Active ingredients: Naproxen
NAPROSYN 250 mg gastro-resistant tablets
NAPROSYN 500 mg gastro-resistant tablets
NAPROSYN 250 mg suppositories
NAPROSYN 500 mg suppositories
NAPROSYN 250 mg granules for oral suspension
NAPROSYN 500 mg granules for oral suspension
NAPROSYN 750 mg modified release tablets
Naprosyn package inserts are available for pack sizes: - NAPROSYN 250 mg gastro-resistant tablets, NAPROSYN 500 mg gastro-resistant tablets, NAPROSYN 250 mg suppositories, NAPROSYN 500 mg suppositories, NAPROSYN 250 mg granules for oral suspension, NAPROSYN 500 mg granules for oral suspension, NAPROSYN 750 mg modified-release tablets
- NAPROSYN 10% GEL
- NAPROSYN 500 mg powder for solution for injection
Why is Naprosyn used? What is it for?
Naprosyn contains the active ingredient naproxen.
Naproxen belongs to a class of medicines called non-steroidal anti-inflammatory / antirheumatic drugs (NSAIDs) that perform a variety of activities, with an important function in pain control. Naprosyn is used to treat symptoms of:
- an inflammatory joint disease (rheumatoid arthritis)
- a degenerative joint disease (osteoarthritis or degenerative arthritis)
- an inflammatory disease of the spine (ankylosing spondylitis)
- a disease due to the presence of uric acid crystals in the joints (gouty arthropathy)
- diseases affecting the joints, bones, tendons (lumbosciatica, myalgia, neuralgia, root syndromes, periarthritis, fibromyositis).
Contraindications When Naprosyn should not be used
Do not take Naprosyn
- if you are allergic to the active substance or any of the other ingredients of this medicine
- if you suffer from a lesion of the stomach wall or duodenum (gastroduodenal ulcer and ongoing peptic ulcer)
- if you suffer from inflammation of the colon (ulcerative colitis)
- if you have a history of bleeding or perforation of the stomach or intestines due to previous treatments or a history of frequent bleeding / breakdown of the stomach wall (peptic ulcer) (two or more distinct episodes)
- if you have severe heart problems (severe heart failure)
- if you have had allergic manifestations such as asthma, itching (hives), allergic cold (rhinitis), severe and rapid general allergic reaction (anaphylactic or anaphylactoid reactions), presence of drop-shaped nodules inside the nose (nasal polyps), associated the use of aspirin (acetyl salicylic acid) and / or other non-steroidal anti-inflammatory drugs (NSAIDs)
- if it is for a child under the age of 2
- if you are pregnant or breastfeeding
- if you have severe kidney problems
Precautions for use What you need to know before taking Naprosyn
Talk to your doctor or pharmacist before taking Naprosyn.
In particular, tell your doctor:
- if you are taking other non-steroidal anti-inflammatory medicines (NSAIDs)
- if you have a history of stomach wall injury with bleeding / perforation (gastrointestinal haemorrhage, ulceration or perforation)
- if you have or have ever had acute inflammation of the gastrointestinal tract or if you have ever had stomach or bowel problems after using medicines for rheumatic diseases
- if you have a history of stomach or intestinal toxicity: report any unusual symptoms to your doctor, especially at the start of treatment
- if you are taking anti-inflammatory medicines (oral corticosteroids), medicines to thin the blood (anticoagulants such as warfarin), medicines for depression (selective serotonin reuptake inhibitors) or medicines such as "aspirin or similar (see" Other medicines and Naprosyn " )
- if you suffer from chronic inflammatory disease of the stomach and intestines (ulcerative colitis or Crohn's disease)
- if you have heart problems
- if you have liver problems
- if you have kidney problems
- if you have high blood pressure and / or heart problems (heart failure), known ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease
- if you experience skin reactions, some of which can be fatal (exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis)
- if you have a history of swelling in the legs, arms, face, mouth or tongue (angioedema) or difficulty in breathing (bronchospasm, asthma and rhinitis) and drop-shaped lumps inside the nose (nasal polyps)
- if you have severe and rapid general allergic reactions (anaphylactic or anaphylactoid reactions)
- if you have bleeding problems (haemostasis disorders)
- if you are planning a pregnancy
- if you have fertility problems or are investigating fertility
If you notice skin rashes (rash), mucosal lesions or any other signs of allergic (hypersensitivity) reaction with the use of Naprosyn, stop treatment immediately and contact your doctor.
