Naprosyn (Naproxen)




Anti-inflammatory – Analgesic

Action And Clinical Pharmacology: Naproxen has demonstrated anti-inflammatory, analgesic and antipyretic properties in classical animal test systems. In patients with rheumatoid arthritis, the anti-inflammatory action has been shown by a reduction in joint swelling, pain, and duration of morning stiffness, and by enhanced grip strength and increased mobility. It exhibits an anti-inflammatory effect even in adrenalectomized animals, and therefore its action is not mediated through the pituitary-adrenal axis. It is not a corticosteroid.

During clinical trials, naproxen has been found to be less likely to cause gastrointestinal bleeding in doses usually used than is ASA.

Human clinical trials have shown the clinical activity of 500 mg of naproxen daily to be similar to that of 3.6 g of ASA daily.

From clinical trials, it appears that naproxen enteric-coated tablets have reduced potential for severe complaints when compared to standard naproxen.

Naproxen is rapidly and completely absorbed from the gastrointestinal tract. After oral administration of naproxen, peak plasma levels of naproxen anion are attained in 2 to 4 hours, with steady-state conditions normally achieved after 4 to 5 doses. Plasma naproxen levels and areas under plasma concentration vs. time curves increased linearly with dose increments up to 500 mg twice a day, but larger doses resulted in a plateau effect. The time to reach peak plasma concentration following rectal administration of naproxen 500 mg suppository relative to the oral tablet was not significantly different. 0 to 24 hour areas under the plasma concentration versus time curves for the 500 mg dose of either naproxen tablets or suppository were similar. The mean biological half-life of the anion in humans is approximately 13 hours, and at therapeutic levels it is greater than 99% albumin bound. Approximately 95% of the dose is excreted in the urine, primarily as naproxen, 6-0-desmethyl naproxen or their conjugates. The rate of excretion has been found to coincide closely with the rate of drug disappearance from the plasma. The drug does not induce metabolizing enzymes.

In children with rheumatic diseases aged between 5 to 16 years, naproxen reached peak plasma levels 2 to 4 hours following oral dosing and the mean plasma half-life was 11.5 to 14.1 hours. Naproxen suspension was found to have similar bioavailability to the naproxen tablets in 2 single dose studies done in 24 healthy male volunteers. No clinically significant differences in tolerance were reported between the 2 dosage forms.

When naproxen is administered in the sustained release form (Naprosyn SR), the peak plasma levels are delayed and the maximum plasma concentrations are reduced compared to those seen with standard release formulations of naproxen. The minimum plasma concentrations, at steady state, are equivalent between naproxen sustained release given once a day and the corresponding standard dosage given twice a day. The peak to trough plasma concentration ratio of 2.2 and 2.6 observed with the standard tablet formulation (375 mg b.i.d. and 500 mg b.i.d. respectively) is reduced to 1.6 and 1.8 with 750 and 1 000 mg sustained release tablets respectively, resulting in smaller fluctuations in plasma concentrations of naproxen with the sustained release tablets. The average Tmax of naproxen in subjects receiving the 1 000 mg sustained release tablet immediately after a high fat meal did not differ significantly when compared to the fasting state (7.7 hours postprandial; 9.7 hours fasting). The average Cmax increased significantly from 63.1 g/mL (fasting) to 86.1 g/mL (postprandial). This increase in Cmax was still lower than that observed with the 1000 mg dose of standard naproxen tablets. Based upon the 95% confidence interval, the AUC’s were equivalent when the SR tablet was administered under fasting and nonfasting conditions. A 28 day study of chromium-51-labeled red blood cell loss in feces was conducted with the 750 mg sustained release naproxen tablets in 20 patients. There was no statistically significant differences in red blood cell loss between patients 60 years of age or younger and those over 60.

