Acute Onset of Pancreatitis with Concomitant Use of Tenofovir and Didanosine

Abstract

Spanish

French

OBJECTIVE

To report a case of pancreatitis associated with the combined use of didanosine and tenofovir.

Case Summary

A 51-year-old white man with HIV was initiated on antiretroviral therapy with didanosine 250 mg/day, tenofovir 300 mg/day, lamivudine 300 mg/day, stavudine 60 mg/day, and efavirenz 600 mg/day. Didanosine was prescribed at a reduced dosage due to the known interaction with tenofovir. Despite this dosage adjustment, the patient developed acute pancreatitis 10 weeks after antiretrovirals were initiated. Pancreatitis resolved spontaneously after antiretroviral discontinuation.

DISCUSSION

Our report of didanosine-induced pancreatitis secondary to concurrent use with tenofovir is the third reported case that utilized a reduced didanosine dosage. Five previous pancreatitis reports have been described using full-strength didanosine with tenofovir. The exact mechanism of action for this interaction is unknown. Utilizing the Naranjo probability scale to assess causality, a possible adverse drug reaction was determined.

CONCLUSIONS

Tenofovir and didanosine may be used cautiously in antiretroviral combination therapy. Reduced didanosine dosage (250 mg) should be used to reduce serum didanosine concentrations and subsequent toxicities. Practitioners should be aware that a significant drug interaction with resulting pancreatitis may occur even when a reduced dosage is prescribed.

Keywords

didanosine pancreatitis tenofovir

Get full access to this article

View all access options for this article.

References

1. Package insert. Viread (tenofovir DF). Foster City, CA: Gilead Sciences, October 2003.

2. Barditch-Crovo

Deeks

Collier

Safrin

Coakley

Miller

Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus—infected adults. Antimicrob Agents Chemother 2001;45:2733–9.

3. Schooley

Ruane

Myers

Beall

Lampiris

Berger

Tenofovir DF in antiretroviral-experienced patients: results from a 48–week, randomized, double-blind study. AIDS 2002;16:1257–63.

4. Staazewski

Gallant

Pozniak

Suleiman

JMAH

DeJesus

Sayre

Efficacy and safety of tenofovir DF vs. stavudine when used in combination with lamivudine and efavirenz in antiretroviral naîve patients: 96–week preliminary interim results (poster 564b). Presented at: 10th Conference of Retroviruses and Opportunistic Infections, Boston, February 10–14, 2003.

5. Department of Health and Human Services, the Kaiser Family Foundation. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. www.aidsinfo.nih.gov (accessed 2004 Apr 27).

6. Kearney

Flaherty

Wolf

Barriere

Wong

Chen

Coadministration of tenofovir DF and didanosine: a pharmacokinetic and safety evaluation (poster 172). Presented at: 8th European Conference on Clinical Aspects and Treatment of HIV Infection, Athens, October 28–31, 2001.

7. Kearney

Damle

Plummer

Sayre

Namini

Ryan

Pharmacokinetic evaluation of tenofovir DF and enteric-coated didanosine (poster 9026). Presented at: 14th International AIDS Conference, Barcelona, July 7–12, 2002.

8. Package insert. Videx EC (didanosine). Princeton, NJ: Bristol-Myers Squibb, January 2002.

9. Yarchoan

Pluda

Thomas

Mitsuya

Brouwers

Wyvill

Long-term toxicity/activity profile of 2′,3′dideoxyinosine in AIDS or AIDS-related complex. Lancet 1990;336:526–9.

10.

10. Blanchard

Wohlfeiler

Canas

King

Longeran

JT.

Pancreatitis treated with didanosine and tenofovir disoproxil fumarate. Clin Infect Dis 2003;37:e57–62.

11.

11. Davies

Yoganathan

Fatal acute pancreatitis in an HIV-positive man—the result of an interaction between tenofovir disoproxil fumarate (TDF) and didanosine (ddI) (P124). Presented at: Sixth International Congress on Drug Therapy in HIV Infection, Glascow, November 17–21, 2002.

12.

12. Murphy

O'Hearn

Chou

Fatal lactic acidosis and acute renal failure after addition of tenofovir to an antiretroviral regimen containing didanosine. Clin Infect Dis 2003;36:1082–5.

13.

13. Rivas

Polo

de Gorgolas

Fernandez-Guerrero

ML.

Fatal lactic acidosis associated with tenofovir (letter). BMJ 2003;327:711.

14.

14. Callens

de Schacht

Huyst

Colebunders

Pancreatitis in an HIV-infected person on a tenofovir, didanosine and stavudine containing highly active antiretroviral treatment. J Infect 2003;47:188–9.

15.

15. Rollot

Nazal

Chauvelot-Moachon

Kelaidi

Daniel

Saba

Tenofovir-related Fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: the role of lopinavir-ritonavir-didanosine. Clin Infect Dis 2003;37:e174–6.

16.

16. DeChristoforo

Penzak

SR.

Tenofovir: a nucleotide analogue reverse-transcriptase inhibitor for treatment of HIV infection. Am J Health Syst Pharm 2004;61:86–100.

17.

17. Kearney

Isaacson

Sayre

Plummer

Cheng

Didanosine and tenofovir DF drug-drug interaction: assessment of didanosine dose reduction (poster 533). Presented at: 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 10–14, 2003.

18.

18. Food and Drug Administration. FDA/Bristol Myers Squibb issues caution for HIV combination therapy with Zerit and Videx in pregnant women (talk paper T01–02). Rockville, MD: US Department of Health and Human Services, January 5, 2001.

19.

19. Raffi

Saag

Cahn

Wolff

Pearce

Molina

A randomized, double-blind, multicenter comparison of emtricitabine QD to stavudine BID in treatment-naîve HIV-infected patients. Presented at: 2nd IAS Conference on Pathogenesis and Treatment, Paris, July 13–16, 2003.

20.

20. Gerstoft

Kirk

Obel

Pedersen

Mathiesen

Nielsen

Low efficacy and high frequency of adverse events in a randomized trial of the triple nucleoside regimen abacavir, stavudine and didanosine. AIDS 2003;17:2045–52.

21.

21. Barrios

Negredo

Vilaro-Rodriguez

Domingo

Estrada

Labarga

Safety and efficacy of a QD simplification regimen (poster 566). Presented at: 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, February 8–11, 2004.

22.

22. Martinez

Milinkovic

de Lazzari

Ravasi

Blanco

Larrousse

Pancreatic toxic effects associated with co-administration of didanosine and tenofovir in HIV-infected adults. Lancet 2004;364:65–7.

23.

23. Naranjo

Busto

Sellers

Sandor

Ruiz

Roberts

A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239–45.

24.

24. Pecora Fulco

Kirian

Effect of tenofovir on didanosine absorption in patients with HIV. Ann Pharmacother 2003;37:1325–8.