MEFENAMIC ACID
Drugs in Pregnancy and Lactation.
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Name: MEFENAMIC ACID
Class: Nonsteroidal Anti-inflammatory
Risk Factor: CM*
Fetal Risk Summary
Mefenamic acid, a nonsteroidal anti-inflammatory drug (NSAID), is used for the short-term treatment of pain and for primary dysmenorrhea. It is in the same NSAID subclass (fenamates) as meclofenamate.
Although mefenamic acid causes toxic effects in pregnant animals similar to those produced by other agents in this class (decreased fertility, delayed parturition, increase in the number of resorptions, and decreased pup survival), no congenital malformations were observed in studies involving rats, rabbits, and dogs at doses up to 10 times those used in humans (1). In one study of pregnant rats, inhibition of parturition by mefenamic acid appeared to be dose-related (2).
Consistent with its low molecular weight (about 241), mefenamic acid crosses the human placenta to the fetus. Fetal concentrations of the drug, 40180 minutes after a 500-mg dose administered to 13 women at 1522 weeks' gestation, were 32%54% of the maternal plasma concentrations (3).
A combined 2001 population-based observational cohort study and a case-control study estimated the risk of adverse pregnancy outcome from the use of NSAIDs (4). The use of NSAIDs during pregnancy was not associated with congenital malformations, preterm delivery, or low birth weight, but a positive association was discovered with spontaneous abortions (SABs) (see Ibuprofen for details).
Mefenamic acid, 500 mg 3 times a day, was used as a tocolytic in a double-blind, randomized human study (5). Compared with controls, preterm delivery occurred less in the mefenamic acid group (15% vs 40%, p<0.005), and birth weights were higher. No adverse effects were observed in the newborns exposed in utero to mefenamic acid.
An infant, delivered by urgent cesarean section at 34 weeks' gestation, had marked cyanosis after in utero exposure to mefenamic acid used to prevent premature delivery (6). Echocardiography of the infant demonstrated a small (1- to 2-mm) patent ductus arteriosus. The authors concluded that the maternal drug therapy was responsible for the premature closure of the ductus.
Constriction of the ductus arteriosus in utero is a pharmacologic consequence arising from the use of prostaglandin synthesis inhibitors during pregnancy, as is inhibition of labor, prolongation of pregnancy, and suppression of fetal renal function (see also Indomethacin) (7). Persistent pulmonary hypertension of the newborn may occur if these agents are used in the 3rd trimester close to delivery (7). Women attempting to conceive should not use any prostaglandin synthesis inhibitor, including mefenamic acid, because of the findings in a variety of animal models that indicate these agents block blastocyst implantation (8,9). Moreover, as noted above, NSAIDs have been associated with SABs.
[*Risk Factor D if used in 3rd trimester or near delivery.]
Breast Feeding Summary
Small amounts of mefenamic acid are excreted into breast milk and absorbed by the nursing infant (10). Ten nursing mothers in the immediate postpartum period were given a 500-mg oral loading dose followed by 250 mg 3 times daily for 3 days. Blood and milk samples were obtained 2 hours after the first daily dose on postpartum days 24. Blood and urine samples were obtained from the infants 1 hour after nursing on postpartum day 4. The averages of the mean daily concentrations of mefenamic acid in maternal plasma and milk were 0.94 and 0.17 ΅g/mL, respectively, corresponding to a milk:plasma ratio of 0.18. In three of the mothers, breast milk concentrations of mefenamic acid plus metabolites ranged from 0.62 to 1.99 ΅g/mL. The mean infant blood concentration of mefenamic acid was 0.08 ΅g/mL, whereas the mean urine concentration of mefenamic acid plus metabolites was 9.8 ΅g/mL.
One reviewer concluded that, because of the potential toxicity of mefenamic acid, other agents (diclofenac, fenoprofen, flurbiprofen, ibuprofen, ketoprofen, ketorolac, and tolmetin) were safer alternatives if a NSAID was required during nursing (11). However, the American Academy of Pediatrics classifies mefenamic acid as usually compatible with breast feeding (12).
References
- Product information. Ponstel. Parke-Davis, 1995.
- Powell JG Jr, Cochrane RL. The effects of a number of non-steroidal anti-inflammatory compounds on parturition in the rat. Prostaglandins 1982;23:46988.
- MacKenzie IZ, Graf AK, Mitchell MD. Prostaglandins in the fetal circulation following maternal ingestion of a prostaglandin synthetase inhibitor during mid-pregnancy. Int J Gynaecol Obstet 1985;23:4558.
- Nielsen GL, Sorensen HT, Larsen H, Pedersen L. Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study. Br Med J 2001;322:26670.
- Mital P, Garg S, Khuteta RP, Khuteta S, Mital P. Mefenamic acid in prevention of premature labor. J R Soc Health 1992;112:2146.
- Menahem S. Administration of prostaglandin inhibitors to the mother; the potential risk to the fetus and neonate with duct-dependent circulation. Reprod Fertil Dev 1991;3:48994.
- Levin DL. Effects of inhibition of prostaglandin synthesis on fetal development, oxygenation, and the fetal circulation. Semin Perinatol 1980;4:3544.
- Matt DW, Borzelleca JF. Toxic effects on the female reproductive system during pregnancy, parturition, and lactation. In Witorsch RJ, ed. Reproductive Toxicology. 2nd ed. New York, NY: Raven Press, 1995:17593.
- Dawood MY. Nonsteroidal anti-inflammatory drugs and reproduction. Am J Obstet Gynecol 1993;169:125565.
- Buchanan RA, Eaton CJ, Koeff ST, Kinkel AW. The breast milk excretion of mefenamic acid. Curr Ther Res Clin Exp 1968;10:5926.
- Anderson PO. Medication use while breast feeding a neonate. Neonatal Pharmacol Q 1993;2:314.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
Q&A about Mefenamic Acid
Can you take paracetamol/ ibuprofen/ mefenamic acid pills if you have an inflamed or swollen pimple? will it reduce the redness and pain since these drugs are anti-inflammatory, antipyretic and analgesic? will taking them orally be effective? how will they find their way to the pimple?
Some says its bad... I dont know why. Can it have some bad effect?
i went to the dentist for third molar extraction and i've found out that im 5 days pregnant at that time.i have experienced spotting and abdominal pain but gone after a few days.i had my ultrasound and the embryo are in good activity.the cervix is closed but subchorionic hemorrhage as described.it measures 1.5 X 1.7 X 0.8 cm.
my dog( a dalmatian) has a swollen front left leg, especially on the ankle part.
best of luck to your dog
i found that aspirin is associated with a deadly disease called reye syndrome, and aspirin and mefenamic acid are a bit similar...i know someone who have measles and has taken mefenamic acid, and im really bothered, pls help...tnx
I think your friend with Measles is probably quite safe.
do they match? i still get cramos while on the pill Mycrogynon 30 and i take mefenamic acid to treat the cramps, is it safe? does the effectiveness of the pill wear out?