DailyMed Label: Nabumetone 500 mg

DailyMed Label: Nabumetone 500 mg

2024

DailyMed Prescription

Nabumetone 500 mg

Nabumetone

LGM PHARMA SOLUTIONS, LLC

NDC: 79739-7076

NDC: 79739-7077

NDC: 79739-7078

NDC: 79739-7076

NDC: 79739-7077

NDC: 79739-7078

NDC: 79739-7076

NDC: 79739-7077

NDC: 79739-7078

NDC: 79739-7076

NDC: 79739-7077

NDC: 79739-7078

NDC: 79739-7076

NDC: 79739-7076

NDC: 79739-7077

NDC: 79739-7077

NDC: 79739-7078

NDC: 79739-7078

Nabumetone is a naphthylalkanone designated chemically as 4-(6-methoxy-2-naphthalenyl)-2-butanone. It has the following structure: C 15 H 16 O 2 M.W. 228.3 Nabumetone is a white to off-white crystalline substance. It is nonacidic and practically insoluble in water, but soluble in alcohol and most organic solvents. It has an n-octanol:phosphate buffer partition coefficient of 2,400 at pH 7.4. Each tablet, for oral administration, contains either 500 mg, 750 mg, or 1000 mg of nabumetone. In addition, each tablet contains the following inactive ingredients: povidone, croscarmellose, magnesium stearate, sodium lauryl sulfate, and colloidal silicon dioxide. The coating contains hydroxypropyl cellulose and hypromellose. Structural Formula - Nabumetone

Carefully consider the potential benefits and risks of nabumetone tablets and other treatment options before deciding to use nabumetone tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ). Nabumetone tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis.

Carefully consider the potential benefits and risks of nabumetone tablets and other treatment options before deciding to use nabumetone tablets. 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 nabumetone tablets, the dose and frequency should be adjusted to suit an individual patient's needs. The recommended starting dose is 1,000 mg taken as a single dose with or without food. Some patients may obtain more symptomatic relief from 1,500 mg to 2,000 mg per day. Nabumetone tablets can be given in either a single or twice-daily dose. Dosages greater than 2,000 mg per day have not been studied. The lowest effective dose should be used for chronic treatment (see WARNINGS ). Patients weighing under 50 kg may be less likely to require dosages beyond 1,000 mg; therefore, after observing the response to initial therapy, the dose should be adjusted to meet individual patients’ requirements.

Nabumetone tablets are contraindicated in patients with known hypersensitivity to nabumetone or product excipients. Nabumetone tablets should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS and PRECAUTIONS ). Nabumetone tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).

