Laboratory Abnormalities in Patients Prescribed Terbinafine for Onychomycosis
Laboratory Abnormalities in Patients Prescribed Terbinafine for Onychomycosis
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This study analyzed the frequency of baseline and monitoring laboratory abnormalities in 944 patients treated with oral terbinafine for 12 weeks for onychomycosis. Of the total, 27 (2.9%) had abnormal baseline liver function tests (LFTs), 91.3% and 92.6% of which were either an increased alanine transaminase (ALT) only or aspartate aminotransferase (AST) and ALT. Of those with abnormal baseline LFTs, 24 patients' abnormalities resolved with additional monitoring, and the remaining 3 patients completed treatment without complication. Of the overall study population, 32 (3.4%) had abnormal baseline blood counts, the majority (84.3%) of which were a grade 1 anemia. Among these, 27patients' abnormal laboratory values resolved with monitoring. Patients with laboratory abnormalities were 3 times more likely to be 65 years or older than the overall study population.
- Laboratory abnormalities in healthy adult patients prescribed terbinafine for onychomycosis are uncommon but more likely to occur in older adults. Grade 1 laboratory abnormalities at baseline are not contraindications to prescribing terbinafine, but these patients may benefit from laboratory monitoring.
– Margaret Hammond, MD
This study analyzed the frequency of baseline and monitoring laboratory abnormalities in 944 patients treated with oral terbinafine for 12 weeks for onychomycosis. Of the total, 27 (2.9%) had abnormal baseline liver function tests (LFTs), 91.3% and 92.6% of which were either an increased alanine transaminase (ALT) only or aspartate aminotransferase (AST) and ALT. Of those with abnormal baseline LFTs, 24 patients' abnormalities resolved with additional monitoring, and the remaining 3 patients completed treatment without complication. Of the overall study population, 32 (3.4%) had abnormal baseline blood counts, the majority (84.3%) of which were a grade 1 anemia. Among these, 27patients' abnormal laboratory values resolved with monitoring. Patients with laboratory abnormalities were 3 times more likely to be 65 years or older than the overall study population.
- Laboratory abnormalities in healthy adult patients prescribed terbinafine for onychomycosis are uncommon but more likely to occur in older adults. Grade 1 laboratory abnormalities at baseline are not contraindications to prescribing terbinafine, but these patients may benefit from laboratory monitoring.
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Monitoring for Liver Function Tests When Taking Terbinafine
In the United States, the terbinafine package insert (2019) indicates that liver function tests (LFTs) should be performed before prescribing terbinafine because hepatotoxicity may occur in patients with and without pre-existing liver disease.1 It goes on to state that cases of liver failure, sometimes requiring liver transplant or resulting in a fatality, have occurred in individuals with and without pre-existing liver disease. Periodic monitoring of LFTs is recommended. Terbinafine should be discontinued if biochemical or clinical evidence of liver injury occurs. In three US/Canadian trials designed to evaluate the safety and efficacy of terbinafine in the treatment of onychomycosis in adults, liver enzyme abnormalities (≥2x upper limit of normal range) were seen in 3.3% of those taking terbinafine and in 1.4% taking placebo (n = 465 and n = 137, respectively). Terbinafine was discontinued in 0.2% of patients taking the active drug, whereas none in the placebo group discontinued.
Stolmeier et al. reviewed data from 4309 patients receiving terbinafine.2 With regards to ALT measurements, at baseline, there were 3.6% with elevated measurements (n = 95; grade 1 = 3.5%; grade ≥2 = 0.1%). With regards to patients who were being monitored, 3.5% had elevated ALT measurements (n = 61; grade 1= 3.3%; grade ≥2 = 0.2%). There were 10 patients (0.4%) with actionable ALT measurements at baseline and 10 patients (0.6%) being monitored where action had to be taken (retest or discontinuation).
With regards to AST measurements, at baseline, there were 3.5% with elevated measurements (n = 84; grade 1 = 3.2%; grade ≥2 = 0.3%). With regards to patients who were being monitored, 3.1% had elevated ALT measurements (n = 46 grade 1= 3.0%; grade ≥2 = 0.07%). There were 7 patients (0.3%) with actionable ALT measurements at baseline and 8 patients (0.5%) being monitored where action had to be taken (retest or discontinuation).
