In self-medication, Aleve is approved for short-term treatment for a maximum of three days and for the following indications:

• Back pain,
• Pain in the region of joints and ligaments,
• Pain after injuries,
• Menstrual pain,
• Tooth pain,
• Headaches,
• Fever associated with influenzal illnesses.

Usual dosage 
Adults and adolescents aged 16 years and older: 
1 film-coated tablet every 8 to 12 hours. 
The starting dose may be two film-coated tablets, if necessary followed by one film-coated tablet 12 hours later. 
Maximum dose for self-medication: Three Aleve film-coated tablets (600 mg naproxen) per 24 hours. Without medical prescription, Aleve is indicated for short-term treatment for a maximum of three days.

Specific dosing instructions 
Older patients over the age of 65 years: If not prescribed otherwise, a maximum of two film-coated tablets per day. 

Correct mode of administration 
The film-coated tablets to be taken whole with an adequate amount of water. 
Children and adolescents under the age of 16: 
In self-medication, Aleve is not approved for use in children and adolescents under the age of 16.

− Hypersensitivity to the active ingredient or one of the excipients according to the composition. − A history of bronchial spasm, urticaria or allergy-like symptoms after the intake of acetylsalicylic acid or other non-steroidal antirheumatics. − Third trimester of pregnancy (see “Pregnancy/lactation”). − Active peptic and/or duodenal ulcers or gastrointestinal bleeding. − Inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis). − Severe liver dysfunction (liver cirrhosis and ascites). − Severe renal insufficiency (creatinine clearance <30 ml/min). − Severe cardiac insufficiency (NYHA III-IV). − Treatment of postoperative pain after coronary bypass surgery (or use of a heart-lung machine).

General precaution for use of systemic non-steroidal antirheumatics: 
During treatment with non-steroidal antirheumatics (NSAR), COX-2-selective or not, gastrointestinal ulcers, bleeding or perforations may occur at any time, even without warning symptoms or history. To reduce this risk, the smallest effective dose should be administered during the shortest possible therapy period. 
In placebo-controlled studies, certain selective COX-2 inhibitors showed an increased risk of thrombotic cardiac and cerebrovascular complications. It is not known whether this risk is directly correlated with COX-1/COX-2 selectivity of the individual NSARs. Since no comparable clinical study data for the maximum dosage and long-term therapy of naproxen are currently available, a similar increased risk cannot be excluded. Until availability of relevant data, naproxen should be used for clinically documented coronary artery disease, cerebrovascular diseases, peripheral arterial occlusive disease or in patients with major risk factors (e.g., high blood pressure, hyperlipidaemia, diabetes mellitus, smoking) only after careful benefit-risk assessment. Also due to this risk, the smallest effective dose should be administered during the shortest possible therapy period. 
Renal effects of NSARs include fluid retention with oedemas and/or arterial hypertension. In patients with impaired heart function and other conditions that predispose to fluid retention, naproxen should only be administered with caution. Caution should also be taken in patients on concurrent diuretics or ACE inhibitors as well as with an increased risk of hypovolaemia.  

Caution should be taken in the following situations or Aleve must be taken only as prescribed and under medical supervision: 

−    In patients of advanced age, caution must be taken due to general medical considerations.
In addition, the plasma level of naproxen not bound to proteins is increased in elderly persons, although the total concentration level remains stable. It is particularly recommended to use the lowest possible effective dosage in frail elderly patients or in those with a low body weight.
−    In patients who are suffering or have previously suffered from bronchial asthma, naproxen may induce bronchial spasm.
−    In patients with renal insufficiency.
−    In patients with cardiac insufficiency.
−    In patients with liver dysfunction or hepatic insufficiency.
−    Haematologic effects: As with other non-steroidal anti-inflammatory drugs, naproxen may reduce platelet aggregation and prolong bleeding time.
This effect has to be taken into account when measuring the bleeding time. Patients with coagulation disorders or who receive medicinal therapies that impact homeostasis have to be carefully monitored during treatment with naproxen-containing products. Patients with a high bleeding risk as well as patients who are completely anticoagulated (e.g., with dicoumarol derivatives) may show a higher tendency for bleeding in case of concomitant administration of naproxen-containing products.

