Naprosyn

Tell your doctor if you are breastfeeding or plan to breastfeed. 

You should not take Naprosyn if you are breastfeeding. It may be excreted in your breast milk and may harm your nursing child.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Belching
• bruising
• difficult or labored breathing
• feeling of indigestion
• headache
• itching skin
• large, flat, blue, or purplish patches in the skin
• pain in the chest below the breastbone
• skin eruptions
• stomach pain
• swelling
• tightness in the chest

• Bloating
• bloody or black, tarry stools
• blurred or loss of vision
• burning upper abdominal or stomach pain
• cloudy urine
• constipation
• decrease in urine output or decrease in urine-concentrating ability
• disturbed color perception
• double vision
• fast, irregular, pounding, or racing heartbeat or pulse
• halos around lights
• indigestion
• loss of appetite
• nausea or vomiting
• night blindness
• overbright appearance of lights
• pale skin
• pinpoint red or purple spots on the skin
• severe and continuing nausea
• severe stomach burning, cramping, or pain
• skin rash
• swelling or inflammation of the mouth
• troubled breathing with exertion
• tunnel vision
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting of material that looks like coffee grounds
• weight loss

• Anxiety
• back or leg pains
• bleeding gums
• blindness
• blistering, peeling, or loosening of the skin
• blood in the urine or stools
• blue lips and fingernails
• canker sores
• change in the ability to see colors, especially blue or yellow
• chest pain or discomfort
• clay-colored stools
• cold sweats
• coma
• confusion
• cool, pale skin
• cough or hoarseness
• coughing that sometimes produces a pink frothy sputum
• cracks in the skin
• darkened urine
• decreased vision
• depression
• diarrhea
• difficult, burning, or painful urination
• difficult, fast, or noisy breathing
• difficulty with swallowing
• dilated neck veins
• dizziness
• dry cough
• dry mouth
• early appearance of redness, or swelling of the skin
• excess air or gas in the stomach
• extreme fatigue
• eye pain
• fainting
• fever with or without chills
• fluid-filled skin blisters
• flushed, dry skin
• frequent urination
• fruit-like breath odor
• greatly decreased frequency of urination or amount of urine
• hair loss
• high fever
• hives
• increased hunger
• increased sensitivity of the skin to sunlight
• increased sweating
• increased thirst
• increased urination
• increased volume of pale, dilute urine
• irregular breathing
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• late appearance of rash with or without weeping blisters that become crusted, especially in sun-exposed areas of skin, may extend to unexposed areas
• light-colored stools
• lightheadedness
• loss of heat from the body
• lower back or side pain
• nervousness
• nightmares
• no blood pressure
• no breathing
• no pulse
• nosebleeds
• numbness or tingling in the hands, feet, or lips
• pain in the ankles or knees
• pain or burning in the throat
• pain or discomfort in the arms, jaw, back, or neck
• painful, red lumps under the skin, mostly on the legs
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale or blue lips, fingernails, or skin
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid, shallow breathing
• red, irritated eyes
• red skin lesions, often with a purple center
• red-green color blindness
• redness or other discoloration of the skin
• redness, swelling, or soreness of the tongue
• scaly skin
• seizures
• severe sunburn
• shakiness
• skin thinness
• slurred speech
• sneezing
• sore throat
• sores, ulcers, or white spots on the lips or tongue or inside the mouth
• sores, welting, or blisters
• spots on your skin resembling a blister or pimple
• stiff neck or back
• stomach cramps or tenderness
• stomach upset
• swelling in the legs and ankles
• swelling of the face, fingers, feet, or lower legs
• swollen, painful, or tender lymph glands in the neck, armpit, or groin
• tiny bumps on the inner lining of the eyelid
• unexplained weight loss
• unpleasant breath odor
• watery or bloody diarrhea
• weakness or heaviness of the legs
• weight gain
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Bleeding under the skin
• confusion about identity, place, and time
• muscle tremors
• restlessness
• sleepiness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Continuing ringing or buzzing or other unexplained noise in the ears
• hearing loss

• Acid or sour stomach
• change in hearing
• feeling of constant movement of self or surroundings
• passing gas
• sensation of spinning
• stomach soreness or discomfort

• Appetite changes
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• burning, dry, or itching eyes
• difficulty with moving
• discharge, excessive tearing
• general feeling of discomfort or illness
• lack or loss of strength
• menstrual changes
• muscle aching, cramping, stiffness, or weakness
• not able to concentrate
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• seeing, hearing, or feeling things that are not there
• shakiness in the legs, arms, hands, or feet
• swollen joints
• trembling or shaking of the hands or feet
• trouble getting pregnant
• trouble performing routine tasks
• trouble sleeping
• unusual drowsiness, dullness, or feeling of sluggishness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• It is used to ease pain, swelling, and fever.
• It is used to ease painful period (menstrual) cycles.
• It is used to treat arthritis.
• It is used to treat ankylosing spondylitis.
• It is used to treat gout attacks.
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take Naprosyn. This includes your doctors, nurses, pharmacists, and dentists.
• Have your blood work checked if you are on this medicine for a long time. Talk with your doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Naprosyn.
• High blood pressure has happened with drugs like this one. Have your blood pressure checked as you have been told by your doctor.
• Talk with your doctor before you drink alcohol.
• If you smoke, talk with your doctor.
• Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
• Do not take this medicine for longer than you were told by your doctor.
• If you have asthma, talk with your doctor. You may be more sensitive to Naprosyn.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• The chance of heart failure is raised with the use of drugs like this one. In people who already have heart failure, the chance of heart attack, having to go to the hospital for heart failure, and death is raised. Talk with the doctor.
• The chance of heart attack and heart-related death is raised in people taking drugs like this one after a recent heart attack. People taking drugs like this one after a first heart attack were also more likely to die in the year after the heart attack compared with people not taking drugs like this one. Talk with the doctor.
• If you are taking aspirin to help prevent a heart attack, talk with your doctor.
• If you are on a low-sodium or sodium-free diet, talk with your doctor. Some of these products have sodium.
• Do not switch brands or types of this medicine (like tablets, liquid) unless you talk with the doctor. They may not work the same.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Naprosyn (naproxen suspension) with your other drugs.
• Liver problems have happened with drugs like this one. Sometimes, this has been deadly. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• NSAIDs like Naprosyn may affect egg release (ovulation) in women. This may cause you to not be able to get pregnant. This goes back to normal when this medicine is stopped. Talk with your doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant. If you are pregnant or you get pregnant while taking Naprosyn, call your doctor right away.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Belly pain or heartburn.
• Upset stomach or throwing up.
• Loose stools (diarrhea).
• Hard stools (constipation).
• Gas.
• Dizziness.
• Feeling sleepy.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time Naprosyn is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Naprosyn or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Naprosyn (naproxen suspension). This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Naproxen is a proprionic acid derivative related to the arylacetic acid group of nonsteroidal anti-inflammatory drugs.

The chemical names for naproxen and naproxen sodium are (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid and (S)-6-methoxy-α-methyl-2-naphthaleneacetic acid, sodium salt, respectively. Naproxen and naproxen sodium have the following structures, respectively:

Naproxen has a molecular weight of 230.26 and a molecular formula of C14H14O3. Naproxen sodium has a molecular weight of 252.23 and a molecular formula of C14H13NaO3.

Naproxen is an odorless, white to off-white crystalline substance. It is lipid-soluble, practically insoluble in water at low pH and freely soluble in water at high pH. The octanol/water partition coefficient of naproxen at pH 7.4 is 1.6 to 1.8. Naproxen sodium is a white to creamy white, crystalline solid, freely soluble in water at neutral pH.

Naprosyn (naproxen tablets) is available as yellow tablets containing 250 mg of naproxen, pink tablets containing 375 mg of naproxen and yellow tablets containing 500 mg of naproxen for oral administration. The inactive ingredients are croscarmellose sodium, iron oxides, povidone and magnesium stearate.

EC-Naprosyn (naproxen delayed-release tablets) is available as enteric-coated white tablets containing 375 mg of naproxen and 500 mg of naproxen for oral administration. The inactive ingredients are croscarmellose sodium, povidone and magnesium stearate. The enteric coating dispersion contains methacrylic acid copolymer, talc, triethyl citrate, sodium hydroxide and purified water. The dissolution of this enteric-coated naproxen tablet is pH dependent with rapid dissolution above pH 6. There is no dissolution below pH 4.

