Active ingredients: Naproxen (naproxen sodium)
Aleve 220 mg film-coated tablets
Aleve package inserts are available for packs:- Aleve 220 mg film-coated tablets
- Aleve 660 mg modified release tablets
Why is Aleve used? What is it for?
WHAT IS THAT
Aleve belongs to the category of non-steroidal anti-inflammatory / antirheumatic drugs.
WHY IT IS USED
Aleve is used for the symptomatic treatment of headache, back pain, joint and muscle pain, toothache, and colds. It is also indicated against menstrual pains and minor pains in arthritis.
Contraindications When Aleve should not be used
- Hypersensitivity to the active substance, to other closely related substances from a chemical point of view or to any of the excipients.
- History of asthma, urticaria or allergic-type reactions following the intake of acetylsalicylic acid or other analgesics, antipyretics, non-steroidal anti-inflammatory drugs.
- Severe renal insufficiency (creatinine clearance less than 20 ml / min)
- Severe heart failure
- Cirrhosis of the liver and severe hepatitis
- During intensive therapy with diuretics
- Gastric and duodenal ulcer
- People with ongoing bleeding or at risk of bleeding
- During treatment with anticoagulants as it synergizes their action.
- Pregnancy and breastfeeding (see: What to do during pregnancy and breastfeeding)
- Adolescents under the age of 16
- History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
Precautions for use What you need to know before taking Aleve
Analgesics, antipyretics, non-steroidal anti-inflammatory drugs can cause hypersensitivity reactions, potentially fatal. These reactions can occur in subjects with a history of angioedema, altered bronchial reactivity (asthma), rhinitis, nasal polyposis, allergic diseases, chronic respiratory diseases or sensitivity to acetylsalicylic acid. This can also occur in patients who experience allergic reactions (skin reactions, urticaria) to naproxen or other NSAIDs.
Serious 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: Undesirable Effects). higher risk: the onset of the reaction occurs in most cases within the first month of treatment.
Aleve should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Elderly: Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see: How to use this medicine).
Gastrointestinal bleeding, ulceration and perforation: Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs, at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see: When it should not be used), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increased doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (see below: Which medicines or foods can change the effect of the medicine).
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see: Which Medicines or Foods May Modify the effect of the medicine).
When gastrointestinal bleeding or ulceration occurs in patients taking Aleve the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see: Undesirable effects).
Caution is required (discuss with your doctor or pharmacist) before starting treatment in patients with a history of hypertension and / or heart failure as fluid retention, hypertension and edema have been reported in association with treatment with NSAIDs.
Serious hepatic reactions, including jaundice and hepatitis (including some fatal cases) have been reported with the use of naproxen sodium or other non-steroidal anti-inflammatory drugs. Cross-reactivity has also been reported.
The use of Aleve, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.
Aleve should be discontinued in women who have fertility problems or who are undergoing fertility investigations due to effects on ovulation, reversible upon discontinuation of treatment.
People with bleeding disorders, or on anticoagulant therapy, should be carefully monitored as naproxen inhibits platelet aggregation and can prolong bleeding time.
In case of hepatic insufficiency, concomitant treatment with other drugs such as other analgesics, steroids or under intensive diuretic therapy, or in case of previous side effects with analgesics, antipyretics, non-steroidal anti-inflammatory drugs, the product should be administered under strict medical supervision.
The use of Aleve should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms.
In case of persistence of pain or redness / swelling of the painful part or the onset of symptoms new to those for which you have taken the medicine, consult your doctor.
Interactions Which drugs or foods can modify the effect of Aleve
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Cyclosporine: With the concomitant use of cyclosporine the concentration of the latter may be increased, increasing the risk of nephrotoxicity.
Lithium: Lithium levels may be increased, which can induce nausea, polydipsia, polyuria, tremor and confusion.
Methotrexate: The use of Aleve concomitantly with methotrexate (at doses higher than 15 mg / week) can lead to an increase in methotrexate concentrations, with an increased risk of toxicity of this substance
NSAIDs: Do not administer the medicine in combination with drugs based on naproxen, acetylsalicylic acid or other analgesics, antipyretics, anti-inflammatories due to an increased risk of gastrointestinal bleeding.
