• Users Online: 439
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 4  |  Issue : 1  |  Page : 61-63

Hallucination in kidney transplant recipient: A rare complication of voriconazole


1 Department of Nephrology, Christian Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Pharmacology, Christian Medical College and Hospital, Ludhiana, Punjab, India

Date of Web Publication19-Dec-2016

Correspondence Address:
Manmeet Singh Jhawar
Department of Nephrology, Christian Medical College and Hospital, Ludhiana, Punjab
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2348-3334.196071

Rights and Permissions
  Abstract 

Postkidney transplant recipients are more susceptible to opportunistic infections including fungal infections. Voriconazole is a broad-spectrum antifungal with a good safety profile even in patients with renal dysfunction. Hallucination is a rare and underreported complication of oral voriconazole therapy, especially in kidney transplant recipients. Two patients of postrenal transplant who developed hallucination following oral therapy with voriconazole have been highlighted here. Symptoms improved in both patients following a reduction in dosage or cessation of therapy. This case report highlights the fact that even though voriconazole-induced hallucinations are a rare complication, it is important to be aware of the same so as to be able to diagnose it and institute appropriate corrective measures.

Keywords: Hallucinations, kidney transplant, voriconazole


How to cite this article:
Jhawar MS, George P, Das J, Badyal DK. Hallucination in kidney transplant recipient: A rare complication of voriconazole. CHRISMED J Health Res 2017;4:61-3

How to cite this URL:
Jhawar MS, George P, Das J, Badyal DK. Hallucination in kidney transplant recipient: A rare complication of voriconazole. CHRISMED J Health Res [serial online] 2017 [cited 2019 Dec 6];4:61-3. Available from: http://www.cjhr.org/text.asp?2017/4/1/61/196071


  Introduction Top


Antifungal therapy with voriconazole provides a good option, especially in patients with renal dysfunction. The most commonly observed adverse drug reactions (ADRs) with voriconazole are visual disturbances followed by skin rashes. Hallucinations are rare, especially when oral voriconazole therapy is being used, with the prevalence of visual hallucination around 5%. [1] These are often underreported complication of voriconazole therapy and can be misdiagnosed for neuropsychiatric disturbances, especially in critically ill patients. These cases highlight visual and auditory hallucination due to voriconazole in a postkidney transplant recipients in whom such complications have previously not been reported.


  Case reports Top


Case 1

A sixty-five-year-old male postkidney transplantation on treatment at an outside center (on prednisolone, tacrolimus, mycophenolate mofetil, and everolimus) on antituberculosis therapy (ATT) (isoniazid and pyrazinamide) for 6 months presented with fever, breathlessness, and decreased urine output. He had acute worsening of renal function (creatinine - 1.8 mg/dl), anemia (Hb - 9.8 g/dl), respiratory failure (pO 2 - 62.5) with metabolic acidosis (bicarbonate - 11.3), and normal liver function tests. A septic screen was done and he was initiated on meropenem, renal modified oral acyclovir (for oral herpetic lesions), trimethoprim, and continued on ATT. Computerized tomography (CT) of the chest showed multiple centrilobular nodules and ground glass opacities. He did not consent for bronchoscopy lavage and biopsy. Oral voriconazole (at a dose of 200 mg twice a day) was initiated in view of CT findings and sputum culture positive for candida nonalbicans, with close monitoring of tacrolimus targeting trough levels of 3-7 ng/ml. He improved after initiation of therapy and was afebrile. On the 3 rd day of treatment, he had visual (sense of children playing in the room, raindrops appearing on the wall) and auditory hallucinations (voices of children and adults talking with him), tremulousness, and headache. Clinically, there were no features of meningitis and patient refused imaging and cerebrospinal fluid. Voriconazole-induced hallucination was suspected. Serum drug levels of voriconazole could not be done due to nonavailability. Voriconazole dose was reduced by 50%, hallucination improved over the next 48 h and therapy was continued for a total of 8 days.

Case 2

A sixty-nine-year-old male postkidney transplantation (on prednisolone, tacrolimus, and mycophenolate mofetil) chronic allograft nephropathy presented with fever in Type I respiratory failure (pO 2 - 58), anemia (Hb - 7.4 g/dl), and creatinine (5.8 mg/dl). High-resolution CT chest was suggestive of ground glass appearance with the presence of nodules. A possibility of fungal pneumonia was kept; bronchoscopy could not be done in view of concurrent atrial fibrillation. Oral voriconazole therapy (at a dose of 200 mg twice a day) was started, with tacrolimus trough levels 4.24 ng/dl during therapy. On the 3 rd day of therapy, he developed visual hallucination (sense of his bed going on the road with people sitting next to him) which persisted over the next 2 days. Voriconazole was discontinued on day 6 and changed over to caspofungin. His hallucination subsided on the next day. A possibility of voriconazole-induced hallucination was suspected. Serum drug levels of voriconazole could not be done due to nonavailability.


  Discussion Top


Posttransplant patients are at a high risk for opportunistic infections including fungal infections. Treatment of multiple opportunistic fungal infections with voriconazole, a broad spectrum second generation azole antifungal agent, has shown to result in favorable outcomes. [2]

Visual disturbances, in the form of altered color discrimination, blurred vision, and photopsia, are the most common side effect of voriconazole with skin rashes being the second most common side effect. Elevation of liver enzymes occurs as with other azole group of drugs. [3] Visual hallucination is a less common side effect noted with voriconazole at a rate of 5% and is clearly different from photopsia. [1] Adverse neurological events are associated with elevated serum voriconazole levels, and its measurement can improve the drug safety profile. [4]

Hallucination is a rare complication of voriconazole therapy and is often overlooked or misdiagnosed. Visual and auditory hallucinations are significantly more frequent (32%) at voriconazole concentrations of >5 mg/L as compared to ≤5 mg/L (P < 0.01). [5] Analysis of a retrospective pharmacovigilance database showed 13.3% patients on voriconazole had a visual hallucination; however, the hallucinations were not distinguished from visual changes. [6] A prospective natural cohort study of 72 patients showed 12 patients who experienced hallucination while on voriconazole therapy. Hallucinations occurred mainly after intravenous (IV) formulations though they were also seen with oral formulations. Symptoms disappeared when IV is switched over to oral treatment; hence, it was advisable to continue with oral therapy in critically ill conditions. [7]

Our case 1 had a serious ADR with visual and auditory hallucination following administration of voriconazole with Naranjo index score of seven (probable adverse reaction) and case 2 had serious visual hallucinations with Naranjo index score of eight (probable adverse reaction). [8] Case 1 was on isoniazid which results in increased serum level or effect of voriconazole by affecting hepatic enzyme CYP2C19 metabolism. It is possible that due to the above interaction, his levels of voriconazole were high, which may have returned to therapeutic levels following dose reduction. However, in the absence of drug levels, this cannot be absolutely ascertained. In case 2 due to severe debilitation due to visual hallucination, voriconazole was switched over to caspofungin following which his symptoms subsided. Major metabolic pathway for voriconazole, CYP2C19, is highly dependent on genetic polymorphism. Low CYP2C19 activity is seen in 15%-20% of Asian descent, resulting in four times higher voriconazole levels than in those with normal metabolism. [9] Saturation of voriconazole metabolism leads to nonlinear pharmacokinetics and substantial intersubject variability in serum concentrations. [10] It is possible that due to the above genetic polymorphism, our case 2 had increased voriconazole drug levels leading to hallucinations.


  Conclusions Top


Voriconazole-induced hallucination in postkidney transplant recipient patient, especially with oral medication, is a rare and underreported complication. Interactions with other medications which patient is receiving or genetic polymorphism may result in these rare adverse effects. It is important to be aware of the same, so as to diagnose it correctly and institute appropriate corrective measures.

Financial Support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002;346:225-34.  Back to cited text no. 1
    
2.
Denning DW, Ribaud P, Milpied N, Caillot D, Herbrecht R, Thiel E, et al. Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 2002;34:563-71.  Back to cited text no. 2
    
3.
Johnson LB, Kauffman CA. Voriconazole: A new triazole antifungal agent. Clin Infect Dis 2003;36:630-7.  Back to cited text no. 3
    
4.
Imhof A, Schaer DJ, Schanz U, Schwarz U. Neurological adverse events to voriconazole: Evidence for therapeutic drug monitoring. Swiss Med Wkly 2006;136:739-42.  Back to cited text no. 4
    
5.
Dolton MJ, Ray JE, Chen SC, Ng K, Pont LG, McLachlan AJ. Multicenter study of voriconazole pharmacokinetics and therapeutic drug monitoring. Antimicrob Agents Chemother 2012;56:4793-9.  Back to cited text no. 5
    
6.
Eiden C, Peyrière H, Cociglio M, Djezzar S, Hansel S, Blayac JP, et al. Adverse effects of voriconazole: Analysis of the French Pharmacovigilance Database. Ann Pharmacother 2007;41:755-63.  Back to cited text no. 6
    
7.
Zonios DI, Gea-Banacloche J, Childs R, Bennett JE. Hallucinations during voriconazole therapy. Clin Infect Dis 2008;47:e7-10.  Back to cited text no. 7
    
8.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 8
    
9.
Balian JD, Sukhova N, Harris JW, Hewett J, Pickle L, Goldstein JA, et al. The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: A population study. Clin Pharmacol Ther 1995;57:662-9.  Back to cited text no. 9
    
10.
Purkins L, Wood N, Ghahramani P, Greenhalgh K, Allen MJ, Kleinermans D. Pharmacokinetics and safety of voriconazole following intravenous- to oral-dose escalation regimens. Antimicrob Agents Chemother 2002;46:2546-53.  Back to cited text no. 10
    




 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case reports
Discussion
Conclusions
References

 Article Access Statistics
    Viewed1065    
    Printed16    
    Emailed0    
    PDF Downloaded73    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]