Medicines such as Naprosyn 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.
If you have heart problems or a history of stroke or think you may be at risk for these conditions (for example if you have high blood pressure, diabetes or high cholesterol or are a smoker) you should discuss your treatment with your doctor or pharmacist.
In the elderly and in patients with a history of ulcer, particularly if complicated with bleeding or perforation (see section Do not take Naprosyn), the risk of gastrointestinal bleeding, ulceration or perforation increases with increasing dose. These patients should start treatment with the lowest dose available.
If you use Naprosyn for prolonged treatments you should have your eyesight checked regularly.
Children and adolescents
It is not intended for use in children. The doctor may prescribe Naprosyn only in cases of absolute necessity and in children over 2 years of age.
Senior citizens
If you are elderly you are more likely to experience some of the side effects caused by Naprosyn such as bleeding / perforation of the stomach and intestines
Interactions Which drugs or foods can change the effect of Naprosyn
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. The effects of Naprosyn can be affected or affect the following medicines:
- Hydantoins (to treat epilepsy), sulphonylureas (to treat diabetes), sulfonamides (antibiotics), coumarin anticoagulants (to thin the blood), barbiturates (sedatives used to treat diseases such as epilepsy), other medicines non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid as they can increase the amount of Naprosyn in the blood and cause side effects.
- Diuretics, ACE inhibitors and angiotensin II antagonists (to treat high blood pressure) as they may have a reduced effect when taken together with Naprosyn and increase the risk of kidney damage in some dehydrated or elderly patients who already have kidney function compromised.
- Furosemide (for the treatment of high blood pressure) as co-administration may reduce the effect of this medicine.
- Lithium (for the treatment of manic depressive illness) as the amount of lithium in the blood can become too high.
- Propanolol and beta-blockers (to treat high blood pressure) as Naprosyn may reduce the effect of these medicines.
- Probenecid (for the treatment of gout) as it increases the amount and permanence of Naprosyn in the body.
- Methotrexate (for the treatment of tumors and for diseases of the body's defense system) as it stays longer in the body with the possibility of increasing its toxicity.
- Anticoagulants (to thin the blood) as non-steroidal anti-inflammatory medicines (NSAIDs) may increase the effects of anticoagulants, such as warfarin or coumarin-type anticoagulants (see section "What you need to know before you take Naprosyn").
- Antiplatelet agents (aspirin or similar medicines) and selective serotonin reuptake inhibitors - SSRIs (used for depression) as they increase the risk of stomach and bowel bleeding (see "What you need to know before you take Naprosyn").
- Corticosteroids (anti-inflammatory hormones) as they increase the risk of injury or bleeding to the stomach and intestines (see "What you need to know before you take Naprosyn").
- Naproxen may decrease the effectiveness of birth control devices (uterine devices).
The simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) including Naprosyn with:
- naproxen sodium
- acetylsalicylic acid
- quinolones (antibiotics).
Naprosyn with alcohol
Avoid drinking alcohol while taking Naprosyn.
The results of some laboratory tests (such as the adrenal function test or some tests for urinary 5-hydroxyindolacetic acid) can be modified by Naprosyn
Warnings It is important to know that:
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Do not use Naprosyn during pregnancy and breastfeeding.
Driving and using machines
Due to the possible onset of lightheadedness, somnolence, dizziness or depression Naprosyn may impair the ability to drive and use machines. In these cases, avoid activities that require vigilance.
Naprosyn granules for oral suspension contains
sucrose: if you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine;
less than 1 mmol (23 mg) sodium per sachet, i.e. it is essentially "sodium-free"
Naprosyn 750 mg modified release tablets contain sunset yellow E110 (a dye): may cause allergic reactions.
Naprosyn 500 mg gastro-resistant tablets contain less than 1 mmol (23 mg) sodium per tablet, ie it is essentially "sodium-free".
Dosage and method of use How to use Naprosyn: Dosage
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Adults
- Attack therapy
The recommended dose is:
- 500-1000 mg per day, divided into two doses, every 12 hours (in the morning during breakfast and in the evening during dinner) or in a single dose (during the midday meal or in the evening) or 1 tablet of Naprosyn 750 mg modified-release tablets once daily
The recommended dose is 1000 mg (2 x 500 mg) once a day:
- if you have severe pain at night and / or with morning stiffness
- if you have unsuccessfully taken other medicines for rheumatism in high doses
- if you have inflammatory joint disease (osteoarthritis), when pain is the main symptom.
