In humans, budesonide is rapidly and extensively metabolized in the liver. Two major metabolites (16alpha-hydroxyprednisolone and 6beta-hydroxybudesonide) are formed via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4)-catalysed biotransformation. Known metabolic inhibitors of CYP3A4 (e.g., ketoconazole), or significant hepatic impairment, may increase the systemic exposure of unmetabolized budesonide. in vitro studies on the binding of the two primary metabolites to the glucocorticoid receptor indicate that they have less than 1% of the affinity for the receptor as the parent compound, budesonide. In vitro studies have evaluated sites of metabolism and showed negligible metabolism in the skin, lungs, and serum. No qualitative difference between the in vitro and in vivo metabolic patterns could be detected. Pregnancy Results from prospective epidemiological studies and from worldwide post marketing experience indicate no increased risk for overall congenital malformations from the use of inhaled or intranasal budesonide during early pregnancy. As with other drugs the administration of BUDENASE AQ Nasal Spray during pregnancy requires that the benefits for the mother are weighed against the risk for the foetus. Lactation Budesonide is excreted in breast milk. However, at therapeutic doses of budesonide nasal spray no effects on the breast fed child are anticipated. Budesonide nasal spray can be used during breast feeding. Based on data from inhaled budesonide and the fact budesonide exhibits linear PK properties within the therapeutic dosage intervals after nasal, inhaled, oral and rectal administrations at therapeutic doses of budesonide, exposure to the breast-fed child is anticipated to be low. Dosing considerations include prescription or titration to the lowest clinically effective dose and use of budesonide nasal spray immediately after breastfeeding to maximize the time interval between dosing and breastfeeding to minimize infant exposure.