They are limited, in adults and children from the age of 15 years, to the symptomatic treatment of painful affections, of mild to moderate intensity and / or febrile conditions.

Administration mode

Oral use.

The tablets should be swallowed as such with a glass of water, preferably in the course of a meal.

Dosage

The occurrence of adverse reactions can be minimized by the use of the lowest dose possible for the shortest period of treatment necessary to relieve symptoms (see section 4.4). ).

1 tablet to 220 mg, to be renewed if necessary every 8 to 12 hours.

In case of pain or fever, intense, 2 tablets with 220 mg in one catch.

Do not exceed 3 tablets at 220 mg, or 660 mg per day.
Elderly subjects

· Clinical and biological monitoring is recommended, in case of high dosage. One study showed that in the elderly the plasma concentration of free naproxen ion was doubled although the total plasma concentration was unchanged. >
· A reduction in dosage should be considered in the event of decreased kidney elimination

Frequency of administration

The systematic catch should prevent the oscillations of fever or pain and should be spaced about 8 hours apart.

OTHER ANALGESICS AND ANTIPYRETICS

(N: Nervous system, central).
Naproxen sodium is a non-steroidal anti-inflammatory, derived from the aryl-carboxylic acid belonging to the group of propionics. It has the following properties:

· Anti-inflammatory activity

· Analgesic activity

· Antipyretic activity

· Inhibitory activity of platelet functions.

All of these properties are related to an inhibition of the synthesis of prostaglandins.


Prevent patients from the possible appearance of vertigo and visual disturbances.

This medication is contraindicated in the following cases

· Over 24 weeks of amenorrhea (5 months of pregnancy) (see section Pregnancy and lactation)

· A history of allergy or asthma triggered by the use of naproxen sodium or of substances of similar activity such as other NSAIDs acetylsalicylic acid

· Hypersensitivity to any of the excipients

· History of hemorrhage or perforation, digestive during previous NSAID treatment

· Evolutionary peptic ulcer, history of peptic ulcer or recurrent hemorrhage (2 or more distinct episodes of haemorrhage or ulceration)
>
· Severe hepatocellular insufficiency

· Severe renal impairment

· Severe heart failure.

Warnings

The concomitant use of ALEVETABS 220 mg film-coated tablets with other NSAIDs, including selective cyclooxygenase 2 (cox-2) inhibitors, should be avoided.

The occurrence of adverse reactions can be minimized by the use of the lowest dose possible during the shortest duration of treatment necessary to alleviate symptoms (see Dosage and Mode of Administration and Paragraphs "Effects, gastrointestinal" and "Cardiovascular and cerebrovascular effects" below)

Patients with asthma associated with chronic rhinitis, sinusitis and / or nasal polyposis have a risk of allergic manifestation when taking acid, acetylsalicylic and / or non-inflammatory drugs; Steroid higher than the rest of the population. The administration of this specialty may lead to an asthma attack, particularly in certain subjects who are allergic to acetylsalicylic acid or to an NSAID (see section Contraindications).

Elderly subject

Elderly subjects have an increased risk of adverse reactions to NSAIDs, particularly gastrointestinal haemorrhage and potentially fatal perforations (see Dosage and Mode of Administration and below)

Gastrointestinal effects

Gastrointestinal haemorrhages, ulcers, or gastrointestinal perforations, sometimes fatal, have been reported with all NSAIDs at any time of treatment without necessarily warning signs or, History of adverse events, serious gastrointestinal tract

The risk of hemorrhage, ulceration or gastrointestinal perforation increases with the dose used in patients with a history of ulceration, particularly in the case of hemorrhage or perforation complications (see , Contraindications) and in the elderly. In these patients, treatment should be started at the lowest dose possible. Protective treatment of the mucosa (eg, misoprostol or proton pump inhibitor) should be considered for these patients, as for patients requiring treatment with low doses, aspirin or other medicinal products , Which may increase gastrointestinal risk (see below and section Interactions with other medicinal products and other forms of interactions)

Patients with a history of gastrointestinal distress, especially in elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially at the beginning of treatment. Br>

Particular attention should be paid to patients receiving treatment, associates liable to increase risk, ulceration or hemorrhage, such as oral corticosteroids, oral anticoagulants such as warfarin, inhibitors; Selective serotonin reuptake inhibitors (SSRIs) and antiplatelet agents such as acetylsalicylic acid (see section Interactions with other medicinal products and other forms of interaction)
< Br>

In case of onset, hemorrhage or ulceration occurring in a patient receiving ALEVETABS 220 mg, tablet, film-coated, treatment should be stopped.
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NSAIDs should be administered with caution and under close surveillance in patients with a history of gastrointestinal illness (Hemorrhagic Recto-Colitis, Crohn's Disease) due to a risk of aggravation of the pathology (See section Effects, undesirable).

