montelukast and Drug-Hypersensitivity

Rapid desensitization is a process in which drug-allergic patients receive their target dose in incremental steps, resulting in a state of temporary tolerization. In this manner, first-line therapy can be delivered safely, even in patients who present with severe hypersensitivity reactions (HSRs) to the given agent. A small subset of patients has persistent HSRs during rapid desensitization that can be refractory to antihistamines and corticosteroids.. To increase the safety and tolerability of rapid desensitization by prostaglandin and leukotriene blockade in patients with refractory mast cell mediator-related symptoms.. Fourteen adult patients developed HSRs to platinum chemotherapy that persisted during rapid desensitization. All patients had cutaneous symptoms (flushing, pruritus, or urticaria), many with associated systemic reactions. These patients were then pretreated with acetylsalicylic acid, 325 mg orally, and montelukast, 10 mg orally, 2 days before and on the day of desensitization. Response to subsequent desensitizations was assessed by medical record review and was compared with a group of matched historic control patients who received methylprednisolone for HSRs during desensitization.. Seventy-eight desensitizations in 14 patients were performed. Using acetylsalicylic acid and montelukast, 86% of patients (12/14) experienced substantial improvement in symptoms (grade 0.5 vs grade 2.14, P < .0001). Reduction in symptoms during desensitization was also significantly greater than that experienced by historic control patients who received methylprednisolone pretreatment (grade 0.5 vs grade 1.75, P = .0008). All patients received their target dose of chemotherapy, and there were no severe systemic HSRs.. Pretreatment with acetylsalicylic acid and montelukast lessens the severity of HSRs during rapid desensitization.

Topics: Acetates; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Aspirin; Colonic Neoplasms; Cyclopropanes; Desensitization, Immunologic; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Inflammation Mediators; Mast Cells; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Quinolines; Reference Standards; Sulfides

Aspirin-exacerbated respiratory disease can be diagnosed with oral aspirin challenges and treated with aspirin desensitization.. To evaluate whether controller medications, particularly leukotriene modifier drugs, taken during oral aspirin challenges can reduce the risk of severe asthmatic responses.. The medical records of 676 patients who had undergone oral aspirin challenges, followed by aspirin desensitization, were reviewed. Asthmatic responses were stratified based on severity of bronchospastic response or lack of response. The effect of pretreatment with controller medications on the outcome of oral aspirin challenges was measured.. Leukotriene modifier drugs had the most significant effect in protecting the lower airways from severe reactions (P = .004). The protective effect of leukotriene modifier drugs was observed in patients already taking systemic corticosteroids, where the addition of leukotriene modifier drugs significantly shifted the response toward a milder asthmatic response (P < .001).. Protection from significant aspirin-induced bronchospasm during oral aspirin challenge can be accomplished with leukotriene modifier drugs. The use of a combination of inhaled corticosteroids, long-acting beta-agonists, systemic corticosteroids, and leukotriene modifier drugs stabilized underlying airways in preparation for a reasonably safe and accurate oral aspirin challenge. However, only pretreatment with leukotriene modifier drugs enhanced the safety of oral aspirin challenge in patients with aspirin-exacerbated respiratory disease by significantly decreasing the degree of asthmatic responses. Therefore, outpatient oral aspirin challenges in most well-selected patients appear to be a reasonable decision.

Topics: Acetates; Adolescent; Adrenal Cortex Hormones; Adult; Aged; Anti-Asthmatic Agents; Aspirin; Asthma; Cyclopropanes; Desensitization, Immunologic; Drug Hypersensitivity; Female; Forced Expiratory Volume; Humans; Hydroxyurea; Indoles; Leukotriene Antagonists; Lipoxygenase Inhibitors; Male; Middle Aged; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Tosyl Compounds; Treatment Outcome

