Mefenamic acid dosing

Q4 What is the dose of mefenamic acid that can be given to a child of 3... 

The daily dosing regimen for this patient would be 25 mg X 15 kg = 375 mg. Mefenamic acid suspension is available as 50 mg/5 ml. The patient therefore must be given 37.5 ml to receive the total daily dose of 375 mg 37.5 ml divided into three doses in a day would be equivalent to 12.5 ml. This means that the patient must be given 10 ml on a three times daily (t.d.s.) basis. 

Mefenamic acid is given orally (1500 mg/day maximal dose). 

A patient who deliberately took potassium iodide solution 50 ml and a small dose of mefenamic acid (six capsules) as part of a suicide attempt developed acute renal insufficiency necessitating hemodialysis (72). Normal renal function returned after 10 days of hemodialysis. 

The authors postulated that iodide toxicity had resulted in hemolysis and hemoglobinuria, which, together with acute interstitial nephritis secondary to inhibition of prostaglandin synthesis from mefenamic acid ingestion, had resulted in acute renal insufficiency. The mechanism of hemolysis resulting from toxic doses of iodine is not clear, although it may reflect inhibition of various red cell enzymes. 

Figure 6.1 Plot of the fraction of dose absorbed for various drugs as a function of Z. Key A acyclovir B chlorothiazide solution D hydrochlorothiazide E phenytoin F prednisolone G digoxin (Lanoxicaps) I cimetidine J mefenamic acid.

Flufenamic acid and meclofenamic acid are anthranilic acid derivatives similar to mefenamic acid. The withdrawal rate because of adverse effects is 7-31% and is higher in longterm studies. Flufenamic acid and meclofenamic acid are not widely prescribed and so there is little evidence to show whether they have any advantages over other NSAIDs. Both have a high incidence of gastrointestinal adverse effects (30-60% of patients at recommended doses). Diarrhea affects 11 6% of patients (SEDA-4, 68) (SEDA-6, 99) (SEDA-7, 116) (SEDA-14, 95). Thrombocytopenia with positive rechallenge has been described (1). Rashes occur in under 10% of patients. Meclofenamic acid exacerbates psoriasis in psoriatic arthropathy (2). 

Five days before he presented with esophageal ulceration, a 35-year-old man took two capsules of mefenamic acid (total dose 500 mg) in bed with a small amount of water. The following morning he noted severe retrosternal pain, which persisted until he was seen 4 days later. Endoscopy showed a 3 cm esophageal ulcer near the aortic arch. Within a few days there was complete resolution of ulceration. 

The dosage of mefenamic acid that is used in preterm infants to induce closure of patent ductus arteriosus must not exceed 2 mg/kg/day in three divided doses, to avoid the danger of renal insufficiency (SEDA-19, 97). The promotion of mefenamic acid in Pakistan for fever in children, as a drug of unsurpassed efficacy compared to [paracetamol] in fever control and better tolerance , has been criticized by the Medical Lobby for Appropriate Marketing. In fact, there have been no controlled comparisons of mefenamic acid with a reference drug or placebo, and its safety and efficacy have not been established in children (SEDA-19, 97). 

The development of acute papillary necrosis, as a consequence of the use of a single NSAID, at recommended dosing levels, is an extremely rare event. In preclinical studies, nearly all of the NSAIDs produced papillary necrosis in experimental animal models. Although, as already identified, clinical toxicity is exceedingly rare it has been reported for ibuprofen [103], phenylbutazone [109,110], fenoprofen [105], and mefenamic acid [104] and, according to prescribing information, several other NSAIDs. 

The measurement of urinary uronic acid has been used as an early indicator in the development of renal papillary necrosis in rats given multiple doses of N-phenylanthranilic acid or mefenamic acid [217]. A significant elevation of uronic acid in urine occurred was well ahead of the development of histological evidence of renal papillary necrosis. The biochemical basis of these changes appears to be related to acid mucopolysaccharides accumulation [218]. 

Meclofenamate is indicated in the relief of mild to moderate pain (50 mg/6 hours) in the treatment of primary dysmenorrhea (100 mg t.i.d.) and in acnte and chronic rhenmatoid arthritis and osteoarthritis (200 to 400 mg/day in 3 to 4 equal doses). Meclofenamate is a nonsteroidal antiinflammatory agent that has analgesic and antipyretic properties. The menstrual cycle is associated with two potentially incapacitating events dysmenorrhea and the premenstrnal syndrome. Substantial evidence indicates that the excessive production of prostaglandin 2 is the major sonrce of painful menstruation. The nonsteroidal antiinflammatory drngs such as aspirin, ibuprofen, meclofenamate, mefenamic acid, and naproxen are used to treat dysmenorrhea. 

These drugs are absorbed rapidly and have short durations of action. In humans, approximately 50% of a dose of mefenamic acid is excreted in the urine, primarily as the 3-hydroxymethyl and 3-carboxyl metabolites and their conjugates. Twenty percent (20%) of the drug is recovered in the feces, mainly as the unconjugated 3-carboxyl metabolite. 

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