Naproxen Other names: Naproxen sodium

If steroid dosage is reduced or eliminated during therapy, the steroid dosage should be reduced slowly and the patients must be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

As with all NSAIDs, caution should be taken when co-administering with cortico-steroids because of the increased risk of gastrointestinal ulceration or bleeding.

Concomitant administration of antacid can delay the absorption of naproxen but does not affect its extent.

Co-administration of naproxen with antidiabetic tablets enhances the action of antidiabetic tablets.

Patients at high risk of bleeding or who use coumarin derivatives or heparin alongside naproxen have an increased risk of bleeding. The benefits in that case should be weighed up against the risks. In any case concomitant use of naproxen with a high dose of heparin (or derivatives thereof) is not recommended.

Increased risk of GI bleeding when anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs.

NSAIDs may increase plasma cardiac glycosides levels.

Caution is advised when naproxen is co-administered with diuretics as there can be a decreased diuretic effect. The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Concomitant administration of naproxen with beta-blockers may reduce their antihypertensive effect.

Concomitant administration of naproxen with beta ACE inhibitors may increase the risk of renal impairment associated with the use of ACE inhibitors or angiotensin II receptor antagonists.

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Concomitant use of bisphosphonates and NSAIDs may increase the risk of gastric mucosal damage.

The combination of naproxen-containing products and other NSAIDs, including cyclooxygenase-2 selective inhibitors, is not recommended, because of the cumulative risks of inducing serious NSAID-related adverse events.

Clinical pharmacodynamic data suggest that concomitant naproxen usage for more than one day consecutively may inhibit the effect of low-dose acetylsalicylic acid on platelet activity and this inhibition may persist for up to several days after stopping naproxen therapy. The clinical relevance of this interaction is not known.

Concomitant administration of colestyramine can delay the absorption of naproxen but does not affect its extent. Naproxen should be taken at least one hour before or four to six hours after colestyramine.

In coadministration of naproxen with ciclosporin, there is increased risk of nephrotoxocity.

The natriuretic effect of furosemide has been reported to be inhibited by some drugs of NSAIDs.

Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations has also been reported following administration of NSAIDs.

Caution is advised where methotrexate is given concurrently because of possible enhancement of its toxicity, since naproxen, among other non-steroidal anti-inflammatory drugs, has been reported to reduce the tubular secretion of methotrexate in an animal model.

NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Co-administration of naproxen with phenytoin enhances phenytoin activity.

Probenecid given concurrently increases naproxen plasma levels and extends its half-life considerably.

Co-administration of naproxen with sodium bicarbonate increases the absorption of naproxen.

Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

There is an increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.

Caution is required if naproxen administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.

Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding.

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Mild peripheral oedema has been observed in a few patients receiving naproxen. Although sodium retention has not been reported in metabolic studies, it is possible that patients with questionable or compromised cardiac function may be at a greater risk when taking Naproxen.

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). Although data suggest that the use of naproxen (1000mg daily) may be associated with a lower risk, some risk cannot be excluded.

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with naproxen after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

In patients with systemic lupus erythrematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis, when naproxen is administered.

Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. As with other drugs of this type, naproxen produces delay in parturition in animals and also affects the human foetal cardiovascular system (closure of ductus arteriosus). Use of naproxen in the last trimester of pregnancy is contraindicated. NSAIDs should not be used during the first two trimesters of pregnancy, unless the potential benefit to the patient outweighs the potential risk to the foetus.

Naproxen has been found in the milk of lactating women. The use of naproxen should be avoided in patients who are breast-feeding.

Undesirable effects such as dizziness, vertigo, insomnia, drowsiness, fatigue and visual disturbances or depression are possible after taking naproxen. If patient experiences these or similar undesirable effects, they should not drive or operate machinery.

The following adverse events have been reported with NSAIDs and with naproxen.

Gastrointestinal disorders: The most commonly observed events are gastrointestinal in nature. Heartburn, nausea, vomiting, constipation, diarrhoea, flatulence, dyspepsia, abdominal discomfort and epigastric distress. More serious reactions which may occur are gastro-intestinal bleeding, which is sometimes fatal, particularly in older people, inflammation, ulceration, perforation, and obstruction of the upper and lower gastrointestinal tract, melaena, haematemesis, stomatitis, exacerbation of ulcerative colitis and Crohn’s disease, oesophagitis, gastritis and pancreatitis.

Blood and lymphatic system disorders: Neutropenia, thrombocytopenia, granulocytopenia including agranulocytosis, eosinophilia, leucopenia, aplastic anaemia and haemolytic anaemia.

Immune system disorders: Hypersensitivity reactions have been reported following treatment with NSAIDs in patients with, or without, a history of previous hypersensitivity reactions to NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or © assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme)

Metabolic and nutrition disorders: Hyperkalaemia.

Psychiatric disorders: Insomnia, dream abnormalities, depression,confusion and hallucinations

Cardiac disorders: Oedema, palpitations, cardiac failure and congestive heart failure have been reported in association with NSAID treatment..

Clinical trial and epidemiological data suggest that use of coxibs and some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

Vascular disorders: Hypertension, vasculitis.

Hepatobiliary disorders: Abnormal liver function, hepatitis (including some fatalities) and jaundice.

Nervous system disorders: Convulsions, dizziness, headache, lightheadedness, drowsiness, inability to concentrate and cognitive dysfunction, retrobulbar optic neuritis, paraesthesia, exacerbation of parkinson’s disease, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever and disorientation, nervousness, euphoria, low temperature and drowsiness.

Haematological: Thrombocytopenia, eosinophilia, leucopenia, neutropenia, agranulocytosis, decreased platelet aggregation, prolonged bleeding time, aplastic anaemia and haemolytic anaemia. decrease in hemoglobin levels and/or hematocrit, granulocytopenia

Eye Disorders: Corneal opacity, blurred vision, visual disturbances, papillitis and papilloedema.

Ear and Labyrinth disorders: Hearing disturbances including impairment, tinnitus, and vertigo.

Respiratory, thoracic and mediastinal disorders: Dyspnoea, asthma, eosinophilic pneumonitis and pulmonary oedema.

Skin and subcutaneous tissue disorders: Skin rashes including fixed drug eruption, itching (pruritus), urticaria, ecchymoses, purpura, sweating. Alopecia, erythema multiforme, skin eruption, Stevens Johnson syndrome, erythema nodosum, lichen planus, pustular reaction, SLE, epidermal necrolysis, very rarely toxic epidermal necrolysis, photosensitivity reactions (including cases in which skin resembles porphyria cutanea tarda “pseudoporphyria”) or epidermolysis bullosa-like reactions which may occur rarely.

If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored.

Musculoskeletal and connective tissue disorders: Myalgia and muscle weakness.

Renal and urinary disorders: Including, but not limited to, glomerular nephritis, interstitial nephritis, nephrotic syndrome, haematuria, raised serum creatinine, renal papillary necrosis and renal failure.

Reproductive system and breast disorders: Female infertility.

General disorders and administration site conditions: Thirst, pyrexia, fatigue and malaise.