Cardiovascular and cerebrovascular effects

Adequate monitoring and recommendations are required in patients with a history of hypertension and / or mild, moderate, retention, hydrosodic and edema having been reported in combination with treatment By NSAIDs.
Clinical studies and epidemiological data suggest that the use of coxibs and some NSAIDs (especially when used, at high doses and over a long period of time) may be associated with a slight increase in risk; Arterial thrombotic event (eg, myocardial infarction or stroke, cerebral). Although these data suggest that the use of naproxen (1000 mg per day) is associated with a lower risk, the risk can not be totally ruled out.
Patients with uncontrolled hypertension, congestive heart failure, heart disease, ischemic heart disease, peripheral arterial disease, and / or history of stroke (including transient ischemic stroke) should Be treated, by naproxen only after careful examination.

Similar attention should be given to the initiation of long-term treatment in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidemia, diabetes or smoking) Code>
Skin effects

Severe skin reactions, including fatal events, including exfoliative dermatitis, Stevens-Johnson syndromes, and Lyell syndromes have been reported very rarely during NSAID treatments (see section 4.4).

ALEVETABS 220 mg, film-coated tablet should be discontinued at the start of treatment, the time of onset being in most cases during the first month of treatment. Onset of rash, skin, mucosal lesions or any other signs of hypersensitivity

Renal impairment, functional

NSAIDs, by inhibiting the vasodilating action of renal prostaglandins, are capable of causing renal insufficiency, functional by decreasing glomerular filtration, and this adverse effect is dose-dependent. >

At the beginning of treatment or after an increase in dosage, diuresis and renal function monitoring is recommended in patients with the following risk factors
< Br>
· Elderly

· Associated drugs such as: IEC, sartans, diuretics (see section Interactions with other medicinal products and other forms of interaction)
· Hypovolemia whatever the cause

· Heart failure

· Chronic renal insufficiency

· Nephrotic syndrome

· Lupus nephropathy

· Decompensated liver cirrhosis.

Since naproxen and its metabolites are largely eliminated (95%) in the urine by glomerular filtration, naproxen should be used with caution in patients with impaired renal function, creatinine control is The lowest possible doses should be used in these patients.


Hydro-sodium retention with possibility of edema, hypertension or hypertension, aggravation of heart failure. Clinical monitoring is required from the start of treatment in case of hypertension or heart failure. A reduction in the effect of antihypertensive agents is possible (see section Interactions with other medicinal products and other forms of interaction).
Hyperkalemia

Hyperkalemia, favored by diabetes or concomitant therapy, hyperkalaemic drugs (see section Interactions with other medicinal products and other forms of interactions)
< Code>
Regular monitoring of serum potassium should be carried out under these circumstances.
Precautions for use

At the beginning of treatment, careful monitoring of the volume of diuresis and renal function is necessary in patients with cardiac, hepatic and renal failure, chronic, in patients taking a diuretic, after major surgery Hypovolemia, and especially in the elderly

Naproxen, like any drug, inhibits the synthesis of cyclooxygenases and prostaglandins, can alter fertility. Its use is not recommended for women who wish to conceive a child

This product should be used with caution in infections of an infectious nature or with an infectious risk even if well controlled, indeed

· Naproxen may be able to reduce the body's natural defenses against infection

· Naproxen may be liable to mask the usual signs and symptoms of the infection

Risk related to hyperkalaemia

Some medicines or therapeutic classes are likely to promote the occurrence of hyperkalaemia, potassium salts, diuretics, hyperkalaemicants, ACE inhibitors, angiotensin II antagonists, anti-inflammatory drugs , Steroids, heparins (low molecular weight or non-fractionated), immunosuppressants such as ciclosporin and tacrolimus, trimethoprim.

