Symbicort Use In Pregnancy & Lactation

Turbuhaler: For SYMBICORT or the concomitant treatment with formoterol and budesonide, no clinical data on exposed pregnancies are available. Animal studies with respect to reproductive toxicity of the combination have not been performed.
There are no adequate data from use of formoterol in pregnant women. In animal studies formoterol has caused adverse effects in reproduction studies at very high systemic exposure levels (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Data on approximately 2000 exposed pregnancies indicate no increased teratogenic risk associated with the use of inhaled budesonide. In animal studies glucocorticosteroids have been shown to induce malformations (see Pharmacology: Toxicology: Preclinical safety data under Actions). This is not likely to be relevant for humans given recommended doses.
Animal studies have also identified an involvement of excess prenatal glucocorticoids in increased risks for intrauterine growth retardation, adult cardiovascular disease and permanent changes in glucocorticoid receptor density, neurotransmitter turnover and behaviour at exposures below the teratogenic dose range.
During pregnancy, SYMBICORT should only be used when the benefits outweigh the potential risks. The lowest effective dose of budesonide needed to maintain adequate asthma control should be used.
A clinical pharmacology study has shown that inhaled budesonide is excreted in breast milk. However, budesonide was not detected in nursing infant blood samples. Based on pharmacokinetic parameters, the plasma concentration in the child is estimated be less than 0.17% of the mother's plasma concentration. Consequently, no effects due to budesonide are anticipated in breast-fed children whose mothers are receiving therapeutic doses of SYMBICORT. It is not known whether formoterol passes into human breast milk. In rats, small amounts of formoterol have been detected in maternal milk. Administration of SYMBICORT to women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.
Rapihaler: Fertility: There are no animal studies on the effect of the budesonide/eformoterol combination on fertility.
Long-term treatment of female mice and rats with eformoterol fumarate causes ovarian stimulation, the development of ovarian cysts, and hyperplasia of granulosa/theca cells as a result of the β-agonist properties of the compound. A study by another company showed no effect on fertility of female rats dosed orally with eformoterol fumarate at 60 mg/kg/day for two weeks. This finding was repeated in an AstraZeneca study where no effect was seen on the fertility of female rats dosed orally with eformoterol fumarate at 15 mg/kg/day for two weeks.
Testicular atrophy was observed in mice given eformoterol fumarate in the diet at 0.2 to 50 mg/kg/day for 2 years, but no effect on male fertility was observed in rats dosed orally at 60 mg/kg/day for 9 weeks, in studies undertaken by another company.
Pregnancy: For the concomitant treatment with budesonide and eformoterol, no clinical data on exposed pregnancies are available. Fetal malformations (umbilical hernia and cleft palate), typical of glucocorticoid toxicity in animals, occurred in rats dosed with the Symbicort Rapihaler formulation at the inhaled dose of 12 μg/kg/day budesonide and 0.66 μg/kg/day eformoterol, with plasma AUC values for both drugs below that expected in patients at the maximum recommended clinical dose. No teratogenic effect was detected at 2.5 μg/kg/day of budesonide and 0.14 μg/kg/day of eformoterol.
Symbicort Rapihaler should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Only after special consideration should Symbicort Rapihaler be used during the first 3 months and shortly before delivery.
Because β-agonists, including eformoterol, may potentially interfere with uterine contractility due to a relaxant effect on uterine smooth muscle, Symbicort Rapihaler should be used during labour only if the potential benefit justifies the potential risk.
Budesonide: Results from a large prospective epidemiological study and from world-wide post marketing experience indicate no adverse effects of inhaled budesonide during pregnancy on the health of the fetus/newborn child.
If treatment with glucocorticosteroids during pregnancy is unavoidable, inhaled corticosteroids such as budesonide should be considered due to their lower systemic effect. The lowest effective dose of budesonide to maintain asthma control should be used.
Eformoterol: No teratogenic effects were observed in rats receiving eformoterol fumarate at doses up to 60 mg/kg/day orally or 1.2 mg/kg/day by inhalation. Foetal cardiovascular malformations were observed in one study in which pregnant rabbits were dosed orally at 125 or 500 mg/kg/day during the period of organogenesis, but similar results were not obtained in another study at the same dose range. In a third study, an increased incidence of subcapsular hepatic cysts was observed in foetuses from rabbits dosed orally at 60 mg/kg/day. Decreased birth weight and increased perinatal/postnatal mortality were observed when eformoterol fumarate was given to rats at oral doses of 0.2 mg/kg/day or greater during late gestation.
Lactation: Budesonide is excreted in breast milk. However, due to the relatively low doses used via the inhalational route the amount of drug present in the breast milk, if any, is likely to be low.
It is not known whether eformoterol passes into human breast milk. In rats, eformoterol was excreted into breast milk. There are no studies in lactating animals using the budesonide/eformoterol combination. Increased postnatal mortality at maternal eformoterol doses of 0.2 mg/kg/day PO or greater, and retardation of pup growth at 15 mg/kg/day PO were observed in a rat study. There are no well-controlled human studies using Symbicort Rapihaler in nursing mothers. Because many drugs are excreted in human breast milk, administration of Symbicort Rapihaler to women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.