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see: Precautions for use).
Anticoagulants: NSAIDs may increase the effects of anticoagulants such as warfarin (increased prothrombin time and decreased platelet aggregation) (see: Precautions for use).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding (see: Precautions for use). Naproxen decreases platelet aggregation and prolongs bleeding time. This must be taken into account when determining the bleeding time.
Diuretics ACE inhibitors and angiotensin antagonists II:
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs.In some patients with impaired renal function (e.g. dehydrated patients or elderly patients with impaired renal function) the co-administration of an ACE inhibitor or angiotensin II antagonist and agents that inhibit the cyclo-oxygenase system may lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking Aleve concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients.
Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy.
Foods: the rate of absorption of naproxen can be slowed by the simultaneous intake of food while the amount absorbed is not changed
Interference with laboratory tests: naproxen sodium interferes with the analysis of urinary 17-ketosteroids and 5-indolacetic acid.
Warnings It is important to know that:
When it can be used only after consulting your doctor
Aleve should not be used in adolescents under 16 years of age.
Medicines such as Aleve may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke. Any risk is more likely with high doses and prolonged treatments. Do not exceed the recommended dose or duration of treatment (7 days for symptomatic pain relief and 3 days for colds).
If you have heart problems or a history of stroke or if you think you may be at risk for these conditions (e.g. if you have high blood pressure, diabetes or high cholesterol or smoking) you should discuss your treatment with your doctor or pharmacist.
Analgesics, antipyretics, non-steroidal anti-inflammatory drugs can cause water retention which rarely, especially in elderly patients, can precipitate congestive heart failure.
Analgesics, antipyretics, non-steroidal anti-inflammatory drugs can cause hypersensitivity reactions, potentially fatal, including those of the anaphylactic (anaphylactoid) type, even in subjects with no history of hypersensitivity following exposure to this type of drug. The risk of hypersensitivity reactions after taking naproxen is greater in subjects who have experienced such reactions after the use of other analgesics, antipyretics, non-steroidal anti-inflammatory drugs (see: When it should not be used).
After administration of analgesics, antipyretics, non-steroidal anti-inflammatory drugs, worsening of asthma is possible.
The product is not indicated for pain in the gastrointestinal tract.
What to do during pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Aleve should not be used during pregnancy and lactation. Its use should also be avoided if you suspect pregnancy or wish to plan a maternity leave.
Effects on ability to drive and use machines
Due to the possible onset of somnolence, dizziness, vertigo or insomnia Aleve may impair the ability to drive and use machines
In this case, avoid these activities or others that require particular vigilance.
Important information about some of the ingredients
One Aleve tablet contains about 20 mg of sodium. Taking the maximum daily dosage of 3 tablets results in a maximum sodium intake of approximately 2.6 mmol / day. This should be taken into account in patients with impaired renal function or on a low sodium diet.
Dosage and method of use How to use Aleve: Dosage
How many
Adults and adolescents over 16 years: 1 tablet every 8-12 hours.
You may benefit most by starting with 2 tablets followed by 1 tablet every 12 hours, as needed.
Use the lowest effective dose, particularly in elderly patients.
The maximum daily dose is 3 tablets.
Warning: do not exceed the indicated doses without medical advice.
If one or more of the situations listed under Precautions for use occur, seek medical attention.
When and for how long
Do not use for more than 7 days for symptomatic pain relief and for more than 3 days for colds without medical supervision.
Consult your doctor if the disorder occurs repeatedly or if you have noticed any recent changes in its characteristics.
Like
Take this medicine on a full stomach.
Swallow the tablets whole, accompanying them with a glass of water or other beverage.
Overdose What to do if you have taken too much Aleve
In case of accidental ingestion / intake of an excessive dose of ALEVE, notify your doctor immediately or go to the nearest hospital.
If you have any questions about the use of ALEVE, ask your doctor or pharmacist.
Dizziness, lethargy, heartburn, epigastric pain, digestive disturbances, nausea and vomiting, transient changes in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea and disorientation may occur as signs of overdose. Seizures have been reported in some patients but it is unclear whether these were related to naproxen overdose.