Renal impact 
Caution must be taken in patients whose diseases lead to reduction in the blood volume and/or the renal blood flow and in whom renal prostaglandins support renal perfusion. In these patients, use of naproxen-containing products and other NSARs may lead to dose-dependent reduction of prostaglandin formation in the kidneys and induce manifest renal decompensation or renal failure. Patients treated with diuretics or ACE-inhibitors with renal dysfunction, hypovolaemia, cardiac insufficiency, liver dysfunction or hyponatraemia, as well as elderly patients, are at the highest risk in this regard. Naproxen-containing products have to be used with the greatest caution in these patients, and monitoring of the serum creatinine levels and/or creatinine clearance is recommended. To prevent the risk of excessive accumulation of naproxen metabolites in these patients, reduction of the daily dose should be considered. 
Aleve is not recommended in patients whose baseline creatinine clearance is lower than 20 ml/min., because accumulation of naproxen metabolites has been observed in such cases. 
Due to the high protein binding of naproxen, its plasma level cannot be reduced by haemodialysis. 

Dermatologic effects 
In rare cases, photosensitivity may occur. During treatment with naproxen, exposure to sunlight (UV light) should therefore be avoided, if possible. 

Concomitant administration of antacids or cholestyramine as well as concomitant food intake may delay absorption of naproxen, but has no influence on the extent of absorption. 
Due to the high plasma albumin binding of naproxen, interactions with other albumin-binding drugs, e.g., coumarin-type anticoagulants, sulphonylureas, hydantoins, other non-steroidal anti-inflammatory drugs and acetylsalicylic acid are potentially possible. Patients who are concomitantly treated with hydantoins (phenytoin), sulphonamides or sulphonylureas should be carefully monitored with regard to a potential dose adjustment. 
Although clinical studies have shown no interactions between naproxen and anticoagulants or sulphonylureas, caution must be taken all the same, since interactions with other products of this substance class have been observed. 
Naproxen can retard the irreversible inhibition of platelets induced by acetylsalicylic acid. Pharmacodynamic data suggest that the effect of low-dose acetylsalicylic acid on platelet activity is inhibited, once naproxen is taken for longer than one day concomitantly with low-dose acetylsalicylic acid. This effect may persist for several days after discontinuation of naproxen. The clinical relevance of this interaction is not known. Treatment with naproxen in patients with an increased cardiovascular risk may reduce the cardioprotective effect of acetylsalicylic acid.  

Concomitant administration of probenecid increases the blood level and prolongs the biological half-life of naproxen. 
In case of concomitant administration of Aleve and methotrexate, caution must be taken, because naproxen and some other non-steroidal anti-inflammatory drugs have demonstrated a reduced tubular secretion of methotrexate in an animal model, which may increase its toxicity. 
Furthermore, naproxen can reduce the antihypertensive effect of beta-blockers. 
It has been suggested that the natriuretic effect of furosemide is inhibited by some products of this substance class. 
Inhibition of renal lithium clearance, which leads to increased lithium plasma levels, has also been reported. 

Pregnancy: 
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformations, and gastroschisis after the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is thought to increase with the dose and duration of treatment.  
Animal studies showed that administration of a prostaglandin inhibitor leads to increased pre- and post-implantation loss and to embryo/foetal lethality. Furthermore, increased incidence of several deformities, including cardiovascular deformities, was reported in animals receiving a prostaglandin inhibitor during organogenesis.  
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, naproxen is contraindicated. All prostaglandin inhibitors may:  

• expose the foetus to the following risks:
  • cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
  • renal dysfunction that may progress to renal failure with oligohydramniosis;
• expose mother and child to the following risks:
  • possible prolongation of bleeding time, an anti-platelet aggregation effect which may occur even at very low doses;
  • inhibition of uterine contractions resulting in delayed
  • or prolonged labour.

Fertility: Use of naproxen may affect female fertility and is thus not recommended in women who plan to become pregnant. Women who have difficulty in becoming pregnant or who are undergoing infertility investigations should consider discontinuing naproxen. 