Nabumetone tablets 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. The pharmacological activity of nabumetone tablets in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions. Borderline elevations of 1 or more liver function tests may occur in up to 15% of patients taking NSAIDs including nabumetone tablets. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately 3 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 a more severe hepatic reaction while on therapy with nabumetone tablets. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), nabumetone tablets should be discontinued. Anemia is sometimes seen in patients receiving NSAIDs, including nabumetone tablets. 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 nabumetone tablets, 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 nabumetone tablets who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored (see CLINICAL PHARMACOLOGY ). 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 non-steroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, nabumetone tablets should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma. Based on ultraviolet (U.V.) light photosensitivity testing, nabumetone may be associated with more reactions to sun exposure than might be expected based on skin tanning types. 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. Cardiovascular Thrombotic Events Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately (see WARNINGS ). Nabumetone tablets, 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 signs or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. Patients should be apprised of the importance of this follow-up (see WARNINGS) . Nabumetone tablets, like other NSAIDs, can cause serious skin side effects such as exfoliative dermatitis, SJS, and TEN, which may result in hospitalization 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. Heart Failure and Edema Patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians. Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur (see WARNINGS ). Patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., 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. Patients should be informed of the signs of an anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or throat). If these occur, patients should be instructed to seek immediate emergency help (see WARNINGS ). Fetal Toxicity Inform pregnant women to avoid use of Nabumetone and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. If treatment with Nabumetone is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours [see WARNINGS; Fetal Toxicity, PRECAUTIONS; Pregnancy ]. Serious Skin Reactions, including DRESS Advise patients to stop taking Nabumetone immediately if they develop any type of rash or fever and to contact their healthcare provider as soon as possible [see WARNINGS ]. 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 (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, nabumetone tablets should be discontinued. Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors. When nabumetone tablets are administered with aspirin, its protein binding is reduced, although the clearance of free nabumetone is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of nabumetone tablets and aspirin is not generally recommended because of the potential of increased adverse effects. Clinical studies, as well as postmarketing observations, have shown that nabumetone tablets 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 ), as well as to assure diuretic efficacy. 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. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate. 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. In vitro studies have shown that, because of its affinity for protein, 6MNA may displace other protein-bound drugs from their binding site. Caution should be exercised when administering nabumetone tablets with warfarin since interactions have been seen with other NSAIDs. Concomitant administration of an aluminum-containing antacid had no significant effect on the bioavailability of 6MNA. When administered with food or milk, there is more rapid absorption; however, the total amount of 6MNA in the plasma is unchanged (see CLINICAL PHARMACOLOGY ). In 2 year studies conducted in mice and rats, nabumetone had no statistically significant tumorigenic effect. Nabumetone did not show mutagenic potential in the Ames test and mouse micronucleus test in vivo ; however, nabumetone- and 6MNA-treated lymphocytes in culture showed chromosomal aberrations at 80 mcg/mL and higher concentrations (equal to the average human exposure to nabumetone at the maximum recommended dose). Nabumetone did not impair fertility of male or female rats treated orally at doses of 320 mg/kg/day (1,888 mg/m 2 ) before mating. Risk Summary Use of NSAIDs, including Nabumetone, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of Nabumetone use between about 20 and 30 weeks of gestation and avoid Nabumetone use at about 30 weeks of gestation and later in pregnancy [see WARNINGS; Fetal Toxicity ]. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including Nabumetone, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. There are no adequate, well-controlled studies in pregnant women. Nabumetone tablets should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors, such as nabumetone, resulted in increased pre- and post-implantation loss. Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. Clinical Considerations Fetal/Neonatal Adverse Reactions Premature Closure of Fetal Ductus Arteriosus: Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including Nabumetone, can cause premature closure of the fetal ductus arteriosus [see WARNINGS; Fetal Toxicity ]. Oligohydramnios/Neonatal Renal Impairment If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If Nabumetone treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue Nabumetone and follow up according to clinical practice (see WARNINGS; Fetal Toxicity ). Data Human Data Premature Closure of Fetal Ductus Arteriosus: Published literature reports that the use of NSAIDs at about 30 weeks of gestation and later in pregnancy may cause premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment: Published studies and postmarketing reports describe material NSAID use at about 20 weeks gestation or later in pregnancy associated with fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. In many cases, but not all, the decrease in amniotic fluid was transient and reversible with cessation of the drug. There have been a limited number of case reports of maternal NSAID use and neonatal renal dysfunction without oligohydramnios, some of which were irreversible. Some cases of neonatal renal dysfunction required treatment with invasive procedures, such as exchange transfusion or dialysis. Methodological limitations of these postmarketing studies and reports include lack of a control group; limited information regarding dose, duration, and timing of drug exposure; and concomitant use of other medications. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAID use. Because the published safety data on neonatal outcomes involved mostly preterm infants, the generalizability of certain reported risks to the full-term infant exposed to NSAIDs through maternal use is uncertain. 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. The effects of nabumetone tablets on labor and delivery in pregnant women are unknown. It is not known whether this drug is excreted in human milk, however 6MNA is excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from nabumetone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Safety and effectiveness in pediatric patients have not been established. As with any NSAIDs, caution should be exercised in treating the elderly (65 years and older). Of the 1,677 patients in U.S. clinical studies who were treated with nabumetone, 411 patients (24%) were 65 years or older; 22 patients (1%) were 75 years or older. No overall differences in efficacy or safety were observed between these older patients and younger ones. Similar results were observed in a 1 year, non-U.S. postmarketing surveillance study of 10,800 patients treated with nabumetone, of whom 4,577 patients (42%) were 65 years or older.

