet; Veradol; Vimovo; Xenar
Indications
For the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, and acute gout. Also for the relief of mild to moderate pain and the treatment of primary dysmenorrhea.
Pharmacology
Naproxen is a member of the arylacetic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Naproxen has analgesic and antipyretic properties. As with other NSAIDs, its mode of action is not fully understood; however, its ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect.
Mechanism of Action
The mechanism of action of naproxen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals. The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity.
Absorption
Naproxen itself is rapidly and completely absorbed from the GI tract with an in vivo bioavailability of 95%. Although naproxen itself is well absorbed, the sodium salt form is more rapidly absorbed resulting in higher peak plasma levels for a given dose. Food causes a slight decrease in the rate absorption.
Toxicity
ORAL (LD50): Acute: 248 mg/kg [Rat]. 360 mg/kg [Mouse]. Symptoms of overdose include drowsiness, heartburn, indigestion, nausea, and vomiting.
Biotrnasformation / Drug Metabolism
Naproxen is extensively metabolized to 6-0-desmethyl naproxen and both parent and metabolites do not induce metabolizing enzymes.
Contraindications
All naproxen products are contraindicated in patients who have had allergic reactions to prescription as well as
to over-the-counter products containing naproxen. Anaphylactoid reactions may occur in patients without previous
known exposure or hypersensitivity to aspirin, naproxen, or other NSAIDs, or in individuals with a history of
angioedema, urticaria, bronchospastic reactivity (e.g. asthma), and nasal polyps. Anaphylactoid reactions, like
anaphylaxis, may have a fatal outcome. Therefore, careful questioning of patients for such things as asthma, nasal
polyps, urticaria, and hypotension associated with NSAIDs before starting therapy is important. In addition, if such
symptoms occur during therapy, treatment with Naprelan should be discontinued.
Drug Interactions
The use of NSAIDs in patients who are receiving ACE inhibitors may potentiate renal disease states.
In vitro studies have shown that naproxen anion, because of its affinity for protein, may displace from
their binding sites other drugs which are also albumin-bound .
Theoretically, the naproxen anion itself could likewise be displaced. Short-term controlled studies failed to show
that taking the drug significantly affects prothrombin times when administered to individuals on coumarin-type
anticoagulants. Caution is advised nonetheless, since interactions have been seen with other nonsteroidal agents of
this class. Similarly, patients receiving the drug and a hydantoin, sulfonamide or sulfonylurea should be observed
for signs of toxicity to these drugs.
Concomitant administration of naproxen and aspirin is not recommended because naproxen is displaced from its
binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations and peak
plasma levels.
The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Inhibition of
renal lithium clearance leading to increases in plasma lithium concentrations has also been reported. Naproxen and
other NSAIDs can reduce the antihypertensive effect of propranolol and other beta-blockers.
Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life
significantly.
Caution should be used if naproxen is administered concomitantly with methotrexate. Naproxen, naproxen sodium and
other NSAIDs have been reported to reduce the tubular secretion of methotrexate in an animal model, possibly
increasing the toxicity of methotrexate.
Drug/Laboratory Test Interactions
Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when
bleeding times are determined. The administration of naproxen may result in increased urinary values for 17-ketogenic
steroids because of an interaction between the drug and/or its metabolites with m-dinitrobenzene used in this assay.
Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is
suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed
if the Porter-Silber test is to be used.
Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).
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