- Maintenance therapy
Depending on the attack dose, the severity of the disease and the intensity of the pain, the recommended dose is:
- 750-250 mg divided into two doses, every 12 hours (in the morning during breakfast and in the evening during dinner) or in a single dose (during the midday meal or in the evening)
- If you suffer from acute gout
The recommended dose is:
- 500 mg as a starting dose
- 250 mg every 8 hours for the first 24 hours
- 250 mg twice daily for 6-7 days as a maintenance dose.
Senior citizens
If you are elderly, your doctor will carefully determine the dose you should take, evaluating a possible reduction in the doses indicated above.
The sachets of Naprosyn granules for oral suspension, suitably dissolved in water, allow for a more rapid absorption of the active principle and perform a quicker action against pain (analgesic); they are also more suitable if you have difficulty swallowing.
The use of Naprosyn gastro-resistant tablets should be avoided in acute painful states where rapid action against pain is required.
Children and adolescents
It is not intended for use in children. The doctor may prescribe Naprosyn only in cases of absolute necessity and in children over 2 years of age.
If you have liver problems (liver failure) or kidney problems (kidney failure)
Your doctor will prescribe the lowest effective dose for you and will periodically check you to evaluate clinical and laboratory parameters.
Do not take Naprosyn if you have severe kidney failure.
Overdose What to do if you have taken too much Naprosyn
If you take more Naprosyn than you should
If you take too much Naprosyn, tell your doctor immediately or go to the nearest hospital.
If you take more Naprosyn than you should, dizziness, drowsiness, abdominal discomfort, stomach pain, nausea or vomiting, transient changes in liver and kidney function, decrease in a substance in the blood which causes easy bleeding (hypoprothrombinaemia) may occur. , accumulation of acids in the blood, shortness of breath, disorientation. Bleeding of the stomach and intestines may occur.
If you forget to take Naprosyn
Do not take a double dose to make up for a forgotten dose.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Naprosyn
Like all medicines, this medicine can cause side effects, although not everybody gets them.
- The most commonly observed adverse events are gastrointestinal in nature. Injury, bleeding or perforation of the stomach and intestines (peptic ulcers, gastrointestinal perforation or haemorrhage), sometimes fatal, particularly in the elderly, may occur (see Warnings and precautions). Nausea, vomiting, diarrhea, flatulence (air coming out of the anus), constipation (constipation), indigestion (dyspepsia), pain in the abdomen and stomach, heartburn (heartburn), blood in the stool (melaena), vomiting blood (haematemesis), inflammation of the mouth (ulcerative stomatitis), worsening of chronic inflammatory bowel disease (exacerbation of colitis and Crohn's disease), inflammation of the esophagus (esophagitis), inflammation of the pancreas (pancreatitis). observed inflammation of the stomach (gastritis).
Other side effects that may occur with the use of Naprosyn are:
- change in the concentration of certain types of cells in the blood (thrombocytopenia, granulocytopenia, leukopenia, eosinophilia, aplastic or haemolytic anemia)
- severe and rapid general allergic reactions (anaphylactic or anaphylactoid type reactions)
- high concentration of potassium in the blood (hyperkalaemia)
- strange dreams
- depression
- insomnia
- dizziness
- disorientation
- convulsions
- headache (headache)
- drowsiness
- inflammation of the optic nerve (retrobulbar optic neuritis)
- cognitive dysfunctions
- difficulty concentrating
- inflammation of the membranes surrounding the brain (aseptic meningitis)
- visual disturbances (papillitis, papilloedema, visual disturbances, corneal opacity)
- hearing disturbance (hearing disturbances, ringing in the ears, tinnitus, vertigo)
- irregular or strong heartbeat (palpitations)
- rapid heartbeat (tachycardia)
- heart function problems (congestive heart failure, heart failure, myocardial infarction)
- injury to the vessels of the brain (stroke)
- high blood pressure (hypertension)
- inflammation of blood vessels (vasculitis)
- swelling (edema)
- breathing difficulties (dyspnoea, asthma and bronchospasm)
- inflammation of the lungs (eosinophilic pneumonia)
