Avoiding smoking and other products with nicotine are recommended since it may lead to nicotine overdose. Although overdose is rare, it can be problematic, especially in children and pets. The symptoms of nicotine overdose include headache, pale skin and mouth, belly pain, weakness, diarrhea, tremors or seizures, agitation, confusion, restlessness, high or low blood pressure, fast or irregular heartbeat, fast breathing, and cold sweats.Limited evidence exists regarding long-term NRT use. Safety
Pregnancy
Nicotine is not safe to use in any amount during pregnancy. Nicotine crosses the placenta and is found in the breast milk of mothers who smoke as well as mothers who inhale passive smoke. There are possible harms to the baby if NRT is used during pregnancy. Thus, pregnant women and those who are breastfeeding should also consult a physician before initiating NRT. The gum, lozenge, and nasal spray are pregnancy category C. The transdermal patch is pregnancy category D. The transdermal patch is considered less safe for the fetus because it delivers continuous nicotine exposure, as opposed to the gum or lozenge, which delivers intermittent and thus lower nicotine exposure.Strong evidence suggests that nicotine cannot be regarded as a safe substance of cigarette use. Nicotine itself could be at least partly responsible for many of the adverse after birth health results related to cigarette use while the mother was pregnant. There is evidence that nicotine negatively affects fetal brain development and pregnancy outcomes. There is also risk of stillbirth and pre-term birth. Nicotine use will probably harm fetal neurological development.
Ivacaftor is a medication used to treat cystic fibrosis in people with certain mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (primarily the G551D mutation), who account for 4–5% cases of cystic fibrosis. It is also included in combination medications, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and elexacaftor/tezacaftor/ivacaftor which are used to treat people with cystic fibrosis.Ivacaftor was developed by Vertex Pharmaceuticals in conjunction with the Cystic Fibrosis Foundation and is the first medication that treats the underlying cause rather than the symptoms of the disease. It was approved by the U.S. Food and Drug Administration (FDA) in January 2012. It is one of the most expensive drugs, costing over US$300,000 per year, which has led to criticism of the high cost. The combination drug lumacaftor/ivacaftor was approved by the FDA in July 2015.Cystic fibrosis is caused by any one of several defects in the CFTR protein, which regulates fluid flow within cells and affects the components of sweat, digestive fluids, and mucus. One such defect is the G551D mutation, in which the amino acid glycine (G) in position 551 is replaced with aspartic acid (D). G551D is characterized by a dysfunctional CFTR protein on the cell surface. In the case of G551D, the protein is trafficked to the correct area, the epithelial cell surface, but once there the protein  cannot transport chloride through the channel.