Many modern pharmaceuticals (e.g. Prozac, Paxil) contain “organofluorines.” An organofluorine is a chemical compound that contains both carbon and fluorine. The fact, however, that a pharmaceutical is made with an organofluorine does not mean that it will increase your exposure to fluoride. This is because the fluorine in the drug forms a very strong bond with the carbon and this bond resists metabolizing into fluoride ion. It is generally believed, therefore, that most organofluorine drugs do not contribute to daily fluoride exposure.

There are some organofluorine drugs, however, that do metabolize into fluoride. This is evident by studies finding elevated levels of fluoride showing up in the urine or blood following use of the drug. Because organofluorine drugs contain high quantities of fluorine, any drug that metabolizes into fluoride will likely be a very large source of daily exposure. Drugs that are known to break down into fluoride ion include: fluorinated anesthetics, Cipro, Niflumic acid, Flecainide, and Voriconazole.  It is possible, and indeed likely, that other drugs do so as well, but have not yet been discovered.

The following are a list of studies documenting inorganic fluoride exposure from the use of organofluorine drugs:

Anesthetics (click for more studies: Isoflurane, Sevoflurane)

Blanco et al, (1995). Comparison of maintenance and recovery characteristics of sevoflurane-nitrous oxide and enflurane-nitrous oxide anaesthesia. European Journal of Anaesthesiology 12(5):517-23.

Cabibel et al. (2018). Complete Nephrogenic Diabetes Insipidus After Prolonged Sevoflurane Sedation: A Case Report About 3 Cases. A&A Practice.

Funk et al. (1996). Sevoflurane or halothane in inhalational anesthesia induction in childhood. Anesthesia quality and fluoride level. Der Anaesthesist 45(1):22-30.

Hoggard et al. (2019). Gaseous Anesthetics. StatPearls [Internet]. April 6.

Hoemberg M, et al. (2012). Plasma fluoride concentrations during prolonged administration of isoflurane to a pediatric patient requiring renal replacement therapy. Paediatric Anaesthia 22(4):412-3.

Lermon et al. (1994). The pharmacology of sevoflurane in infants and children. Anesthesiology 80(4):814-24.

Natsume et al. (1990). Teratogenicity caused by halothane, enflurane, and sevoflurane, and changes depending on O2 concentration. Teratology 42(6):30A.

Nishiyama et al. (1996). Inorganic fluoride kinetics and renal tubular function after sevoflurane anesthesia in chronic renal failure patients receiving hemodialysis. Anesthesia and Analgesia 83(3):574-7.

Oc B, et al. (2012). The effects of sevoflurane anesthesia and cardiopulmonary bypass on renal function in cyanotic and acyanotic children undergoing cardiac surgery. Renal Failure 34(2):135-41.

Rohm et al. (2009). Renal integrity in sevoflurane sedation in the intensive care unit with the anesthetic-conserving device: a comparison with intravenous propofol sedation. Anesthesia and Analgesia108(6):1848-54.

Steffey(2005) et al. Effects of sevoflurane dose and mode of ventilation on cardiopulmonary function and blood biochemical variables in horses. American Journal of Veterinary Research 66(4):606-14.

Wang, et al. (2013). Neonatal sevoflurane anesthesia induces long-term memory impairment and decreases hippocampal PSD-95 expression without neuronal loss. European Review for Medical and Pharmacological Sciences 17(7):941-50.

Waugh DT. (2019). Cancer and Other Outcomes After Surgery With Fluoridated Anesthesia. JAMA Network Open. June 26.

Wiesner et al. (1996). Serum fluoride concentrations and exocrine kidney function with sevoflurane and enflurane. An open, randomized, comparative phase III study of patients with healthy kidneys. Anaesthesist 45(1):31-6.

Enflurane and Halothane

Mazze et al. (1977). Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers. Anesthesiology 46(4):265-71.

Cipro:

Pradhan KM, et al. (1995). Safety of ciprofloxacin therapy in children: magnetic resonance images, body fluid levels of fluoride and linear growth. Acta Paediatrica 84(5):555-60.

Flecainide:

Rimoli CN, et al. (1991). Relationship between serum concentrations of flecainide and fluoride in humans. Boll. Chim. Farmaceutico 130(7):279-82.

Niflumic Acid:

Gras-Champel V, et al. (2003). [Chronic fluorine intoxication during prolonged treatment with niflumic acid]. [Article in French] Presse Med. 2003 Jun 7;32(20):933.

Welsch M, et al. (1990). [Iatrogenic fluorosis. 2 cases]. [Article in French] Therapie. 45(5):419-22.

Meunier PJ, et al. (1980). Niflumic acid-induced skeletal fluorosis: iatrogenic disease or therapeutic perspective for osteoporosis? Clin Orthop Relat Res. 148:304-9.

Prost A, et al. (1978). [Fluorine osteosis caused by a very long-term niflumic acid treatment in 2 cases of rheumatoid arthritis]. [Article in French] Rev Rhum Mal Osteoartic. 45(12):707-16.

Voriconazole – See more studies here

Chen L, Milligan ME. (2011). Medication-induced periostitis in lung transplant patients: periostitis deformans revisited. Skeletal Radiology 40:143-48.

Moon et al. (2014). Plasma fluoride level as a predictor of voriconazole induced periostitis in patients with skeletal pain. Clinical Infectious Diseases 59(9):1237-45.

Rad et al. (2015). Fluorosis and periostitis deformans as complications of prolonged voriconazole treatment. Annals of Clinical Biochemistry 52(Pt 5):611-4.

Wermers RA, et al. (2011). Fluoride excess and periostitis in transplant patients receiving long-term voriconazole therapy. Clinical Infectious Diseases 52(5):604-11.

Hospital Personnel

Cakmak et al. (2018). Genetic damage of operating and recovery room personnel occupationally exposed to waste anaesthetic gases. Human & Experimental Toxicology.

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