Correspondence

Ondansetron for Pruritus Due to Cholestasis

N Engl J Med 1994; 330:1540May 26, 1994

Article

To the Editor:

Pruritus is a common, often distressing symptom in patients with cholestatic disease of various malignant and nonmalignant origins. Its exact cause is poorly understood, and treatment is often unsatisfactory1. In August and September 1993, five patients (four men and one woman) were admitted to our hospital with severe pruritus. On a 10-point rating scale measuring subjective intensity (0 was no pruritus and 10 the worst pruritus imaginable), two patients each assigned values of 9 and 8 to their symptoms, and one a value of 7.

Three of the patients had progressive liver metastases from renal, colorectal, and cholangiocellular carcinoma, and one had recurrent chronic hepatitis B after undergoing orthotopic liver transplantation in 1985. The woman was given a diagnosis of acute hepatitis A. The total serum bilirubin level was elevated in all patients (range, 9 to 15.7 mg per deciliter), as were the results of other liver-function tests. Three patients had been treated unsuccessfully with cholestyramine (3 g per day) and ursodiol (750 mg per day), drugs that have been reported to relieve pruritus in cholestatic liver disease1,2.

Because of a recent report3 and in view of the role of serotonin in nociception,4 we decided to treat our patients with an 8-mg dose of ondansetron, a widely used antiemetic agent. Pruritus resolved promptly within 30 to 60 minutes after the intravenous injection of the drug. It resolved completely in the three patients with metastatic liver disease and was markedly reduced in the two others, an effect that lasted for 5 to 16 hours. Treatment was continued with oral ondansetron in the three patients with cancer, and a twice-daily dose of 8 mg resulted in a decrease in the severity of their symptoms to a value of less than 2 on the subjective pruritus scale. Two of the patients with cancer were treated successfully for two and four weeks (i.e., until death), and the third has been followed for seven weeks without a recurrence of symptoms.

These findings, along with the recent report of a similar outcome in a patient with primary biliary cirrhosis,3 suggest a potential role for serotonin in the development or perception of pruritus due to cholestasis. Because of the sustained relief of pruritus induced by ondansetron in our patients, we believe a controlled trial is warranted to establish the role of serotonin-receptor antagonists as a novel therapeutic tool in the management of this distressing, sometimes intractable condition.

Markus Raderer, M.D.
Christian Muller, M.D.
Werner Scheithauer, M.D.
Vienna University Medical School, A-1090 Vienna, Austria

4 References

1. 1

   Lorette G, Vaillant L. Pruritus: current concepts in pathogenesis and treatment. Drugs 1990;39:218-223
   CrossRef | Web of Science | Medline

2. 2

   Matsuzaki Y, Tanaka N, Osuga T, et al. Improvement of biliary enzyme levels and itching as a result of long-term administration of ursodeoxycholic acid in primary biliary cirrhosis. Am J Gastroenterol 1990;85:15-23
   Web of Science | Medline

3. 3

   Schworer H, Ramadori G. Improvement of cholestatic pruritus by ondansetron. Lancet 1993;341:1277-1277
   CrossRef | Web of Science | Medline

4. 4

   Richardson BP. Serotonin and nociception. Ann N Y Acad Sci 1990;600:511-520
   CrossRef | Web of Science | Medline

Citing Articles (40)

Citing Articles

1. 1

   Martin Steinhoff, Ferda Cevikbas, Akihiko Ikoma, Timothy G. Berger. (2011) Pruritus: Management Algorithms and Experimental Therapies. Seminars in Cutaneous Medicine and Surgery 30:2, 127-137
   CrossRef

2. 2

   F.-F. TSAI, S.-Z. FAN, Y.-M. YANG, K.-L. CHIEN, Y.-N. SU, L.-K. CHEN. (2010) Human opioid μ-receptor A118G polymorphism may protect against central pruritus by epidural morphine for post-cesarean analgesia. Acta Anaesthesiologica Scandinavica 54:10, 1265-1269
   CrossRef

3. 3

   Joyce A. Generali, Dennis J. Cada. (2009) Off-Label Drug Uses - Ondansetron: Cholestatic Pruritus (Adults). Hospital Pharmacy 44:10, 868-870
   CrossRef

4. 4

   Franco Marinangeli, Cristiana Guetti, Chiara Angeletti, Cristina Bonetti, Antonella Paladini, Alba Piroli, Giustino Varrassi. (2009) Intravenous Naloxone Plus Transdermal Buprenorphine in Cancer Pain Associated with Intractable Cholestatic Pruritus. Journal of Pain and Symptom Management 38:4, e5-e8
   CrossRef