- increased fluid in the lungs (pulmonary edema)
- swelling of the throat (larynx edema)
- yellow skin (jaundice)
- inflammation of the liver (hepatitis)
- skin rashes
- itch
- urticaria
- bruising (bruising)
- rapid swelling of the legs, arms, face or tongue (angioedema)
- appearance of red and swollen nodules under the skin (erythema multiforme, erythema nodosum, fixed drug erythema, lichen planus)
- red spots on the body (purple)
- blistering reactions including a disease called Stevens-Johnson syndrome with severe injury to the skin, mouth and other parts of the body with high fever, vomiting, diarrhea and joint pain
- skin death (toxic epidermal necrolysis)
- abnormal and exaggerated reaction of the skin to light (photosensitivity reactions)
- hair loss (alopecia)
- muscle pain (myalgia)
- muscle weakness
- blood in the urine (haematuria)
- decreased renal function, renal damage (interstitial nephritis, nephrotic syndrome, renal failure, renal papillary necrosis)
- infertility in women
- mild swelling in the extremities (peripheral edema)
- excessive thirst
- fever and chills
- malaise
- alteration of the laboratory test to evaluate the functioning of the liver
- increased creatinine in the blood (hypercreatinemia)
With the formulation suppositories have also been reported:
- pain, rectal irritation
- rectal burning and inflammation (proctitis)
- itch
- painful spasm of the anus (tenesmus)
Medicines such as Naprosyn may be associated with a modest increased risk of heart attack (myocardial infarction) or stroke.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date which is stated on the carton after "Expiry". The expiry date refers to the last day of that month
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Naprosyn contains
Naprosyn 500 mg gastro-resistant tablets
- The active ingredient is: naproxen. Each gastro-resistant tablet contains 500 mg of naproxen.
- The other ingredients are: povidone, croscarmellose sodium, magnesium stearate, methacrylic acid copolymer, talc, sodium hydroxide, triethyl citrate, simethicone.
Naprosyn 500 mg suppositories
- The active ingredient is: naproxen. Each suppository contains 500 mg of naproxen.
- The other ingredients are: semisynthetic glycerides.
Naprosyn 500 mg granules for oral suspension
- The active ingredient is: naproxen. Each sachet contains 500 mg of naproxen.
- The other ingredients are: mannite, povidone, acrylic resin (Eudragit), sodium saccharinate, lemon flavor, citric acid, precipitated silica, sucrose.
Naprosyn 750 mg modified release tablets
- The active ingredient is: naproxen. Each modified-release tablet contains 750 mg of naproxen.
- The other ingredients are: hypromellose, magnesium stearate, sunset yellow (E 110).
What Naprosyn looks like and contents of the pack
Naprosyn 500 mg gastro-resistant tablets are available in packs of 30 tablets.
Naprosyn 500 mg suppositories is available in packs of 10 suppositories.
Naprosyn 500 mg granules for oral suspension are available in packs of 30 sachets.
Naprosyn 750 mg modified release tablets are available in packs of 20 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
NAPROSYN
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
NAPROSYN 250 mg gastro-resistant tablets
Each gastro-resistant tablet contains:
Active principle: naproxen 250 mg.
NAPROSYN 500 mg gastro-resistant tablets
Each gastro-resistant tablet contains:
Active principle: naproxen 500 mg.
NAPROSYN 500 mg suppositories
Each suppository contains:
Active principle: naproxen 500 mg.
NAPROSYN 250 mg suppositories
Each suppository contains:
Active principle: naproxen 250 mg.
NAPROSYN 500 mg granules for oral suspension
Each sachet contains:
Active principle: naproxen 500 mg.
NAPROSYN 250 mg granules for oral suspension
Each sachet contains:
Active principle: naproxen 250 mg.
NAPROSYN 750 mg modified release tablets
Each modified-release tablet contains:
Active principle: naproxen 750 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Gastro-resistant tablets.
Suppositories.
Granules for oral suspension.
Modified-release tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic treatment of the following conditions: rheumatoid arthritis, osteoarthritis, (degenerative arthritis) ankylosing spondylitis, gouty arthropathy and various forms of extraarticular rheumatism (lumbosciatica, myalgia, neuralgia, root syndromes, periarthritis, fibromyositis).