Montelukast, a cysteinyl-leukotriene receptor antagonist, was reported to have a protective effect against exercise-induced bronchoconstriction (EIB). Aspirin-induced asthma (AIA) is characterized by overproduction of cysteinyl-leukotrienes.. The aim of the study was to compare the response to exercise and the effect of montelukast on EIB in AIA as compared to aspirin-tolerant asthma (ATA).. A placebo-controlled, double blind, cross-over randomized study was performed in 19 AIA and 21 ATA patients with stable asthma. A single dose of montelukast (10 mg) or placebo (PL), was given orally one hour prior to exercise challenge. FEV1 was measured before and 5, 10, 15 min after exercise and then at 15-minute intervals for 4 h. Urinary LTE4 excretion and blood eosinophil count were measured at baseline, 2 h and 4 h following exercise challenge.. Positive bronchial response to exercise was observed in 47.5% of all patients studied. Exercise led to almost identical maximal fall in FEV1 in AIA and ATA patients (23.5% +/- 6.8% vs. 21.8% +/- 12.0%, respectively; P = 0.7). Montelukast, as compared to PL, significantly attenuated EIB in 63.2% of 19 patients with positive exercise test preceded by PL. The mean of maximum fall in FEV1 from the pre-exercise value was 10.2% +/- 13.8 after montelukast as compared to 22.5% +/- 10.2 after placebo (P < 0.001). No significant differences between protective effect of montelukast was observed in AIA as compared to ATA patients (P = 0.63, anova). Urinary LTE4 excretion showed no change following exercise, irrespective of the result of the test in all subjects.. Patients with AIA and ATA react similarly to exercise challenge and obtain similar protection against EIB by montelukast.

Topics: Acetates; Adult; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma, Exercise-Induced; Cross-Over Studies; Cyclopropanes; Double-Blind Method; Drug Hypersensitivity; Exercise Test; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene E4; Lung; Male; Middle Aged; Quinolines; Sulfides

Leukotriene antagonists block the proinflammatory actions of leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of leukotrienes. We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.

Topics: Acetates; Administration, Oral; Adult; Aged; Anti-Asthmatic Agents; Aspirin; Asthma; Cyclopropanes; Double-Blind Method; Drug Hypersensitivity; Drug Monitoring; Female; Forced Expiratory Volume; Humans; Leukotriene Antagonists; Leukotriene E4; Male; Middle Aged; Peak Expiratory Flow Rate; Quality of Life; Quinolines; Sulfides; Treatment Outcome

Topics: Acetates; Administration, Oral; Adult; Airway Obstruction; Allergens; Anti-Asthmatic Agents; Aspirin; Asthma, Aspirin-Induced; Cyclopropanes; Drug Hypersensitivity; Female; Humans; Immunization; Male; Mast Cells; Middle Aged; Plasma; Quinolines; Respiratory System; Sulfides; Tryptases

Topics: Acetates; Allergens; Anaphylaxis; Anti-Infective Agents; Antibiotic Prophylaxis; beta-Lactams; Cetirizine; Cyclopropanes; Cystic Fibrosis; Desensitization, Immunologic; Drug Hypersensitivity; Extracorporeal Membrane Oxygenation; Famotidine; Female; Humans; Immune Tolerance; Male; Quinolines; Respiratory Insufficiency; Sulfides

The angiotensinogen (AGT) gene enhances the effect of several bronchoconstrictors and produces a peptide that is accumulated in the airways of asthma patients; events that may underpin the pathogenesis of aspirin-intolerant asthma (AIA). To carry out a case-control analysis between AGT and aspirin-induced bronchospasm following treatment with an anti-asthma drug, montelukast (MLK), 38 single nucleotide polymorphisms (SNPs) in AGT were genotyped in 56 AIA cohort. Genotyping was performed with TaqMan assay and haplotypes were inferred using PHASE algorithm ver. 2.0. Statistical analyses of each SNPs and haplotypes were performed using SAS version 9.1. Among 13 variants displaying significant signals, two SNPs (+2401C>G and +2476C>T) in the intronic region of AGT were significantly associated with modification of drug response even after correction for multiple testing (P=0.0009-0.002; P(corr)=0.02-0.03). Furthermore, the two variants also exhibited associations with MLK response rate (P=0.0003-0.0006; P(corr)=0.006-0.01). Although our results are preliminary and further replication in a larger-scale group of subjects should be warranted, these observations provide evidence that AGT variants might be one of genetic factors involved in the response of anti-asthma drugs in AIA patients.

Topics: Acetates; Adolescent; Adult; Aged; Algorithms; Angiotensinogen; Anti-Asthmatic Agents; Asian People; Aspirin; