Naproxeno 500mg

Naproxen sodium in TABLETS of 550 mg and 275 mg.

Indications: NAPROXEN is an analgesic, antipyretic and anti-inflammatory. NAPROXEN 550 mg is indicated as an analgesic for acute migraine attacks, for the treatment of gout, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and for the relief of acute and/or chronic pain in which there is an inflammatory component. NAPROXEN 275 mg is indicated for: Headache, tooth and tooth pain, muscle pain, lumbago, rheumatic pain, menstrual pain, pain and fever due to flu and colds, fever and pain after a vaccine.

NAPROXEN 275 mg: In cases of hypersensitivity to naproxen or naproxen sodium. Patients who have had an allergic reaction after receiving acetylsalicylic acid or other prostaglandin synthetase inhibitors, such as asthma, rhinitis or urticaria. The earlier occurrence of gastrointestinal bleeding or perforation due to NSAID use. Active ulcer/bleeding, or that has previously occurred repeatedly (two or more clear periods of proven ulcers or bleeding). Ulcers of the gastrointestinal tract, congestive gastritis or atrophic gastritis. Gastrointestinal bleeding or other hemorrhages such as cerebrovascular hemorrhages. Hemorrhagic diathesis or treatment with anticoagulants. Renal insufficiency. Severe heart failure. Third trimester of pregnancy.

NAPROXEN 55 0mg: Hypersensitive to naproxen or naproxen sodium or in whom acetylsalicylic acid (aspirin) or other non-steroidal analgesic/anti-inflammatory agents induce allergic manifestations, such as asthma, nasal polyps, rhinitis and urticaria. Serious anaphylactic-type reactions have been reported in these types of patients. With a history of or suffering from peptic or gastrointestinal ulcers, chronic dyspepsia or active gastrointestinal bleeding or perforations related to previous NSAID treatments With a history of or suffering from recurrent peptic ulcer/bleeding (two or more distinct and proven episodes of ulceration or bleeding) no related to previous treatments with NSAIDs. Less than two years old, since safety has not been evaluated in this age group. With severe heart failure. In the treatment of perioperative pain associated with coronary artery surgery (CABG). With severe liver impairment.

During medication with naproxen (sodium), the following side effects and symptoms were observed, to different degrees and with different frequencies, which did not lead to discontinuation of treatment in all cases. Data resulting from clinical trials and epidemiological data suggest that the use of certain NSAIDs, especially at high doses and long-term use, may be associated with a small increased risk of thrombosis in the arteries (e.g., myocardial infarction or stroke). Edema formation, hypertension and heart failure have been reported in association with NSAID-based treatments. Gastrointestinal: The most frequently observed adverse reactions were gastrointestinal in nature. Peptic ulcers, perforation or gastrointestinal bleeding, sometimes fatal, may occur, especially in elderly patients (see section 4.4). Cases of nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, blood in stool, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported after administration. Gastritis was observed less frequently. The following adverse reactions are classified by frequency range: the most common first, according to the following classification: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), or not known frequency (cannot be estimated from the available data). Gastrointestinal disorders: - Common: peptic ulcers, perforations or blood loss of the gastrointestinal tract, sometimes with fatal results, especially in elderly patients (see section 4.4), nausea, dyspepsia, vomiting, heartburn, stomach pain , flatulence, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4). Uncommon: diarrhea, constipation. Very rarely: colitis, stomatitis. Gastritis has been observed less frequently. Nervous system disorders - Common: headache, drowsiness, dizziness. Very rarely: meningitis-like reactions. Labyrinth and ear disorders – Uncommon: tinnitus, hearing disorders Eye disorders. Uncommon: visual disturbances.

