| Indication |
For the relief of mild to moderate pain, for the treatment of
primary dysmenorrhea and for the treatment of idiopathic heavy menstrual
blood loss. Also for relief of the signs and symptoms of acute and
chronic rheumatoid arthritis and osteoarthritis. |
| Pharmacodynamics |
Meclofenamic acid is a nonsteroidal agent which has demonstrated
anti-inflammatory, analgesic, and antipyretic activity in laboratory
animals. |
| Mechanism of action |
The mode of action, like that of other nonsteroidal
anti-inflammatory agents, is not known. Therapeutic action does not
result from pituitary-adrenal stimulation. In animal studies,
meclofenamic acid was found to inhibit prostaglandin synthesis and to
compete for binding at the prostaglandin receptor site. In vitro
meclofenamic acid was found to be an inhibitor of human leukocyte
5-lipoxygenase activity. These properties may be responsible for the
anti-inflammatory action of meclofenamic acid. There is no evidence that
meclofenamic acid alters the course of the underlying disease. |
| Absorption |
Rapidly absorbed in man following single and multiple oral doses
with peak plasma concentrations occurring in 0.5 to 2 hours. The
concomitant administration of antacids (aluminum and magnesium
hydroxides) does not interfere with absorption of meclofenamic acid.
Unlike most NSAIDs, which when administered with food have a decrease in
rate but not in extent of absorption, meclofenamic acid is decreased in
both. It has been reported that following the administration of
meclofenamic acid capsules one-half hour after a meal, the average
extent of bioavailability decreased by 26%, the average peak
concentration (Cmax) decreased fourfold and the time to Cmax was delayed by 3 hours. |
| Volume of distribution |
|
| Protein binding |
Greater than 99% bound to plasma proteins over a wide drug concentration range. |
| Metabolism |
Hepatic. Meclofenamic acid is extensively metabolized to an
active metabolite (Metabolite I; 3-hydroxymethyl metabolite of
meclofenamic acid) and at least six other less well characterized minor
metabolites. Only Metabolite I has been shown in vitro to inhibit
cyclooxygenase activity with approximately one fifth the activity of
meclofenamic acid. |
| Route of elimination |
Other metabolites, whose excretion rates are unknown, account for
the remaining 35% to 62% of the dose excreted in the urine. The
remainder of the administered dose (approximately 30%) is eliminated in
the feces (apparently through biliary excretion). Trace amounts of
meclofenamate sodium are excreted in human breast milk. |
| Half life |
In a study in 10 healthy subjects following a single oral dose the
apparent elimination half-life ranged from 0.8 to 5.3 hours. Metabolite
I (3-hydroxymethyl metabolite of meclofenamic acid) has a mean
half-life of approximately 15 hours. |
| Clearance |
|
| Toxicity |
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. |
