Acute Porphyria Drugs

Acute Porphyria Drug Database

N01BB01 - Bupivacaine
Not porphyrinogenic
NP
Rationale
Used uneventfully in 56 patients with latent or active acute porphyria. By clinical criteria the local anaesthetic bupivacaine is not porphyrinogenic. One report of increased porphyrinogenic activity following an operation where bupivacaine was used in epidural anaesthesia, but causality was not established.
Chemical description
Bupivacaine hydrochloride is a local anesthetic of the amide type. Bupivacaine occurs as a 50:50 racemic mixture of the R- and S-enantiomers, but the S(-)-isomer levobupivacaine is also used.
Therapeutic characteristics
Local anaesthetic. Administration in combination with vasoconstrictor such as epinephrine (adrenaline) (not porphyrinogenic) prolongs the effect of bupivacaine, and reduces hepatic exposure and the risk of systemic reactions.
Hepatic exposure
Volume required to obtain uM concentrations when injected intravenously: approximately 5 ml (of bupivacaine 5 mg/ml).
Metabolism and pharmakokinetics
Bupivacaine is principally metabolized to pipecolylxylidine (PPX) by N-dealkylation, probably in the liver. Bupivacaine is excreted in urine as small amounts of PPX, unchanged drug (5%), and other metabolites as yet unidentified. Rendic (2002) reports that bupivacaine is a substrate of CYP3A4 (major reaction), CYP1A2, CYP2C19 and 2D6 (minor reaction).
Personal communication
Thunell, S., study to be published: 48 patients exposed without porphyric adverse reaction reported. Peters: According to our experience not porphyrinogenic.
Published experience
Used uneventfully in AIP woman during delivery (Aggarwal, N., Bagga, R. et al, 2002). Used uneventfully for epidural anaesthesia during delivery by woman with latent VP (Consolo, D., Ouardirhi, Y. et al, 2005). Used uneventfully twice over two years in the same patient (one epidural and one spinal injection), an AIP woman (McNeill, M.J. & Bennet, A., 1990). Used uneventfully in epidural anaesthesia to relieve postoperative pain in AIP patient presenting with elevated PBG (Messmer, M., Gerheuser, F. et al, 2004). Used uneventfully as epidural, during surgery and post operativly in VP woman (Minoda,Y., Yoshimine, K. et al, 1997). Used uneventfully as spinal epidural in AIP woman (Sahu, M.T., Rajaram, S. et al, 2006). Used uneventfully as epidural, during surgery and post operativly, in HCP man (Yamamori, Y., Sumi, M. et al, 1996). Used uneventfully as spinal anesthesia in VP man (Bohrer, H. & Schmidt, H., 1992). Listed as safe in review by James and Hift (James, M.F. & Hift, R.J., 2000). One report of increased porphyrinogenic activity following an operation where bupivacaine was used in epidural anaesthesia, but causality was not established (Ii, C., Tanaka, N. et al, 1993).
IPNet drug reports
Uneventful use reported in 5 patients with acute porphyria.

References

  1. Scientific articles
  2. Aggarwal, N., Bagga, R. et al. Pregnancy with acute intermittent porphyria: A case report and review of literature. J Obstet Gynaecol Res 2002; 28(3): 160-2. #2485
  3. Bohrer, H., Schmidt, H. Regional Anesthesia as Anesthetic Technique of Choice in Acute Hepatic Porphyria. J Clin Anesth 1992; 4: 259. PMID 1610588. #4643
  4. Consolo, D.,Ouardirhi, Y. et al.[Obstetrical anaesthesia and porphyrias].Annales Françaises d’Anesthésie et de Réanimation 2005;24: 428-431. #2487
  5. de Verneuil,H., Deybach,J.C. et al. Study of anaesthetic agents for their ability to elicit porphyrin biosynthesis in chick embryo liver. Biochem Pharmacol 1982; 32: 1011-18. #1192
  6. Ii, C., Tanaka, N. et al. [Anesthetic management of a patient with acute intermittent porphyria]. Masui 1993; 42: 1849-52. #2488
  7. James,M.F., Hift,R.J. Porphyrias.Br J Anaesth 2000; 85, 143-53. PMID 10928003. #4644
  8. McNeill, MJ, Bennet, A. Use of regional anaesthesia in a patient with acute porphyria. Br J Anaesth 1990;64: 371-3. #2491
  9. Messmer, M., Gerheuser, F. et al.[Desflurane in acute intermittent porphyria.] Anaesthesist 2004; 53:244-8. DOI 10.1007/s00101-003-0615-7 #2492
  10. Minoda, Y., Yoshimine, K. et al. Anesthetic management of a patient with variegate porphyria. Anesth 1997;11:307-8. #2493
  11. Parikh, RK, Moore, MR. Effect of certain anaesthetic agents on the activity of rat hepatic delta-aminolaevulinate synthase. Br J Anaesth 1978; 50:1099-1103. PMID 718778. #4376
  12. Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
  13. Thunell, S. Evidence-based porphyrogenicity assessment of seven local anasthetics (2009, to be published). #2497
  14. Yamamori,Y., Sumi, M. et al. Safety of isoflurane and epidural anesthesia in a patient with hereditary coproporphyria. J Anesth 1996;10:80-2. #2496
  15. Drug reference publications
  16. McEvoy GK, editor. Bupivacaine Hydrochloride. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (January 2009). #2490
  17. Sweetman SC, editor. Martindale: The complete drug reference. Bupivacaine Hydrochloride. Pharmaceutical Press 2009. #2495
  18. Summary of Product Characteristics
  19. Norwegian medicines agency. Summary of Product Characteristics (SPC). Marcain-adrenalin. #2494
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