APO-NAPROXEN 250MG

Indications

• Pain and inflammation in osteoarthritis
• Pain and inflammation in rheumatoid arthritis
• Management of acute pain
• Musculoskeletal disorders

Dosage

Adults: 1 g once daily, taken at night, or 0.5–1 g daily, taken in the morning and 1 g at night depending on severity.

Mechanism of action

Naproxen exerts its clinical effects by blocking both COX-1 and COX-2 enzymes, which decreases prostaglandin synthesis. COX-1 is constitutively active and found in normal tissues, while COX-2 is inducible and primarily associated with pain, fever, and inflammation. The inhibition of COX-2 mediates the desired antipyretic, analgesic, and anti-inflammatory effects, while COX-1 inhibition is linked to gastrointestinal and renal side effects.

Pharmacodynamics

Naproxen displays anti-inflammatory, analgesic, and antipyretic activity. Its pharmacological effects stem from the inhibition of cyclooxygenase, which reduces prostaglandin synthesis in various tissues, including synovial fluid and gastric mucosa. While effective for pain relief, naproxen can raise blood pressure and increase the risk of gastrointestinal bleeding, especially when combined with other risk factors such as corticosteroids or anticoagulants.

Pharmacokinetics

Naproxen is absorbed after oral administration, with peak plasma concentrations typically occurring within 2 to 4 hours. It has a half-life of approximately 12 to 17 hours, allowing for twice-daily dosing in many cases. The drug is extensively metabolized in the liver, primarily via oxidation and glucuronidation, and is excreted mainly via the urine. Renal impairment can affect its clearance, necessitating caution in patients with existing kidney issues.

Contra-indications

• History of hypersensitivity to aspirin or any other NSAID
• Severe hepatic impairment
• Severe renal impairment
• Active gastrointestinal bleeding or peptic ulcer disease

Adverse effects

• Gastrointestinal upset
• Nausea
• Dizziness
• Headache
• Drowsiness
• Rash
• Renal toxicity
• Increased blood pressure
• Gastrointestinal bleeding
• Hypersensitivity reactions (e.g., angioedema, urticaria)

Interactions

• Increased risk of gastrointestinal bleeding with anticoagulants or corticosteroids
• May reduce the antihypertensive effect of certain antihypertensives
• Increased risk of nephrotoxicity when used with other nephrotoxic agents

Precautions

• Use with caution in patients with a history of gastrointestinal disorders
• Monitor renal function in patients with renal impairment
• Caution in patients with cardiovascular disease due to potential increase in blood pressure
• Use lowest effective dose for the shortest duration necessary

Pregnancy

Avoid unless the potential benefit outweighs the risk. Avoid during the third trimester due to risk of fetal ductus arteriosus closure.

Breast-feeding

Use with caution during breast-feeding as it is present in milk; manufacturer advises avoiding if possible.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral tablet
• Orodispersible tablet
• Oral suspension

Mechanism of action

As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Naproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme. Naproxen has pharmacologic actions similar to those of other prototypical nonsteroidal anti-inflammatory agents (NSAIAs). The drug exhibits anti-inflammatory, analgesic, and antipyretic activity. The exact mechanisms have not been clearly established, but many of the actions appear to be associated principally with the inhibition of prostaglandin synthesis. Naproxen inhibits the synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase; at least 2 isoenzymes, cyclooxygenase-1 (COX-1) and -2 (COX-2) (also referred to as prostaglandin G/H synthase-1 (PGHS-1) and -2 (PGHS-2), respectively), have been identified that catalyze the formation of prostaglandins in the arachidonic acid pathway. Naproxen, like other prototypical NSAIAs, inhibits both COX-1 and COX-2. Although the exact mechanisms have not been clearly established, NSAIAs appear to exert anti-inflammatory, analgesic, and antipyretic activity principally through inhibition of the COX-2 isoenzyme; COX-1 inhibition presumably is responsible for the drugs' unwanted effects on GI mucosa and platelet aggregation. The anti-inflammatory, analgesic, and antipyretic effects of naproxen and other nonsteroidal anti-inflammatory agents (NSAIAs), including selective inhibitors of COX-2 (e.g., celecoxib, rofecoxib), appear to result from inhibition of prostaglandin synthesis. While the precise mechanism of the anti-inflammatory and analgesic effects of NSAIAs continues to be investigated, these effects appear to be mediated principally through inhibition of the COX-2 isoenzyme at sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Naproxen stabilizes lysosomal membranes and inhibits the response of neutrophils to chemotactic stimuli. The drug does not possess glucocorticoid or adrenocorticoid-stimulating properties. Naproxen lowers body temperature in patients with fever. Although the mechanism of the antipyretic effect of nonsteroidal anti-inflammatory agents is not known, it has been suggested that suppression of prostaglandin synthesis in the CNS (probably in the hypothalamus) may be involved. Naproxen-induced inhibition of prostaglandin synthesis may result in decreased frequency and intensity of uterine contractility. Prostaglandins E2 and F2alpha increase the amplitude and frequency of uterine contractions in pregnant women; current evidence suggests that primary dysmenorrhea is also mediated by these prostaglandins. Whether the increased production of prostaglandins associated with primary dysmenorrhea is mediated by COX-1 or COX-2 remains to be determined. Blood concentrations of a metabolite of prostaglandin F2alpha have been found to decrease in women with dysmenorrhea who were receiving naproxen. Therapy with naproxen has been effective in relieving menstrual pain and has reduced blood loss in women with menorrhagia, probably by inhibiting the formation of these prostaglandins. Administration of naproxen during late pregnancy may prolong gestation by inhibiting uterine contractions.

Pharmacodynamics

Naproxen is an established non-selective NSAID and is useful as an analgesic, anti-inflammatory and antipyretic. Similar to other NSAIDs, the pharmacological activity of naproxen can be attributed to the inhibition of cyclo-oxygenase, which in turn reduces prostaglandin synthesis in various tissues and fluids including the synovial fluid, gastric mucosa, and the blood. Although naproxen is an effective analgesic, it can have unintended deleterious effects in the patient. For instance, naproxen can adversely affect blood pressure control. A study found that use of naproxen induced an increase in blood pressure, although the increase was not as significant as that found with ibuprofen use. Further, studies have found that the risk of upper gastrointestinal bleeding is on average four-fold higher for individuals taking NSAIDs. Other factors that increase the risk of upper gastrointestinal bleeding include concurrent use of corticosteroids or anticoagulants, and a history of gastrointestinal ulcers.