Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 8189  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Article Submission Resources Sections Etcetera Contact
 
  NAVIGATE Here 
  Search
 
 :: Next article
 :: Previous article 
 :: Table of Contents
  
 RESOURCE Links
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::Related articles
 ::  Article in PDF (219 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
 ::  Case Report
 ::  Discussion
 ::  References

 Article Access Statistics
    Viewed3681    
    Printed195    
    Emailed6    
    PDF Downloaded149    
    Comments [Add]    
    Cited by others 4    

Recommend this journal


 


 
ADR REPORT
Year : 2010  |  Volume : 56  |  Issue : 1  |  Page : 44-45

Interaction between voriconazole and glimepiride


Department of Clinical Pharmacology, Nizam's Institute of Medical Sciences, Hyderabad-500 082, India

Date of Submission13-Apr-2009
Date of Decision22-Oct-2009
Date of Acceptance04-Dec-2009
Date of Web Publication12-Apr-2010

Correspondence Address:
J C Shobha
Department of Clinical Pharmacology, Nizam's Institute of Medical Sciences, Hyderabad-500 082
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.62422

Rights and Permissions


 :: Abstract 

Voriconazole, a triazole antifungal, is gaining popularity in the treatment of invasive fungal infections, mostly in the immuno-compromised patients. Voriconazole, a CYP2C9 inhibitor, has many potential drug interactions. Its interactions are both due to its pharmacokinetic properties and the genetic polymorphism of CYP2C9 enzymes. Here is a case report of one such drug-drug interaction between voriconazole and glimepiride, an oral hypoglycemic agent, which led to prolonged and persistent hypoglycemia for 48 h. It was diagnosed by the temporal association of the occurrence of symptoms with voriconazole intake. The patient stabilized on withdrawal of the responsible drugs. Due to the high incidence of co-prescribing voriconazole with other drugs, caution has to be exercised while prescribing it. Clinicians' awareness, a high index of suspicion and constant monitoring for adverse drug reactions, expected or unexpected drug interactions has to be emphasized, even if the co-prescribed drugs are in normal therapeutic doses.


Keywords: Drug interaction, glimepiride, hypoglycemia, voriconazole


How to cite this article:
Shobha J C, Muppidi M R. Interaction between voriconazole and glimepiride. J Postgrad Med 2010;56:44-5

How to cite this URL:
Shobha J C, Muppidi M R. Interaction between voriconazole and glimepiride. J Postgrad Med [serial online] 2010 [cited 2019 Nov 15];56:44-5. Available from: http://www.jpgmonline.com/text.asp?2010/56/1/44/62422


Voriconazole is a triazole antifungal medication which is gaining popularity over Amphotericin B, for serious, life-threatening, invasive fungal infections which are generally seen in immunocompromised patients. They include candidiasis, aspergillosis and certain emerging fungal infections. [1] It is also indicated for prophylaxis as well as for empirical antifungal therapy in immunocompromised patients with febrile neutropenia who are at a high risk for breakthrough fungal infections. [1]

Voriconazole, a CYP2C9 inhibitor has to be cautiously prescribed as it has many potential drug interactions. [2] Especially with CYP2C9 substrates, we need to exercise more caution as the genetic polymorphism of CYP2C9 adds to the unexpected possibility of adverse drug reactions and drug-drug interactions even at normal therapeutic doses. [3] Here is a case of such a potential interaction between voriconazole and glimepiride at therapeutic doses, which has not been studied clinically. [2]


 :: Case Report Top


A 69-year-old male with Myelodysplasia RAEB II (on 5-Azacytidine chemotherapy) progressed to acute myeloid leukemia and developed febrile neutropenia. He was a known diabetic for seven months on Tablet glimepiride (Amaryl) 1 mg OD with good glycemic control. As empirical antifungal therapy was indicated, Tablet voriconazole (Vfend) 400 mg 12-hourly (two doses) followed by 200 mg 12-hourly daily orally was started. Baseline liver function tests, renal function tests and ophthalmic examination were done before starting the course. The patient was instructed to take the tablet one hour before or after food and was asked to report immediately if visual disturbance, rash or gastrointestinal disturbances occurred. On the second day of the course, two hours after the first 200 mg dose of voriconazole, the patient suddenly developed excessive and pressured speech, confusion and delirium. His blood glucose was recorded to be 40 mg/dl. Serum electrolytes and liver function tests were found to be normal. Immediate 25% dextrose infusion stabilized the patient. Despite constant monitoring, the patient dropped into unconsciousness two hours after stabilization. It was found that he had hypoglycemia (blood glucose=38mg/dl). With 25% dextrose, the patient regained consciousness. Suspecting a drug-drug interaction, voriconazole and glimepiride were stopped. An hourly blood glucose monitoring for a day followed by two-hourly monitoring revealed that the patient had persistent and prolonged, hypoglycemia which lasted for a period of 48 h after withdrawing the drug. He was unable to maintain normal blood glucose levels if the dextrose infusion was stopped. The patient was treated with continuous infusion of 5% dextrose and non-diabetic diet until he stabilized on the third day with maintainable blood glucose levels. Tab. voriconazole was restarted and glimepiride was substituted with subcutaneous insulin for the rest of the period. No such reaction or hypoglycemia occurred further in the course of treatment.