5. 5

   Keith D. Lindor, M. Eric Gershwin, Raoul Poupon, Marshall Kaplan, Nora V. Bergasa, E. Jenny Heathcote. (2009) Primary biliary cirrhosis. Hepatology 50:1, 291-308
   CrossRef

6. 6

   Nora V. Bergasa. (2008) Pruritus in Primary Biliary Cirrhosis: Pathogenesis and Therapy. Clinics in Liver Disease 12:2, 385-406
   CrossRef

7. 7

   E Anthony Jones. (2008) Pruritus and fatigue associated with liver disease: is there a role for ondansetron?. Expert Opinion on Pharmacotherapy 9:4, 645-651
   CrossRef

8. 8

   Gustav Paumgartner, Thomas Pusl. (2008) Medical Treatment of Cholestatic Liver Disease. Clinics in Liver Disease 12:1, 53-80
   CrossRef

9. 9

   Nora V. Bergasa. (2008) Update on the Treatment of the Pruritus of Cholestasis. Clinics in Liver Disease 12:1, 219-234
   CrossRef

10. 10

    Sanjay H. Shah. (2006) Paraneoplastic Liver Dysfunction in Prostate Cancer. Journal of Pain and Symptom Management 32:6, 511-513
    CrossRef

11. 11

    Nora V. Bergasa. (2006) Medical Palliation of the Jaundiced Patient with Pruritus. Gastroenterology Clinics of North America 35:1, 113-123
    CrossRef

12. 12

    J. W. O'Donohue, S. P. Pereira, A. C. Ashdown, C. G. Haigh, J. R. Wilkinson, R. Williams. (2005) A controlled trial of ondansetron in the pruritus of cholestasis. Alimentary Pharmacology and Therapeutics 21:8, 1041-1045
    CrossRef

13. 13

    H.K. Bell, G.J. Poston, J. Vora, N.J.E. Wilson. (2005) Cutaneous manifestations of the malignant carcinoid syndrome. British Journal of Dermatology 152:1, 71-75
    CrossRef

14. 14

    Nora V. Bergasa. (2004) Pruritus in chronic liver disease: Mechanisms and treatment. Current Gastroenterology Reports 6:1, 10-16
    CrossRef

15. 15

    D. Landi, D. Santini, B. Vincenzi, A. La Cesa, C. Dianzani, G. Tonini. (2003) Dramatic improvement of psoriasis with gemcitabine monotherapy. British Journal of Dermatology 149:6, 1306-1307
    CrossRef

16. 16

    Zbigniew Zylicz, Malgorzata Krajnik, Adriaan Alistar van Sorge, Massimo Costantini. (2003) Paroxetine in the treatment of severe non-dermatological pruritus: a randomized, controlled trial. Journal of Pain and Symptom Management 26:6, 1105-1112
    CrossRef

17. 17

    A. M. Korhonen, J. V. Valanne, R. M. Jokela, P. Ravaska, K. Korttila. (2003) Ondansetron does not prevent pruritus induced by low-dose intrathecal fentanyl. Acta Anaesthesiologica Scandinavica 47:10, 1292-1297
    CrossRef

18. 18

    L. BOSONNET. (2003) Pruritis: scratching the surface. European Journal of Cancer Care 12:2, 162-165
    CrossRef

19. 19

    M. Mela, A. Mancuso, A. K. Burroughs. (2003) Pruritus in cholestatic and other liver diseases. Alimentary Pharmacology and Therapeutics 17:7, 857-870
    CrossRef

20. 20

    M. Murphy, D. Reaich, P. Pai, P. Finn, A.J. Carmichael. (2003) A randomized, placebo-controlled, double-blind trial of ondansetron in renal itch. British Journal of Dermatology 148:2, 314-317
    CrossRef

21. 21

    Yavuz G??rkan, Kamil Toker. (2002) Prophylactic Ondansetron Reduces the Incidence of Intrathecal Fentanyl-Induced Pruritus. Anesthesia & Analgesia 95:6, 1763-1766
    CrossRef

22. 22

    I. Genvresse, B. Flath, K. Akrivakis, T. Beinert, E. Späth-Schwalbe, K. Possinger. (2000) Resolution of psoriatic skin lesions after chemotherapy with gemcitabine and vinorelbine. British Journal of Dermatology 143:6, 1326-1327
    CrossRef