04.2 Posology and method of administration
Adults
As attack therapy it is recommended to administer 500-1000 mg per day, divided into two doses, at a 12-hour interval (in the morning during breakfast and in the evening during dinner) or in a single administration (during noon or evening meal).
For this purpose, one tablet of NAPROSYN 750 mg modified release tablets once a day may also be indicated.
The dose of 1000 mg (2 x 500 mg) per day in a single administration is recommended:
- in subjects with severe night pains and / or morning stiffness;
- in patients already unsuccessfully treated with other high-dose antirheumatic drugs;
- in osteoarthritis when pain is the predominant symptom.
As maintenance therapy, depending on the attack dose, the severity of the disease and the painful component, a daily dose of 750-250 mg in a single administration or in two administrations at 12 hours intervals is indicated.
In acute gout attacks, a starting dose of 500 mg is recommended, followed by doses of 250 mg every 8 hours for the first 24 hours, subsequently switching to maintenance doses of 250 mg twice daily for 6-7 days.
Senior citizens
In elderly subjects and in general in subjects most at risk, the dose must be carefully established by the doctor who will have to evaluate a possible reduction of the dosages indicated above.
Children
The use of the product is not foreseen in pediatric age, except, in the opinion of the doctor in cases of absolute necessity in children over 2 years of age.
Undesirable effects can be minimized by using the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.4).
Hepatic insufficiency
In patients with impaired hepatic function, periodic monitoring of clinical and laboratory parameters should be resorted to, especially in the case of prolonged treatment.
Such patients should be treated with the lowest effective dose (see section 4.4).
Kidney failure
In patients with impaired renal function, periodic monitoring of clinical and laboratory parameters should be resorted to, especially in the case of prolonged treatment.
Chronic treatment with NAPROSYN is contraindicated in patients with creatinine clearance below 20 ml / minute (see section 4.4).
The sachets of NAPROSYN granules for oral suspension (250 mg and 500 mg), suitably dissolved in water, allow for a more rapid absorption of the active substance and perform a quicker analgesic action; they are also more suitable for patients with swallowing difficulties and / or digestive disorders.
NAPROSYN gastro-resistant tablets is a gastroprotected formulation, therefore particularly indicated in all those patients in whom dissolution of the drug in the stomach is not recommended.
The use of NAPROSYN gastro-resistant tablets should however be avoided in acute painful states in which a prompt analgesic action is required.
04.3 Contraindications
• Hypersensitivity to the active substance or to other closely related substances from a chemical point of view and / or to any of the excipients.
• Gastroduodenal ulcer and peptic ulcer in progress.
• Ulcerative colitis.
• 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).
• Severe heart failure.
• Due to the possibility of cross-sensitivity, NAPROSYN is contraindicated in patients in whom acetylsalicylic acid and / or other NSAIDs induce allergic manifestations such as asthma, hives, rhinitis, anaphylactic or anaphylactoid reactions and have caused nasal polyps.
• The use of the product is contraindicated in children under 2 years of age, as the safety of the product in this age group has not been established.
• Pregnancy and breastfeeding.
• Renal insufficiency (creatinine clearance less than 20 ml / min).
04.4 Special warnings and appropriate precautions for use
Undesirable effects can be minimized with the use of the lowest effective dose for the shortest possible duration of treatment needed to control symptoms (see section 4.2 and the paragraphs below on gastrointestinal and cardiovascular risks).
Particular caution should be exercised when treating patients with severely reduced cardiac, hepatic or renal function. In such patients, periodic monitoring of clinical and laboratory parameters should be used, especially in case of prolonged treatment.
In particular, chronic treatment with NAPROSYN is not recommended in patients with creatinine clearance below 20 ml / minute.
Patients with impaired hepatic function should be treated with the lowest effective dose. As with other NSAIDs, elevations in liver function tests may occur as a result of hypersensitivity rather than direct toxicity. Some serious hepatic reactions, including jaundice and hepatitis, some with fatal outcome, have been reported following administration of the product, as well as other NSAIDs.
Caution should be exercised in patients with a history of hypertension and / or heart failure as fluid retention and edema have been reported in association with NSAID therapy.
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.
NAPROSYN should be discontinued at the first appearance of skin rash, mucosal lesions or any other signs of hypersensitivity.
