Nabumetone : Drug class, uses, dosage, side effects and interactions

Relafen (Nabumetone): Side Effects, Interactions, Warning, Dosage

What is nabumetone?

Nabumetone is a nonsteroidal anti-inflammatory agent from the diclofenac family which is named as aryl alkanoic acid family. It is marketed under the brand name Relafen. Unlike other NSAIDs, nabumetone seems to have a lower risk of gastrointestinal side effects.

Nabumetone molecular structure, formula, weight, IUPAC name and srug class

IUPAC name: 4-(6-methoxynaphthalen-2-yl)butan-2-one

Molecular formula: C15H16O2

Molecular weight: 228.3 g/mol

Drug class: Nabumetone belongs to the class of organic compounds known as naphthalenes which are compounds containing a naphthalene moiety, that consists of two fused benzene rings.
Molecular structure:

nabumetone molecular structure

The mechanism of action of nabumetone

Nabumetone is a nonsteroid anti-inflammatory agent and its active component is a potent inhibitor of prostaglandin synthesis. It acts by binding the receptors named COX-1 and COX-2 thereby inhibiting the prostaglandin synthesis. The parent compound of this drug is a prodrug which biotransformed into active component after undergoing hepatic metabolism. The active component of nabumetone is 6MNA (6-methoxy-2-naphthyl acetic acid).

Pharmacokinetics of nabumetone

Nabumetone is rapidly and well absorbed from gastrointestinal tract. The rate of absorption is increased when co-administration with food and also the appearance of its active metabolite (6MNA) in plasma is increased with concurrent administration of food. The active metabolite of nabumetone (6MNA) effectively bound to plasma protein (more than 99%). It is metabolized into its principal active metabolite (6-methoxy-2-naphthyl acetic acid) followed by rapid biotransformation.  Half of the administered dose of nabumetone gets converted into unidentified metabolites which excreted in the urine. The elimination half-life of nabumetone is 23 hours, which is estimated for its active metabolite, 6-MNA. In patients with impaired renal function, the half-life is increased.

How long nabumetone stays in your system?

The elimination half-life of nabumetone is 23 hours and the elimination of the drug takes place is equal to 5 times to that of elimination half-life. Therefore nabumetone will be out of your system in 5 to 6 days completely.

What are the indications of nabumetone?

Nabumetone is mainly indicated for the treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis. One should use the minimum effective dose and should also be used for the shortest duration which should remain consistent with treatment goals in a patient.

Nabumetone dosage for rheumatoid arthritis and osteoarthritis

The recommended starting dose of nabumetone 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 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. 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.

What are the side effects of the nabumetone?

Nabumetone can cause serious side effects, you should seek emergency medical help in case you have signs such as hives, swelling of the face, lips, tongue, or throat or difficulty in breathing. Stop immediately taking nabumetone if you see any of following side effects:

  • Chest pain, weakness, shortness of breath, slurred speech, problems with vision or balance
  • Black, bloody, or tarry stools
  • A cough associated with blood
  • Vomit like coffee grounds
  • Weight gain or swelling of the body
  • Urinating less than usual
  • No urination at all
  • Nausea, stomach pain, fever, loss of appetite, dark urine
  • Clay-colored stools
  • Yellowing of skin and eyes (Jaundice)
  • A sore throat, headache with skin rashes or bruising, severe tingling, numbness, pain, muscle weakness
  • Severe peeling or blistering of the skin often accompanied by a headache
  • Severe peeling or blistering of skin, often accompanied with headache

Less serious side effects of the nabumetone include:

  • Upset stomach, mild heartburn, stomach pain, diarrhoea, and constipation
  • Bloating and gas
  • A headache, nervousness, and dizziness
  • Skin rashes and itching of the skin
  • Vision disturbances
  • Ringing in ears
  • Blurred vision

Here the list of side effects given is not complete, you may suffer from other complicated or uncomplicated side effects, in such case, contact your doctor immediately.

Can nabumetone be taken with alcohol?

Nabumetone should never be administered with alcohol as their concurrent administration may cause severe gastrointestinal blood loss. It can also cause the reduced integrity of gastrointestinal lining because of combined local effects as well as combined inhibition of prostaglandins. You should refrain yourself from consuming alcohol while taking nabumetone or other potential NSAIDs.

Can nabumetone be taken with Aspirin?

