Allopathy
Prescription Required
DCGI (Drugs Controller General of India)
Schedule H
Nabumetone is an sympathomimetic amines belonging to Non-Steroidal anti-inflammatory drug.
Nabumetone is used in the treatment of Osteoarthritis and Rheumatoid arthritis.
Nabumetone is Well absorbed from the GI tract. Bioavailability: Approx 35 % (6-MNA). Time to peak plasma concentration: Approx 3 hr (6-MNA) and Diffuses into synovial fluid. Crosses placenta and enters breast milk. Volume of distribution 7.5 L (6-MNA). Plasma protein binding: >99% (6-MNA).It Undergoes rapid and extensive first-pass metabolism in the liver into active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), and some inactive metabolites; further metabolised via O-methylation and conjugation. It get excreted Via urine (approx 80% as inactive or conjugated metabolites, <1% as unchanged 6-MNA; faeces (9%). Elimination half-life: Approx 24 hr (6-MNA).The Tmax of Nabumetone is approximately 1-4 hours.
Nabumetone shows common side effects like headache dizziness nausea stomach pain constipation swelling of the hands, feet, and ankles mild rash ringing in the ears sensitivity to the sun
Nabumetone is available in the form of tablets.
Nabumetone is available in India, Germany, Canada, Italy, USA.
Nabumetone is a naphthylalkanone derivative, non-active prodrug which is converted to the active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA) which is structurally similar to naproxen. 6-MNA reversibly inhibits cyclooxygenase-1 and 2 enzymes resulting in inhibition of prostaglandin synthesis.
Nabumetone is available in the form of tablets.
Oral: Administer with or without foodNabumetone is used in the treatment of Osteoarthritis and Rheumatoid arthritis.
Nabumetone is a naphthylalkanone derivative, non-active prodrug which is converted to the active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA) which is structurally similar to naproxen. 6-MNA reversibly inhibits cyclooxygenase-1 and 2 enzymes resulting in inhibition of prostaglandin synthesis.
Nabumetone is approved for use in the following clinical indications
Osteoarthritis: Relief of signs and symptoms of osteoarthritis.
Rheumatoid arthritis: Relief of signs and symptoms of rheumatoid arthritis.
- Osteoarthritis: Oral: Initial: 1 g as a single dose; adjust dose based on patient response up to 2 g/day in 1 to 2 divided doses; doses >2 g/day have not been studied.
- Rheumatoid arthritis: Oral: Initial: 1 g as a single dose; adjust dose based on patient response up to 2 g/day in 1 to 2 divided doses; doses >2 g/day have not been studied.
Nabumetone is available in various strengths as 500 mg, 750 mg.
Nabumetone is available in the form of tablets.
- Dosage Adjustment in Kidney Patient
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 49 mL/minute: Initial maximum dose: 750 mg once daily; maximum 1.5 g/day.
CrCl <30 mL/minute: Initial maximum dose: 500 mg once daily; maximum 1 g/day.
Hemodialysis: Nondialyzable.
KDIGO 2012 guidelines provide the following recommendations for NSAIDs:
eGFR 30 to <60 mL/minute/1.73 m2: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.
eGFR <30 mL/minute/1.73 m2: Avoid use.
Hypersensitivity to nabumetone or any component of the formulation; history of asthma, urticaria, or allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs); use in the setting of coronary artery bypass graft surgery.
Concerns related to adverse effects:
- Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.
- Cardiovascular events: Relative risk of serious adverse cardiovascular thrombotic events appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor blood pressure; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure.Avoid use in patients with a recent myocardial infarction (MI) unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.
- CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
- Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.
- GI events: Avoid use in patients with active GI bleeding due to increased risk of serious GI events. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis. Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended.
- Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).
- Hepatic effects: Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal) severe hepatic reactions (eg, fulminant hepatitis, liver necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if signs or symptoms of hepatic disease develop or if systemic manifestations occur.
- Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.
- Photosensitivity reactions: May cause photosensitivity reactions.
- Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, heart failure, hypovolemia, hepatic impairment, those taking diuretics and ACE inhibitors, and elderly patients are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.
- Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning, discontinue use at first sign of skin rash (or any other hypersensitivity).
- Common Adverse effects:
Headache dizziness nausea stomach pain constipation swelling of the hands, feet, and ankles mild rash ringing in the ears sensitivity to the sun
- Less Common Adverse effects:
Burning feeling in the chest or stomach, indigestion, stomach tenderness or upset swelling or inflammation of the mouth vomiting
- Rare Common Adverse effects:
Bleeding gums blistering, peeling, loosening of the skin bloody or black, tarry stools bloody or cloudy urine burning upper abdominal or stomach pain changes in vision chest pain or tightness chills clay-colored stools constipation cough dark-colored urine diarrhea difficulty swallowing
Increased risk of GI bleeding w/ corticosteroids, anticoagulants (e.g. warfarin), SSRIs, antiplatelets (e.g. clopidogrel). May induce hyperkalaemia w/ ACE-inhibitors. May decrease elimination of lithium, methotrexate. Increased risk of nephrotoxicity w/ ciclosporin, tacrolimus. Increased risk of haematological toxicity w/ zidovudine.
Potentially Fatal: Increased GI complications w/ other NSAIDs (e.g. aspirin).
The common side effects of Nabumetone include the following Insomnia, Dizziness, Headache, Dry mouth, Nervousness, Restlessness, Diarrhea, Constipation, Increased heart rate, High blood pressure.
Symptoms: Headache, nausea, vomiting, epigastric pain, GI bleeding, diarrhoea, disorientation, excitation, coma, drowsiness, tinnitus, convulsions. Acute renal failure, liver damage.
Management: Symptomatic and supportive treatment. Consider admin of activated charcoal. Perform gastric lavage immediately following large ingestion. Convulsions can be treated w/ IV diazepam. Ensure good urine output.
Pharmacodynamics
Nabumetone is a sympathomimetic stimulant drug marketed as an appetite suppressant. Chemically, it is the N,N-diethyl analog of cathinone. Its mechanism of action is similar to other appetite suppressants such as sibutramine, phentermine and dextroamphetamine.
Pharmacokinetics
- Abosrption: Well absorbed from the GI tract. Bioavailability: Approx 35 % (6-MNA). Time to peak plasma concentration: Approx 3 hr (6-MNA).
- Distribution: Diffuses into synovial fluid. Crosses placenta and enters breast milk. Volume of distribution 7.5 L (6-MNA). Plasma protein binding: >99% (6-MNA).
- Metabolism: Undergoes rapid and extensive first-pass metabolism in the liver into active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), and some inactive metabolites; further metabolized via O-methylation and conjugation.
- Excretion: Via urine (approx 80% as inactive or conjugated metabolites, <1% as unchanged 6-MNA; faeces (9%). Elimination half-life: Approx 24 hr (6-MNA).
- https://clinicaltrials.gov/ct2/show/NCT04430790
- https://clinicaltrials.gov/ct2/show/NCT02820025
- https://pubmed.ncbi.nlm.nih.gov/27612991/
- https://clinicaltrials.gov/ct2/show/NCT03894189
- https://www.rxlist.com/dopram-drug.htm
- https://www.mims.com/india/drug/info/Nabumetone?type=full&mtype=generic
- https://go.drugbank.com/drugs/DB00561
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/