Like other non-steroidal anti-inflammatory drugs, naproxen should be used with caution in patients with current or previous allergic manifestations as it can cause bronchospasm and other allergic phenomena. Anaphylactic and anaphylactoid reactions can also occur in patients with and without previous hypersensitivity to aspirin , other NSAIDs or other naproxen products. Anaphylactic and anaphylactoid reactions can also occur in subjects with previous angioedema, bronchial reactivity (asthma), rhinitis or nasal polyps. Anaphylactic reactions, as well as anaphylactoids, can be fatal. Bronchospasm can be triggered in patients with previous or current allergy or asthma, or with hypersensitivity to acetylsalicylic acid.
Since ocular alterations have been detected in animal studies with non-steroidal anti-inflammatory drugs, it is recommended that periodic ophthalmological checks be carried out in case of prolonged treatments.
The use of NAPROSYN should be avoided concomitantly with NSAIDs, including selective COX-2 inhibitors.
Cardiovascular and cerebrovascular effects
Adequate monitoring and instruction are required in patients with a history of mild to moderate hypertension and / or congestive heart failure as fluid retention and edema 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) Although some data suggest that the use of naproxen (1000 mg / day) may be associated with a lower risk, some risks cannot be excluded.
Patients with uncontrolled hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease and / or cerebrovascular disease should only be treated with naproxen after careful consideration. Similar considerations should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (eg.hypertension, hyperlipidemia, diabetes mellitus, smoking).
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.
Patients with current or history of acute inflammatory diseases of the gastrointestinal tract or who have complained of gastrointestinal disorders following other antirheumatic drugs, should only undergo the treatment under strict medical supervision.
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 dose aspirin 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 aspirin (see section 4.5).
When gastrointestinal bleeding or ulceration occurs in patients taking NAPROSYN 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 - undesirable effects).
NAPROSYN may decrease platelet aggregation and prolong bleeding time. Caution should be exercised when treating patients with haemostatic disorders or on anticoagulant therapy.
Naproxen can decrease fever and inflammation, reducing their usefulness as diagnostic symptoms.
The use of NAPROSYN, like any drug that inhibits prostaglandin synthesis and cyclooxygenase, is not recommended in women who intend to become pregnant.
Administration of NAPROSYN should be discontinued in women who have fertility problems or who are undergoing fertility investigations.
NAPROSYN granules for oral suspension contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption, or sucrase isomaltase insufficiency should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
As interactions have been observed between non-steroidal anti-inflammatory drugs and highly protein bound drugs, such as hydantoins, sulfonylureas, sulfonamides and coumarin anticoagulants, barbiturates, other NSAIDs and acetylsalicylic acid, patients receiving NAPROSYN concomitantly and these drugs should be observed in order to exclude overdose effects. .
In patients treated with other non-steroidal anti-inflammatory drugs and with coumarin-type anticoagulants, increased prothrombin time and decreased platelet aggregation have been observed.
Anticoagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section 4.4).
Corticosteroids: increased risk of gastrointestinal ulceration or bleeding (see section 4.4).
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 (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 NAPROSYN 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.
A decrease in the natriuretic effect of furosemide has been reported following co-administration with some non-steroidal anti-inflammatory drugs.
The association of these drugs with lithium leads to a decrease in renal clearance and consequent increase in the plasma concentration of the latter.
NAPROSYN, like other non-steroidal anti-inflammatory drugs, may reduce the antihypertensive effect of propanolol and other beta-blockers.
Probenecid, given at the same time as NAPROSYN, increases its plasma levels and considerably prolongs its half-life.
The combination with methotrexate should be used with caution as naproxen has been reported to reduce tubular secretion of methotrexate in animal models.
It is suggested that NAPROSYN therapy be temporarily suspended 48 hours prior to performing adrenal function tests as NAPROSYN may interfere with some tests for 17-ketogenic steroids. Similarly, NAPROSYN may interfere with some tests for urinary 5-hydroxyindolacetic acid.
Avoid alcohol intake.
Naproxen can decrease the effectiveness of intrauterine devices.
The use of non-steroidal anti-inflammatory drugs at the same time as quinolone drugs is not recommended.
NAPROSYN should not be used at the same time as its salt (naproxen sodium) or vice versa as both circulate in the blood in anionic form.
Use at the same time as acetylsalicylic acid or other NSAIDs is not recommended.
NAPROSYN can be used simultaneously with gold salts and / or corticosteroids.