Naproxen enteric-coated tablets are designed to be dispersed and dissolved in the small bowel rather than the stomach, so the absorption is delayed until the stomach is emptied. Naproxen enteric-coated tablets were bioequivalent to the standard 375 and 500 mg tablets, except for a substantially increased time to peak plasma concentration (Tmax). The average maximum plasma concentration (Cmax) following the 375 mg, 2´250 mg and 500 mg enteric-coated tablets were 47.9, 58.2 and 60.7 g/mL, while the Cmax following the 375 and 500 mg standard immediate release tablets were 46.6 and 63.1 g/mL, respectively. The Tmax’s were 4.5, 4.2 and 4.2 hours for the respective enteric-coated formulations as compared to 2.3 and 2.6 hours after standard naproxen tablets. At steady state (multiple dosing) naproxen enteric coated and the standard naproxen were equivalent to each other with respect to Cmax, Cave, Cmax/Cave, 0 to 12 hours. AUC and half-life. In addition, fluctuation in plasma levels about Cave were considerably less with naproxen enteric-coated tablets as compared to the standard naproxen (49.3 vs 85.3%). Administration of 500 mg enteric-coated naproxen tablets with food and antacid did not alter the extent of absorption of naproxen as compared to the fasting condition. However, antacid treatment resulted in a higher Cmax (70.7 vs 58.5 g/mL) and earlier Tmax (5.2 vs 8.7 hours) in comparison to the fasting condition. Relative to the fasting state, the average Tmax was delayed following a high fat meal (5.6 to 8.7 hours fasting, 9.2 to 10.8 hours post-prandial) while the average Cmax and AUC were bioequivalent.

Indications And Clinical Uses: Treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and juvenile rheumatoid arthritis.

Naproxen is also indicated for the relief of minor aches and pains in muscles, bones and joints, mild to moderate pain accompanied by inflammation in musculoskeletal injuries (sprains and strains) and primary dysmenorrhea.

Modified release formulations of naproxen (i.e., enteric-coated and sustained release) are not recommended for initial treatment of acute pain because the absorption of naproxen is delayed.

Contra-Indications: In patients with active peptic ulcers or active inflammatory diseases of the gastrointestinal tract. Known hypersensitivity to naproxen or to naproxen sodium. Since cross sensitivity has been demonstrated, do not give naproxen to patients in whom ASA or other nonsteroidal anti-inflammatory drugs induce the syndrome of asthma, rhinitis or urticaria. Sometimes severe and occasionally fatal anaphylactoid reactions have occurred in such individuals.

Naproxen suppositories are contraindicated in children under 12 years of age. The suppositories are also contraindicated in patients with any inflammatory lesions of rectum or anus and in patients with recent history of rectal or anal bleeding.

Manufacturers’ Warnings In Clinical States: Peptic ulceration, perforation and gastrointestinal bleeding, sometimes severe and occasionally fatal, have been reported during therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) including naproxen. Naproxen should be given under close supervision to patients prone to gastrointestinal tract irritation; particularly those with a history of peptic ulcer, diverticulosis, or other inflammatory disease of the gastrointestinal tract. In these cases the physician must weigh the benefits of treatment against the possible hazards.

Patients taking any NSAID including this drug should be instructed to contact a physician immediately if they experience symptoms or signs suggestive of peptic ulceration or gastrointestinal bleeding. These reactions can occur without warning symptoms or signs and at any time during the treatment.

Elderly, frail and debilitated patients appear to be at higher risk from a variety of adverse reactions from NSAIDs. For such patients, consideration should be given to a starting dose lower than usual, with individual adjustment when necessary and under close supervision. See Precautions for further advice.

Pregnancy and Lactation: Naproxen’s safety in pregnancy and lactation has not been established, and its use is therefore not recommended. Reproduction studies have been performed in rats, rabbits and mice. In rats, pregnancy was prolonged when naproxen was given before the onset of labour, and when given after the delivery process had begun, labour was protracted. Similar results have been found with other nonsteroidal anti-inflammatory agents, and the evidence suggests that this may be due to decreased uterine contractility resulting from the inhibition of prostaglandin synthesis. Moreover, because of the known effect of drugs of this class on the human fetal cardiovascular system (closure of ductus arteriosus), use during late pregnancy should be avoided. Naproxen readily crosses the placental barrier. It has also been found in the milk of lactating women at a concentration approximately 1% of that found in the plasma.

