Acute Porphyria Drug Database

N01AB08 - Sevoflurane
Propably not porphyrinogenic
PNP

Important Information
Risk for gastrointestinal adverse events in the form of nausea and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.
Side effects
Common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are nausea and vomiting.
Rationale
Sevoflurane is subject to rapid pulmonary elimination and minimal of the drug is therefore available for CYP interaction.
Therapeutic characteristics
Sevoflurane is indicated for induction and maintenance of general anaesthesia in adult and paediatric patients for inpatient and outpatient surgery.
Metabolism and pharmakokinetics
Sevoflurane is a respiratory gas with very low solubility in blood and tissues and is therefore subject to rapid pulmonary elimination. Less than 5 per cent is metabolized in the liver by CYP2E1 to hexafluoroisopropanol (HFIP). HFIP is rapidly conjugated to glucuronic acid and is eliminated via urine (Kharasch 1995 and SPC).
Published experience
A Japanese report 1993 described an anesthetic management, including sevoflurane (and fentanyl, NO, O2 and bupivacaine), of a patient with AIP undergoing hysterectomy. She had a history of frequent episodes of reddish discoloration of urine after physical strain. After operation reddish urine and rapid respiration suggested a possible exacerbation of AIP (Ii 1993). This was most probably due to surgical and mental stress in a strongly susceptible carrier and not as a result of the drugs administered. There are two case reports of safe use of sevoflurane in adult carriers of acute porphyria (Takahashi 2005, Hsieh 2006) and two in children, one in a child with homozygous acute porphyria (Sheppard 2005) and one in a 9 year old male with a confirmed genetic marker for AIP. No AIP symptoms had occurred or reported after 72 hours or 1 month (Olutunmbi 2014).
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.

References

  1. Scientific articles
  2. Hsieh, Hung, et al. (2006). "The use of rocuronium and sevoflurane in AIP - a case report." Acta Anaesth taiwan #2423
  3. Ii, C., N. Tanaka, et al. (1993). "[Anesthetic management of a patient with acute intermittent porphyria]." Masui 42(12): 1849-1852. #2424
  4. Kharasch, E. D., M. D. Karol, et al. (1995). "Clinical sevoflurane metabolism and disposition. I. Sevoflurane and metabolite pharmacokinetics." Anesthesiology 82(6): 1369-1378. #2425
  5. Olutunmbi, Y., H. G. Gurnaney, et al. (2014). "Ultrasound-guided regional anesthesia in a pediatric patient with acute intermittent porphyria: literature review and case report." Middle East J Anesthesiol 22(5): 511-514. #2427
  6. Sheppard, L. and T. Dorman (2005). "Anesthesia in a child with homozygous porphobilinogen deaminase deficiency: a severe form of acute intermittent porphyria." Paediatr Anaesth 15(5): 426-428. #2428
  7. Takahashi, S., Y. Shiraishi, et al. (2005). "[A case report of rapid inhalation induction with sevoflurane in a patient with porphyria]." Masui 54(11): 1292-1294. #2429
  8. Summary of Product Characteristics
  9. Norwegian medicines agency. Summary of Product Characteristics (SPC). Sevoflurane. Last edition: 16.07.14 #2426

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