A few cases of reversible acute renal failure have been described.
If advised by your doctor, it may be helpful to try to induce vomiting and promptly give an adequate amount of activated charcoal (activated charcoal is a medicine; ask your pharmacist if necessary) to reduce the absorption of the medicine.
Side Effects What are the side effects of Aleve
Like all medicines, Aleve can cause side effects, although not everybody gets them.
The side effects seen with naproxen are generally common to other analgesics, antipyretics, non-steroidal anti-inflammatories.
The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or bleeding, sometimes fatal, may occur, particularly in the elderly. Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Aleve.
Gastritis has been observed less frequently.
Edema, hypertension and heart failure have been reported in association with NSAID treatment. Bullous reactions including Stevens Johnson syndrome and toxic epidermal necrolysis have occurred very rarely.
Medicines such as Aleve may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke.
Aleve causes a modest, transient, dose-dependent increase in bleeding time. However, these values often do not exceed the upper limit of the reference range.
The table below lists the undesirable effects observed with naproxen and naproxen sodium medicines, including those subject to medical prescription.
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
These side effects are usually transient. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Request and fill in the Undesirable Effects report form available at the pharmacy.
Expiry and Retention
Expiry: see the expiry date printed on the package
The expiry date refers to the product in intact packaging, correctly stored. Warning: do not use the medicine after the expiry date shown on the package. The expiry date refers to the last day of the month.
Store in the original package to protect the medicine from light.
Keep this medicine out of the reach and sight of children.
It is important to always have the information on the medicine available, so keep both the box and the package leaflet. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications you no longer use. This will help protect the environment.
COMPOSITION
One tablet contains 220 mg naproxen sodium (equivalent to 200 mg of naproxen.)
Excipients: microcrystalline cellulose, povidone K 30, talc, magnesium stearate; film coating: Opadry Blue YS 1-4215.
HOW IT LOOKS
Aleve comes in the form of film-coated tablets. The contents of the pack are 10,12,20 or 24 tablets.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
ALEVE 220 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One film-coated tablet contains: 220 mg naproxen sodium, equivalent to 200 mg of naproxen.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic treatment of headache, back pain, joint and muscle pain, toothache and colds. It is also indicated against menstrual pains and minor pains in arthritis.
04.2 Posology and method of administration
Method of administration
The film-coated tablet should be taken orally with a glass of water, on a full stomach.
Dosage
Adults and adolescents over 16 years: 1 tablet every 8 - 12 hours.
You may benefit most by starting with 2 tablets followed by 1 tablet every 12 hours, as needed.
The maximum daily dose is 3 tablets.
Undesirable effects can be reduced by using the lowest effective dose for the shortest possible duration of treatment to control symptoms (see section 4.4).
Do not use for more than 7 days for symptomatic pain relief and for more than 3 days for colds without medical supervision.
Special populations
Senior citizens
Use the lowest dosage.
Patients with renal, hepatic or cardiac insufficiency
In patients with renal and / or cardiac insufficiency and / or severe hepatic insufficiency a dose reduction may be necessary.
Pediatric population
The safety and efficacy in children under 16 have not yet been established (see section 4.3).
04.3 Contraindications
• Hypersensitivity to the active substance, or to any of the excipients, listed in section 6.1.
• History of asthma, urticaria or allergic-type reactions following the intake of acetylsalicylic acid or other analgesics, antipyretics, non-steroidal anti-inflammatory drugs.
• Severe renal insufficiency (creatinine clearance less than 20 ml / min)
• Severe heart failure
• Cirrhosis of the liver and severe hepatitis
• During intensive therapy with diuretics
• Gastric and duodenal ulcer
• People with ongoing bleeding or at risk of bleeding
• During treatment with anticoagulants as it synergizes their action
• Pregnancy and lactation (see section 4.6)
• Adolescents under the age of 16
• History of gastrointestinal bleeding or perforation related to previous active treatments or history of recurrent peptic ulcer / haemorrhage (two or more distinct episodes of proven ulceration or bleeding).
04.4 Special warnings and appropriate precautions for use
The product is not indicated for pain in the gastrointestinal tract.
