Severe Liver Injury after Treatment with the Leukotriene Receptor Antagonist Zafirlukast

Reinus, John F.; Persky, Seth E.; Burkiewicz, Jill S.; Quan, David; Bass, Nathan M.; Davern, Timothy J.

doi:10.7326/0003-4819-133-12-200012190-00011

Cited by 70 publications

(30 citation statements)

References 8 publications

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“…A major disadvantage is that it suppresses all the three leukotriene receptors. Moreover, its hepatotoxicity is well documented [20]. Because most of the studies have focused on zafirlukast, little is known about montelukast.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Montelukast and Antiadhesion Barrier Solution on the Capsule Formation after Insertion of Silicone Implants in a White Rat Model

et al. 2013

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Background and Purposes: Capsular contracture is one of the most severe complications that can occur in breast surgery following silicone implant insertion. The purpose of this study was to investigate the effect of montelukast and antiadhesion barrier solution (AABS) on reducing capsular formation and their possible synergism. Materials andMethods: This study was approved by the Animal Ethics Committee (Reference No. KNU 2012-33) and was conducted in accordance with the Kyungpook National University - Institutional Animal Care and Use Committee, Animal Ethics Committee. The experiments in this study were conducted in vivo in 4 groups of 24 rats. Following silicone implant insertion, the pocket was injected with different agents. Group I (control group) was given normal saline injections into the pocket and fed with pure water. Group II was given injections of AABS and fed with pure water. Group III was given injections of normal saline and the medication montelukast during the experimental period. Group IV was given injections of AABS and montelukast as postoperative medication. Peri-implant capsules were excised after 8 weeks and were evaluated for transparency, inflammatory cell content, capsule thickness, collagen pattern and TGF-β expression. Results: The capsules in the experimental groups (i.e., groups II-IV) were significantly more transparent than those in group I (controls; p < 0.05, Student's t test). The mean capsule thickness of the experimental groups II (296 ± 14.76 μm), III (280 ± 14.77 μm) and IV (276 ± 39.28 μm) was smaller than that of the control group I (361 ± 35.43 μm). Compared to the control group, the histologic findings in the experimental groups suggested a decreased inflammatory response occurring in the peri-implant capsules as they exhibited minor vascularization and a reduced number of mast cells and macrophages. The collagen patterns in the experimental groups were of a lower density than in the control group with the former showing a loose, tidy collagen pattern. The amounts of TGF-β and collagen I were higher in the control group than in the experimental groups. Group IV (the synergic effect group) had a more pronounced effect on all the parameters examined than that in groups II and III with separate drug administration. Conclusions: Montelukast and AABS reduced the thickness, the inflammatory cell infiltrate and the myofibroblast content of the peri-implant capsules around silicone implants in this white rat model. They lowered the expression of the fibrotic mediator, TGF-β, and inhibited the peri-implant capsular fibrosis. Therefore, montelukast and AABS are effective in the reduction of silicone-induced peri-implant capsular formation.

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Section: Discussionmentioning

confidence: 99%

The Effect of Montelukast and Antiadhesion Barrier Solution on the Capsule Formation after Insertion of Silicone Implants in a White Rat Model

et al. 2013

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“…Compliance taking LMs may be superior compared with patients using an inhaled corticosteroid or inhaled long-acting beta 2 -agonist, 34 but other studies do not confirm these results. 35 Side effects of LMs are usually mild and may include headache, dizziness, or nausea; however, there have been reports of liver failure with zafirlukast, 36 and LMs may potentially cause Churg-Strauss syndrome. 37 Side effects of inhaled corticosteroids are also usually mild and may include cough, dysphonia, or oral thrush.…”

Section: Discussionmentioning

confidence: 99%

Analysis of the Effectiveness and Cost Benefit of Leukotriene Modifiers in Adults With Asthma in the Ohio Medicaid Population

Heaton¹,

Guo²,

Hornung³

et al. 2006

JMCP

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“…The increasing use of these drugs, coupled with the monitoring of liver function, may lead to more asymptomatic cases emerging. On the basis of a review of the literature, we recommend that liver function be tested within 4 weeks of the start of therapy with any leukotriene modifier, and that testing be repeated at 3, 6, and 12 months (39).…”

Section: Discussionmentioning

confidence: 99%

Effects and Zafirlukast on Capsular Contracture: Long-Term Results

Mazzocchi

Dessy

Alfano

et al. 2012

Int J Immunopathol Pharmacol

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Capsular contracture is a distressing complication after breast augmentation for both the patient and surgeon. Although capsular contracture is a multifactorial process, one common denominator in the successful treatment of this complication is believed to be the abatement of inflammation. Leukotriene antagonists have recently emerged as effective prophylactic agents in reactive airway diseases. A prospective study was carried out on 60 female patients (120 prostheses implanted) with mild/severe capsular contracture in at least one breast. The hardness of capsular contracture was assessed by means of the mammary compliance method. Patients received zafirlukast (AccolateTM) for a 6-month period. Mammary compliance was assessed at the start of the study and thereafter monthly, during drug intake and for one year after drug withdrawal. The results show a significant decrease in breast compliance values in the first 6 months, followed by a significant increase one year after the end of drug intake. Indeed, zafirlukast-treated patients displayed a 6.93% reduction in mammary compliance after 1 month, 14.42% after 3 months, 22.05% after 6 months and 22.52% after 7 months (1 month after the withdrawal of the drug). Thereafter, mammary compliance values gradually increased. A 5.47% reduction in mammary compliance was observed 1 year after drug withdrawal. The present study suggests that zafirlukast may be effective in reducing breast capsule distortion in patients with long-standing contracture, though reduced capsular contracture values are strictly related to the duration of drug intake. Capsular contracture is the most common problem and cause of patient dissatisfaction following augmentation mammaplasty and mammary reconstruction with breast implants; the reported rates of this complication range from 0.5 to 59% (1).Every patient who undergoes implantation with an alloplastic implant experiences capsules around the prostheses. Fibrotic tissue promotes compression around the implant, which in tum distorts and deforms the mass, compromising the aesthetic result and causing pain (2-7). Breast firmness that is so marked as to result in a painful, hard breast, on occasion with visible distortion, has been termed fibrous capsular contracture (8). A number of intraoperative and postoperative factors may be linked to capsular contracture. Unfortunately, as few strictly-controlled studies have been conducted to investigate the causes and possible prevention of capsular contracture, there are as yet no definite data on the aetiopathogenesis of this complication (8). Although the pathogenesis of capsular contractere is still unclear, most reports indicate a multifactor explanation (2-6).The development of a fibrotic capsule around

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Severe Liver Injury after Treatment with the Leukotriene Receptor Antagonist Zafirlukast

Abstract: Patients receiving zafirlukast may develop severe liver injury and should be observed for signs and symptoms of hepatitis.

Cited by 70 publications

References 8 publications

The Effect of Montelukast and Antiadhesion Barrier Solution on the Capsule Formation after Insertion of Silicone Implants in a White Rat Model

The Effect of Montelukast and Antiadhesion Barrier Solution on the Capsule Formation after Insertion of Silicone Implants in a White Rat Model

Analysis of the Effectiveness and Cost Benefit of Leukotriene Modifiers in Adults With Asthma in the Ohio Medicaid Population

Effects and Zafirlukast on Capsular Contracture: Long-Term Results

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