 :: Discussion Top


Voriconazole and its metabolites are inhibitors of CYP2C9 liver enzymes. Glimepiride, a sulphonylurea is a substrate for CYP2C9 enzymes. Voriconazole inhibited the metabolism of glimepiride and prolonged its action which led to the persistent hypoglycemia. Also, CYP2C9 iso enzymes exhibit genetic polymorphism which is why its substrates can cause unexpected adverse effects or drug-drug interactions even under normal therapeutic doses. [3] The temporal association of persistent hypoglycemia and the administration of voriconazole is prominent and, the drug dechallenge led to maintainable blood glucose level.

Glimepiride has a half life of 3.4 h, peaks at 2-3 h and has a duration of action of 12-24 h.The incidence of hypoglycemia with glimepiride is low (2%) when compared to other long-acting second generation sulphonylureas (20-30%). [4] In this patient, though the chance of glimepiride alone causing persistent hypoglycemia cannot be ruled out, the chances are low, more so, after seven months of good glycemic control.

Even though voriconazole and glimepiride were administered in normal therapeutic doses, due to the chance of a potential pharmacokinetic drug interaction and the genetic polymorphism of CYP2C9, the patient had unexpected life-threatening hypoglycemia. Hence, clinicians' awareness and close monitoring for adverse drug reactions and interactions has to be emphasized while prescribing drugs like voriconazole. It is advisable to monitor drug interactions known to occur with other azoles until more clinical reports and experience is gained with voriconazole. [5]

 
 :: References Top

1.Walsh T, Pappas P, Winston D, Lazarus H, Petersen F, Raffalli J, et al. Voriconazole compared with liposomal amptotericin B for empirical anti-fungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002;346:225-34.  Back to cited text no. 1      
2.University of Pennsylvania Medical Center (Internet).Guidelines for Antimicrobial therapy, UPHS Drug dosing and administration Guidelines, Voriconazole usage guidelines; pennsylavania (USA); 2003. Available from: http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/voriguide.htm. [cited in 2003].  Back to cited text no. 2      
3.Rose MJ, Adithan C. The pharmacogenetics of CYP2C9 and CYP2C19: Ethnic variation and clinical significance. Curr Clin Pharmacol 2007;2:93-109.   Back to cited text no. 3      
4.Davis SN. Oral hypoglycemics. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman′s the pharmacological basis of therapeutics, 11 th ed. USA: McGraw-Hill Professional; 1941. p. 1635-8.  Back to cited text no. 4      
5.Bennett JE. Antifungal agents. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman′s the pharmacological basis of therapeutics, 11 th ed. USA: McGraw-Hill Professional; 1941. p. 1225-40.  Back to cited text no. 5      



This article has been cited by
1 Antifungal drugs
Aronson, J.K.
Side Effects of Drugs Annual. 2012; 34: 427-439
[Pubmed]
2 Inhibition potential of glimepiride (gli) towards important UDP-glucuronosyltransferase (UGT) isoforms in human liver
Fu, J.-F. and Ren, Q.-Y. and Zhang, N.-Y. and Gao, B. and Tu, Y.-Y. and Fu, G.-Q. and Li, D.-H. and Zhang, Y.-S.
Pharmazie. 2012; 67(8): 715-717
[Pubmed]
3 Enteral voriconazole induced hypoglycemia: A potentially life threatening complication
Ghatak, T. and Singh, R.K. and Baronia, A.K.
Indian Journal of Pharmacology. 2012; 44(1): 138-139
[Pubmed]
4 Current awareness: Pharmacoepidemiology and drug safety
Pharmacoepidemiology and Drug Safety. 2010; 19(11): i
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
Previous article Next article
Online since 12th February '04
2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow