Naproxen 500 mg Tablet, 20-count — NDC 68071-4381-2 (Billing 68071-4381-02)

CAREFULLY CONSIDER THE POTENTIAL BENEFITS AND RISKS OF NAPROXEN AND OTHER TREATMENT OPTIONS BEFORE DECIDING TO USE NAPROXEN TABLETS. USE THE LOWEST EFFECTIVE DOSE FOR THE SHORTEST DURATION CONSISTENT WITH INDIVIDUAL PATIENT TREATMENT GOALS (SEE WARNINGS: GASTROINTESTINAL BLEEDING, ULCERATION, AND PERFORATION). NAPROXEN TABLETS ARE INDICATED: FOR THE RELIEF OF THE SIGNS AND SYMPTOMS OF RHEUMATOID ARTHRITIS.

FOR THE RELIEF OF THE SIGNS AND SYMPTOMS OF OSTEOARTHRITIS FOR THE RELIEF OF THE SIGNS AND SYMPTOMS OF ANKYLOSING SPONDYLITIS FOR THE RELIEF OF THE SIGNS AND SYMPTOMS OF JUVENILE ARTHRITIS NAPROXEN TABLETS ARE ALSO INDICATED: FOR RELIEF OF THE SIGNS AND SYMPTOMS OF TENDONITIS FOR RELIEF OF THE SIGNS AND SYMPTOMS OF BURSITIS FOR RELIEF OF THE SIGNS AND SYMPTOMS OF ACUTE GOUT FOR THE MANAGEMENT OF PAIN FOR THE MANAGEMENT OF PRIMARY DYSMENORRHEA

CAREFULLY CONSIDER THE POTENTIAL BENEFITS AND RISKS OF NAPROXEN AND OTHER TREATMENT OPTIONS BEFORE DECIDING TO USE NAPROXEN TABLETS. USE THE LOWEST EFFECTIVE DOSE FOR THE SHORTEST DURATION CONSISTENT WITH INDIVIDUAL PATIENT TREATMENT GOALS (SEE WARNINGS; GASTROINTESTINAL BLEEDING, ULCERATION, AND PERFORATION). AFTER OBSERVING THE RESPONSE TO INITIAL THERAPY WITH NAPROXEN TABLETS, THE DOSE AND FREQUENCY SHOULD BE ADJUSTED TO SUIT AN INDIVIDUAL PATIENT'S NEEDS.

DIFFERENT DOSE STRENGTHS AND FORMULATIONS (I.E., TABLETS, SUSPENSION) OF THE DRUG ARE NOT NECESSARILY BIOEQUIVALENT. THIS DIFFERENCE SHOULD BE TAKEN INTO CONSIDERATION WHEN CHANGING FORMULATION. ALTHOUGH NAPROXEN TABLETS, NAPROXEN SUSPENSION, NAPROXEN DELAYED-RELEASED TABLETS, AND NAPROXEN SODIUM TABLETS ALL CIRCULATE IN THE PLASMA AS NAPROXEN, THEY HAVE PHARMACOKINETIC DIFFERENCES THAT MAY AFFECT ONSET OF ACTION.

ONSET OF PAIN RELIEF CAN BEGIN WITHIN 1 HOUR IN PATIENTS TAKING NAPROXEN. 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; HEPATOTOXICITY, AND RENAL TOXICITY AND HYPERKALEMIA, AND PRECAUTIONS; GERIATRIC USE).

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 THE RECOMMENDED DOSE IS 250 MG, 375 MG, OR 500 MG TWICE DAILY. 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 NAPROXEN TABLETS MAY NOT ALLOW FOR THE FLEXIBLE DOSE TITRATION NEEDED IN PEDIATRIC PATIENTS WITH JUVENILE ARTHRITIS.

A LIQUID FORMULATION MAY BE MORE APPROPRIATE. 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.

ONE-HALF OF THE 250 MG TABLET WILL BE NEEDED FOR DOSING LOWER-WEIGHT CHILDREN. DOSING WITH NAPROXEN TABLETS IS NOT APPROPRIATE FOR CHILDREN WEIGHING LESS THAN 25 KILOGRAMS. THE RECOMMENDED TOTAL DAILY DOSE OF NAPROXEN IS APPROXIMATELY 10 MG/KG GIVEN IN 2 DIVIDED DOSES (I.E., 5 MG/KG GIVEN TWICE A DAY).

NAPROXEN TABLETS ARE NOT WELL SUITED TO THIS DOSAGE SO USE OF NAPROXEN ORAL SUSPENSION IS RECOMMENDED FOR THIS INDICATION. MANAGEMENT OF PAIN, PRIMARY DYSMENORRHEA, AND ACUTE TENDONITIS AND BURSITIS BECAUSE THE SODIUM SALT O… [Excerpted — this section continues on DailyMed.]