General warnings
The use of Aleve should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see below on gastrointestinal and cardiovascular risks).
Anaphylactic / anaphylactoid reactions
Analgesics, antipyretics, non-steroidal anti-inflammatory drugs can cause hypersensitivity reactions, potentially fatal, including those of the anaphylactic (anaphylactoid) type, even in subjects with no history of hypersensitivity following exposure to this type of drug.
These reactions can occur in subjects with a history of angioedema, altered bronchial reactivity (asthma), rhinitis, nasal polyposis, allergic diseases, chronic respiratory diseases or sensitivity to acetylsalicylic acid. This can also occur in patients who experience allergic reactions (skin reactions, urticaria) to naproxen or other NSAIDs. After administration of analgesics, antipyretics, non-steroidal anti-inflammatory drugs, worsening of asthma is possible.
Anaphylactoid reactions, such as anaphylaxis, can be fatal.
Skin reactions
Serious 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). In the early stages of therapy patients appear to be at higher risk: the onset of the reaction occurs in most cases within the first month of treatment. Aleve should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Senior citizens
Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).
Gastrointestinal bleeding, ulceration and perforation:
Gastrointestinal bleeding, ulceration and perforation, which can be fatal, have been reported during treatment with all NSAIDs at any time, with or without warning symptoms or a previous history of serious gastrointestinal events.
In the elderly and in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), the risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs. These patients should start treatment with the lowest available dose. Concomitant use of protective agents (misoprostol or proton pump inhibitors) should be considered for these patients and also for patients taking low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events (see below and section 4.5). .
Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual gastrointestinal symptoms (especially gastrointestinal bleeding) particularly in the initial stages of treatment.
Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking Aleve the treatment should be discontinued.
NSAIDs should be administered with caution to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated (see section 4.8).
Sodium and fluid retention in cardiovascular diseases and peripheral edema
Caution is required before starting treatment in patients with a history of hypertension and / or heart failure as fluid retention, hypertension and edema have been reported in association with treatment with NSAIDs.
Cardiovascular and cerebrovascular effects
Clinical studies and epidemiological data suggest that the use of coxibs and some NSAIDs (especially at high doses and for long-term treatment) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke Although some data suggest that the use of naproxen (1000 mg / day) may be associated with a lower risk, a certain risk cannot be excluded. There are insufficient data regarding the effects of the low dose of naproxen 220 to 660 mg to arrive at precise conclusions on possible thrombotic risks.
Hepatic effects
Serious hepatic reactions, including jaundice and hepatitis (including some fatal cases) have been reported with the use of naproxen sodium or other non-steroidal anti-inflammatory drugs. Cross-reactivity has also been reported.
Precautions regarding fertility
The use of Aleve, like any prostaglandin synthesis and cyclooxygenase inhibitor drug, is not recommended in women intending to become pregnant due to effects on ovulation, reversible upon discontinuation of treatment (see section 4.6).
Aleve should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
People with bleeding disorders should be carefully monitored as naproxen inhibits platelet aggregation and can prolong bleeding time.
In case of hepatic insufficiency, concomitant treatment with other drugs, such as other analgesics, steroids or intensive diuretic therapy, or in case of previous undesirable effects with analgesics, antipyretics and non-steroidal anti-inflammatory drugs, the product should be administered with caution.
Sodium content
One Aleve tablet contains about 20 mg of sodium. Taking the maximum daily dosage of 3 tablets results in a maximum sodium intake of approximately 2.6 mmol / day. This should be taken into account in patients with impaired renal function or on a low sodium diet.
04.5 Interactions with other medicinal products and other forms of interaction
Interactions with other medicines
Cyclosporine : With the concomitant use of cyclosporine the concentration of the latter may be increased, increasing the risk of nephrotoxicity.
Lithium : Lithium levels may be increased, which can induce nausea, polydipsia, polyuria, tremor and confusion.
Methotrexate The use of Aleve concomitantly with methotrexate (at doses higher than 15 mg / week) can lead to increased concentrations of methotrexate, with an increased risk of toxicity of this substance.