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors. When nabumetone tablets are administered with aspirin, its protein binding is reduced, although the clearance of free nabumetone is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of nabumetone tablets and aspirin is not generally recommended because of the potential of increased adverse effects. Clinical studies, as well as postmarketing observations, have shown that nabumetone tablets 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 ), as well as to assure diuretic efficacy. 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. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate. 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. In vitro studies have shown that, because of its affinity for protein, 6MNA may displace other protein-bound drugs from their binding site. Caution should be exercised when administering nabumetone tablets with warfarin since interactions have been seen with other NSAIDs. Concomitant administration of an aluminum-containing antacid had no significant effect on the bioavailability of 6MNA. When administered with food or milk, there is more rapid absorption; however, the total amount of 6MNA in the plasma is unchanged (see CLINICAL PHARMACOLOGY ).

Nabumetone tablets USP, 500 mg are white, coated, modified capsule-shaped tablets, debossed with “HT” on one side and “500” on the other. They are available in bottles of: 100 tablets - NDC 79739-7076-1 500 tablets - NDC 79739-7076-5 Nabumetone tablets USP, 750 mg are white, coated, modified capsule-shaped tablets, debossed with “HT” on one side and “750” on the other. They are available in bottles of: 100 tablets - NDC 79739-7077-1 500 tablets - NDC 73739-7077-5 Nabumetone tablets USP, 1000 mg are white, coated, modified capsule-shaped tablets, deep bisect on one side and debossed logo “NB 1000” on the other. They are available in bottles of: 30 tablets – NDC 79739-7078-3 60 tablets – NDC 79739-7078-6 100 tablets - NDC 79739-7078-1 Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Manufactured by: LGM Pharma Solutions, LLC, Irvine, CA 92614 Rev 04/2021

