Classic nonsteroid antiinflammatory drugs

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The group of acidic antiphlogistics shows only a very low M/P ratio -distinctly under ! - because of its acidity and its high plasma binding (up to 99%). With a daily intravenous administration of 1200mg aza-propazone, the dosage that reaches the infant via the mother's milk is calculated to be O.Sing/kg, or 4% of the maternal weight-related dosage at maximum (Bald 1990).

Diclofenac and flufenamic acid also have short half-lives. The amount that passes into the mother's milk is, apparently, minimal. With flufenamic acid, it is a maximum of 0.2% (Buchanan 1969A). The importance of the active metabolites in diclofenac is unclear.

Ibuprofen has a half-life of only 2 hours. Following therapeutic administration of 800-1600 mg daily, it could not be detected in the mother's milk. The detection limit in both of the available studies was given as 1 or 0.5 mg/1. There have been no reports of any side effects on breastfed children (Townsend 1984, Wcibert 1983), including in a prospective study covering 21 mother-child pairs (Ito 1993).

The half-life of flurbiprofen is 3 hours. After administration for 3 days postpartum, using 100-200 mg daily, it could only be detected at a maximum level of 0.08 mg/1 in 3 milk samples during a study of 12 women. Thus, an infant receives 0.012 mg/kg per day or, at most, 0.5% of the maternal dosage per kg of bodyweight. No toxic effects have been described (Smith 1989, Cox 1987).

Indoprofen and suprofen can be similarly rated.

Following the ingestion of indomethacin, a seizure attack was observed in one breastfed infant (Eeg-OIofsson 1978). However, in a study of 16 mothers who received 75-300 mg daily for several days, only a maximum of 1% of the maternal weight-related dosage was calculated for the children. They showed no symptoms (Lebedevs 1991).

For ketorolac, a maximum of 0.3% of the maternal weight-related dosage is calculated for the infant (Wischnik 1989).

In the case of long-term therapy of a mother with naproxen, a maximum relative dosage of 3.6% was indicated for the infant (Jamali 1983). In another case of long-term therapy, a prolonged aggregation time for prothrombin and thrombocytes was found (Fidalgo 1989). Of 20 treated mothers, 10 reported slight sedation in their breastfed infants (Ito 1993).

With piroxicam, there is a transfer of about 8%. However, no substance could be detected in the serum of the clinically unremarkable infant (Ostensen 1988). Half-lives of naproxen and piroxicam are 14 and up to 60 hours respectively - considerably longer than those in the antiphlogistics previously mentioned.

Mefenamic acid and tenoxicam pass into the milk at a maximum level of 0.8% of the relative dosage (Heintz 1993, Buchanan 1969B).

There is insufficient experience to evaluate the other nonsteroid antirheumatics, including acemetacin, dexketoprojen, etofenamat, fen-bufen, ketoprofen, lonazolac, lornoxicam, meloxicam, nabumetone, niflumic acid, nimesulide, proglumetacin, sulindac, and tiaprofen.

Recommendation. Among the nonsteroid antirheumatics, the acidic antiphlogistics ibuprofen and flurbiprofen are the drugs of choice during breastfeeding. Occasional use of azapropazon, diclofenac, and flufenamic acid is also permissible. Accidental administration of one of the other nonsteroid antirheumatics does not require any limitation of breastfeeding, although the medication should be changed.

4 1.6 Pyrazolone- and phenylbutazone derivatives

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