Precautions: Naproxen should not be used concomitantly with the related drug naproxen sodium since they both circulate in plasma as the naproxen anion.

Gastrointestinal: If peptic ulceration is suspected or confirmed, or gastrointestinal bleeding or perforation occurs naproxen should be discontinued, and appropriate treatment instituted and patient closely monitored.

There is no definitive evidence that the concomitant administration of a H2-receptor antagonist and/or antacids will either prevent the occurrence of gastrointestinal side effects or allow continuation of naproxen therapy when and if these adverse reactions appear.

Naproxen suppositories should be given under close supervision in patients with any rectal or anal pathology (see Contraindications).

Renal Effects: As with other nonsteroidal anti-inflammatory drugs, long-term administration of naproxen to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with hematuria, proteinuria, and occasionally nephrotic syndrome.

A second form of renal toxicity has been seen in patients with prerenal conditions leading to the reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, extracellular volume depletion, sodium restrictions, heart failure, liver dysfunction, those taking diuretics, and the elderly. Assessment of renal function in these patients before and during therapy with naproxen is recommended. Discontinuation of nonsteroidal anti-inflammatory therapy is typically followed by recovery to the pretreatment state.

Naproxen and its metabolites are eliminated primarily by the kidneys, therefore, the drug should be used with great caution in patients with significantly impaired renal function and the monitoring of serum creatinine and/or creatinine clearance is advised in these patients. A reduction in daily dosage should be anticipated to avoid the possibility of excessive drug accumulation.

Naproxen should not be used chronically in patients having baseline creatinine clearance less than 20 mL/min. During long-term therapy, kidney function should be monitored periodically.

Peripheral edema has been observed in some patients receiving naproxen. Therefore, as with many other NSAIDs, the possibility of precipitating congestive heart failure in elderly patients or those with compromised cardiac function should be borne in mind. Although sodium retention has not been reported in metabolic studies, the drug should be used with caution in patients with fluid retention, hypertension or heart failure.

Naproxen formulated as a suspension (25 mg/mL) contains sodium chloride (20 mg/mL). This should be considered in patients whose overall intake of sodium must be restricted.

With NSAID treatment, there is a potential risk of hyperkalemia particularly in patients with conditions such as diabetes mellitus or renal failure; elderly patients; and patients receiving concomitant therapy and other beta adrenergic blockers, angiotensin converting enzyme inhibitors or some diuretics. Serum electrolytes should be monitored periodically during long-term therapy, especially those patients at risk.

Anaphylactoid reactions to naproxen or naproxen sodium, whether of the true allergic type or the pharmacologic idiosyncratic (e.g., ASA syndrome) type, usually but not always occur in patients with a known history of such reactions. Therefore, careful questioning of patients for such things as asthma, nasal polyps, urticaria, and hypotension associated to nonsteroidal anti-inflammatory drugs before starting therapy is important. In addition, if such symptoms occur during therapy, treatment should be discontinued.

Geriatrics: One study indicated that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. The implication of this finding for naproxen dosing is unknown, but caution is advised when high doses are required. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients with Impaired Liver Function: As with other nonsteroidal anti-inflammatory drugs, borderline elevations of one or more liver tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of more severe hepatic reaction while on therapy with this drug. Severe hepatic reactions including jaundice and cases of fatal hepatitis have been reported with this drug as with other nonsteroidal anti-inflammatory drugs. Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc.), this drug should be discontinued. During long-term therapy, liver function tests should be monitored periodically. If this drug is to be used in the presence of impaired liver function, it must be done under strict observation.

Chronic alcoholic liver disease and probably also other forms of cirrhosis reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. The implication of this finding for naproxen dosing is unknown, but caution is advised when high doses are required. It is prudent to use the lowest effective dose.

Hematology: Drugs inhibiting prostaglandin biosynthesis do interfere with platelet function to some degree; therefore, patients who may be adversely affected by such an action should be carefully observed when naproxen is administered. Blood dyscrasias associated with the use of NSAIDs are rare but could be with severe consequences.

Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined frequently.

Infection: The anti-inflammatory, antipyretic and analgesic effects of naproxen may mask the usual signs of infection and the physician should be alert for development of infection in patients receiving naproxen.

Ophthalmology: Because of adverse eye findings in animal studies with drugs of this class it is recommended that ophthalmic studies be carried out within a reasonable period of time after starting therapy and at periodic intervals thereafter if the drug is to be used for an extended period of time.

Occupational Hazards: Caution should be exercised by patients whose activities require alertness if they experience drowsiness, dizziness, vertigo or depression during therapy with the drug.

Drug Interactions: Naproxen may displace from their binding sites other drugs which are also albumin-bound and may lead to drug interactions. For example, in a patient receiving bishydroxycoumarin or warfarin, the addition of naproxen to therapy could prolong the prothrombin time. Patients receiving both drugs should be under careful observation. Similarly, patients receiving naproxen and a hydantoin, sulfonamide or sulfonylurea should be observed for signs of toxicity.

The natriuretic effect of furosemide has been reported to be inhibited by some drugs of this class. Inhibition of renal lithium clearance leading to increases in plasma lithium concentrations have also been reported.

Naproxen and other nonsteroidal anti-inflammatory drugs can reduce the anti-hypertensive effect of propranolol and other beta blockers as well as other antihypertensive agents.

The rate of absorption of naproxen is altered by concomitant administration of antacids but is not adversely influenced by the presence of food. Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.

Caution is advised in the concomitant administration of naproxen and methotrexate since naproxen and other nonsteroidal anti-inflammatory agents have been reported to reduce the tubular secretion of methotrexate in an animal model, thereby possibly enhancing its toxicity.

Laboratory Tests: Naproxen decreases platelet aggregation and prolongs bleeding time. This effect should be kept in mind when bleeding times are determined. Other laboratory tests in patients on naproxen therapy have shown sporadic abnormalities but no definite trend was seen that would indicate potential toxicity.

The administration of naproxen may result in increased urinary values for 17-ketogenic steroids because of an interaction between the drug and/or its metabolites with m-dinitrobenzene used in this assay. Although 17-hydroxy corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that Naprosyn therapy be temporarily discontinued 48 hours before adrenal function tests are performed.

The drug may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).

Adverse Reactions: The most common adverse reactions encountered with NSAIDs are gastrointestinal, of which peptic ulcer, with or without bleeding, is the most severe. Fatalities have occurred on occasion, particularly in the elderly.

A clinical study found gastrointestinal reactions to be more frequent and more severe in rheumatoid arthritis patients taking daily doses of 1 500 mg naproxen compared to those taking 750 mg naproxen.

Adverse reactions reported in controlled clinical trials in 960 patients treated for rheumatoid arthritis or osteoarthritis with the naproxen standard tablets are listed below. (1) Denotes incidence of reported reaction between 3% and 9%. (2) Denotes incidence of reported reactions between 1% and 3%. Reactions occurring in less than 1% of the patients are unmarked.

Gastrointestinal: heartburn (1), constipation (1), abdominal pain (1), nausea (1), diarrhea (2), dyspepsia (2), stomatitis (2), diverticulitis (2), gastrointestinal bleeding, hematemesis, melena, peptic ulceration with or without bleeding and/or perforation, vomiting, ulcerative stomatitis.

In addition to the above, rectal burning (1) has been reported occasionally and rectal bleeding rarely, with the use of naproxen suppositories.

CNS: headache (1), dizziness (1), drowsiness (1), lightheadedness (2), vertigo (2), depression (2) and fatigue (2). Occasionally patients had to discontinue treatment because of the severity of some of these complaints (headache and dizziness). Other adverse effects were inability to concentrate, malaise, myalgia, insomnia and cognitive dysfunction (i.e. decreased attention span, loss of short-term memory, difficulty with calculations).