Nabumetone is a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic properties in pharmacologic studies. As with other non-steroidal anti-inflammatory agents, its mode of action is not known; however, the ability to inhibit prostaglandin synthesis may be involved in the anti-inflammatory effect. The parent compound is a prodrug, which undergoes hepatic biotransformation to the active component, 6-methoxy-2-naphthylacetic acid (6MNA), that is a potent inhibitor of prostaglandin synthesis. 6-methoxy-2-naphthylacetic acid (6MNA) It is acidic and has an n-octanol:phosphate buffer partition coefficient of 0.5 at pH 7.4. 6MNA Structural Formula After oral administration, approximately 80% of a radiolabeled dose of nabumetone is found in the urine, indicating that nabumetone is well absorbed from the gastrointestinal tract. Nabumetone itself is not detected in the plasma because, after absorption, it undergoes rapid biotransformation to the principal active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). Approximately 35% of a 1,000 mg oral dose of nabumetone is converted to 6MNA and 50% is converted into unidentified metabolites which are subsequently excreted in the urine. Following oral administration of nabumetone, 6MNA exhibits pharmacokinetic characteristics that generally follow a one-compartment model with first order input and first order elimination. 6MNA is more than 99% bound to plasma proteins. The free fraction is dependent on total concentration of 6MNA and is proportional to dose over the range of 1,000 mg to 2,000 mg. It is 0.2% to 0.3% at concentrations typically achieved following administration of 1,000 mg of nabumetone and is approximately 0.6% to 0.8% of the total concentrations at steady state following daily administration of 2,000 mg. Steady-state plasma concentrations of 6MNA are slightly lower than predicted from single-dose data. This may result from the higher fraction of unbound 6MNA which undergoes greater hepatic clearance. Coadministration of food increases the rate of absorption and subsequent appearance of 6MNA in the plasma but does not affect the extent of conversion of nabumetone into 6MNA. Peak plasma concentrations of 6MNA are increased by approximately one third. Coadministration with an aluminum-containing antacid had no significant effect on the bioavailability of 6MNA. Table 1: Mean Pharmacokinetic Parameters of Nabumetone Active Metabolite (6MNA) at Steady State Following Oral Administration of 1,000 mg or 2,000 mg Doses of Nabumetone Abbreviation (units) Young Adults Mean ± SD 1,000 mg n = 31 Young Adults Mean ± SD 2,000 mg n = 12 Elderly Mean ± SD 1,000 mg n = 27 T max (hr) 3.0 (1.0 to 12.0) 2.5 (1.0 to 8.0) 4.0 (1.0 to 10.0) t 1/2 (hr) 22.5 ± 3.7 26.2 ± 3.7 29.8 ± 8.1 CL ss /F (mL/min) 26.1 ± 17.3 21.0 ± 4.0 18.6 ± 13.4 Vd ss /F (L) 55.4 ± 26.4 53.4 ± 11.3 50.2 ± 25.3 The simulated curves in the graph below illustrate the range of active metabolite plasma concentrations that would be expected from 95% of patients following 1,000 mg to 2,000 mg doses to steady state. The cross-hatched area represents the expected overlap in plasma concentrations due to intersubject variation following oral administration of 1,000 mg to 2,000 mg of nabumetone. Nabumetone Active Metabolite (6MNA) Plasma Concentrations at Steady State Following Once-Daily Dosing of Nabumetone 1,000 mg (n = 31) 2,000 mg (n = 12) Nabumetone Active Metabolite (6MNA) Plasma Concentrations at Steady State Following Once-Daily Dosing of Nabumetone 1,000 mg (n = 31) 2,000 mg (n = 12) 6MNA undergoes biotransformation in the liver, producing inactive metabolites that are eliminated as both free metabolites and conjugates. None of the known metabolites of 6MNA has been detected in plasma. Preliminary in vivo and in vitro studies suggest that unlike other NSAIDs, there is no evidence of enterohepatic recirculation of the active metabolite. Approximately 75% of a radiolabeled dose was recovered in urine in 48 hours. Approximately 80% was recovered in 168 hours. A further 9% appeared in the feces. In the first 48 hours, metabolites consisted of: - nabumetone, unchanged not detectable - 6-methoxy-2-naphthylacetic acid (6MNA), unchanged < 1% - 6MNA, conjugated 11% - 6-hydroxy-2-naphthylacetic acid (6HNA), unchanged 5% - 6HNA, conjugated 7% - 4-(6-hydroxy-2-naphthyl)-butan-2-ol, conjugated 9% - O -desmethyl-nabumetone, conjugated 7% - unidentified minor metabolites 34% Total % Dose: 73% Following oral administration of dosages of 1,000 mg to 2,000 mg to steady state, the mean plasma clearance of 6MNA is 20 to 30 mL/min and the elimination half-life is approximately 24 hours. Nabumetone Active Metabolite Plasma Concentrations Steady-state plasma concentrations in elderly patients were generally higher than in young healthy subjects (see Table 1 f or summary of pharmacokinetic parameters). In moderate renal insufficiency patients (creatinine clearance 30 to 49 mL/min), the terminal half-life of 6MNA was increased by approximately 50% (39.2 ± 7.8 hrs, N = 12) compared to the normal subjects (26.9 ± 3.3 hrs, N = 13), and there was a 50% increase in the plasma levels of unbound 6MNA. Additionally, the renal excretion of 6MNA in the moderate renal impaired patients decreased on average by 33% compared to that in the normal patients. A similar increase in the mean terminal half-life of 6MNA was seen in a small study of patients with severe renal dysfunction (creatinine clearance < 30 mL/min). In patients undergoing hemodialysis, steady-state plasma concentrations of the active metabolite 6MNA were similar to those observed in healthy subjects. Due to extensive protein binding, 6MNA is not dialyzable. Dosage adjustment of nabumetone generally is not necessary in patients with mild renal insufficiency (≥ 50 mL/min). Caution should be used in prescribing nabumetone to patients with moderate or severe renal insufficiency. The maximum starting doses of nabumetone in patients with moderate or severe renal insufficiency should not exceed 750 mg or 500 mg, respectively once daily. Following careful monitoring of renal function in patients with moderate or severe renal insufficiency, daily doses may be increased to a maximum of 1,500 mg and 1,000 mg, respectively (see WARNINGS ). Data in patients with severe hepatic impairment are limited. Biotransformation of nabumetone to 6MNA and the further metabolism of 6MNA to inactive metabolites is dependent on hepatic function and could be reduced in patients with severe hepatic impairment (history of or biopsy-proven cirrhosis). Nabumetone was compared to aspirin in inducing gastrointestinal blood loss. Food intake was not monitored. Studies utilizing 51 Cr-tagged red blood cells in healthy males showed no difference in fecal blood loss after 3 or 4 weeks’ administration of 1,000 mg or 2,000 mg of nabumetone daily when compared to either placebo-treated or non-treated subjects. In contrast, aspirin 3,600 mg daily produced an increase in fecal blood loss when compared to subjects who received nabumetone, placebo, or no treatment. The clinical relevance of the data is unknown. The following endoscopy trials entered patients who had been previously treated with NSAIDs. These patients had varying baseline scores and different courses of treatment. The trials were not designed to correlate symptoms and endoscopy scores. The clinical relevance of these endoscopy trials, i.e., either G.I. symptoms or serious G.I. events, is not known. Ten endoscopy studies were conducted in 488 patients who had baseline and post-treatment endoscopy. In 5 clinical trials that compared a total of 194 patients on 1,000 mg of nabumetone daily or naproxen 250 mg or 500 mg twice daily for 3 to 12 weeks, treatment with nabumetone resulted in fewer patients with endoscopically detected lesions (> 3 mm). In 2 trials a total of 101 patients administered 1,000 mg or 2,000 mg of nabumetone daily or piroxicam 10 mg to 20 mg for 7 to 10 days, there were fewer patients treated with nabumetone with endoscopically detected lesions. In 3 trials of a total of 47 patients on 1,000 mg of nabumetone daily or indomethacin 100 mg to 150 mg daily for 3 to 4 weeks, the endoscopy scores were higher with indomethacin. Another 12 week trial in a total of 171 patients compared the results of treatment with 1,000 mg of nabumetone daily to ibuprofen 2,400 mg/day and ibuprofen 2,400 mg/day plus misoprostol 800 mcg/day. The results showed that patients treated with nabumetone had a lower number of endoscopically detected lesions (> 5 mm) than patients treated with ibuprofen alone but comparable to the combination of ibuprofen plus misoprostol. The results did not correlate with abdominal pain. In 1 week, repeat-dose studies in healthy volunteers, 1,000 mg of nabumetone daily had little effect on collagen-induced platelet aggregation and no effect on bleeding time. In comparison, naproxen 500 mg daily suppressed collagen-induced platelet aggregation and significantly increased bleeding time.

