Is there a risk for the nursing infant if the mother is treated with Ketogan Novum (ketobemidone) a

Fråga: Is there a risk for the nursing infant if the mother is treated with Ketogan Novum (ketobemidone) and Meronem (meropenem)?

A woman, who was delivered a week ago has had hemorrhagic and infectious complications and is now treated with Ketogan in a PCA (patient-controlled analgesia) pump approximately 20-30 mg/day and Meronem 1g intravenous three times per day, wants to breast-feed her child.

Sammanfattning: Ketobemidone is considered safe in lactation. The data on meropenem are scarce, but it has been used in infants without signs of toxicity. However, it might possibly cause some intestinal symptoms.

Svar: Breast-feeding on ketobemidone has been investigated earlier and an update has not revealed any new information. After a dose of 5 mg subcutaneously to the mother the systemic dose to the child can be calculated to 1-2 ug (1). Assuming the higher calculation for intravenous administration, the nursing infant in this case will still get less than 10 ug/day of ketobemidone.

The breast-feeding data on meropenem are scanty. According to data-on-file low levels were detectable in milk in animal experiments and the oral bioavailability is said to be very low (2) or even nil (3). Another carbapenem antibiotic, imipenem/cilastatin, has been shown in a japanese study to pass to human milk in low concentrations "similar to other beta lactam antibiotics". Other beta lactam antibiotics pass to maternal milk in a milk:plasma ratio of 7% for ceftazidime, 3-4% for ceftriaxone, 16-21% for cefaclor, and 2-13% for penicillin G (4).

Assuming a milk:plasma ratio of 25% for meropenem and a maternal maximal plasma concentration of 50 mg/L, the milk concentration would be 13 mg/L. If the child weighs 4 kg and suckles 150 ml/kg, the exposure will be approximately 8 mg/day. This might alter bowel flora and cause intestinal discomfort, but might also cause resistant bacteria in the infants´ bowel. The systemic exposure will be negligible.

As a comparison, meropenem is used in septic infants at a dose of 20-40 mg/kg intravenous. three times daily (ie 7-15 times the exposure of the suckling child) (5). 1 Drugline no 15697 (year 1999).

2 Patrik Malmros, AstraZeneca AB, Södertälje, Sweden, personal communication 2003-02-13.
3 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999.
4 Briggs GB, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Baltimore: Williams & Wilkins; 2002.

5 FASS 2002 (The Swedish catalogue of approved medical products).