ANAPROX (naproxen sodium tablets) is available as blue tablets containing 275 mg of naproxen sodium and ANAPROX DS (naproxen sodium tablets) is available as dark blue tablets containing 550 mg of naproxen sodium for oral administration. The inactive ingredients are magnesium stearate, microcrystalline cellulose, povidone and talc. The coating suspension for the ANAPROX 275 mg tablet may contain hydroxypropyl methylcellulose 2910, Opaspray K-1-4210A, polyethylene glycol 8000 or Opadry YS-1-4215. The coating suspension for the ANAPROX DS 550 mg tablet may contain hydroxypropyl methylcellulose 2910, Opaspray K-1-4227, polyethylene glycol 8000 or Opadry YS-1-4216.

Naprosyn (naproxen suspension) is available as a light orange-colored opaque oral suspension containing 125 mg/5 mL of naproxen in a vehicle containing sucrose, magnesium aluminum silicate, sorbitol solution and sodium chloride (39 mg/5 mL, 1.5 mEq), methylparaben, fumaric acid, FD&C Yellow No. 6, imitation pineapple flavor, imitation orange flavor and purified water. The pH of the suspension ranges from 2.2 to 3.7.

Cardiovascular Effects 

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS: Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation). 

Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).

Hypertension

NSAIDs, including Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Congestive Heart Failure and Edema

Fluid retention, edema, and peripheral edema have been observed in some patients taking NSAIDs. Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension should be used with caution in patients with fluid retention, hypertension, or heart failure. Since each ANAPROX or ANAPROX DS tablet contains 25 mg or 50 mg of sodium (about 1 mEq per each 250 mg of naproxen), and each teaspoonful of Naprosyn Suspension contains 39 mg (about 1.5 mEq per each 125 mg of naproxen) of sodium, this should be considered in patients whose overall intake of sodium must be severely restricted.

Gastrointestinal Effects – Risk of Ulceration, Bleeding, and Perforation

NSAIDs, including Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal.

These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only 1 in 5 patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic.

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

Epidemiological studies, both of the case-control and cohort design, have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. In two studies, concurrent use of an NSAID or aspirin potentiated the risk of bleeding (see PRECAUTIONS: Drug Interactions). Although these studies focused on upper gastrointestinal bleeding, there is reason to believe that bleeding at other sites may be similarly potentiated.

NSAIDs should be given with care to patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn’s disease) as their condition may be exacerbated.

Renal Effects

Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory 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, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, those taking diuretics and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and the elderly. Discontinuation of nonsteroidal anti-inflammatory drug therapy is usually followed by recovery to the pretreatment state (see WARNINGS: Advanced Renal Disease). 

Advanced Renal Disease

No information is available from controlled clinical studies regarding the use of Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension in patients with advanced renal disease. Therefore, treatment with Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension is not recommended in these patients with advanced renal disease. If Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension therapy must be initiated, close monitoring of the patient’s renal function is advisable and patients should be adequately hydrated. 

Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension. Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS: Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs. Anaphylactoid reactions, like anaphylaxis, may have a fatal outcome.

Skin Reactions

NSAIDs, including Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Pregnancy

In late pregnancy, as with other NSAIDs, Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension should be avoided because it may cause premature closure of the ductus arteriosus.

General

Naproxen-containing products such as Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS, Naprosyn SUSPENSION, ALEVE®, and other naproxen products should not be used concomitantly since they all circulate in the plasma as the naproxen anion.

Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

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

The pharmacological activity of Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, noninflammatory painful conditions.

Because of adverse eye findings in animal studies with drugs of this class, it is recommended that ophthalmic studies be carried out if any change or disturbance in vision occurs.

Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension. Hepatic abnormalities may be the result of hypersensitivity rather than direct toxicity. These laboratory abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.

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 Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension.

If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc.), Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension should be discontinued.

Chronic alcoholic liver disease and probably other diseases with decreased or abnormal plasma proteins (albumin) reduce the total plasma concentration of naproxen, but the plasma concentration of unbound naproxen is increased. Caution is advised when high doses are required and some adjustment of dosage may be required in these patients. It is prudent to use the lowest effective dose.

Hematological Effects

Anemia is sometimes seen in patients receiving NSAIDs, including Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.

NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving either Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.

Preexisting Asthma

Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

Information for Patients

Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

1. Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS: Cardiovascular Effects).
   
2. Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and even death. Although serious GI tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS: Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation).
   
3. Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalizations and even death. Although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. Patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible.
   
4. Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians.
   
5. Patients should be informed of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, patients should be instructed to stop therapy and seek immediate medical therapy.
   
6. Patients should be informed of the signs of an anaphylactoid reaction (eg, difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS).
   