04.6 Pregnancy and lactation
The use of NAPROSYN, like any drug that inhibits the synthesis of prostaglandins and cyclooxygenases, is not recommended in women who intend to become pregnant.
Administration of NAPROSYN should be discontinued in women who have fertility problems or who are undergoing fertility investigations (see section 4.4).
The product is contraindicated (see section 4.3) during pregnancy and lactation.
Inhibition of prostaglandin synthesis can adversely affect pregnancy and / or embryo / fetal development.
Results of epidemiological studies suggest an increased risk of miscarriage and cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiac malformations increased from less than 1% up 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 increased loss of pre- and post-implantation and of 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.
The use of the drug close to childbirth determines the delay of the birth itself; moreover, the drug can cause, if administered in this period, alterations to the haemodynamics of the small circulation of the unborn child, with serious consequences for breathing.
04.7 Effects on ability to drive and use machines
Due to the possible onset of lightheadedness, somnolence, dizziness or depression, NAPROSYN may impair the ability to drive and use machines. Caution should be exercised by those patients whose activity requires vigilance in case they notice lightheadedness, sleepiness or dizziness or depression during naproxen therapy.
04.8 Undesirable effects
Changes in the blood and lymphatic system: alterations such as thrombocytopenia, granulocytopenia, leukopenia, eosinophilia, aplastic or haemolytic anemia occurred sporadically.
Alterations of the immune system: as with other non-steroidal anti-inflammatory drugs, anaphylactic or anaphylactoid-type reactions, even severe ones, may occur in patients with or without previous exposure to drugs belonging to this class.
Alterations of metabolism and nutrition: hyperkalaemia.
Psychiatric disorders: depression, insomnia, abnormal dreams.
Alterations of the nervous system: dizziness, disorientation, retrobulbar optic neuritis, convulsions, headache, somnolence, cognitive dysfunction, difficulty concentrating, aseptic meningitis.
Eye disorders: visual disturbances, corneal opacity, papillitis, papilloedema.
Alteration of the auditory system and the labyrinth: vertigo, hearing problems, ringing in the ears, tinnitus.
Cardiac alterations: palpitations, tachycardia, congestive heart failure. Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Vascular pathologies: hypertension, vasculitis.
Clinical studies and epidemiological data suggest that the use of 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) ( see section 4.4).
Alterations of the respiratory system, thorax and mediastinum: dyspnoea, pulmonary edema, asthma, eosinophilic pneumonia, bronchospasm, larynx edema.
Alterations of the gastrointestinal system: 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 and epigastric pain, heartburn, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4), oesophagitis and pancreatitis.
Gastritis has been observed less frequently.
Alterations of the hepatobiliary system: hepatitis (some cases have been fatal), jaundice.
Alteration of the skin and subcutaneous tissue: rash, pruritus, ecchymosis, urticaria, angioedema, erythema multiforme, erythema nodosum, fixed drug erythema, lichen planus, purpura, bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rarely), photosensitivity reactions, alopecia .
Alterations of the musculoskeletal system and connective tissue: myalgia, muscle weakness.
Renal and urinary disorders: haematuria, interstitial nephritis, nephrotic syndrome, decreased renal function, renal failure, renal papillary necrosis.
Disorders of the reproductive system and breast: female infertility.
General disorders and alteration of the administration site: mild peripheral edema, excessive thirst, fever and chills, malaise.
Diagnostic investigations: liver function test abnormal, hypercreatinemia.
Minor local side effects have also been reported with the suppository formulation, such as rectal pain and irritation, burning and itching.
There have also been isolated cases of rectal haemorrhage, tenesmus and proctitis.
However, the incidence of these effects is low.
04.9 Overdose
Dizziness, drowsiness, abdominal discomfort, epigastric pain, nausea or vomiting, transient changes in liver and kidney function, hypoprothrombinemia, metabolic acidosis, apnea, disorientation may occur as signs of overdose. Gastrointestinal bleeding may occur.
In case of accidental or deliberate ingestion of a large amount of naproxen, gastric emptying should be performed and the normal measures required in these cases implemented. Treatment is symptomatic and there is no specific antidote.
The prompt administration of an adequate quantity of activated charcoal can significantly reduce the absorption of the drug.
Forced diuresis, hemodialysis or hemoperfusion are probably useless because naproxen binds strongly to plasma proteins.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Therapeutic class: Non-steroidal anti-inflammatory and antirheumatic products, derivatives of propionic acid.
