Nabumetone

Drug Interactions ACE-Inhibitors 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. Aspirin 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.

Diuretics 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. Lithium 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. Methotrexate 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. Warfarin 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 ].

Pregnancy 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 ]. 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…

Nursing Mothers 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.