Lactation: 
NSARs pass into breast milk. As a precaution, naproxen should not be taken by lactating women. If treatment is essential, the infant should be switched to infant formula. 

Aleve may change reactivity so that the ability to drive or use machines may be affected (see chapter «Undesirable effects»). 

The following undesirable effects have been observed for Aleve and higher doses of naproxen subject to prescription: 
Incidence: Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1,000), very rare (<1/10,000). 

Blood and lymphatic system 
Very rare: Leukopenia, thrombocytopenia, agranulocytosis, aplastic anaemia, eosinophilia, haematolytic anaemia. 

Immune system 
Very rare: Anaphylaxis, anaphylactoid reactions, angioneurotic oedema. 

Psychiatric disorders 
Very rare: Psychotic symptoms, depression, insomnia. 

Nervous system 
Common: Headache, dizziness, drowsiness, tiredness. 
Very rare: Aseptic meningitis, cognitive dysfunction, seizures. 

Eyes 
Very rare: Impaired vision, corneal clouding, papillitis, retrobulbar neuritis, papilloedema. 

Ear and labyrinth 
Uncommon: Vertigo. 
Very rare: Auditory defects, tinnitus. 

Heart and vessels 
Very rare: Cardiac insufficiency, hypertension, pulmonary oedema, vasculitis. 

Respiratory organs 
Uncommon: Dyspnoea, asthma. 
Very rare: Eosinophilic pneumonia. 

Gastrointestinal disorders 
Common: Dyspepsia, nausea, heartburn, abdominal pain. 
Uncommon: Diarrhoea, obstipation, vomiting. 
Rare: Peptic ulcers with or without bleeding/perforations, gastrointestinal bleeding, haematemesis, melaena. 

Very rare: Pancreatitis, colitis, aphthae, stomatitis, oesophagitis, intestinal ulceration. 

Hepatobiliary disorders 
Very rare: Hepatitis, icterus. 

Skin 
Uncommon: Exanthemas (rash), pruritus, urticaria. 
Very rare: Hair loss (mostly reversible), porphyria, Hebra’s disease, epidermal necrolysis, erythema 
nodosum, fixed drug exanthema, lichen ruber planus, pustular reaction, systemic lupus erythematosus, 
photosensitivity including cases similar to symptomatic porphyria (“pseudoporphyria”) or epidermolysis bullosa. 

Renal and urinary tract 
Uncommon: Renal dysfunction, oedema formation. 
Very rare: Interstitial nephritis, papillary necrosis, nephrotic syndrome, acute renal insufficiency. 

Pregnancy-related, puerperal and perinatal symptoms 
Very rare: Induction of labour. 

General disorders 
Rare: Pyrexia. 

 

To report any side effect(s) 
National Pharmacovigilance and Drug Safety Center (NPC). 
Fax: + 966 - 11 - 205 - 7662. 
Call NPC at +966 - 11 - 2038222, 
Ext.: 2317 - 2356 - 2353 - 2354 - 2334 - 2340. 
Toll - free: 8002490000. 
E - mail: npc.drug@sfda.gov.sa. 
Website: www.sfda.gov.sa/npc 

Severe overdose of naproxen may lead to drowsiness, somnolence, upper abdominal pain, abdominal problems, digestive problems, nausea, transient liver dysfunction, hypoprothrombinemia, renal 
dysfunction, metabolic acidosis, apnoea, disorientation or vomiting. Because Aleve is sometimes quickly absorbed, high blood levels of the active ingredient are to be expected shortly after administration. Some 
few patients experienced seizures; however, it is not clear whether they were related to naproxen or not. If a patient accidentally or deliberately takes a high number of naproxen-containing products, his/her 
stomach should be emptied and the usual supportive measures taken. Tests in animals suggest that taking 50-100 g medicinal carbon (over the course of 15 minutes) in the form of a thin purée within two 
hours after the overdose could considerably lower absorption of the product. 
Due to the high protein binding of naproxen, its plasma level cannot be reduced by haemodialysis. 

