N01BB01 - Bupivacaine

Not porphyrinogenic

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 pharmacokinetics

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.

Similar drugs

Explore alternative drugs in similar therapeutic classes N01B / N01BB or go back.

References

#	Citation details	PubMed ID
1.	Pregnancy with acute intermittent porphyria: a case report and review of literature. Aggarwal N, Bagga R, et al. J Obstet Gynaecol Res. 2002 Jun; 28(3):160-2.	12214832
2.	Regional anesthesia as anesthetic technique of choice in acute hepatic porphyria. Böhrer H, Schmidt H. J Clin Anesth. 1992; 4(3):259.	1610588
3.	[Obstetrical anaesthesia and porphyrias]. Consolo D, Ouardirhi Y, et al. Ann Fr Anesth Reanim. 2005 Apr; 24(4):428-31.	15826795
4.	Study of anaesthetic agents for their ability to elicit porphyrin biosynthesis in chick embryo liver. de Verneuil H, Deybach JC, et al. Biochem Pharmacol. 1983 Mar; 32(6):1011-8.	6838647
5.	[Anesthetic management of a patient with acute intermittent porphyria]. Ii C, Tanaka N, et al. Masui. 1993 Dec; 42(12):1849-52.	8301837
6.	Porphyrias. James MF, Hift RJ. Br J Anaesth. 2000 Jul; 85(1):143-53.	10928003
7.	Use of regional anaesthesia in a patient with acute porphyria. McNeill MJ, Bennet A. Br J Anaesth. 1990 Mar; 64(3):371-3.	2328186
8.	[Desflurane in acute intermittent porphyria]. Messmer M, Gerheuser F, Forst H. Anaesthesist. 2004 Mar; 53(3):244-8.	15021955
9.	Anesthetic management of a patient with variegate porphyria. Minoda Y, Yoshimine K, et al. J Anesth. 1997 Dec; 11(4):307-308.	28921072
10.	Effect of certain anaesthetic agents on the activity of rat hepatic delta-aminolaevulinate synthase. Parikh RK, Moore MR. Br J Anaesth. 1978 Nov; 50(11):1099-103.	718778
11.	Summary of information on human CYP enzymes: human P450 metabolism data. Rendic S. Drug Metab Rev. 2002; 34(1-2):83-448.	11996015
12.	Safety of isoflurane and epidural anesthesia in a patient with hereditary coproporphyria. Yamamori Y, Sumi M, et al. J Anesth. 1996 Mar; 10(1):80-2.	23839560
Drug reference publications
13.	Sweetman SC, editor. Martindale: The complete drug reference. Bupivacaine Hydrochloride. Pharmaceutical Press 2009.
14.	Bupivacaine Hydrochloride. McEvoy GK, editor. The AHFS Drug Information 2008. Bethesda, MD: American Society of Health-System Pharmacists; 2009. Electronic version (January 2009).
Summary of Product Characteristics
15.	Norwegian medicines agency. Summary of Product Characteristics (SPC). Marcain-adrenalin.
Other sources
16.	Thunell, S. Evidence-based porphyrogenicity assessment of seven local anasthetics (2009, to be published).