Mefenamic acid interaction

J Lithium-mefenamic acid interaction Quoted by Ayd FJ. Int Drug Ther Newslett... 

Mefenamic acid may have interacted with lithium in a patient with reduced renal function (SEDA-13, 83) (684). 

As shown in Equations 20 and 21, the uncoupling activity and antiinflammatory activity of fenamic acid analogs, including flufenamic and mefenamic acids, are very similar in their dependence on both hydro-phobic and electronic effects of substituents. In these equations, the subscript, i, means that the drug activities are calculated on the basis of concentration of the ionized form. It has been suggested that these two biological effects, which are also observed in many other acidic antiinflammatory drugs, have similar physicochemical mechanisms in the interaction with receptors (44). 

Clinically important, potentially hazardous interactions with acitretin, aldesleukin, aminoglycosides, amiodarone, amoxicillin, ampicillin, aspirin, bacampicillin, bismuth, carbenicillin, chloroquine, cisplatin, cloxacillin, co-trimoxazole, dapsone, demeclocycline, dexamethasone, diclofenac, dicloxacillin, etodolac, etoricoxib, etretinate, fenoprofen, flurbiprofen, folic acid antagonists, haloperidol, hydrocortisone, ibuprofen, indomethacin, influenza vaccines, ketoprofen, ketorolac, lithium, magnesium trisalicylate, meclofenamate, mefenamic acid, methicillin, mezlocillin, minocycline, nabumetone, nafcillin, naproxen, NSAIDs, omeprazole, oxacillin, oxaprozin, oxytetracycline, paromomycin, penicillin G, penicillin V, penicillins, phenylbutazone, piperacillin, piroxicam, polypeptide antibiotics, prednisolone, prednisone, probenecid, procarbazine, rofecoxib, salicylates, salsalate, sapropterin, sulfadiazine, sulfamethoxazole, sulfapyridine, sulfasalazine, sulfisoxazole, sulindac, tazobactum, tenoxicam, tetracycline, ticarcillin, tolmetin, trimethoprim, vaccines... 

The pKa values of the N-arylanthranilic acids (4.0-4.2) resemble those of the arylalkanoic acids thus, it is not surprising that they are strongly bound to plasma proteins and that interactions with other highly protein bound drugs are very probable. The most common interactions reported are those of mefenamic acid and meclofenamic acid with oral anticoagulants. Concurrent administration of aspirin results in a reduction of plasma levels of meclofenamic acid. 

Information is very limited but it would appear that if rapid analgesia is needed with either mefenamic acid or tolfenamic acid, magnesium hydroxide can be given concurrently but aluminium hydroxide should be avoided. However, note that this applies to the fasted state, whereas NSAIDs are usually taken with or after food. Also note that magnesium hydroxide increased the endoscopically-detected gastric toxicity of ibuprofen in one study, see NSAIDs Ibuprofen and related drugs -i- Antacids , below. Aluminium hydroxide markedly reduces the speed of absorption. Sodium bicarbonate does not interact. Consider also NSAIDs Miscellaneous + Antacids , p.l42. 

A number of cases of convulsions have been seen in Japanese patients given fenbufen with enoxacin, and there is also one possible case involving ofloxacin. Use of these particular drugs together should be avoided. Normally no interaction seems to occur with most quinolones and NSAIDs, except where there is a predisposition to convulsive episodes. Isolated cases of convulsions, other neurological toxicity or skin eruptions have been seen when ciprofloxacin was given with indometacin, mefenamic acid or naproxen. These appear to be very rare events. 

Uncertain. Mefenamic acid can displace warfarin from its plasma protein binding sites, and in vitro studies have shown that therapeutic concentrations (equivalent to 4 g daily) can increase the unhound and active warfarin concentrations by 140 to 340%, but this interaction mechanism alone is only likely to have a transient eifect. See also Coumarins and related drugs + NSAIDs , p.427. 

Acute lithium toxicity, accompanied by a sharp deterioration in renal function, was seen in a patient taking lithium carbonate with mefenamic acid 500 mg three times daily for 2 weeks. Withdrawal of the drugs and subsequent rechallenge confirmed this interaction." Another case of toxicity was seen in a patient on lithium given mefenamic acid. Her renal function was impaired when the lithium was started, but it had been stable for about 6 months before the NSALD was added." A brief report also mentions another case of this interaction."... 

IvfecDonald J, Neale TJ. Toxic interaction of Ulhium carbonate and mefenamic acid. BMJ... 

Shelley RK. Lithium toxicity and mefenamic acid apossible interaction and the role of prostaglandin inhibition. BrJP chiatry 9 7) 151, 84/-8. 

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