CARDIOVAS CULAR THROMBOTIC EVENTS CLINICAL TRIALS OF SEVERAL COX-2 SELECTIVE AND NON-SELECTIVE 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. BASED ON AVAILABLE DATA, IT IS UNCLEAR THAT THE RISK FOR CV THROMBOTIC EVENTS IS SIMILAR FOR ALL NSAIDS. THE RELATIVE INCREASE IN SERIOUS CV THROMBOTIC EVENTS OVER BASELINE CONFERRED BY NSAID USE APPEARS TO BE SIMILAR IN THOSE WITH AND WITHOUT KNOWN CV DISEASE OR RISK FACTORS FOR CV DISEASE.

HOWEVER, PATIENTS WITH KNOWN CV DISEASE OR RISK FACTORS HAD A HIGHER ABSOLUTE INCIDENCE OF EXCESS SERIOUS CV THROMBOTIC EVENTS, DUE TO THEIR INCREASED BASELINE RATE. SOMEOBSERVATIONAL STUDIES FOUND THAT THIS INCREASED RISK OF SERIOUS CV THROMBOTIC EVENTS BEGAN AS EARLY AS THE FIRST WEEKS OF TREATMENT. THE INCREASE IN CV THROMBOTIC RISK HAS BEEN OBSERVED MOST CONSISTENTLY AT HIGHER DOSES.

TO MINIMIZE THE POTENTIAL RISK FOR AN ADVERSE CV EVENT IN NSAID-TREATED PATIENTS, USE THE LOWEST EFFECTIVE DOSE FOR THE SHORTEST DURATION POSSIBLE. PHYSICIANS AND PATIENTS SHOULD REMAIN ALERT FOR THE DEVELOPMENT OF SUCH EVENTS, THROUGHOUT THE ENTIRE TREATMENT COURSE, EVEN IN THE ABSENCE OF PREVIOUS CV SYMPTOMS. PATIENTS SHOULD BE INFORMED ABOUT THE 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, SUCH AS NAPROXEN, INCREASES THE RISK OF SERIOUS GASTROINTESTINAL (GI) EVENTS (SEE WARNINGS; GASTROINTESTINAL BLEEDING, ULCERATION, AND PERFORATION). STATUS POST CORONARY ARTERY BYPASS GRAFT (CABG) SURGERY 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.

NSAIDS ARE CONTRAINDICATED IN THE SETTING OF CABG (SEE CONTRAINDICATIONS). POST-MI PATIENTS OBSERVATIONAL STUDIES CONDUCTED IN THE DANISH NATIONAL REGISTRY HAVE DEMONSTRATED THAT PATIENTS TREATED WITH NSAIDS IN THE POST-MI PERIOD WERE AT INCREASED RISK OF REINFARCTION, CV-RELATED DEATH, AND ALL CAUSE MORTALITY BEGINNING IN THE FIRST WEEK OF TREATMENT. IN THIS SAME COHORT, THE INCIDENCE OF DEATH IN THE FIRST YEAR POST-MI WAS 20 PER 100 PERSON YEARS IN NSAID-TREATED PATIENTS COMPARED TO 12 PER 100 PERSON YEARS IN NON-NSAID EXPOSED PATIENTS.

ALTHOUGH THE ABSOLUTE RATE OF DEATH DECLINED SOMEWHAT AFTER THE FIRST YEAR POST-MI, THE INCREASED RELATIVE RISK OF DEATH IN NSAID USERS PERSISTED OVER AT LEAST THE NEXT FOUR YEARS OF FOLLOW-UP. AVOID THE USE OF NAPROXEN IN PATIENTS WITH A RECENT MI UNLESS THE BENEFITS ARE EXPECTED TO OUTWEIGH THE RISK OF RECURRENT CV THROMBOTIC EVENTS. IF NAPROXEN IS USED IN PATIENTS WITH A RECENT MI, MONITOR PATIENTS FOR SIGNS OF CARDIAC ISCHEMIA.

GASTROINTESTINAL BLEEDING, ULCERATION, AND PERFORATION NSAIDS, INCLUDING NAPROXEN CAUSE SERIOUS GASTROINTESTINAL (GI) ADVERSE EVENTS INCLUDING INFLAMMATION, BLEEDING, ULCERATION, AND PERFORATION OF THE ESOPHAGUS, 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 OCCURRED IN APPROXIMATELY 1% OF PATIENTS TREATED FOR 3-6 MONTHS, AND IN ABOUT 2%- 4% OF PATIENTS TREATED FOR ONE YEAR. HOWEVER, EVEN SHORT-TERM NSAID THERAPY IS NOT WITHOUT RISK. RISK FACTORS FOR GI BLEEDING, ULCERATION, AND PERFORATION PATIENTS WITH A PRIOR HISTORY OF PEPTIC ULCER DISEASE AND/OR GI BLEEDING WHO USED NSAIDS HAD A GREATER THAN 10-FOLD INCREASED RISK FOR DEVELOPING A GI BLEED COMPARED TO PATIENTS WITHOUT THESE RISK FACTORS.

OTHER FACTORS THAT INCREASE THE RISK… [Excerpted — this section continues on DailyMed.]