General disorders and administration site conditions – Uncommon: chills, edema (including peripheral edema). Immune system disorders - Uncommon: allergic reactions, (including facial edema and angioedema). Psychiatric disorders - Uncommon: insomnia, excitement. Kidney and urinary disorders. Uncommon: abnormal kidney function. Skin and subcutaneous tissue disorders - Uncommon: rash/pruritus. Very rarely: photosensitivity, alopecia, blistering skin rash including Stevens-Johnson syndrome and toxic epidermal necrolysis. Vascular disorders - Uncommon: hematomas. Blood and lymphatic system disorders – Very rarely: aplastic or hemolytic anemia, thrombocytopenia, granulocytopenia. Cardiac disorders. Very rarely: tachycardia, edema, hypertension and heart failure have been reported in relation to NSAID treatments. Hepatobiliary disorders – Very rarely: jaundice, hepatitis, liver failure. Examinations – Very rarely: increased blood pressure. Respiratory, thoracic and mediastinal disorders – Very rarely: dyspnoea, asthma. As with other NSAIDs, anaphylactic or anaphylactoid type allergic reactions may occur in patients who use this type of medication for the first time or who have previously used it. The characteristic symptoms of an anaphylactic reaction are: severe or sudden hypotension, acceleration or deceleration of heart rate, unusual tiredness or weakness, anxiety, agitation, loss of consciousness, difficulty breathing or swallowing, itching, hives with or without angioedema, redness of the skin, nausea, vomiting, abdominal cramps, diarrhea.

NAPROXEN 275mg: Acetylsalicylic acid: Clinical pharmacodynamic data suggest that concomitant use of naproxen for more than one consecutive day may inhibit the effect of low-dose acetylsalicylic acid on platelet activity and this inhibition may persist for a few days after discontinuation of use. of naproxen. The clinical relevance of this interaction is unknown. Combination with other prostaglandin synthase inhibitors is not recommended due to harms of combination therapy and lack of evidence of any therapeutic benefit. Naproxen may increase the effects of oral anticoagulants and heparin (increased risk of bleeding as a result of inhibition of platelet aggregation). Anticoagulants: NSAIDs can potentiate the effects of anticoagulants such as warfarin (see special warnings and precautions for use section below). The risk of increased effects of sulfonylurea compounds (oral antidiabetics) due to the displacement of plasma proteins must be taken into account. Only exceptionally high doses of naproxen could cause the release and overdose symptoms of thiopental and hydantoin. Concomitant administration of probenecid increases the plasma levels of naproxen and clearly prolongs the plasma half-life. A severe increase in the toxicity of methotrexate has been observed in combination with naproxen. The mechanism of interaction is unclear; may be due to decreased renal clearance of methotrexate. Combined treatment of naproxen with methotrexate should be avoided. As with other similar medicines, it cannot be ruled out that the sodium diuretic effect of furosemide is reduced by naproxen. Reduced renal clearance of lithium following administration of these products has also been reported. Likewise, the antihypertensive effect of propranolol and other beta-blocking medications may be reduced. As may occur with other prostaglandin synthetase inhibitors, naproxen may increase the risk of impaired renal function if administered concomitantly with ACE (Angiotensin Converting Enzyme) inhibitors. Some in vitro studies have shown that naproxen can affect the metabolism of zidovudine (AZT). However, in a brief 4-day study of concomitant use of naproxen and AZT, no significant changes in serum levels of zidovudine and its glucuronide metabolite were observed. The clinical relevance of long-term concomitant use of these products is unknown. Prostaglandin synthetase inhibitors such as naproxen may cause increased cyclosporine nephrotoxicity due to their effects on renal prostaglandins. Corticosteroids: may increase the risk of gastrointestinal ulcer or bleeding (see special warnings and precautions for use section). Platelet aggregation inhibitors and Selective Serotonin Reuptake Inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see special warnings and precautions for use section). Laboratory tests: Before carrying out adrenal cortex functionality tests, it is recommended to first interrupt treatment with naproxen for 48 hours, since interaction with certain reactions to 17-ketosteroids is possible. Interaction with determinations of 5-hydroxyindoleacetic acid in urine is also possible.

