Montelukast-Induced Adverse Drug Reactions: A Review of Case Reports in the Literature

Calapai, Gioacchino; Casciaro, Marco; Miroddi, Marco; Calapai, Fabrizio; Navarra, Michele; Gangemi, Sebastiano

doi:10.1159/000366164

Cited by 80 publications

(87 citation statements)

References 59 publications

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“…Like for bromocriptin, no published data are available investigating the effect of montelukast on BSEP function. But this compound has been reported to induce liver injury in pediatric and adult patients, which cannot be related to bile acid accumulation and hepatic transporter inhibition to date 45,46 . Our study here clearly demonstrates no cis-inhibitory effect of this compound on BSEP in the vesicle-based assay.…”

Section: Discussionmentioning

confidence: 99%

Flagging Drugs That Inhibit the Bile Salt Export Pump

et al. 2015

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The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bile duct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to identify new BSEP inhibitors and therefore potential cholestasis perpetrators. Just Accepted "Just Accepted" manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides "Just Accepted" as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. "Just Accepted" manuscripts appear in full in PDF format accompanied by an HTML abstract. "Just Accepted" manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). "Just Accepted" is an optional service offered to authors. Therefore, the "Just Accepted" Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the "Just Accepted" Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these "Just Accepted" manuscripts. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 Table of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 1 Flagging drugs that inhibit the bile salt export pump AbstractThe bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepa...

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Section: Discussionmentioning

confidence: 99%

Flagging Drugs That Inhibit the Bile Salt Export Pump

et al. 2015

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“…In addition, allergic granulomatous angiitis (Churg‐Strauss syndrome) may also be associated with the use of montelukast (Calapai et al. ).…”

Section: Introductionmentioning

confidence: 99%

Adverse drug reactions of montelukast in children and adults

Haarman

Hunsel

Vries

2017

Pharmacology Res & Perspec

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Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase® until 2016. Depression was reported most frequently in the whole population to the global database VigiBase® (reporting odds ratio (ROR) 6.93; 95% CI: 6.5–7.4). In the VigiBase®, aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5–32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61–3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase®. These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.

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“…1b). Montelukast is a leukotriene receptor antagonist, and has been shown to be associated with possible increase in suicidal behavior and depression [31]. …”

Section: Resultsmentioning

confidence: 99%

Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders

Sun

Narayan

Wittenberg

2016

BMC Pharmacol Toxicol

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BackgroundSide effects, or the adverse effects of drugs, contain important clinical phenotypic information that may be useful in predicting novel or unknown targets of a drug. It has been suggested that drugs with similar side-effect profiles may share common targets. The diagnostic class, Major Depressive Disorder, is increasingly viewed as being comprised of multiple depression subtypes with different biological root causes. One ‘type’ of depression generating substantial interest today focuses on patients with high levels of inflammatory burden, indicated by elevated levels of C-reactive proteins (CRP) and pro-inflammatory cytokines such as interleukin 6 (IL-6). It has been suggested that drugs targeting the immune system may have beneficial effect on this subtype of depressed patients, and several studies are underway to test this hypothesis directly. However, patients have been treated with both anti-inflammatory and antidepressant compounds for decades. It may be possible to exploit similarities in clinical readouts to better understand the antidepressant effects of immune-related drugs.MethodsHere we explore the space of approved drugs by comparing the drug side effect profiles of known antidepressants and drugs targeting the immune system, and further examine the findings by comparing the human cell line expression profiles induced by them with those induced by antidepressants.ResultsWe found 7 immune-modulators and 14 anti-inflammatory drugs sharing significant side effect profile similarities with antidepressants. Five of the 7 immune modulators share most similar side effect profiles with antidepressants that modulate dopamine release and/or uptake. In addition, the immunosuppressant rapamycin and the glucocorticoid alclometasone induces transcriptional changes similar to multiple antidepressants.ConclusionsThese findings suggest that some antidepressants and some immune-related drugs may affect common molecular pathways. Our findings support the idea that certain medications aimed at the immune system may be helpful in relieving depressive symptoms, and suggest that it may be of value to test immune-modulators for antidepressant-like activity in future proof-of-concept studies.

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Montelukast-Induced Adverse Drug Reactions: A Review of Case Reports in the Literature

Cited by 80 publications

References 59 publications

Flagging Drugs That Inhibit the Bile Salt Export Pump

Flagging Drugs That Inhibit the Bile Salt Export Pump

Adverse drug reactions of montelukast in children and adults

Side effect profile similarities shared between antidepressants and immune-modulators reveal potential novel targets for treating major depressive disorders

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