The potential for serious gastrointestinal toxicity such as inflammation, bleeding, ulceration, and perforation is seen when low or high dose aspirin is taken along with nabumetone or other nonsteroidal anti-inflammatory drugs (NSAIDs). The plasma concentration of many NSAIDs may be reduced by concurrent administration of NSAIDs which range from small (in case of drugs like piroxicam, meloxicam, naproxen, tolmetin etc.) to the substantial (in case of drugs like flurbiprofen, ibuprofen etc.). However the factor that does not appear to be effective is therapeutic effect. The mechanism behind the reduced efficacy of NSAID is that aspirin may replace the NSAIDs from the actual plasma protein binding sites which may result in an enhanced concentration of free or unbound drug, or the drug available for clearance. This may also be responsible for some contributory anti-inflammatory effects from the aspirin and may result in an overall reduced therapeutic response.

One should practice the caution, when aspirin is co-administered with other NSAIDs such as nabumetone, especially at anti-inflammatory dosages. Due to the risk of adverse effects, the concurrent therapy is not advised. In case the administration is necessary the patient should be advised to take the medication along with food and he should also consult for reporting to the doctor in case of severe signs and symptoms of gastric ulceration. (like abdominal pain, bleeding, bloating, sudden dizziness, or lightheadedness, nausea, vomiting, and anorexia.

What should be done in case of nabumetone overdose?

An overdose of NSAIDs such as nabumetone can cause lethargy, drowsiness, nausea, vomiting, and epigastric pain which can be treated with supportive care. One can also suffer from gastrointestinal bleeding. Some rare symptoms such as hypertension, acute renal failure, and respiratory depression can also occur.

After NSAIDs overdose, the patient should be managed by symptomatic and supportive care. There are no specific antidotes. In patients with the symptoms of NSAIDs overdose, emesis, activated charcoal or osmotic cathartic can be used. As nabumetone is highly protein bound, the methods such as forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not prove of much use.

Is nabumetone an opiate?

Nabumetone belongs to the non-steroidal anti-inflammatory drugs class and is used for joint pain and arthritis. It works by reducing hormones which are responsible for inflammation and pain in the body. Therefore it is not an opiate and also it cannot get you high.

Can nabumetone be taken during pregnancy?

Nabumetone comes under the pregnancy category C, which means there are no sufficient and well-controlled studies are given in humans, and animal reproduction studies showed the adverse effects on the fetus. It can be used for human only when benefit outweighs the potential risks. This medication is not recommended in the last trimester of pregnancy as it can cause premature closure of ductus arterious. This medication is also not recommended in the women who are planning to get pregnant because it can impair the fertility of such women.

Can nabumetone be taken while breastfeeding?

Administration of other agents in case of joint pain or arthritis while breastfeeding is recommended due to lack of published clinical data. One should make a decision for either to stop the breastfeeding or to stop the medication, followed by the consideration of which one is important. This drug is not to get excreted into the human milk, however, the effect of this drug on the nursing infant is unknown.

Can nabumetone be taken during pregnancy?

Nabumetone comes under the pregnancy category C, which means there are no sufficient and well-controlled studies are given in humans, and animal reproduction studies showed the adverse effects on the fetus. It can be used for human only when benefit outweighs the potential risks. This medication is not recommended in the last trimester of pregnancy as it can cause premature closure of ductus arterious. This medication is also not recommended in the women who are planning to get pregnant because it can impair the fertility of such women.

What are the contraindications of nabumetone?

Nabumetone is contraindicated in patients who have known hypersensitivity to nabumetone or to any ingredient present in the nabumetone formulation. Or in the patients, who have a history of the conditions like asthma, urticaria, or other sensitivity reaction precipitated by aspirin, or in patients who have undergone cardiac artery bypass grafting (CABG) surgery.

Can nabumetone increase the cardiovascular risk?

In patients with or without cardiovascular diseases or who have risk factors of cardiovascular disease, drugs like NSAIDs mainly COX2 inhibitor can increase the risk of serious adverse cardiovascular thrombotic events such as myocardial infarction (MI), stroke etc. As per recent FDA reports, these medications (NSAIAs) can increase the risk of such events by 10-50% or more (depend upon the dosage of drugs). There is an increase in the risk of cardiovascular events in patient with or without cardiovascular diseases, however, the incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in patients who are suffering from cardiovascular diseases as they already have elevated baseline risk. After initiation of the therapy, the risk can be increased and also risk can appear early (most likely in few first weeks). Also, the risk can be increased with duration and high doses.

Can nabumetone cause constipation?

Yes, nabumetone can cause constipation as a common gastrointestinal side effect. The most common gastrointestinal side effects of nabumetone are diarrhea, dyspepsia, and abdominal pain. The common side effects of (in 1% to 10%) nabumetone are constipation, flatulence, nausea, positive stool guaiac, gastritis, dry mouth, stomatitis, and vomiting. Some other gastrointestinal side effects are a duodenal ulcer, gastrointestinal bleeding, gastric ulcers, or stomatitis but they are uncommon or rare.