The use of nabumetone in relieving the signs and symptoms of osteoarthritis (OA) was assessed in double-blind, controlled trials in which 1,047 patients were treated for 6 weeks to 6 months. In these trials, nabumetone in a dose of 1,000 mg/day administered at night was comparable to naproxen 500 mg/day and to aspirin 3,600 mg/day. The use of nabumetone in relieving the signs and symptoms of rheumatoid arthritis (RA) was assessed in double-blind, randomized, controlled trials in which 770 patients were treated for 3 weeks to 6 months. Nabumetone, in a dose of 1,000 mg/day administered at night, was comparable to naproxen 500 mg/day and to aspirin 3,600 mg/day. In controlled clinical trials of rheumatoid arthritis patients, nabumetone has been used in combination with gold, d-penicillamine, and corticosteroids. In clinical trials with osteoarthritis and rheumatoid arthritis patients, most patients responded to nabumetone in doses of 1,000 mg/day administered nightly; total daily dosages up to 2,000 mg were used. In open-labeled studies, 1,490 patients were permitted dosage increases and were followed for approximately 1 year (mode). Twenty percent of patients (n = 294) were withdrawn for lack of effectiveness during the first year of these open-labeled studies. The following table provides patient-exposure to doses used in the U.S. clinical trials: Table 2: Clinical Double-Blinded and Open-Labeled Trials of Nabumetone in Osteoarthritis and Rheumatoid Arthritis       Mean/Mode Duration of Treatment (yr) Dose of Number of Patients Nabumetone OA RA OA RA 500 mg 17 6 0.4/- 0.2/- 1,000 mg 917 701 1.2/1 1.4/1 1,500 mg 645 224 2.3/1 1.7/1 2,000 mg 15 100 0.6/1 1.3/1 As with other NSAIDs, the lowest dose should be sought for each patient. Patients weighing under 50 kg may be less likely to require dosages beyond 1,000 mg; therefore, after observing the response to initial therapy, the dose should be adjusted to meet individual patients’ requirements.

500 mg, 100 Tablets, Container Label NDC 79739-7076-1