The combination of these drugs increases the risk of hyperkalaemia. This risk is particularly important with potassium-sparing diuretics, especially when they are combined with one another or with potassium salts, while the combination of an ACE inhibitor and an NSAID, for example, is To reduce the risk as soon as the recommended precautions are implemented.

To know the risks and levels, specific drug constraints, hyperkalaemia, it is necessary to refer to the interactions specific to each substance

However, certain substances, such as trimethoprim, are not the subject of specific interactions with this risk. However, they may act as promoting factors when they are associated with other medicines such as those mentioned above.


Associations deprecated

+ Other NSAIDs

Increased risk, ulcerative and digestive haemorrhagic fever

+ Acetylsalicylic acid in doses, anti-inflammatory drugs (³, 1 g per dose and / or ³, 3 g daily) or analgesic or antipyretic doses (³ 500 mg per dose and / or Day)

Increased risk, ulcerative and digestive haemorrhagic fever

+ Oral anticoagulants

Increased risk, haemorrhagic (aggression of the mucosa, gastroduodenal by NSAIDs). NSAIDs are likely to increase the effects of anticoagulants, such as warfarin (see Warnings and Precautions).

If the association can not be avoided, close clinical and biological monitoring
+ Methotrexate, used at doses greater than 20 mg / week

Increased hematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory drugs)

+ Pemetrexed (patients with low renal function, moderate creatinine clearance, 45 ml / min to 80 ml / min)
Risk of increased toxicity, pemetrexed (decreased renal clearance by NSAIDs)

Associations that are the subject of precautions for use

+; Ciclosporin, tacrolimus

Risk of addition of nephrotoxic effects, especially in the elderly

Monitoring renal function at the beginning of NSAID treatment

+, Diuretics, ACE inhibitors, angiotensin II receptor antagonists

Acute renal failure in the patient at risk (subject, elderly and / or dehydrated) by decreased glomerular filtration (prostaglandin inhibition, NSAID vasodilator). >
In addition, reduction of the antihypertensive effect.

Hydrate the patient and monitor renal function at the beginning of treatment.
+ Methotrexate, used at doses less than or equal to 20 mg / week

Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory drugs).

Weekly control of the hemogram during the first weeks of the association

Increased monitoring in case of alteration (even mild), renal function, as well as in the subject.



+; Pemetrexed (patients with normal renal function)

Risk of increased toxicity of pemetrexed (decreased renal clearance by NSAIDs

Biological monitoring of renal function

Associations to be taken into account

+ Anti-aggregating acetylsalicylic acid (50 mg to 375 mg per day in 1 or more doses)
Increased risk, ulcerative and digestive haemorrhagic fever

+; Glucocorticoids (except hydrocortisone in treatment; replacement)

Increased risk of ulceration and gastrointestinal hemorrhage (see section Caveats and precautions for use)

+ Serotonin reuptake inhibitors and serotonin reuptake inhibitors (SSRIs)

Increased risk of haemorrhage, gastrointestinal (see Warnings and Precautions for Use).

Unfractionated heparins, low molecular weight and related heparins (doses, preventive)

Increased risk, hemorrhagic.

+; Beta-blockers (except esmolol)

Reduction of the effect, antihypertensive (inhibition of vasodilating prostaglandins, NSAIDs and hydrosodic retention with NSAIDs, pyrazole)

+; Deferasirox

Increased risk, ulcerative and digestive haemorrhagic fever

Not applicable.

· Clinical signs of overdose: drowsiness, heartburn, indigestion, nausea or vomiting

· Conduct to be kept

O Immediate transfer to hospitals

O Rapid evacuation of the product ingested by gastric lavage

O activated charcoal to decrease the absorption of naproxen

O symptomatic treatment

Pregnancy

First-trimester malformative aspect

In the human species, no particular malformative effects have been reported, but additional epidemiological studies are needed to confirm the absence of risk
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Fetotoxic and neonatal: 2nd and 3rd trimesters

This is class toxicity, involving all prostaglandin synthesis inhibitors.