7. In late pregnancy, as with other NSAIDs, Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension should be avoided because it may cause premature closure of the ductus arteriosus.
   
8. Caution should be exercised by patients whose activities require alertness if they experience drowsiness, dizziness, vertigo or depression during therapy with naproxen.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (eg, eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension should be discontinued.

Drug Interactions

Angiotensin Converting Enzyme (ACE)-inhibitors/Angiotensin

Receptor Blockers (ARBs)

NSAIDs may diminish the antihypertensive effect of ACE-inhibitors, ARBs, or beta-blockers (including propanolol).

Monitor patients taking NSAIDs concomitantly with ACE-inhibitors, ARBs, or beta blockers for changes in blood pressure.

In addition, in patients who are elderly, volume-depleted (including those on diuretic therapy), or have compromised renal function, co-administration of NSAIDs with ACE inhibitors or ARBs may result in deterioration of renal function, including possible acute renal failure. Monitor these patients closely for signs of worsening renal function

Antacids and Sucralfate

Concomitant administration of some antacids (magnesium oxide or aluminum hydroxide) and sucralfate can delay the absorption of naproxen.

Aspirin

When naproxen as Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension is administered with aspirin, its protein binding is reduced, although the clearance of free Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of naproxen and naproxen sodium and aspirin is not generally recommended because of the potential of increased adverse effects.

Cholestyramine

As with other NSAIDs, concomitant administration of cholestyramine can delay the absorption of naproxen.

Diuretics

Clinical studies, as well as postmarketing observations, have shown that Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS: Renal Effects), as well as to assure diuretic efficacy.

Lithium

NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.

Methotrexate

NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. Naproxen, naproxen sodium and other nonsteroidal anti-inflammatory drugs have been reported to reduce the tubular secretion of methotrexate in an animal model. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.

Warfarin

The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone. No significant interactions have been observed in clinical studies with naproxen and coumarin-type anticoagulants. However, caution is advised since interactions have been seen with other nonsteroidal agents of this class. The free fraction of warfarin may increase substantially in some subjects and naproxen interferes with platelet function.

Selective Serotonin Reuptake Inhibitors (SSRIs)

There is an increased risk of gastrointestinal bleeding when selective serotonin reuptake inhibitors (SSRIs) are combined with NSAIDs. Caution should be used when NSAIDs are administered concomitantly with SSRIs. 

Other Information Concerning Drug Interactions

Naproxen is highly bound to plasma albumin; it thus has a theoretical potential for interaction with other albumin-bound drugs such as coumarin-type anticoagulants, sulphonylureas, hydantoins, other NSAIDs, and aspirin. Patients simultaneously receiving naproxen and a hydantoin, sulphonamide or sulphonylurea should be observed for adjustment of dose if required.

 Probenecid given concurrently increases naproxen anion plasma levels and extends its plasma half-life significantly.

Due to the gastric pH elevating effects of H2-blockers, sucralfate and intensive antacid therapy, concomitant administration of EC-Naprosyn is not recommended.

Drug/Laboratory Test Interaction

Naproxen may decrease platelet aggregation and prolong bleeding time. This effect should be kept in mind when bleeding times are determined.

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-di-nitrobenzene used in this assay. Although 17-hydroxy-corticosteroid measurements (Porter-Silber test) do not appear to be artifactually altered, it is suggested that therapy with naproxen be temporarily discontinued 72 hours before adrenal function tests are performed if the Porter-Silber test is to be used.

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

Carcinogenesis

A 2-year study was performed in rats to evaluate the carcinogenic potential of naproxen at rat doses of 8, 16, and 24 mg/kg/day (50, 100, and 150 mg/m2). The maximum dose used was 0.28 times the systemic exposure to humans at the recommended dose. No evidence of tumorigenicity was found.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Reproduction studies have been performed in rats at 20 mg/kg/day (125 mg/m2/day, 0.23 times the human systemic exposure), rabbits at 20 mg/kg/day (220 mg/m2/day, 0.27 times the human systemic exposure), and mice at 170 mg/kg/day (510 mg/m2/day, 0.28 times the human systemic exposure) with no evidence of impaired fertility or harm to the fetus due to the drug. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women. Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

There is some evidence to suggest that when inhibitors of prostaglandin synthesis are used to delay preterm labor there is an increased risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus and intracranial hemorrhage. Naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin E levels in preterm infants. Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.