NAPROXEN 550 mg: Concomitant administration of sucralfate or cholestyramine may delay the absorption of naproxen, but does not affect the extent of absorption. Antacids have a variable effect on absorption. Other NSAIDs The combination of products containing naproxen and other NSAIDs, including selective cyclooxygenase 2 (COX-2) inhibitors, is not recommended due to the risk of inducing serious adverse events associated with NSAIDs. Protein binding Naproxen sodium has a high rate of binding to plasma albumin. For this reason, naproxen sodium has a theoretical potential for interaction with other drugs that NAPROXEN® PI 9 bind to albumin, for example, warfarin or bishydroxycoumarin, which may be displaced and induce excessively prolonged prothrombin times. Similarly, patients receiving hydantoins, sulfonamides, or sulfonylureas should be monitored for increased effects or toxicity (see Special Warnings and Precautions for Use - Hematology section). Warfarin Concomitant use of NSAIDs and warfarin has been associated with serious, sometimes fatal, bleeding. The exact mechanism of the interaction between NSAIDs and warfarin is unknown, but may involve increased bleeding from NSAID-induced gastrointestinal ulcers or an additive effect between warfarin anticoagulation and NSAID inhibition of platelet function. . NAPROXEN should be used in combination with warfarin only if absolutely necessary and patients taking this drug combination should be closely monitored. Anticoagulant/antiplatelet agents Patients who have coagulation disorders or who are receiving treatment with medications that interfere with hemostasis should be closely observed if naproxen sodium is administered. Patients on complete anticoagulation therapy (e.g., heparin or dicoumarol derivatives) may have an increased risk of bleeding if naproxen sodium is administered concomitantly. Therefore, the benefits must be weighed against these risks. There is an increased risk of gastrointestinal bleeding when antiplatelet agents are used in combination with NSAIDs. Selective Serotonin Reuptake Inhibitors (SSRIs) There is an increased risk of gastrointestinal bleeding when SSRIs (Selective Serotonin Reuptake Inhibitors) are used in combination with NSAIDs. Steroids If the steroid dose is reduced or eliminated during treatment with NAPROXEN, the steroid dose should be reduced slowly and patients should be closely monitored for evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of underlying diseases. Probenecid Probenecid significantly prolongs the half-life of naproxen (from 14 to 37 hours). This is associated with a decrease in conjugated metabolites and an increase in NAPROXEN® PI 10 6-0-desmethyl naproxen. Methotrexate Concomitant administration of naproxen sodium and methotrexate should be undertaken with caution, as naproxen, as well as other NSAIDs, have been reported to reduce the tubular secretion of methotrexate in animal models and therefore possibly increase the toxicity of methotrexate. Beta-blockers Naproxen sodium and other NSAIDs may reduce the antihypertensive effect of beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), and angiotensin receptor blockers (ARBs). Diuretics As with other NSAIDs, naproxen sodium may inhibit the natriuretic effect of furosemide. Lithium It has been reported that inhibition of renal clearance of lithium results in an increase in plasma lithium concentrations. Sodium bicarbonate Sodium bicarbonate may increase the absorption rate of naproxen. Zidovudine It has been shown in in vitro studies that naproxen may interfere with the metabolism of zidovudine, resulting in higher plasma levels of zidovudine. Therefore, to avoid potential side effects associated with increased plasma levels of zidovudine, a dose reduction should be considered. ACE inhibitors Concomitant use of NSAIDs with ACE inhibitors or angiotensin receptor blockers may increase the risk of renal failure, especially in patients with pre-existing poor renal function (see section 4.4. SPECIAL WARNINGS AND PRECAUTIONS FOR USE) . NAPROXEN® PI 11 Combination of the use of ACE inhibitors or angiotensin receptor antagonists, anti-inflammatory drugs and thiazide diuretics The use of an ACE inhibitor drug (ACE inhibitors or angiotensin receptor antagonists), a drug anti-inflammatory (NSAID or COX-2 inhibitor) and a thiazide diuretic at the same time (triple whammy) increases the risk of kidney failure. This includes use in fixed combinations of products containing more than one drug class. The combined use of these drugs should be accompanied by increasing the frequency of serum creatinine monitoring, particularly at the initial stage of the introduction of the combination. The combination of medications from these three classes should be used with caution, particularly in elderly patients or those with preexisting renal impairment.

Precautions and warnings

NAPROXEN 275 mg: By administering the lowest effective dose for the shortest possible time to control symptoms, side effects can be kept to a minimum (see gastrointestinal and cardiovascular risks below).

Use of naproxen with other NSAIDs, including selective cyclooxygenase 2 (COX-2) inhibitors, should be avoided.

Elderly: Elderly people more frequently experience adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal (see section 4.2).