Skin: pruritus (1), ecchymoses (1), skin eruptions (1), sweating (2), purpura (2), alopecia, urticaria, skin rash, erythema multiforme, Stevens-Johnson syndrome, epidermal necrolysis, photosensitive dermatitis, exfoliative dermatitis and erythema nodosum.

Hepatic: abnormal liver function tests, jaundice, cholestasis and hepatitis.

Cardiovascular: dyspnea (1), peripheral edema (1), palpitations (2), congestive heart failure and vasculitis.

Renal: glomerular nephritis, hematuria, interstitial nephritis, nephrotic syndrome, nephropathy and tubular necrosis.

Hematologic: eosinophilia, granulocytopenia, leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia and hemolytic anemia.

Special Senses: tinnitus (1), hearing disturbances (2), hearing impairment and visual disturbances.

Others: thirst (2), muscle weakness, anaphylactoid reactions, menstrual disorders, pyrexia (chills and fever), angioneurotic edema, hyperglycemia, hypoglycemia, hematuria and eosinophilic pneumonitis.

The adverse reactions reported on both the standard tablets and the sustained release tablets were similar.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Significant overdosage may be characterized by drowsiness, heartburn, indigestion, nausea or vomiting. No evidence of toxicity or late sequelae have been reported 5 to 15 months after ingestion for 3 to 7 days of doses up to 3 000 mg of naproxen. One patient ingested a single dose of 25 g of naproxen and experienced mild nausea and indigestion. It is not known what dose of the drug would be life threatening. The oral LD50 of the drug is 543 mg/kg in rats, 1 234 mg/kg in mice, 4 110 mg/kg in hamsters and greater than 1 000 mg/kg in dogs.

Should the patient ingest a large number of naproxen tablets, the stomach may be emptied and usual supportive measures employed. Animal studies suggest that the prompt administration of 5 g of activated charcoal would tend to reduce markedly the absorption of the drug. In dogs 0.5 g/kg of charcoal was effective in reducing the plasma levels of naproxen. Hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding. However, hemodialysis may still be appropriate in the management of renal failure.

Dosage And Administration: Oral: Adults: The usual total daily dosage for osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis is 500 mg (20 mL) a day in divided doses. It may be increased gradually to 750 or 1 000 mg or decreased, depending on the patient’s response.

Studies have not shown any clinically significant benefit in using doses higher than 1 000 mg/day. In patients who tolerate lower doses of naproxen well and who exhibit only a partial response to 1 000 mg/day, the dose may be increased to 1 500 mg/day for limited periods. Experience with 1 500 mg/day naproxen is limited to using the standard tablets. Naproxen tablets should be swallowed with food or milk.

When treating such patients with naproxen 1 500 mg/day, the physician should observe sufficient increased clinical benefit to offset the potential increased risk (see Adverse Effects).

In addition, patients on 1 500 mg/day need to be followed closely for the development of any adverse events.

During long-term administration the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower dose may suffice for long-term administration.

Patients with rheumatoid arthritis or osteoarthritis maintained on a dose of 750 or 1 000 mg/day in divided doses can be switched to a once daily dose of naproxen sustained release 750 mg or 1 000 mg respectively. The single daily dose of naproxen sustained release should not be exceeded and can be administered in the morning or evening. Naproxen sustained release tablets should be swallowed whole.

Rectal: Adults: 500 mg suppositories can replace one of the oral doses in patients receiving 1 000 mg/day. Suppositories are not indicated in children under 12 years of age.

Naprosyn E and Naprosyn SR have not been studied in subjects under the age of 18.

Juvenile Rheumatoid Arthritis: The recommended total daily dose is approximately 10 mg/kg in 2 divided doses at 12 hour intervals.

Administration of naproxen more frequently than twice daily is not necessary. Clinical experience has shown that steroids can often be decreased, and sometimes eliminated, when naproxen is administered. Bottles of naproxen suspension should be shaken gently before use.

Analgesia/Musculoskeletal Injuries: Oral: The recommended dose is 750 mg/day divided into either 2 or 3 doses/day. This may be increased to 1 000 mg/day if needed. The lowest effective dose should be used.