Overall, performing laboratory tests during monitoring identified 4 cases of grade ≥2 ALT measurements (0.2%) and 1 case of grade ≥2 AST measurement (0.1%).
Stolmeier et al. found that 50% of patients taking terbinafine who had elevated ALT measurements had an elevated ALT measurement at baseline.
Patel et al., in a pediatric practice, reviewed 1302 patients diagnosed with onychomycosis.3 There were 144 patients who had LFTs or CBC monitoring. There were 18 (12.5%) patients with grade 1 laboratory abnormalities either prior to (12 patients, 8.3%) or during therapy (6 patients, 4.2%). In those with abnormal results during therapy, 3 patients discontinued treatment and one reported urticaria, with discontinuation of treatment.
Wang et al. evaluated 944 patients who were 19 years and older and treated with terbinafine for onychomycosis.4 Overall, 27/944 patients had baseline LFT abnormalities (24 resolved with monitoring and 3 patients completed therapy despite abnormal LFTs). In 23/944 patients, there were elevations of LFTs during the monitoring of therapy. In 17/23 patients, the LFT abnormalities resolved upon completion of therapy, in 4/23 the abnormality resolved upon premature discontinuation of therapy, and 2/23 were lost to follow-up. Most of the LFT elevations were a grade 1 elevation.
Of the patients with LFT elevations, 92.6% had AST and ALT elevations and 91.3% had ALT elevation alone. Given that ALT is more likely to be detected because of its longer half-life (ALT half-life, 36 hours; AST half-life, 18 hours), the authors suggest that monitoring ALT alone would pick up the majority of the transaminase elevations, thereby reducing laboratory costs.
Recommendation: Careful patient selection is needed as to who is prescribed terbinafine. Get a good history, review of systems, including concomitant medications, and perform a good examination. Consider baseline LFTs and then monitor as deemed necessary. If cost is an issue, perform ALT alone rather than ALT and AST.
References
- Prescribing information. Novartis; 2019. Accessed May 21, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020539s033lbl.pdf
- Stolmeier DA, Stratman HB, McIntee TJ, Stratman EJ. Utility of laboratory test result monitoring in patients taking oral terbinafine or griseofulvin for dermatophyte infections. JAMA Dermatol. 2018;154(12):1409-1416. https://jamanetwork.com/journals/jamadermatology/fullarticle/2707781
- Patel D, Castelo-Soccio LA, Rubin AI, Streicher JL. Laboratory monitoring during systemic terbinafine therapy for pediatric onychomycosis. JAMA Dermatol. 2017;153(12):1326‐ https://jamanetwork.com/journals/jamadermatology/fullarticle/2664317
- Wang Y, Geizhals S, Lipner SR. Retrospective analysis of laboratory abnormalities in patients prescribed terbinafine for onychomycosis. J Am Acad Dermatol. Published online May 6, 2020. doi:10.1016/j.jaad.2020.04.172 https://www.jaad.org/article/S0190-9622(20)30832-X/pdf
- Written by
Monitoring for Liver Function Tests When Taking Terbinafine
In the United States, the terbinafine package insert (2019) indicates that liver function tests (LFTs) should be performed before prescribing terbinafine because hepatotoxicity may occur in patients with and without pre-existing liver disease.1 It goes on to state that cases of liver failure, sometimes requiring liver transplant or resulting in a fatality, have occurred in individuals with and without pre-existing liver disease. Periodic monitoring of LFTs is recommended. Terbinafine should be discontinued if biochemical or clinical evidence of liver injury occurs. In three US/Canadian trials designed to evaluate the safety and efficacy of terbinafine in the treatment of onychomycosis in adults, liver enzyme abnormalities (≥2x upper limit of normal range) were seen in 3.3% of those taking terbinafine and in 1.4% taking placebo (n = 465 and n = 137, respectively). Terbinafine was discontinued in 0.2% of patients taking the active drug, whereas none in the placebo group discontinued.