Can nabumetone be used for a migraine?

Yes, nabumetone can also use for the prevention of tension headaches, and migraine. Just like other painkillers or NSAIDs, if taken before the main headache stage, nabumetone and other painkillers can prevent the condition from getting worse. As per the study, it is proved safe and effective for a migraine, however, the number of studies has been a few. Moreover, no new studies have been published on the same, therefore one must talk to your doctor before switching to nabumetone for a migraine.

Can nabumetone be used in patients with high blood pressure?

Use of nonsteroidal anti-inflammatory drugs is reported to be associated with fluid retention and edema. In patients with preexisting fluid retention, hypertension, or even a history of heart attack, the NSAIDs therapy should be used with extreme caution. During the initiation and throughout the course of the NSAIDs treatment, the close monitoring of blood pressure and cardiovascular status should be done.

Can nabumetone cause high blood pressure?

The onset of new hypertension or worsening of pre-existing hypertension can occur due to nabumetone or other NSAIDs. Such incidents can even enhance the risk of cardiovascular events. Therefore in patients with existing hypertension, the NSAIDs therapy should be used with extreme caution. Close monitoring of the patient for blood pressure and cardiovascular status should be done.

Can nabumetone be taken in patients with asthma

Approximately 10% of patients with asthma may have aspirin-sensitive asthma, characterized by nasal polyposis, pansinusitis, eosinophilia, and precipitation of asthma and rhinitis attacks after ingestion of aspirin. The use of aspirin in these patients has been associated with severe bronchospasm and fatal anaphylactoid reactions. Since cross-sensitivity has been noted between aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) including nabumetone, therapy with any NSAID should be avoided in asthmatic patients with a history of aspirin or other NSAID sensitivity, and administered cautiously in all patients with preexisting asthma. Prior to initiating therapy with NSAIDs, patients should be questioned about previous allergic-type reactions to these agents. Salicylate salts, salsalate, salicylamide, and acetaminophen may be appropriate alternatives in patients with a history of NSAID-induced bronchospasm, since cross-sensitivity to these agents appears to be low. However, cross-sensitivity has been demonstrated occasionally with high dosages of these agents (e.g., acetaminophen >= 1000 mg), thus it may be appropriate to initiate therapy with low dosages and increase gradually. There is some evidence suggesting that COX-2 inhibitors may be safely used in patients with aspirin-sensitive asthma, although the labeling for these products contraindicate such use. If necessary, aspirin desensitization may also be attempted in some patients under medical surveillance.

Can nabumetone be taken with diuretics?

Nabumetone can decrease the natriuretic effect of furosemide and thiazides such as chlorothiazide in some patients as per post marketing observations. This response has been attributed to inhibition of the renal prostaglandin synthesis. Renal failure can occur in such patients, therefore, they should be monitored closely during concomitant therapy. The diuretic efficacy should also be monitored.

Can nabumetone be taken with lithium?

An elevation in plasma lithium levels and reduction in renal lithium clearance have been reported in patients receiving NSAIDs therapy. Approximately 15% increased lithium concentration and 20% reduction in renal lithium renal concentration was noted. NSAIDs can attribute to the inhibition of the prostaglandin synthesis. The patients should be monitored carefully for the signs of the lithium toxicity, during concurrent administration of the lithium and NSAIDs.

Can nabumetone be taken with methotrexate?

As per a study done on the rabbits, the NSAIDs have been reported to inhibit the methotrexate accumulation competitively in rabbits kidney. It means that they can enhance the toxicity of the methotrexate. When NSAIDs are administered with methotrexate, the caution is needed.

Can nabumetone be taken with warfarin?

Gastrointestinal bleeding can be increased when NSAIDs and warfarin are administered together because they show synergistic effects on gastrointestinal bleeding. The risk is higher in patients who take both drugs together as compared to either drug alone.

Can nabumetone be taken with naproxen?

No, nabumetone should not be administered with naproxen because naproxen is also a nonsteroidal anti-inflammatory drug and the recommended maximum number of medicine in this category (NSAIDs) to be taken is ONE. This combination can outweigh any risks associated with therapeutic duplication. However, you should always check with your doctor, before reaching any conclusion. You can even ask for any dose adjustment needed in this regard.

What if I miss nabumetone dose?

If you miss a dose of nabumetone, take it as soon as you remember, unless it’s almost time for your next dose. In that case, skip the missed dose and continue on your regular medication schedule. Do not double up on doses to make up for a missed one.

How Humira works? What are its uses and how to take it?

About Miljan Krcobic 326 Articles
Miljan Krčobić. has bachelor degree in Pharmacy.