Administration during the 2nd and 3rd quarter exposes to

· Renal Functional Impairment

O utero can be observed as early as 12 weeks, amenorrhea (initiation of diuresis, fetal): oligoamnios (most often reversible at cessation of treatment), or even anamnios Extended exposure.

O at birth, renal insufficiency (reversible or not) may persist especially in cases of late and prolonged exposure (with a risk of delayed severe hyperkalaemia)
< Br>

· A risk of cardiopulmonary disease

Partial or complete constriction in utero of the ductus arteriosus. The constriction of the ductus arteriosus may occur from 5 months and may lead to insufficiency, fetal or neonatal right heart or fetal death, in utero.
This risk is all the more important since the catch is close to the term (lesser, reversible).
This effect exists even for a one-time catch.

· A risk of longer bleeding time for the mother and the child

As a result,

· Up to 12 weeks of amenorrhea, ALEVETABS 220 mg film-coated tablets should only be considered if necessary

· Between 12 and 24 weeks of amenorrhea (between the beginning of the fetal diuresis and 5 months): a brief intake should only be prescribed if necessary. A prolonged take is strongly discouraged.

Over 24 weeks of amenorrhoea (5 months, complete): any single dose is contraindicated (see section Contraindications). An uncommon intake, over 24 weeks of amenorrhea (5 months, over), justifies cardiac and renal, fetal and / or neonatal monitoring according to the term. Br>

The duration of this monitoring will be adapted to the elimination half-life of the molecule.
Breastfeeding

NSAIDs in breast milk should be avoided as a precautionary measure when administered to nursing mothers.

Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially, when used at high doses, over a long period of time) may be associated with mild, increased risk of thrombotic events (Eg, myocardial infarction or stroke) (see Warnings and Precautions for Use).

The most commonly observed adverse reactions are gastrointestinal. Peptic ulcers, perforations, or gastrointestinal haemorrhage, sometimes fatal, may occur, especially in the elderly (see Warnings and Precautions).
< Br>

Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, stomatitis, ulcerative, abdominal pain, melena, hematemesis, exacerbation of recto-colitis or Crohn's Disease Gastritis has been reported following administration of NSAIDs.
Less frequently, gastritis has been observed
Edema, hypertension and heart failure have been reported in association with NSAID therapy.

Gastrointestinal effects

Mostly reported gastrointestinal and epigastralgia-like disorders, usually mild or moderate, nausea, vomiting, abdominal bloating and exceptionally ulcers, gastrointestinal haemorrhage and / or Perforations. These digestive hemorrhages are all the more frequent because the dosage used is high.

Hypersensitivity reactions

Dermatological: skin rash, urticaria, aggravation, chronic urticaria, pruritus

· Respiratory: asthma. The onset of an asthma attack in some subjects may be related to an allergy to acetylsalicylic acid or NSAIDs. In this case, this medication is contraindicated.
General: angioedema, vasculitis, anaphylactoid reactions to components

Effects on the central nervous system

Headache, dizziness, insomnia, tinnitus, hearing impairment, difficulty concentrating, disorders of ideation, visual disturbances

Skin reactions

Very rarely bullous reactions including Stevens-Johnson Syndrome and Lyell's Syndrome have been observed.


· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·,,,,,,,,,,,,,,,,,,,,, Hyperskidemic retention, hyperkalemia (see sections 4.4 and 4.4) and other interactions with other medicinal products and other forms of interaction. >
Acute renal failure (ARI) in patients with risk factors (see Warnings and Precautions)

Organic kidney damage that may result in an ARI: isolated cases of interstitial nephritis, acute tubular necrosis, syndrome, nephrotic necrosis, papillary necrosis have been reported. >

Other

· Eosinophilic pneumonia.

· Ulcerative stomatitis.

· Aseptic meningitis.

· Possible peripheral edema in patients with compromised cardiac function

Some biological changes could be observed

· Hematologic: granulocytopenia, thrombocytopenia, aplastic anemia and haemolytic

· Hepatic: jaundice, exceptionally, severe hepatitis, some cases of alterations, transient and reversible liver function tests have been reported.

They are limited, in adults and children from the age of 15 years, to the symptomatic treatment of painful affections, of mild to moderate intensity and / or febrile conditions.