Pregnancy: The safety of COMBIVENT during human pregnancy has not been established. The inhibitory effect of COMBIVENT on uterine contraction should be taken into account. The benefits of using COMBIVENT during a confirmed or suspected pregnancy must be weighed against possible hazards to the unborn child. The usual precautions regarding the use of drugs in pregnancy, especially during the first trimester, should be observed.
For ipratropium bromide, nonclinical studies have shown no embryotoxic or teratogenic effects following inhalation or intranasal application at doses considerably higher than those recommended in man. For salbutamol sulphate, non- inhalation nonclinical studies did not indicate direct or indirect harmful effects unless the inhalation Maximum Recommended Human Daily Dose (MRHDD) was exceeded.
Lactation: It is not known whether ipratropium bromide and salbutamol sulphate are excreted in breast milk. Although lipid- insoluble quaternary cations pass into breast milk, It is considered unlikely that ipratropium bromide would reach the infant to an important extent, especially when administered by inhalation. However, because many drugs are excreted in breast milk, caution should be exercised when COMBIVENT is administered to nursing mothers.
Fertility: No studies on the effect on human fertility have been conducted for COMBIVENT. Clinical data on fertility are neither available for the combination of ipratropium bromide and salbutamol sulphate nor for each of the two components of the combination. Nonclinical studies performed with ipratropium bromide and salbutamol showed no adverse effect on fertility.