ATC code: M01AE02
Aleve has analgesic, antipyretic and anti-inflammatory properties. 
Naproxen is a non-selective COX inhibitor, the effect of which is based on the inhibition of the COX-1 and COX-2 enzymes. Naproxen inhibits formation of the COX-1-dependent thromboxane synthase A2 (TXA2), which leads to a reduction in the platelet aggregation, and in the COX-2-dependent prostacyclin (PGI2), an important vasodilatory mediator. 
Naproxen inhibits the prostaglandin synthesis, which explains its analgesic and antiphlogistic effect. 

Absorption 
Naproxen sodium is rapidly and virtually completely absorbed in the gastrointestinal tract. After oral administration, peak active substance concentrations are reached within approximately one hour. Concomitant food intake may delay absorption of naproxen sodium, but does not affect the extent of absorption. 
Distribution 
Naproxen has a volume of distribution of 0.16 l/kg. More than 99% of the active ingredient is bound to serum albumin. Doses exceeding 500 mg/day lead to non-proportional increase in the plasma levels, because higher doses lead to an increase of the clearance due to saturation of protein binding. On the other hand, increase of non-bound naproxen continues to be proportional to the administered dose. Naproxen passes into the synovial fluid, passes through the placenta barrier and was found in the milk of lactating mothers in concentrations equalling about 1% of the plasma level. 

Metabolism 
Naproxen is metabolised in the liver mainly into 6-O-desmethylnaproxen. 
Elimination 
Approximately 95% of an Aleve dose is excreted by the kidneys as unchanged naproxen, inactive 6-O-desmethylnaproxen or in the form of naproxen conjugates. Small amounts (≤3%) are excreted in the faeces. 
The clearance of naproxen is 0.13 ml/min/kg. The biological plasma half-life is approximately 14 hours. 

Kinetics of specific patient groups 
Hepatic insufficiency 
Patients with severely limited liver function may have increased plasma levels of unbound naproxen. 
Renal insufficiency 
Because naproxen and its metabolites are excreted mainly by the kidneys, accumulation associated with renal insufficiency is basically possible. Elimination of naproxen is reduced in patients with severely limited renal function. 

Carcinogenicity 
Naproxen had been administered with food to Sprague-Dawley rats at doses of 8, 16 and 24 mg/kg/day for 24 months. Naproxen was not carcinogenic in rats. 
Mutagenicity 
In Salmonella typhimurium (5 cell line), Saccharomyces cerevisiae (1 cell line) as well as in mouse lymphoma tests, no mutagenicity was observed. 
Fertility 
Oral administration of naproxen doses of 30 g/kg/day in male rats and 20 mg/kg/day in female rats did not show any impact on fertility. 
Teratogenicity 
Oral administration of naproxen at doses of 20 mg/kg/day during organogenesis did not show teratogenicity in rats and rabbits. 

Perinatal/postnatal reproduction 
Oral administration of naproxen to pregnant rats at doses of 2, 10 and 20 mg/kg/day during the third trimester caused complications during labour. This is a known effect of this substance class and has also been shown with acetylsalicylic acid and indomethacin. 

Other particulars 
Impact on diagnostic methods 
Since Aleve may interfere with certain measurements of 17-ketosteroids, treatment should be discontinued 48 hours before performance of the adrenal gland function test. Similarly, Aleve may interfere with measurement of 5-hydroxyindolacetic acid in urine. 

Naproxen leads to irreversible inhibition of platelet aggregation and prolongs bleeding time. This effect has to be taken into account when measuring the bleeding time. 

Microcrystalline cellulose, Povidone K30, Talc, Magnesium stearate, Hydroxypropyl methylcellulose, Purified water. 
Coating: 
Titanium dioxide, Polyethylene glycol 8000, Indigo carmine E132, Purified water. 

NA

2 years

Do not store above 30°C. Store in original packagin g. 
Do not use this medicine after the expiry date, which is stated on the container labelled “EXP”. 
Keep out of the reach of children.  

Aleve film-coated tablets with 220 mg: 12 film-coated tablets [C] 

NA