Table 3.
Summary of evidences for the use of second-line anti-tuberculosis drugs during pregnancy and breastfeeding (see separate word document)
| WHO Group | Drug | FDA Category | Animal and human evidences | Breastfeeding |
|---|---|---|---|---|
| A | Levofloxacin [1] | C | There are no or limited amount of data in pregnant women. No effect of foetuses in rats except for delayed maturation as a result of maternal toxicity. However, levofloxacin showed effects on cartilage (blistering and cavities) in rats and dogs. | No data in lactating or nursing women. However other fluoroquinolones are excreted in breast milk. |
| Moxifloxacin [2] | C | There are no or limited amount of data in pregnant women. Observed teratogenic potential in rabbits and rats at higher doses than those recommended in humans. | No data in lactating or nursing women. Preclinical data indicate that small amounts of moxifloxacin are secreted in milk | |
| Bedaquiline [3] | B | There are no or limited amount of data in pregnant women. No adverse effects observed in a pre- and post- natal development study in rats. | Unknown whether bedaquiline or its metabolites are excreted in human milk. In rats, bedaquiline concentrations in milk were 6- to 12-fold higher than the maximum concentration observed in maternal plasma | |
| Linezolid [4] | C | There are no or limited amount of data in pregnant women. Not teratogenic effect in mice and rats at exposures 4 times or equivalent to those in humans; however, the same concentrations caused maternal toxicity in mice and were related to increased embryo death. Minor maternal toxicity was observed at exposures lower than clinical exposures in rats. | Linezolid and its metabolites may be excreted in human milk | |
| B | Clofazimine [5] | C | There are no or limited amount of data in pregnant women. Cases of skin pigmentation at birth from infants born to pregnant mothers who had received clofazimine during pregnancy. In mice studies clofazimine induced embryotoxicity and fetotoxicity at doses equivalent to the 0.6 times maximum recommended human daily dose. No developmental effects observed in rats or rabbits. | Excreted in human milk. Skin discoloration observed in breast fed neonates of mothers receiving clofazimine. |
| Cycloserine [6] | C | There are no or limited amount of data in pregnant women. No teratogenic effect observed in rats | Excreted in human milk in concentrations that can be similar to maternal serum levels | |
| Terizidone [7] | C | There are no or limited amount of data in pregnant women. Animal data do not indicate potential for teratogenicity | May be excreted in human milk but no adverse effects observed | |
| C | Amikacin, streptomycin [8] | D | Aminoglycosides can cause foetal harm. Reports of total and irreversible bilateral congenital deafness in children born from mothers exposed to streptomycin during pregnancy. Foetal adverse effects have not been reported in pregnant women exposed to other aminoglycosides. | Streptomycin is excreted in human milk, no data for amikacin |
| Ethionamide [9] | C | There are no or limited amount of data in pregnant women. Reported teratogenic effects in mice, rabbits and rats at doses considerably higher than those recommended in humans. | No data in lactating or nursing women. | |
| Prothionamide [10] | C | There are no or limited amount of data in pregnant women. Embryotoxic and teratogenic effects in mice, rabbits and rats | Excreted in human milk. | |
| Delamanid [11] | Not assigned | There are no or limited amount of data in pregnant women. Embryo-fetal toxicity observed at maternally toxic dosages in rabbits | No data in lactating or nursing women. In lactating rats, the maximum concentration for delamanid in breast milk was 4-fold higher than plasma | |
| Para-aminosalicylic acid [12] | C | There are no or limited amount of data in pregnant women. In an embryofoetal development study in rats observed potential for malformations including bone defects at doses below those proposed clinically. In the rabbit, no effects on embryofoetal development; however, the doses evaluated were below those proposed clinically. | Para-aminosalicylic acid is excreted in human milk. There is insufficient information on the effects of para-aminosalicylic acid in newborns/infants.. | |
| Imipenem-cilastatin [13] | C | There are no or limited amount of data in pregnant women. In cynomolgus monkeys, at doses 3 times the usual recommended daily human intravenous dose, there was minimal maternal intolerance, no teratogenicity, but an increase in embryonic loss relative to control groups | Imipenem and cilastatin are excreted into the mother’s milk in small quantities. | |
| Meropenem [14] | B | There are no or limited amount of data in pregnant women. No teratogenic potential in studies in rats up to 750 mg/kg and in monkeys up to 360 mg/kg. | Small amounts of meropenem have been reported to be excreted in human milk. |
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