Labor and Delivery

In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. Naproxen-containing products are not recommended in labor and delivery because, through its prostaglandin synthesis inhibitory effect, naproxen may adversely affect fetal circulation and inhibit uterine contractions, thus increasing the risk of uterine hemorrhage. The effects of Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension on labor and delivery in pregnant women are unknown.

Nursing Mothers

The naproxen anion has been found in the milk of lactating women at a concentration equivalent to approximately 1% of maximum naproxen concentration in plasma. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, use in nursing mothers should be avoided.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 2 years have not been established. Pediatric dosing recommendations for juvenile arthritis are based on well-controlled studies (see DOSAGE AND ADMINISTRATION). There are no adequate effectiveness or dose-response data for other pediatric conditions, but the experience in juvenile arthritis and other use experience have established that single doses of 2.5 to 5 mg/kg (as naproxen suspension, see DOSAGE AND ADMINISTRATION), with total daily dose not exceeding 15 mg/kg/day, are well tolerated in pediatric patients over 2 years of age.

Geriatric Use

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nonsteroidal anti-inflammatory drugs. Elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. Most spontaneous reports of fatal GI events are in the geriatric population (see WARNINGS).

Naproxen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nonsteroidal anti-inflammatory drugs (see WARNINGS: Renal Effects).

Carefully consider the potential benefits and risks of Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension and other treatment options before deciding to use Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS and Naprosyn Suspension. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

After observing the response to initial therapy with Naprosyn, EC-Naprosyn, ANAPROX, ANAPROX DS or Naprosyn Suspension, the dose and frequency should be adjusted to suit an individual patient’s needs.

Different dose strengths and formulations (ie, tablets, suspension) of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although Naprosyn, Naprosyn Suspension, EC-Naprosyn, ANAPROX and ANAPROX DS all circulate in the plasma as naproxen, they have pharmacokinetic differences that may affect onset of action. Onset of pain relief can begin within 30 minutes in patients taking naproxen sodium and within 1 hour in patients taking naproxen. Because EC-Naprosyn dissolves in the small intestine rather than in the stomach, the absorption of the drug is delayed compared to the other naproxen formulations (see CLINICAL PHARMACOLOGY).

The recommended strategy for initiating therapy is to choose a formulation and a starting dose likely to be effective for the patient and then adjust the dosage based on observation of benefit and/or adverse events. A lower dose should be considered in patients with renal or hepatic impairment or in elderly patients (see WARNINGS and PRECAUTIONS).

Geriatric Patients

Studies indicate that although total plasma concentration of naproxen is unchanged, the unbound plasma fraction of naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients. As with other drugs used in the elderly, it is prudent to use the lowest effective dose.

Patients With Moderate to Severe Renal Impairment

Naproxen-containing products are not recommended for use in patients with moderate to severe and severe renal impairment (creatinine clearance <30 mL/min) (see WARNINGS: Renal Effects). 

Rheumatoid Arthritis, Osteoarthritis and Ankylosing Spondylitis

To maintain the integrity of the enteric coating, the EC-Naprosyn tablet should not be broken, crushed or chewed during ingestion. Naprosyn Suspension should be shaken gently before use.

During long-term administration, the dose of naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

In patients who tolerate lower doses well, the dose may be increased to naproxen 1500 mg/day for limited periods of up to 6 months when a higher level of anti-inflammatory/analgesic activity is required. When treating such patients with naproxen 1500 mg/day, the physician should observe sufficient increased clinical benefits to offset the potential increased risk. The morning and evening doses do not have to be equal in size and administration of the drug more frequently than twice daily does not generally make a difference in response (see CLINICAL PHARMACOLOGY).

Juvenile Arthritis

The use of Naprosyn Suspension is recommended for juvenile arthritis in children 2 years or older because it allows for more flexible dose titration based on the child’s weight. In pediatric patients, doses of 5 mg/kg/day produced plasma levels of naproxen similar to those seen in adults taking 500 mg of naproxen (see CLINICAL PHARMACOLOGY). 

