This information is intended for use by health professionals
Adolescents (post puberty) and adult females between the ages of 15 and 50:On the first day 2 tablets (500 mg) should be taken initially and then one tablet (250 mg) after 6 to 8 hours if needed.On the second and third day, if needed, one tablet (250mg) should be taken every 6 to 8 hours. Not more than 3 tablets to be taken per day. The maximum duration of continuous treatment in any one cycle (period) is 3 days.
Cardiovascular, Hepatic Impairment and Renal failure linked to reduced prostaglandin production:The administration of an NSAID may cause a dose dependant reduction in prostaglandin formation and precipitate renal failure. Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly. Renal function should be monitored in these patients (see also section 4.3). Cardiovascular and cerebrovascular effectsCaution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or mild to moderate heart failure as fluid retention, hypertension and oedema have been reported in association with NSAID therapy.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 infaction or stroke). Although data suggest that the use of naproxen (1000 mg daily) may be associated with a lower risk, some risk cannot be excluded. There are insufficient data regarding the effects of low dose naproxen 250mg 750mg daily to draw firm conclusions on possible thrombotic risks.Patients with cardiac impairment should only use naproxen with great caution and under their doctor's supervision.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 disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking). Renal EffectsThere have been reports of impaired renal function, renal failure, acute interstitial nephritis, haematuria, proteinuria, renal papillary necrosis and occasionally nephrotic syndrome associated with naproxen.Use in patients with impaired renal functionAs naproxen is eliminated to a large extent (95%) by urinary excretion via glomerular filtration, it should be used with great caution in patients with impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised in these patients. Naproxen is contraindicated in patients having a baseline creatinine clearance of less than 30ml/minute.Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding.The use of NSAIDs may result in a deterioration of renal function.When renal blood flow is compromised, such as in extracellular volume depletion, cirrhosis of the liver, sodium restriction, congestive heart failure, and pre-existing renal disease, patients should have renal function assessed before and during naproxen therapy. A reduction in daily dosage should be considered to avoid the possibility of excessive accumulation of naproxen metabolites in these patients.Patients with impaired liver function should only take naproxen under the supervision of their doctor. When liver function is impaired, the plasma concentration of unbound naproxen is increased. The significance of this is unknown but caution is advised when high doses are required.Use in patients with impaired liver functionChronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for Naproxen dosing is unknown but it is prudent to use the lowest effective dose.Gastrointestinal effectsGI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at anytime during treatment, with or without warning symptoms or a previous history of serious GI events.Although naproxen is usually well tolerated, there have been reported incidences of gastro-intestinal bleeding. Therefore, patients with a history of gastro-intestinal disease should not take naproxen without being closely monitored by their doctor.The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).Patients with a history of GI toxicity should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment. Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin-reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).If GI bleeding or ulceration occurs in patients receiving the product, the treatment should be withdrawn.Serious gastro-intestinal adverse reactions may occur at any time in patients on therapy with non-steroidal anti-inflammatory drugs. The duration of therapy does not seem to change the risk of occurrence. Studies to date have not identified any subset of patients not at risk of developing peptic ulcer and bleeding. However, elderly and debilitated patients tolerate gastro-intestinal ulceration or bleeding less well than others. Most of the serious gastro-intestinal events associated with non-steroidal anti-inflammatory drugs occurred in this patient population.NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as their condition may be exacerbated (see section 4.8).HaematologicalPatients who have coagulation disorders or patients who are receiving drug therapy that interferes with haemostasis should be carefully observed if naproxen-containing products are administered.Patients at high risk of bleeding or those on full anti-coagulation therapy (e.g. dicoumarol derivatives) can be at increased risk of bleeding if given naproxen-containing products concurrently.Anaphylactic (anaphylactoid) reactionsIn susceptible individuals hypersensitivity reactions may occur. Anaphylactic (anaphylactoid) reactions may occur both in patients with and without a history of hypersensitivity or exposure to aspirin, other non-steroidal anti-inflammatory drugs or naproxen-containing products. They may also occur in individuals with a history of angioedema, bronchospastic reactivity (e.g. asthma), rhinitis and nasal polyps.Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.SteroidsPatients taking steroids should not take naproxen except under the supervision of their doctor. If steroid dosage is eliminated or reduced 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.Ocular effectsStudies have not shown any changes in the eye attributable to naproxen administration. Rarely, adverse ocular disorders including papillitis, retrobulbar optic neuritis and papilledema, have been reported in users of NSAIDs including naproxen, although a cause-and-effect relationship cannot be established; accordingly, patients who develop visual disturbances during treatment with naproxen-containing products should have an ophthalmological examination. SLE and mixed connective tissue disease:In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis (see section 4.8).DermatologicalSerious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see section 4.8). Patients appear to be at highest risk for these reactions early in the course of the therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. The product should be discontinued at the first appearance of skin rash, mucosal lesion, or any other sign of hypersensitivity.Precautions related to female fertility:The use of naproxen, as with any drug known to inhibit cyclooxygenase/prostaglandin synthesis, may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of fertility, withdrawal of naproxen should be considered.This product should not be taken, except on the advice of a doctor, by women who first experience period pain more than a year after starting menstruation.This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. The label will include:
|Read the enclosed leaflet before taking this product.Do not take if you- have or have ever had a stomach ulcer, perforation or bleeding- are allergic to naproxen or any other ingredient of the product, aspirin, ibuprofen or other related painkillers- are taking other NSAID painkillers, or aspirinSpeak to a pharmacist or your doctor before taking this product if- you have asthma, liver, heart, kidney or bowel problems- there is a chance you may be pregnantIf symptoms persist or worsen, consult your doctor.|
PregnancyInhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, Naproxen should not be given unless clearly necessary. If Naproxen is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible. During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to: - cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); - renal dysfunction, which may progress to renal failure with oligo-hydroamniosis; the mother and the neonate, at the end of pregnancy, to: - possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses. - inhibition of uterine contractions resulting in delayed or prolonged labour. Consequently, Naproxen is contraindicated during the third trimester of pregnancy. Labour and deliveryNaproxen containing products are not recommended in labour and delivery because, through its prostaglandin synthesis inhibitory effect, naproxen may adversely affect foetal circulation and inhibit contractions, with an increased bleeding tendency in both mother and child (See section 4.3 Contraindications). The onset of labour may be delayed and the duration increasedLactationNaproxen/NSAIDs can appear in the breast milk of lactating women. The use of naproxen/NSAIDs should be avoided in patients who are breast feeding. See section 4.4 Special warning and precautions for use, regarding female fertility.
SymptomsHuman experiences of overdosage with naproxen may result in drowsiness, heartburn, indigestion, headache, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, dizziness, tinnitus, fainting, nausea or vomiting. In cases of significant poisoning acute renal failure and liver damage are possible.Respiratory depression and coma may occur after the ingestion of NSAIDs but are rare.In one case of naproxen overdose, transient prolongation of the prothrombin time due to hypothrombinaemia may have been due to selective inhibition of the synthesis of vitamin-K dependent clotting factors.A few patients have experienced seizures, but it is not known whether these were naproxen-related or not. It is not known what dose of the drug would be life-threatening.
Therapeutic measuresPatients should be treated symptomatically as required.The stomach may be emptied by inducing emesis or aspiration and lavage. Activated charcoal may reduce the absorption of naproxen. (See section 5.2 Pharmacokinetic properties). Further treatment is symptomatic. Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose.Good urine output should be closely monitored.Renal and liver functions should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts.Frequently or prolonged convulsions should be treated with intravenous diazepam.Other measures may be indicated by the patient's clinical condition.Haemodialysis does not decrease the plasma concentration of naproxen because of the high degree of protein binding. However, haemodialysis may still be appropriate for a patient with renal failure who has taken naproxen.Correction of severe electrolyte abnormalities should be considered.
CarcinogenicityNaproxen was administered with food to Sprague-Dawley rats for 24 months at doses of 8, 16 and 24mg/kg/day. Naproxen was not carcinogenic in rats.
MutagenicityMutagenicity was not seet in Salmonella typhimurium (5 cell lines), Sachharomyces cerevisisae (1 cell line), and mouse lymphoma tests.
FertilityNaproxen did not affect the fertility of rats when administered orally at doses of 30mg/kg/day to males and 20mg/kg/day to females.
TeratogenicityNaproxen was not teratogenic when administered orally at does of 20mg/kg/day during organogenesis to rats and rabbits.
Perinatal/Postnatal ReproductionOral administration of naproxen to pregnant rats at doses of 2, 10 and 20mg/kg/day during the third trimester of pregnancy resulted in difficult labour. These are known effects of this class of compounds and were demonstrated in pregnant rats with aspirin and indometacin.