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 , Renal Effects), 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 , Pharmacokinetics).
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.
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.
Because of the known effects of non-steroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.
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.
Adverse reaction information was derived from blinded-controlled and open-labeled clinical trials and from worldwide marketing experience. In the description below, rates of the more common events (greater than 1%) and many of the less common events (less than 1%) represent results of U.S. clinical studies.
Of the 1,677 patients who received nabumetone during U.S. clinical trials, 1,524 were treated for at least 1 month, 1,327 for at least 3 months, 929 for at least a year, and 750 for at least 2 years. More than 300 patients have been treated for 5 years or longer.
The most frequently reported adverse reactions were related to the gastrointestinal tract and included diarrhea, dyspepsia, and abdominal pain.
Diarrhea (14%), dyspepsia (13%), abdominal pain (12%), constipation*, flatulence*, nausea*, positive stool guaiac*, dry mouth, gastritis, stomatitis, vomiting.
Dizziness*, headache*, fatigue, increased sweating, insomnia, nervousness, somnolence.
*Incidence of reported reaction between 3% and 9%. Reactions occurring in 1% to 3% of the patients are unmarked.
Anorexia, jaundice, duodenal ulcer, dysphagia, gastric ulcer, gastroenteritis, gastrointestinal bleeding, increased appetite, liver function abnormalities, melena, hepatic failure.
Asthenia, agitation, anxiety, confusion, depression, malaise, paresthesia, tremor, vertigo.
Bullous eruptions, photosensitivity, urticaria, pseudoporphyria cutanea tarda, toxic epidermal necrolysis , erythema multiforme, Stevens-Johnson syndrome.
Dyspnea, eosinophilic pneumonia , hypersensitivity pneumonitis , idiopathic interstitial pneumonitis.
Albuminuria, azotemia, hyperuricemia , interstitial nephritis , nephrotic syndrome , vaginal bleeding , renal failure.
Anaphylactoid reaction , anaphylaxis , angioneurotic edema.
*Adverse reactions reported only in worldwide postmarketing experience or in the literature, not seen in clinical trials, are considered rarer and are italicized.
Bilirubinuria, duodenitis, eructation, gallstones, gingivitis, glossitis, pancreatitis, rectal bleeding.
Angina, arrhythmia, hypertension, myocardial infarction, palpitations, syncope, thrombophlebitis.
Dysuria, hematuria, impotence, renal stones.
Anemia, leukopenia, granulocytopenia.
Hyperglycemia, hypokalemia, weight loss.
Symptoms following acute NSAIDs overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression, and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.
Patients should be managed by symptomatic and supportive care following a NSAIDs overdose. There are no specific antidotes. Emesis and/or activated charcoal (60 to 100 grams in adults, 1 to 2 g/kg in children), and/or osmotic cathartic may be indicated in patients seen within 4 hours of ingestion with symptoms or following a large overdose (5 to 10 times the usual dose). Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
There have been overdoses of up to 25 grams of nabumetone reported with no long-term sequelae following standard emergency treatment (i.e., activated charcoal, gastric lavage, IV H 2 -blockers, etc.).
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 , Renal Effects). 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 USP are available as follows:
750 mg: Beige, oval-shaped, unscored, film-coated tablet debossed with the numbers “93” on one face of the tablet and “16” on the other. They are available in bottles of 40 tablets (NDC 43063-859-40).
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).
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
|Medication Guide for Nonsteroidal Anti-inflammatory Drugs (NSAIDs)|
|What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?|
|NSAIDs can cause serious side effect, including:|
|Do not take NSAIDs right before or after a heart surgery called a “coronary artery bypass graft (CABG).”|
|Avoid taking NSAIDs after a recent heart attack, unless your healthcare provider tells you to. You may have an increased risk of another heart attack if you take NSAIDs after a recent heart attack.|
|The risk of getting an ulcer or bleeding increases with:|
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|NSAIDs should only be used:|
|What are NSAIDs?|
|NSAIDs are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as different types of arthritis, menstrual cramps, and other types of short-term pain.|
|Who should not take NSAIDs?|
|Do not take NSAIDs:|
|Before taking NSAIDs, tell your healthcare provider about all of your medical conditions, including if you:|
|Tell your healthcare provider about all of the medicines you take, including prescription or over-the-counter medicines, vitamins or herbal supplements. NSAIDs and some other medicines can interact with each other and cause serious side effects. Do not start taking any new medicine without talking to your healthcare provider first.|
|What are the possible side effects of NSAIDs?|
|NSAIDs can cause serious side effects, including:|
|See “What is the most important information I should know about medicines called Nonsteroidal Anti-inflammatory Drugs (NSAIDs)?”|
|Get emergency help right away if you get any of the following symptoms:|
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|Stop taking your NSAID and call your healthcare provider right away if you get any of the following symptoms:|
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|If you take too much of your NSAID, call your healthcare provider or get medical help right away.|
These are not all the possible side effects of NSAIDs. For more information, ask your healthcare provider or pharmacist about NSAIDs.
|Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.|
|Other information about NSAIDs|
|General information about the safe and effective use of NSAIDs|
|Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use NSAIDs for a condition for which it was not prescribed. Do not give NSAIDs to other people, even if they have the same symptoms that you have. It may harm them.|
|If you would like more information about NSAIDs, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about NSAIDs that is written for health professionals.|
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Manufactured In Israel By:
TEVA PHARMACEUTICAL IND. LTD.
Jerusalem, 9777402, Israel
Hayward, CA 94544
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