Gastrointestinal bleeding, ulcer and perforation: The risk of gastrointestinal bleeding, ulcer and perforation, which may be fatal, has been reported with the administration of all NSAIDs at any time during treatment, with or without preliminary warning symptoms, or with the occurrence previous serious gastrointestinal adverse reactions. The risk of gastrointestinal bleeding, ulcer and perforation is greater when high doses are used, in patients with a history of ulcer, especially if they were ulcers complicated by bleeding and perforation (see contraindications), and in elderly patients. These patients should begin treatment with the lowest possible dose. It is recommended to evaluate concomitant treatment with protective agents for these patients (for example misoprostol or proton pump inhibitors), which should also be considered in the case of patients requiring low doses of acetylsalicylic acid or other medications that may increase gastrointestinal risk. (see section 4.5).

Special caution is recommended in patients who are receiving concomitant treatment with medications that could increase the risk of ulcer or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, and products that counteract platelet aggregation, such as acetylsalicylic acid.

Patients with a history of gastrointestinal toxicity, and especially the elderly, should be warned to report any unusual abdominal symptoms (mainly bleeding), especially at the start of treatment.

If gastrointestinal bleeding or ulcers occur in patients receiving naproxen, treatment should be discontinued.

NSAIDs should be administered with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease) as they could worsen these pathologies (see section 4.8).

The presence of pain due to gastrointestinal disorders is not an indication to administer naproxen. Cardiovascular and cerebrovascular side effects: Caution is recommended in patients with a history of hypertension and/or heart failure (consult your doctor or pharmacist before treatment). Fluid retention, hypertension, and edema have been reported in association with NSAID therapies.

Data from clinical trials and epidemiological data suggest that the use of some NSAIDs (especially at high doses and long term) may be associated with a slight increased risk of causing thrombosis in the arteries, (such as myocardial infarction or strokes). Although available data suggest that the use of naproxen (1000 mg daily) may be associated with a lower risk, some risk cannot be excluded. The available data on the effects of ingesting naproxen at low doses (275 mg - 825 mg naproxen sodium per day) are insufficient to draw definitive conclusions about the potential risk of thrombosis.

Serious skin reactions, some fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have rarely been reported in association with the administration of NSAIDs (see section 4.8). It would seem that patients are at greater risk of suffering these reactions at the beginning of treatment: The appearance of said adverse reaction would occur in most cases during the first month of treatment. Treatment with naproxen should be discontinued immediately at the first symptoms of skin rash, mucosal lesions or other signs of hypersensitivity.

Anaphylactic reactions generally occur in patients with a known hypersensitivity to naproxen, aspirin, or other prostaglandin synthetase inhibitor agents, but may also occur in patients with no prior exposure or known hypersensitivity to these agents.

Caution is recommended in the elderly and in patients with hepatic impairment. Because naproxen has an anti-inflammatory, analgesic, and antipyretic effect, it can mask certain symptoms of infection. Therefore, caution is recommended when used in patients with infections.

There is some evidence that selective cyclooxygenase/prostaglandin synthesis inhibitory agents reduce fertility in women by having an effect on ovulation. This effect is reversible when treatment is discontinued.

In rare cases, chickenpox can cause a serious infectious complication of the skin and soft tissues. To date, the adjuvant role of NSAIDs in the exacerbation of these infections cannot be ruled out. Therefore, it is recommended to avoid the use of naproxen in case of chickenpox.

Long-term use of any type of headache pain reliever can exacerbate an existing headache. If this situation arises or is suspected of occurring, you should consult your doctor and discontinue treatment.

In patients with frequent or daily headaches, despite (or as a consequence of) the habitual use of headache medications, the diagnosis of headache as a consequence of excessive medication use should be considered. NAPROXEN 550 mg: Thrombotic cardiovascular events Observational studies have indicated that non-selective NSAIDs may be associated with an increased risk of serious cardiovascular events, including myocardial infarction and stroke, which may increase with dose or duration of use. . Patients with cardiovascular disease, a history of atherosclerotic cardiovascular disease, or cardiovascular risk factors may also be at increased risk. To minimize the potential risk of an adverse cardiovascular event in patients taking NSAIDs, especially those with cardiovascular risk factors, the lowest effective dose should be used for the shortest duration possible (see Dosage and Administration). Clinicians and patients should remain alert to the occurrence of such CV events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of severe CV toxicity and the measures to be taken if they occur. There is no consistent evidence to suggest that concurrent use of aspirin mitigates the potential increased risk of serious thrombotic cardiovascular events associated with NSAID use. Data from clinical and epidemiological trials suggest that the use of coxibs and some NSAIDs (particularly at high doses and long-term treatments) may be associated with a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction and stroke ).

