There was negligible urinary excretion of ivacaftor as unchanged parent. The apparent terminal half-life was approximately 12 hours following a single dose in the fed state. The apparent clearance (CL/F) of ivacaftor was similar for healthy subjects and patients with CF. The mean (±SD) of CL/F for the 150 mg dose was 17.3 (8.4) L/h in healthy subjects at steady state. Society and culture
Legal status
The U.S. Food and Drug Administration (FDA) approved ivacaftor in January 2012, and soon afterwards so too did the European Medicines Agency (EMA) and Canada and across some European countries.Lumacaftor/ivacaftor was approved by the FDA in July 2015, under breakthrough therapy status and under a priority review. Economics
The cost of ivacaftor is US$311,000 per year, roughly similar to the price of other medications for extremely rare diseases. In the first nine months of its second year on the market (2014), ivacaftor sales were $339M, representing 54% of Vertexs product sales revenue. During the same period, total drug development expenses were $458M, most of which was spent on cystic fibrosis-related research.An editorial in JAMA called the price of ivacaftor "exorbitant", citing the support by the Cystic Fibrosis Foundation in its development and the contribution made by fundamental scientific research performed by the National Institutes of Health and relied upon by Vertex in its cystic fibrosis drug discovery programs.
Newborns
There has been no established safety and effectiveness for use in premature infants and neonates. Elderly
No overall differences in safety or effectiveness were observed in clinical trials comparing elderly and younger subjects, however the trials could not eliminate the possibility that some older individuals may have a higher level of sensitivity. Additional considerations
People with kidney disease and those on hemodialysis may need the dose adjusted. Cefazolin levels are not significantly affected by liver disease. As with other antibiotics, cefazolin may interact with other medications being taken. Some important drugs that may interact with cefazolin such as probenecid. Side effects
Side effects associated with use of cefazolin therapy include:
Common (1-10%): diarrhea, stomach pain or upset stomach, vomiting, and rash. Uncommon (<1%): dizziness, headache, fatigue, itching, transient hepatitis.Patients with penicillin allergies could experience a potential reaction to cefazolin and other cephalosporins. As with other antibiotics, patients experiencing watery and/or bloody stools occurring up to three months following therapy should contact their prescriber.Like those of several other cephalosporins, the chemical structure of cefazolin contains an N-methylthiodiazole (NMTD or 1-MTD) side-chain. As the antibiotic is broken down in the body, it releases free NMTD, which can cause hypoprothrombinemia (likely due to inhibition of the enzyme vitamin K epoxide reductase) and a reaction with ethanol similar to that produced by disulfiram (Antabuse), due to inhibition of aldehyde dehydrogenase. Those with an allergy to penicillin may develop a cross sensitivity to cefazolin. Mechanism of action
Cefazolin inhibits cell wall biosynthesis by binding penicillin-binding proteins which stops peptidoglycan synthesis.