23. 23

    S. Charuluxananan, W. Somboonviboon, O. Kyokong, K. Nimcharoendee. (2000) Ondansetron for Treatment of Intrathecal Morphine-Induced Pruritus After Cesarean Delivery. Regional Anesthesia and Pain Medicine 25:5, 535-539
    CrossRef

24. 24

    A. R. Dehpour, H. R. Sadeghipour, A. Nowroozi, N. Akbarloo. (2000) The effect of the serotonergic system on opioid withdrawal-like syndrome in a mouse model of cholestasis. Human Psychopharmacology: Clinical and Experimental 15:6, 423-428
    CrossRef

25. 25

    Heui-Ming Yeh, Li-Kuei Chen, Chen-Jung Lin, Wei-Hung Chan, Yen-Po Chen, Chou-Shun Lin, Wei-Zen Sun, Ming-Jiuh Wang, Shen-Kou Tsai. (2000) Prophylactic Intravenous Ondansetron Reduces the Incidence of Intrathecal Morphine-Induced Pruritus in Patients Undergoing Cesarean Delivery. Anesthesia & Analgesia 91:1, 172-175
    CrossRef

26. 26

    Marlyn J. Mayo. (2000) Non-PBC, Non-PSC autoimmune cholangiopathy. Current Treatment Options in Gastroenterology 3:2, 121-131
    CrossRef

27. 27

    José Franco. (1999) Pruritus. Current Treatment Options in Gastroenterology 2:6, 451-456
    CrossRef

28. 28

    Tomomi Yamaguchi, Tetsuro Nagasawa, Masamichi Satoh, Yasushi Kuraishi. (1999) Itch-associated response induced by intradermal serotonin through 5-HT2 receptors in mice. Neuroscience Research 35:2, 77-83
    CrossRef

29. 29

    E. Weisshaar, B. Ziethen, F.-W. Röhl, H. Gollnick. (1999) The antipruritic effect of a 5-HT3 receptor antagonist (tropisetron) is dependent on mast cell depletion - an experimental study. Experimental Dermatology 8:4, 254-260
    CrossRef

30. 30

    Vivek Raj, David R. Lichtenstein. (1999) HEPATOBILIARY MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE. Gastroenterology Clinics of North America 28:2, 491-513
    CrossRef

31. 31

    E. Anthony Jones, Nora V. Bergasa. (1999) The pruritus of cholestasis. Hepatology 29:4, 1003-1006
    CrossRef

32. 32

    JamesM. McGill, AnnP. Kwiatkowski. (1998) Cholestatic liver diseases in adults. The American Journal of Gastroenterology 93:5, 684-691
    CrossRef

33. 33

    P. C. A. KAM, K. H. TAN. (1996) Pruritus-itching for a cause and relief?. Anaesthesia 51:12, 1133-1138
    CrossRef

34. 34

    P. Trioche, D. Samuel, M. Odièvre, P. Labrune. (1996) Ondansetron for pruritus in child with chronic cholestasis. European Journal of Pediatrics 155:11, 990-990
    CrossRef

35. 35

    LYNDA ARAI, STEPHEN STAYER, ROY SCHWARTZ, ALFRED DORSEY. (1996) The use of ondansetron to treat pruritus associated with intrathecal morphine in two paediatric patients. Pediatric Anesthesia 6:4, 337-339
    CrossRef

36. 36

    I. M. Crighton, G. J. Hobbs, M. F. Reid. (1996) Ondansetron for the treatment of pruritis after spinal opioids. Anaesthesia 51:2, 199-200
    CrossRef

37. 37

    Nora Valeria Bergasa. (1995) The pruritus of cholestasis. Seminars in Dermatology 14:4, 302-312
    CrossRef

38. 38

    Peter A. Andrews. (1995) Use of Ondansetron, a New Antiemetic, in Uremia. Seminars in Dialysis 8:4, 245-246
    CrossRef

39. 39

    Lee, Young-Mee, Kaplan, Marshall M., . (1995) Primary Sclerosing Cholangitis. New England Journal of Medicine 332:14, 924-933
    Full Text

40. 40

    Harald Schwörer, Heinz Hartmann, Giuliano Ramadori. (1995) Relief of cholestatic pruritus by a novel class of drugs: 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists: effectiveness of ondansetron. Pain 61:1, 33-37
    CrossRef