Modified release formulations of naproxen (i.e., enteric-coated and sustained release) are not recommended for initial treatment of acute pain because the absorption of naproxen is delayed.

Dysmenorrhea: Oral: The recommended starting dose is two 250 mg tablets, followed by one 250 mg tablet every 6 to 8 hours, as required. The total daily dose should not exceed 5 tablets (1 250 mg). Alternatively, one 500 mg tablet given twice daily may be used.

Modified release formulations of naproxen (i.e., enteric-coated and sustained release) are not recommended for initial treatment of acute pain because the absorption of naproxen is delayed.

Availability And Storage: Suppositories: Each white, opaque suppository contains: naproxen 500 mg. Nonmedicinal ingredients: witepsol H15. Boxes of 30, packed in polyethylene lined white polyvinyl shells in perforated strips of 5 suppositories. Store at room temperature.

Suspension: Each 5 mL contains: naproxen 125 mg. Nonmedicinal ingredients: FD&C Yellow #6, fumaric acid, imitation orange flavor, imitation pineapple flavor, magnesium aluminum silicate, methylparaben, sodium chloride, sorbitol solution and sucrose. Lactose-free. Bottles of 474 mL. Store at room temperature not exceeding 25°C, with protection from light.

Tablets: 250 mg: Each round, yellow tablet, engraved NPR LE 250 on one side and single score on the other, contains: naproxen 250 mg. Nonmedicinal ingredients: croscarmellose sodium, iron oxide, magnesium stearate and povidone. Tartrazine-free. Bottles of 100. Store at room temperature.

375 mg: Each pink, oval tablet, engraved NPR LE 375 on one side, contains: naproxen 375 mg. Nonmedicinal ingredients: croscarmellose sodium, iron oxide, magnesium stearate and povidone. Tartrazine-free. Bottles of 100. Store at room temperature.

500 mg: Each yellow, scored, capsule-shaped tablet, engraved NPR LE 500, contains: naproxen 500 mg. Nonmedicinal ingredients: croscarmellose sodium, iron oxide, magnesium stearate and povidone. Tartrazine-free. Bottles of 50 and 500. Store at room temperature.

Enteric-coated Tablets: 250 mg: Each round, biconvex, enteric-coated tablet, with one side printed in black NPR EC 250, contains: naproxen 250 mg. Nonmedicinal ingredients: croscarmellose sodium, ferric iron, magnesium stearate, methacrylic acid copolymer, povidone, sodium hydroxide, talc and triethyl citrate. Bottles of 100. Store at room temperature.

375 mg: Each oval-shaped, enteric-coated tablet, with one side printed in black NPR EC 375, contains: naproxen 375 mg. Nonmedicinal ingredients: croscarmellose sodium, ferric iron, magnesium stearate, methacrylic acid copolymer, povidone, sodium hydroxide, talc and triethyl citrate. Bottles of 100 and 500. Store at room temperature.

500 mg: Each oblong-shaped, enteric-coated tablet, with one side printed in black NPR EC 500, contains: naproxen 500 mg. Nonmedicinal ingredients: croscarmellose sodium, ferric iron, magnesium stearate, methacrylic acid copolymer, povidone, sodium hydroxide, talc and triethyl citrate. Bottles of 100 and 500. Store at room temperature.

Sustained-release Tablets: Each peach, oval-shaped tablet, NPR SR 750 engraved on one side, contains: naproxen 750 mg. Nonmedicinal ingredients: croscarmellose sodium, FD&C Yellow #6, ferric iron, hydroxypropyl methylcellulose, magnesium stearate, methacrylic acid copolymer, povidone, sodium hydroxide, talc and triethyl citrate. Lactose- and tartrazine-free. Bottles of 100 and 500. Store at room temperature.

With the exception of the suspension which contains sorbitol, all preparations are bisulfite-, erythrosine-, gluten-, sorbitol- and xylitol-free.

NAPROSYN® Roche Naproxen Anti-inflammatory – Analgesic

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