The recommended total daily dose of naproxen is approximately 10 mg/kg given in 2 divided doses (ie, 5 mg/kg given twice a day). A measuring cup marked in 1/2 teaspoon and 2.5 milliliter increments is provided with the Naprosyn Suspension. The following table may be used as a guide for dosing of Naprosyn Suspension:

Patient’s Weight       Dose               Administered as

13 kg (29 lb)            62.5 mg bid       2.5 mL (1/2 tsp) twice daily

25 kg (55 lb)            125 mg bid        5.0 mL (1 tsp) twice daily

38 kg (84 lb)            187.5 mg bid     7.5 mL (1 1/2 tsp) twice daily

Management of Pain, Primary Dysmenorrhea, and Acute Tendonitis and Bursitis

The recommended starting dose is 550 mg of naproxen sodium as ANAPROX/ANAPROX DS followed by 550 mg every 12 hours or 275 mg every 6 to 8 hours as required. The initial total daily dose should not exceed 1375 mg of naproxen sodium. Thereafter, the total daily dose should not exceed 1100 mg of naproxen sodium. Because the sodium salt of naproxen is more rapidly absorbed, ANAPROX/ANAPROX DS is recommended for the management of acute painful conditions when prompt onset of pain relief is desired. Naprosyn may also be used but EC-Naprosyn is not recommended for initial treatment of acute pain because absorption of naproxen is delayed compared to other naproxen-containing products (see CLINICAL PHARMACOLOGY, INDICATIONS AND USAGE).

Acute Gout

The recommended starting dose is 750 mg of Naprosyn followed by 250 mg every 8 hours until the attack has subsided. ANAPROX may also be used at a starting dose of 825 mg followed by 275 mg every 8 hours. EC-Naprosyn is not recommended because of the delay in absorption (see CLINICAL PHARMACOLOGY).

Naprosyn (naproxen) is a nonsteroidal anti-inflammatory drug (NSAID). Naproxen works by reducing hormones that cause inflammation and pain in the body.

Naprosyn is used to treat pain or inflammation caused by conditions such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, gout, or menstrual cramps.

Naprosyn delayed-release tablets are slower-acting forms of naproxen that are used only for treating chronic conditions such as arthritis or ankylosing spondylitis. These forms of naproxen will not work fast enough to treat acute pain.

Use Naprosyn exactly as directed on the label, or as prescribed by your doctor. Do not take this medicine in larger amounts or for longer than recommended. Use the lowest dose that is effective in treating your condition.

Do not crush, chew, or break a Naprosyn tablet. Swallow it whole.

Shake the oral suspension (liquid) well just before you measure a dose. Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

If you change brands, strengths, or forms of naproxen, your dosage needs may change. Ask your pharmacist if you have any questions about the kind of naproxen you are using.

If a child is using this medicine, tell your doctor if the child has any changes in weight. Naproxen doses are based on weight in children, and any changes may affect your child's dose.

If you use Naprosyn long-term, you may need frequent medical tests.

This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using Naprosyn.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Get emergency medical help if you have signs of an allergic reaction to Naprosyn: sneezing, runny or stuffy nose; wheezing or trouble breathing; hives; swelling of your face, lips, tongue, or throat.

Get emergency medical help if you have signs of a heart attack or stroke: chest pain spreading to your jaw or shoulder, sudden numbness or weakness on one side of the body, slurred speech, feeling short of breath.

Stop using Naprosyn and call your doctor at once if you have:

• shortness of breath (even with mild exertion);

• swelling or rapid weight gain;

• the first sign of any skin rash, no matter how mild;

• signs of stomach bleeding - bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• liver problems - nausea, upper stomach pain, itching, tired feeling, flu-like symptoms, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• kidney problems - little or no urinating, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath;

• low red blood cells (anemia) - pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or

• severe skin reaction - fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common Naprosyn side effects may include:

• indigestion, heartburn, stomach pain, nausea;

• headache, dizziness, drowsiness;

• bruising, itching, rash;

• swelling; or

• ringing in your ears.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ask your doctor before using Naprosyn if you take an antidepressant such as citalopram, escitalopram, fluoxetine (Prozac), fluvoxamine, paroxetine, sertraline (Zoloft), trazodone, or vilazodone. Taking any of these medicines with an NSAID may cause you to bruise or bleed easily.

Ask a doctor or pharmacist if it is safe for you to use Naprosyn if you are also using any of the following drugs:

• cholestyramine;

• cyclosporine;

• digoxin;

• lithium;

• methotrexate;

• pemetrexed;

• phenytoin or similar seizure medications;

• probenecid;

• warfarin (Coumadin, Jantoven) or similar blood thinners;

• a diuretic or "water pill";

• heart or blood pressure medication; or

• insulin or oral diabetes medicine.

This list is not complete. Other drugs may interact with naproxen, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.