Hypertension: NSAIDs may cause the development of hypertension or the exacerbation of preexisting hypertension and patients taking antihypertensive agents with NSAIDs may have a poor antihypertensive response. Precautions are recommended when prescribing NSAIDs to patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID treatment and at regular intervals thereafter. Heart failure: Fluid retention and edema have been observed in some patients taking NSAIDs, therefore, caution is recommended in patients with fluid retention or heart failure.

Gastrointestinal: All NSAIDs can cause gastrointestinal upset and, rarely, potentially fatal gastrointestinal effects such as ulcers, irritation, bleeding and perforation, which may increase with dose or duration of use, but can occur at any time, without warning symptoms. Upper gastrointestinal ulcers, heavy bleeding, or perforations caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months and in about 2 to 4% of patients treated for one year. These trends continue with prolonged use, increasing the likelihood of developing a serious gastrointestinal event at some point during the course of treatment. However, not even short-term treatments are risk-free. Precautions are recommended in patients with risk factors for gastrointestinal events who may be at increased risk of developing serious gastrointestinal events, such as elderly patients, debilitated patients, and those with a history of serious gastrointestinal events, smoking, and alcoholism. NSAIDs should be administered carefully to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease), as their condition may be exacerbated. Patients with a history of gastrointestinal toxicity, particularly in elderly patients, should report any unusual symptoms (especially gastrointestinal bleeding), particularly in the initial phases of treatment. When gastrointestinal bleeding or ulceration occurs in patients receiving NSAIDs, treatment should be discontinued immediately. Clinicians should warn patients about the signs and symptoms of severe gastrointestinal toxicity. Studies conducted so far have not identified any subset of patients who are not at risk of developing peptic ulcer or bleeding. However, elderly patients have a higher frequency of adverse effects to NSAIDs, especially bleeding and gastrointestinal perforation, which can be fatal. Debilitated patients do not seem to tolerate ulceration or bleeding as well as others. The majority of fatal gastrointestinal events associated with NSAIDs occurred in elderly and/or debilitated patients. In patients with active peptic ulcer or inflammatory disease of the gastrointestinal tract and active rheumatoid arthritis, an attempt should be made to treat the arthritis with a non-ulcerogenic medication. Caution is recommended in patients receiving concomitant medications, which could increase the risk of ulceration or bleeding (see section Interactions with other medications and other forms of interaction). Concomitant use of aspirin and NSAIDs also increases the risk of serious gastrointestinal effects. Patients with risk factors should begin treatment with the lowest available dose.

Hematology: Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be taken into account when determining bleeding times (see Special Warnings and Precautions for Use – Effects on Laboratory Tests section). Patients who have coagulation disorders or who are receiving treatment with medications that interfere with hemostasis should be closely observed if NAPROXEN is administered. Patients at high risk of bleeding and those on treatment with anticoagulants (e.g., heparin or dicoumarol derivatives) may have an increased risk of bleeding if NAPROXEN is administered concomitantly. Therefore, the benefits of prescribing NAPROXEN must be weighed against these risks. Patients with initial hemoglobin values of 10 grams or less, and those who will receive long-term treatment, should have their hemoglobin values determined frequently. Patients treated with other medications such as hydantoins, sulfonamides, sulfonylureas or methotrexate should be monitored to determine if there is an increase in effects or toxicity (see section Interactions with other medications and other forms of interaction).

Serious skin reactions: In very rare cases, NSAIDs may cause serious skin adverse events, such as exfoliative dermatitis, Stevens-Johnson syndrome (SJS), Eosinophilia drug reaction with systemic symptoms (DRESS) and toxic epidermal necrolysis (TEN), which can be fatal and can occur without warning. These serious adverse events are idiosyncratic and are independent of dose or duration of use. Patients should be counseled to recognize the signs and symptoms of serious skin reactions and to consult their physician after the first appearance of a rash or any other sign of hypersensitivity. DRESS has been reported in patients taking NSAIDs. Some of these events have been fatal or life-threatening. DRESS typically, but not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis. Sometimes the symptoms of DRESS can resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in presentation, other organ systems not mentioned here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even if the rash is not evident. If such signs or symptoms are present, discontinue the NSAID and evaluate the patient immediately.

