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Lamotrigine-Associated Rash and Blood Dyscrasias in a Methadone-Treatment Patient With Hepatitis C

Received January 25, 2005; revised March 24, 2005; accepted April 20, 2005. From the Dept. of Psychiatry, State Univ. of New York (SUNY); Upstate Medical Univ., Syracuse; and the VA Center for Integrated Healthcare, VA Healthcare Network, Upstate New York, Syracuse. Address correspondence and reprint requests to Dr. Batki, Dept. of Psychiatry, State Univ. of New York, Upstate Medical Univ., 713 Harrison St., Syracuse, NY 13210. e-mail: batkis{at}upstate.edu

Key Words: lamotrigine • rash • blood dyscrasias • methadone • hepatitis C • bipolar disorder

INTRODUCTION

TOP INTRODUCTION Case Report Discussion Conclusions REFERENCES

 
Individuals with hepatitis C infection and those in methadone treatment are known to have high rates of mood disorders. Lamotrigine is an anticonvulsant approved by the FDA for the treatment of bipolar disorder, particularly for bipolar depression. Rash has been reported as the most frequent adverse effect of lamotrigine, whereas blood dyscrasias have been noted rarely.¹ We report the occurrence of rash, thrombocytopenia, and neutropenia associated with lamotrigine in a methadone-treatment patient with hepatitis C infection.

Case Report

TOP INTRODUCTION Case Report Discussion Conclusions REFERENCES

 
Ms. A is a 40-year-old biracial woman with bipolar disorder and opioid dependence, undergoing methadone maintenance treatment. She had chronic hepatitis C infection, chronic iron deficiency anemia, and venous insufficiency. Her daily medication regimen consisted of methadone 110 mg, furosemide 60 mg, and potassium chloride 30 meq.

Ms. A presented with depressed mood and anxiety. There was a history of past treatment with lamotrigine for 4 weeks without adverse effects, with unclear treatment response, and discontinuation for unknown reasons. Because the current depression presented in the context of bipolar disorder, lamotrigine was initiated at 25 mg per day and increased to 50 mg per day after 2 weeks, with further continuation at the latter dose for another 9 days.

During the fourth week of lamotrigine therapy, Ms. A complained of itching and rash. Physical examination revealed an erythematous, maculopapular rash covering the malar areas of the face, the neck, upper torso, and deltoid areas. Lamotrigine was immediately discontinued, and a referral was made to her primary-care provider and, subsequently, to a hematologist. The patient was followed with serial laboratory tests and physical examinations. Table 1 describes the progress of her leukopenia, neutropenia, and thrombocytopenia.

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TABLE 1. Hematology Laboratory Values Before, During, and After Lamotrigine Treatment

Discussion

TOP INTRODUCTION Case Report Discussion Conclusions REFERENCES

 
Ms. A had some hematological abnormalities pre-dating the use of lamotrigine. She had chronic iron deficiency anemia, with a hematocrit of 29.3% and a slightly low platelet count 13 days before initiation of lamotrigine. However, after 26 days of treatment, platelet, total white blood count, and neutrophil count all decreased dramatically. They returned to baseline levels 53 days after discontinuation, strongly suggesting that lamotrigine was a causal factor.

It is possible that lamotrigine clearance may have been slowed in this patient, raising blood levels, and increasing the risk of adverse reactions. Longer half-life has been noted for lamotrigine in patients with liver impairment.² Furthermore, methadone has been reported to delay the clearance of substrates that undergo glucuronidation.³ It is possible that methadone may have elevated the levels of lamotrigine, which is also glucuronidated. Finally, hepatitis C virus (HCV) infection is also associated with blood dyscrasias, most commonly thrombocytopenia.⁴ Perhaps the separate risk factors of lamotrigine treatment and HCV infection combined to contribute to the adverse events seen in this patient.

Conclusions

TOP INTRODUCTION Case Report Discussion Conclusions REFERENCES

 
Patients with hepatitis C who are receiving methadone treatment may be at risk for rashes and blood dyscrasias in response to lamotrigine treatment. Ms. A had no symptoms or signs attributable to blood dyscrasias, suggesting the need to monitor hematological indices in patients with hepatitis C who develop rash while on lamotrigine. This case demonstrates the need for possibly greater care in the use of lamotrigine in patients with hepatitis C who are undergoing methadone treatment.

ACKNOWLEDGMENTS

 
This work was supported in part by NIDA R01 DA016764 and the VA Center for Integrated Healthcare.

REFERENCES

TOP INTRODUCTION Case Report Discussion Conclusions REFERENCES

 

1. Mackay FJ, Wilton LV, Pearce GL, et al: Safety of long-term lamotrigine in epilepsy. Epilepsia 1997; 38:881–886[CrossRef][Medline]
2. Physicians' Desk Reference. Montvale, NJ, Thomson PDR, 2005, p 1532
3. McCance-Katz EF, Rainey PM, Jatlow P, et al: Methadone effects on zidovudine disposition. J Acquir Immune Defic Syndr 1998; 18:435–443
4. Wang CS, Yao WJ, Wang ST, et al: Strong association of hepatitis C virus (HCV) infection and thrombocytopenia: implications from a survey of a community with hyperendemic HCV infection. Clin Infect Dis 2004; 39:790–796[CrossRef][Medline]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Alleyne, S. Articles by Batki, S. L. Search for Related Content PubMed Citation Articles by Alleyne, S. Articles by Batki, S. L. AIDS/HIV Bipolar Disorder Syndromes Secondary to General Medical Disorders

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