ATC code: M01AE02
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.
05.2 Pharmacokinetic properties
Absorption
In humans, naproxen sodium is absorbed very rapidly orally and plasma concentrations reach their peak on average 1-2 hours after administration.
Steady state is reached on the first day.
Absorption via the rectum is a little slower but allows for longer therapeutic plasma levels.
Distribution
The plasma protein binding is 99%. Naproxen is rapidly distributed in the synovial fluid with a Cmax of 36 mg / l after 7.5 h.
Metabolism
The main site of biotransformation processes is the liver and is mediated by cytochromes CYP 2C9 and CYP 1A2. The metabolites thus produced are 6-O-demethyl-naproxen (which has a COX inhibitory power 100 times lower than naproxen), inactive conjugates (57% glucuronides) and demethylates.
Excretion
Naproxen is mainly excreted via the urine (95%) in part unchanged (about 10%) and in part metabolized (6-O-desmethyl naproxen), in free and conjugated form. Biliary elimination accounts for 1-2% (mainly as conjugates). The plasma half-life of naproxen is approximately 13 hours.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Suppositories
• Semi-synthetic glycerides
250 mg granules for oral suspension
• Sodium chloride
• Sodium dioctyl sulfosuccinate
• Povidone
• Mint aroma
• Anise-mint aroma
• Mannite
• Sodium saccharin
• Sucrose
500 mg granules for oral suspension
• Mannite
• Povidone
• Acrylic resin (Eudragit)
• Sodium saccharin
• Lemon flavor
• Citric acid
• Precipitated silica
• Sucrose
750 mg modified release tablets
• Hypromellose
• Magnesium stearate
• Sunset yellow (E 110)
Gastro-resistant tablets
• Povidone
• Croscarmellose sodium
• Magnesium stearate
• Methacrylic acid copolymer
• Talc
• Sodium hydroxide
• Triethyl citrate
• Simethicone
06.2 Incompatibility
None.
06.3 Period of validity
NAPROSYN "250 mg gastro-resistant tablets" 30 tablets: 36 months.
NAPROSYN "500 mg gastro-resistant tablets" 30 tablets: 36 months.
NAPROSYN "250 mg suppositories" 6 and 10 suppositories: 60 months.
NAPROSYN "500 mg suppositories" 6 and 10 suppositories: 60 months.
NAPROSYN "250 mg granules for oral suspension" 30 sachets: 60 months.
NAPROSYN "500 mg granules for oral suspension" 30 sachets: 36 months.
NAPROSYN "750 mg modified release tablets" 20 tablets: 36 months.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
The tablets are packaged in PVC and aluminum blisters.
The suppositories are packed in PVC shells.
The sachets are packaged in a 3-layer laminate (paper / aluminum / polyethylene).
Blisters, valves and sachets are placed in cardboard boxes together with the package leaflet.
NAPROSYN is also available in gel preparation for topical use and ampoules for injectable use
06.6 Instructions for use and handling
None.
07.0 MARKETING AUTHORIZATION HOLDER
RECORDATI Chemical and Pharmaceutical Industries S.p.A. -Via Matteo Civitali, 1 - 20148 - MILAN
08.0 MARKETING AUTHORIZATION NUMBER
NAPROSYN "500 mg suppositories" - 6 suppositories - A.I.C. n.023177076
NAPROSYN "500 mg suppositories" - 10 suppositories - A.I.C. n. 023177088
NAPROSYN "500 mg granules for oral suspension" - 30 sachets - A.I.C. n. 023177138
NAPROSYN "250 mg suppositories" - 6 suppositories - A.I.C. n. 023177052
NAPROSYN "250 mg suppositories" - 10 suppositories - A.I.C. n. 023177064
NAPROSYN "250 mg granules for oral suspension" - 30 sachets - A.I.C. n. 023177090
NAPROSYN "750 mg modified release tablets" - 20 tablets - A.I.C. n. 023177189
NAPROSYN "250 mg gastro-resistant tablets" - 30 tablets - A.I.C. n. 023177203
NAPROSYN "500 mg gastro-resistant tablets" - 30 tablets - A.I.C. n. 023177215
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
First authorization: 10.02.75
Renewal of the authorization: May 2005
10.0 DATE OF REVISION OF THE TEXT
July 2008