Anaphylactic reactions: Hypersensitivity reactions may occur in susceptible individuals. Anaphylactic (anaphylactoid) reactions may occur in patients with and without a history of hypersensitivity or exposure to aspirin, other NSAIDs, or naproxen-containing products. These may also occur in individuals with a history of angioedema, bronchospastic reactivity (e.g., asthma), rhinitis, and nasal polyps. Anaphylactoid reactions, such as anaphylaxis, can be fatal. Bronchospasm may be triggered in patients who suffer from or have a history of asthma, allergic disease, or sensitivity to aspirin.

Infection: The antipyretic, anti-inflammatory, and analgesic effects of naproxen may mask the usual signs or symptoms of infection.

Ocular events: Ophthalmological adverse effects have been observed with the use of NSAIDs. In rare cases, adverse ocular disorders such as papillitis, retrobulbar optic neuritis, and papilledema have been reported in patients using NSAIDs, including NAPROXEN; although the cause and effect relationship cannot be established. Accordingly, patients who develop visual disturbances during treatment with NAPROXEN should undergo an ophthalmological examination.

Sodium: One 550 mg NAPROXEN tablet contains approximately 50 mg of sodium. This should be taken into account in patients whose total sodium intake must be considerably restricted.

Fluid Retention and Edema: Peripheral edema has been observed in some patients taking NAPROXEN and other NSAIDs. Although sodium retention has not been reported in metabolic studies, it is possible that patients with compromised cardiac function may be at increased risk when taking naproxen. For this reason, naproxen should be administered with caution to patients with fluid retention, hypertension, or heart failure.

Use in liver failure: As with other NSAIDs, an increase in one or more liver functions in laboratory tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may resolve as treatment progresses. The ALT test is probably the most sensitive indicator of liver failure. Significant increases (three times the upper limit of normal) in ALT or AST were observed in less than 1% of patients in controlled clinical studies. Physicians and patients should remain alert regarding hepatotoxicity. Patients should be informed about the signs and/or symptoms of hepatotoxicity. A patient with symptoms and/or signs suggestive of liver failure (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant abdominal tenderness, and flu-like symptoms) or for whom a abnormal liver test result, should be evaluated for evidence of the development of further serious liver reactions during treatment with NAPROXEN. Liver abnormalities may result from hypersensitivity or direct toxicity. Serious hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with naproxen sodium, as well as with other NSAIDs. Cross-reactivity has been reported. Although these reactions are rare, if abnormal liver test results persist or worsen, if clinical signs and symptoms are consistent with the development of liver disease, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.) , the use of NAPROXEN should be discontinued.

Chronic alcoholic liver disease and potentially other forms of cirrhosis reduce the total plasma concentration of naproxen. However, the plasma concentration of non-protein-bound naproxen increases. The implication of this finding on naproxen dosing is unknown. In patients with hepatic impairment, the lowest effective dose is recommended.

Use in renal failure: There are reports of poor renal function, renal failure, acute interstitial nephritis, hematuria, proteinuria, renal papillary necrosis and, occasionally, nephritic syndrome associated with NAPROXEN. NAPROXEN should not be administered to patients with creatinine clearance less than 30 mL/minute, since accumulation of naproxen metabolites has been seen in these patients. As with other NSAIDs, NAPROXEN should be used with caution in patients with renal impairment or a history of kidney disease, as naproxen is an inhibitor of prostaglandin synthesis. Caution should be used in patients with conditions that lead to reduced blood volume and/or renal blood flow, as prostaglandins play a supportive role in maintaining renal perfusion. In these patients, administration of NAPROXEN or other NSAIDs may cause a dose-dependent reduction in prostaglandin formation and may accelerate acute renal decompensation or renal failure. Patients at highest risk are those with renal failure, hypovolemia, heart failure, liver failure, salt depletion, those taking diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and elderly patients. . Generally, after discontinuation of treatment with NAPROXEN, recovery to the state prior to treatment is observed. However, serious adverse events may persist. NAPROXEN should be used with great caution in such patients, monitoring of serum creatinine and/or creatinine clearance is recommended and they should be adequately hydrated. A reduction in the daily dose should be considered to avoid the possibility of excessive accumulation of naproxen metabolites in these patients. Hemodialysis does not decrease the plasma concentration of naproxen due to its high degree of protein binding.

Use in older adults: The lowest effective dose is recommended in elderly patients. Studies indicate that, although the total plasma concentration of naproxen is unchanged, the fraction of naproxen unbound to plasma is increased in older adults. Pediatric use: NAPROXEN is not recommended in children under 5 years of age, as the safety and efficacy profile in this population has not been established.

Effects on laboratory tests: Naproxen sodium decreases platelet aggregation and prolongs bleeding time. This effect must be taken into account when determining bleeding times. NAPROXEN may artificially interfere with some ketogenic steroid tests 17 and may interfere with some urinary 5-hydroxy-indoleacetic acid (5HIAA) tests. Measurements of 17-hydroxycorticosteroids (Porter/Silber test) do not appear to be altered. Naproxen sodium therapy should be temporarily discontinued for at least 72 hours before assessing adrenal function.

Pregnancy and lactation

Pregnancy: Inhibition of prostaglandin synthesis may negatively affect pregnancy and/or development of the embryo/fetus. Data from epidemiological studies suggest an increased risk of abortion and cardiac malformations and gastroschisis after the 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%. It is assumed that the risk increases with the dose and duration of treatment. Administration of prostaglandin synthesis inhibitors in animals resulted in increased pre- and postimplantation loss and embryonic and fetal lethality. In addition, an increased incidence of various malformations, including cardiovascular ones, has been observed in animals that received a prostaglandin synthesis inhibitor during the period of organogenesis. During the first and second trimester of pregnancy, naproxen should not be administered unless it is considered strictly necessary. If a woman trying to become pregnant or during the first and second trimester of pregnancy uses naproxen, the dose and duration of treatment should be reduced as much as possible. During the third trimester of gestation, all prostaglandin synthesis inhibitors can expose the fetus to: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension), renal dysfunction, which can progress to renal failure with oligo- hydroamniosis. In the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the mother and neonate to: possible prolongation of bleeding time, due to an antiplatelet-type effect that can occur even at very low doses, inhibition of uterine contractions, which can cause delay or prolongation of labor. Consequently, naproxen is contraindicated during the third trimester of pregnancy.

Breastfeeding: Naproxen is found in the milk of lactating women. Therefore, lactating women should avoid its use.

Fertility: There is some evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis may affect female fertility through their effect on ovulation. This effect is reversible when treatment is discontinued.

Recommended dose: Adults:

• Naproxen sodium 275 mg coated tablet - 1 tablet every 8 – 12 hours.

• Naproxen sodium 550 mg coated tablet 1 tablet every 24 hours. The dosage range for naproxen sodium is 550 mg to 1,100 mg daily, divided into two doses. The initial dose should not be less than 550 mg daily. The dose can be gradually increased up to 1100 mg daily, depending on the patient's needs. Efficacy, risk factors and the need to continue treatment should be reviewed regularly in patients on long-term treatment.

Considerations: NAPROXEN tablets 275 mg: Children from 12 years of age with a body weight greater than 50 kg: Maximum up to 1 tablet at a time. Do not take more than 2 tablets per day (for 24 hours) with a dosage interval of at least 12 hours. Do not use in children with a body weight less than 50 kg. Adults over 65 years of age: Do not exceed the dose of 2 tablets per day.

Overdose: Overdose symptoms may include nausea, vomiting, abdominal pain, drowsiness, dizziness, disorientation, diarrhea, stomach bleeding, hypernatremia, seizures (rare), and metabolic acidosis. Treatment consists, in the first instance, of preventing absorption through vomiting; Then the patient should drink water or lemonade with activated charcoal (absorbency) and sodium sulfate (laxative effect). If large quantities have been ingested, gastric lavage is indicated, omitting activated charcoal and sodium sulfate. The acid-base balance must be carefully monitored to avoid the possible development of severe metabolic acidosis. The balance of moisture and electrolytes must be maintained. Subsequent treatment is supportive and symptomatic. Hemodialysis does not decrease plasma naproxen levels due to high protein binding.

NAPROXEN® 550 mg blister of 4 tablets in a box of 20 and 120. NAPROXEN® 275 mg in a blister of 4 tablets in a box of 8.