Nabumetone Information
Nabumetone () Description
Nabumetone () , USP is a naphthylalkanone designated chemically as 4-(6-methoxy-2-naphthalenyl)-2-butanone. It has the following structure:
Nabumetone () , USP is a white to off-white crystalline substance with a molecular weight of 228.3. It is freely soluble in acetone, sparingly soluble in alcohol and in methanol and practically insoluble in water. It has an n-octanol:phosphate buffer partition coefficient of 2,400 at pH 7.4.
Each capsule-shaped, film-coated tablet contains 500 mg or 750 mg of Nabumetone () . Inactive ingredients consist of hypromellose, microcrystalline cellulose, polyethylene glycol, sodium lauryl sulfate, sodium starch glycolate and titanium oxide. The 750 mg tablets also contain red iron oxide and yellow iron oxide.
Nabumetone () Clinical Pharmacology
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.
It is acidic and has an n-octanol:phosphate buffer partition coefficient of 0.5 at pH 7.4.
Nabumetone () Clinical Trials
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 1000 mg/day administered at night, was comparable to naproxen 500 mg/day and to aspirin 3600 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 1000 mg/day administered nightly; total daily dosages up to 2000 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 Twenty percent of patients (n = 294) were withdrawn for lack of effectiveness during the first year of these open-labeled studies.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:
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 1000 mg; therefore, after observing the response to initial therapy, the dose should be adjusted to meet individual patients’ requirements.
Nabumetone () Indications And Usage
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 ).
Nabumetone () tablets are indicated for relief of signs and symptoms of osteoarthritis and rheumatoid arthritis.
Nabumetone () Contraindications
Nabumetone () tablets are contraindicated in patients with known hypersensitivity to Nabumetone () or its 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 and ).
Nabumetone () tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see ).
Nabumetone () Warnings
NSAIDs, including Nabumetone () , 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 1 in 5 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 to 6 months, and in about 2% to 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.
In controlled clinical trials involving 1,677 patients treated with Nabumetone () (1,140 followed for 1 year and 927 for 2 years), the cumulative incidence of peptic ulcers was 0.3% (95% CI; 0%, 0.6%) at 3 to 6 months, 0.5% (95% CI; 0.1%, 0.9%) at 1 year and 0.8% (95% CI; 0.3%, 1.3%) at 2 years. In patients with active peptic ulcer, physicians must weigh the benefits of therapy with Nabumetone () against possible hazards, institute an appropriate ulcer treatment regimen and monitor the patients’ progress carefully.
NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a 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.
No information is available from controlled clinical studies regarding the use of Nabumetone () in patients with advanced renal disease. Therefore, treatment with Nabumetone () is not recommended in these patients with advanced renal disease. If Nabumetone () therapy must be initiated, close monitoring of the patient’s renal function is advisable.
Because Nabumetone () undergoes extensive hepatic metabolism, no adjustment of the dosage of Nabumetone () is generally necessary in patients with mild renal insufficiency; however, as with all NSAIDs, patients with impaired renal function should be monitored more closely than patients with normal renal function (see ). In subjects with moderate renal impairment (creatinine clearance 30 to 49 mL/min), there is a 50% increase in unbound plasma 6MNA and dose adjustment may be warranted. The oxidized and conjugated metabolites of 6MNA are eliminated primarily by the kidneys.
Nabumetone () Precautions
Nabumetone () 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 () in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
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.
Nabumetone () Adverse Reactions
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.
Nabumetone () Overdosage
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-blockers, etc.).
Nabumetone () Dosage And Administration
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 ).
After observing the response to initial therapy with Nabumetone () tablets, the dose and frequency should be adjusted to suit an individual patient’s needs.
Nabumetone () How Supplied
Nabumetone () Tablets, USP are available containing 500 mg or 750 mg of Nabumetone () .
The 500 mg tablets are white to off white, film-coated, capsule-shaped unscored tablets, debossed with ‘’ on one side and plain on the other side. They are available as follows:
NDC 0378-3015-91bottles of 60 tablets
NDC 0378-3015-01bottles of 100 tablets
NDC 0378-3015-05bottles of 500 tablets
The 750 mg tablets are orange, film-coated, capsule-shaped unscored tablets, debossed with ‘’ on one side and plain on the other side. They are available as follows:
NDC 0378-3016-91bottles of 60 tablets
NDC 0378-3016-01bottles of 100 tablets
NDC 0378-3016-05bottles of 500 tablets
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Nabumetone () Medication Guide For Non-steroidal Anti-inflammatory Drugs (nsaids)
NSAID medicines are used to treat pain and redness, swelling and heat (inflammation) from medical conditions such as:
These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.
Manufactured in India by: Secunderabad — 500 003, IndiaCode No. MH/DRUGS/25/NKD/89
Distributed by: Morgantown, WV 26505 U.S.A.
75001405
NOVEMBER 2008MX:NABU:R1mc
Nabumetone ()
Nabumetone ()
