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Meclofenamate (Meclofenamate Sodium) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

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 meclofenamate sodium in administered with aspirin, its protein binding is reduced, although the clearance of free meclofenamate sodium is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of meclofenamate sodium capsules and aspirin is not generally recommended because of the potential of increased adverse effects.

Furosemide: Clinical studies, as well as post-marketing observations, have shown that meclofenamate sodium 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 PRECAUTIONS: Renal Effects), 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.

OVERDOSAGE

The following is based on the little information available concerning overdosage with meclofenamate sodium and related compounds. After a massive overdose, CNS stimulation may be manifested by irrational behavior, marked agitation and generalized seizures. Following this phase, renal toxicity (falling urine output, rising creatinine, abnormal urinary cellular elements) may be noted with possible oliguria or anuria and azotemia. A 24 year-old male was anuric for approximately one week after ingesting an overdose of 6 to 7 grams of meclofenamate sodium. Spontaneous diuresis and recovery subsequently occurred.

Management consists of emptying the stomach by emesis or lavage and instilling an ample dose of activated charcoal into the stomach. There is some evidence that charcoal will actively absorb meclofenamate sodium, but dialysis or hemoperfusion may be less effective because of plasma protein binding. The seizures should be controlled by an appropriate anticonvulsant regimen. Attention should be directed throughout, by careful monitoring, to the preservation of vital functions and fluid-electrolyte balance. Dialysis may be required to correct serious azotemia or electrolyte imbalance.

CONTRAINDICATIONS

Meclofenamate sodium capsules are contraindicated in patients with known hypersensitivity to meclofenamate sodium.

Meclofenamate sodium capsules 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 WARNINGS: Anaphylactoid Reactions and PRECAUTIONS: Preexisting Asthma).

Meclofenamate sodium capsules are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

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