In patients with inducible porphyria, naproxen should only be used after a very careful evaluation of the risks and benefits. Patients at high risk of bleeding or patients receiving full anticoagulant therapy (e.g., dicoumarol derivatives) may be at increased risk of bleeding if they receive naproxen-containing products at the same time. Habitual use of painkillers – especially when several painkillers are used in combination – can lead to permanent kidney damage with a risk of kidney failure. Patients should be informed accordingly, if appropriate. At the beginning of treatment, during periods of acute inflammation or when switching from another high-dose NSAID to naproxen, the recommended daily dose is 15 ml (equivalent to 750 mg naproxen) given in two divided doses per day (10 ml of oral naproxen suspension in the morning and 5 ml in the evening or vice versa) or as a single dose (morning or evening). Clinical pharmacodynamic data suggest that concomitant use of naproxen for more than one consecutive day may inhibit the effect of low-dose acetylsalicylic acid on platelet activity, and this inhibition may last for up to several days after discontinuation of naproxen therapy. The clinical relevance of this interaction is unknown. The maintenance dose is 10 ml of oral naproxen suspension (equivalent to 500 mg naproxen) per day, which can be administered either in two divided doses (5 ml in the morning and 5 ml in the evening) or as a single dose (morning or evening). Renal failure, renal failure, acute interstitial nephritis, haematuria, proteinuria, renal papillary necrosis and sometimes naproxen-associated nephrotic syndrome have been reported. In acute pain, naproxen begins to act earlier if taken on an empty stomach. If diabetics treated with sulfonylurea lipid-lowering derivatives are also given naproxen, blood glucose should be monitored with special care to avoid a potential reduction in blood glucose. Due to its pharmacodynamic properties, naproxen – like other NSAIDs – can mask an underlying disease through its analgesic, antipyretic and anti-inflammatory effects. Patients should be advised to seek immediate medical attention if symptoms persist or worsen, such as pain or other signs of inflammation, such as worsening of general well-being or fever during treatment.
Studies have not shown eye changes due to naproxen administration. In rare cases, ocular adverse reactions such as papillitis, retrobulbar optic neuritis and papillary oedema have been reported in users of NSAIDs, including naproxen, although no causal relationship could be established. Therefore, patients who develop visual disturbances during naproxen treatment should undergo an ophthalmological examination. Small amounts of naproxen are excreted in breast milk. The use of naproxen during breastfeeding should be avoided as a precautionary measure. Hypersensitivity reactions may occur in sensitive individuals. Anaphylactic reactions (anaphylactoids) may occur in patients with or without hypersensitivity or previous exposure to acetylsalicylic acid, other NSAIDs or drugs containing naproxen, putting them at risk of such reactions. They may also occur in patients with angioedema, bronchospastic reactions (e.g. asthma), rhinitis or a history of nasal polyps. Anaphylactoid reactions, such as anaphylaxis, can be fatal. Bronchospasm may be triggered in patients with or with a history of asthma, allergic disease or hypersensitivity to acetylsalicylic acid (see section 4.3).
If gastrointestinal bleeding or ulceration occurs during naproxen therapy, treatment should be discontinued. • Possible interference with 17-ketogenic steroids in adrenal function tests and 5-hydroxyindolacetic acid in urine tests: It is recommended to temporarily stop naproxen at least 72 hours before performing such tests. Concomitant use of naproxen with other nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors, should be avoided. Administration of naproxen within 24 hours of methotrexate treatment may result in increased blood levels of methotrexate and therefore increase methotrexate toxicity (either this combination should be avoided or blood counts, liver and kidney function should be monitored very closely). The AUC of naproxen shows linear dose proportionality up to a maximum dose of 500 mg. Beyond this dose, the proportion of unbound naproxen in plasma increases, resulting in an increase in the rate of renal excretion of naproxen. For juvenile rheumatoid arthritis: 10 mg naproxen/kg body weight daily, corresponding to a daily dose of 0.2 ml of oral naproxen suspension per kilogram of body weight, administered in two divided doses (single dose 0.1 ml/kg body weight). The daily dose for adolescents should not exceed 20 ml (1,000 mg).
In some cases, the daily dose may be increased to 20 ml (equivalent to 1,000 mg naproxen). Like other NSAIDs, naproxen can cause the following side effects: Do not take other medications containing aspirin, ibuprofen, or naproxen with this medication. Side effects such as upset stomach, nausea or ulcers may be more likely. Many over-the-counter medications contain aspirin, ibuprofen, or naproxen. Always read labels carefully. Administration of NSAIDs may result in a dose-dependent reduction in prostaglandin formation and trigger renal failure. Patients most at risk of this reaction are patients with renal impairment, cardiac dysfunction, liver dysfunction, patients taking diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists and elderly patients. Renal function should be monitored in these patients (see also section 4.3). Chronic toxicity studies have shown that naproxen has the typical toxicological profile of NSAIDs, i.e.
gastrointestinal toxicity and, at high doses, kidney damage. Patients should be treated symptomatically. There is no specific antidote. Preventive measures to avoid further absorption (e.g. administration of activated charcoal) may be indicated in patients within four hours of ingestion or due to significant overdose. Forced diuresis, urine alkalization, hemodialysis, or hemoperfusion are probably not appropriate due to naproxen`s high protein binding. The dosage should be individually adjusted to the clinical condition. A single dose of 1,000 mg naproxen (20 ml) should not be exceeded. Mutagenicity studies of naproxen have been negative.
95% of an administered dose is excreted in the urine both as unchanged active substance and as 6-O-desmethylnaproxen as a free agent or conjugated.