Stolmeier et al. reviewed data from 4309 patients receiving terbinafine.2 With regards to ALT measurements, at baseline, there were 3.6% with elevated measurements (n = 95; grade 1 = 3.5%; grade ≥2 = 0.1%). With regards to patients who were being monitored, 3.5% had elevated ALT measurements (n = 61; grade 1= 3.3%; grade ≥2 = 0.2%). There were 10 patients (0.4%) with actionable ALT measurements at baseline and 10 patients (0.6%) being monitored where action had to be taken (retest or discontinuation).
With regards to AST measurements, at baseline, there were 3.5% with elevated measurements (n = 84; grade 1 = 3.2%; grade ≥2 = 0.3%). With regards to patients who were being monitored, 3.1% had elevated ALT measurements (n = 46 grade 1= 3.0%; grade ≥2 = 0.07%). There were 7 patients (0.3%) with actionable ALT measurements at baseline and 8 patients (0.5%) being monitored where action had to be taken (retest or discontinuation).
Overall, performing laboratory tests during monitoring identified 4 cases of grade ≥2 ALT measurements (0.2%) and 1 case of grade ≥2 AST measurement (0.1%).
Stolmeier et al. found that 50% of patients taking terbinafine who had elevated ALT measurements had an elevated ALT measurement at baseline.
Patel et al., in a pediatric practice, reviewed 1302 patients diagnosed with onychomycosis.3 There were 144 patients who had LFTs or CBC monitoring. There were 18 (12.5%) patients with grade 1 laboratory abnormalities either prior to (12 patients, 8.3%) or during therapy (6 patients, 4.2%). In those with abnormal results during therapy, 3 patients discontinued treatment and one reported urticaria, with discontinuation of treatment.
Wang et al. evaluated 944 patients who were 19 years and older and treated with terbinafine for onychomycosis.4 Overall, 27/944 patients had baseline LFT abnormalities (24 resolved with monitoring and 3 patients completed therapy despite abnormal LFTs). In 23/944 patients, there were elevations of LFTs during the monitoring of therapy. In 17/23 patients, the LFT abnormalities resolved upon completion of therapy, in 4/23 the abnormality resolved upon premature discontinuation of therapy, and 2/23 were lost to follow-up. Most of the LFT elevations were a grade 1 elevation.
Of the patients with LFT elevations, 92.6% had AST and ALT elevations and 91.3% had ALT elevation alone. Given that ALT is more likely to be detected because of its longer half-life (ALT half-life, 36 hours; AST half-life, 18 hours), the authors suggest that monitoring ALT alone would pick up the majority of the transaminase elevations, thereby reducing laboratory costs.
Recommendation: Careful patient selection is needed as to who is prescribed terbinafine. Get a good history, review of systems, including concomitant medications, and perform a good examination. Consider baseline LFTs and then monitor as deemed necessary. If cost is an issue, perform ALT alone rather than ALT and AST.
References
- Prescribing information. Novartis; 2019. Accessed May 21, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020539s033lbl.pdf
- Stolmeier DA, Stratman HB, McIntee TJ, Stratman EJ. Utility of laboratory test result monitoring in patients taking oral terbinafine or griseofulvin for dermatophyte infections. JAMA Dermatol. 2018;154(12):1409-1416. https://jamanetwork.com/journals/jamadermatology/fullarticle/2707781
- Patel D, Castelo-Soccio LA, Rubin AI, Streicher JL. Laboratory monitoring during systemic terbinafine therapy for pediatric onychomycosis. JAMA Dermatol. 2017;153(12):1326‐ https://jamanetwork.com/journals/jamadermatology/fullarticle/2664317
- Wang Y, Geizhals S, Lipner SR. Retrospective analysis of laboratory abnormalities in patients prescribed terbinafine for onychomycosis. J Am Acad Dermatol. Published online May 6, 2020. doi:10.1016/j.jaad.2020.04.172 https://www.jaad.org/article/S0190-9622(20)30832-X/pdf
Abstract
Journal of the American Academy of Dermatology
Retrospective Analysis of Laboratory Abnormalities in Patients Prescribed Terbinafine for Onychomycosis
J Am Acad Dermatol 2020 May 06;[EPub Ahead of Print], Y Wang, S Geizhals, SR Lipner
posted by dermatica at
May 23, 2020
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