NSAIDs : Do not administer the medicine in combination with drugs based on naproxen, acetylsalicylic acid or other analgesics, antipyretics, anti-inflammatories due to an increased risk of gastrointestinal bleeding.
Corticosteroids : increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants : NSAIDs may increase the effects of anticoagulants such as warfarin (increased prothrombin time and decreased platelet aggregation) (see section 4.4).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs) : increased risk of gastrointestinal bleeding (see section 4.4). Naproxen decreases platelet aggregation and prolongs bleeding time. This should be taken into account when determining bleeding time.
Diuretics, ACE inhibitors and angiotensin II antagonists :
NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with impaired renal function (eg dehydrated patients or elderly patients with impaired renal function) co-administration of an ACE inhibitor or an angiotensin antagonist II and agents that inhibit the cyclo-oxygenase system can lead to further deterioration of renal function, including possible acute renal failure, usually reversible. These interactions should be considered in patients taking Aleve concomitantly with ACE inhibitors or angiotensin II antagonists. Therefore, the combination should be administered with caution, especially in elderly patients.
Patients should be adequately hydrated and monitoring of renal function should be considered after initiation of concomitant therapy.
Clinically significant interactions with the following medicinal products are not expected in short-term use:
• antacids
• antidiabetics
• hydantoinics
• probenecid
• zidovudine
Food interactions
The rate of absorption of naproxen can be slowed by the simultaneous intake of food.
Interference with laboratory tests
Naproxen sodium interferes with urinary 17-ketosteroid and 5-indolacetic acid assays.
04.6 Pregnancy and lactation
Pregnancy
Inhibition of prostaglandin synthesis may adversely affect pregnancy and / or embryo / fetal development. Results from epidemiological studies suggest an increased risk of abortion and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early stages of pregnancy. The absolute risk of cardiac malformations increased from less than 1% to approximately 1.5%. The risk has been considered to increase with dose and duration of therapy. In animals, administration of prostaglandin synthesis inhibitors has been shown to cause an increase in pre- and post-implantation loss and embryo-fetal mortality. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals given prostaglandin synthesis inhibitors during the organogenetic period.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose
the fetus to:
- cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
- renal dysfunction, which can progress to renal failure with oligo-hydroamnios;
the mother and the newborn, at the end of pregnancy, to:
- possible prolongation of bleeding time and antiplatelet effect which may occur even at very low doses;
- inhibition of uterine contractions resulting in delayed or prolonged labor.
Feeding time
Naproxen can pass into breast milk. The medicine is therefore contraindicated during breastfeeding.
Fertility
The "use of naproxen, can" interfere with fertility and female subjects and in particular women who have fertility problems or who are undergoing fertility investigations should be informed of this (see section 4.4). This effect is reversible upon discontinuation of treatment.
04.7 Effects on ability to drive and use machines
Due to the possible onset of somnolence, dizziness, vertigo or insomnia Aleve may impair the ability to drive and use machines.
In this case, avoid these activities or others that require particular vigilance.
04.8 Undesirable effects
Cardiac disorders / vascular disorders
Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Clinical studies and epidemiological data suggest that the use of coxibs and some NSAIDs (especially at high doses and for long-term treatments) may be associated with a modest increased risk of arterial thrombotic events (eg myocardial infarction or stroke. ) (see section 4.4).
Gastrointestinal disorders
The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, gastrointestinal perforation or haemorrhage, sometimes fatal, may occur, particularly in the elderly (see section 4.4).
Nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration of Aleve (see section 4.4).
Gastritis has been observed less frequently.
Skin and subcutaneous tissue disorders
Bullous reactions including Stevens Johnson syndrome and toxic epidermal necrolysis (very rarely).
Aleve causes a modest, transient, dose-dependent increase in bleeding time. However, these values often do not exceed the upper limit of the reference range.
The table below lists the undesirable effects observed with naproxen and naproxen sodium medicines.
The frequency of possible side effects listed below is defined using the following convention: Very common (≥1 / 10), Common (≥1 / 100,
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicine is important as it allows for continuous monitoring of the benefit / risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
Dizziness, lethargy, heartburn, epigastric pain, digestive disturbances, nausea and vomiting, transient changes in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea and disorientation may occur as signs of overdose. Since naproxen sodium is rapidly absorbed, early elevated plasma levels are to be expected. Seizures have been reported in some patients but it is unclear whether these were related to naproxen overdose. A few cases of reversible acute renal failure have been described. It is not known what the life-threatening dose of the drug is.
In case of NSAID overdose, patients should be managed with symptomatic and supportive therapies. The stomach should be emptied and the usual supportive measures implemented. Prompt administration of an adequate amount of activated charcoal may reduce the absorption of the medicinal product.
Hemodialysis does not decrease plasma naproxen concentrations due to high plasma protein binding. There is no specific antidote.
Renal and hepatic function should be monitored.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: non-steroidal anti-inflammatory / antirheumatic drugs
ATC code: M01AE02
Naproxen has a marked anti-inflammatory, antipyretic and analgesic activity. As for other non-steroidal anti-inflammatory drugs, the mechanism of action of naproxen is linked to the reversible inhibition of the enzyme cyclo-oxygenase (COX), responsible for the conversion of arachidonic acid into cyclic endoperoxides, such as to reduce the synthesis of thromboxanes (TXA2) , prostacyclin (PGI2) and prostaglandins (PG). Several studies have also highlighted the hypothesis that naproxen may decrease the levels of some proinflammatory cytokines (IL-6) and neuropeptides (substance P) in plasma and synovial fluid.
Naproxen sodium is a non-selective COX inhibitor, it acts by inhibiting both COX 1 and COX 2. It inhibits the formation of COX 1 thromboxane synthase dependent, A2 (TXA2), which reduces platelet aggregation and prostacyclines dependent COX2 (PGI2) , an important mediator of vasodilation.
05.2 "Pharmacokinetic properties
Absorption
In humans, naproxen is absorbed very rapidly orally and plasma concentrations reach their peak on average 1-2 hours after administration. Absorption may be delayed from food.
Steady state is reached on the first day.
Blood levels increase with increasing dose: from about 50 mcg / ml with 250 mg / day to about 100 mcg / ml with 1000 mg / day.
Distribution
Over 99% of naproxen is bound to serum albumin. The volume of distribution is approximately 0.1 L / kg. Naproxen rapidly distributes into the synovial fluid with a Cmax of 36 mg / L after 7.5 hours.
Metabolism
The main site of metabolism is the liver and is mediated by cytochromes CYP 2C9 and CYP 1 A 2. The metabolites thus produced are 6 -o-desmethyl-naproxen (which has a COX inhibitory power 100 times lower than naproxen), conjugated inactive (glucuronides 57%) and demethylated. Pharmacokinetics are linear at the recommended dosages.
Excretion
95% of the administered dose is excreted in the urine, partly unchanged (10%) and partly as 6-o-desmethyl naproxen, in free or conjugated form.
Biliary elimination accounts for 1-2% (mainly as conjugates).
The elimination half-life is approximately 14 hours.
Patients with severe hepatic impairment may have higher free naproxen levels. In severe renal insufficiency the elimination of naproxen is reduced, but no significant accumulation was observed at the recommended dosages.
05.3 Preclinical safety data
There is no further information on preclinical data other than that already reported elsewhere in this Summary of Product Characteristics (see section 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Microcrystalline cellulose, povidone K 30, talc, magnesium stearate; film coating: Opadry Blue YS 1-4215.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Store in the original package to protect the medicine from light.
06.5 Nature of the immediate packaging and contents of the package
PVC blister. Packs of 10, 12, 20 and 24 film-coated tablets.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
Bayer S.p.A. Viale Certosa 130, 20156 Milan
08.0 MARKETING AUTHORIZATION NUMBER
"220 mg film-coated tablets" 10 tablets AIC n ° 032790014
"220 mg film-coated tablets" 20 tablets AIC n ° 032790026
"220 mg film-coated tablets" 12 tablets AIC n ° 032790038
"220 mg film-coated tablets" 24 tablets AIC n ° 032790040
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Renewal: July 2007
10.0 DATE OF REVISION OF THE TEXT
March 2015
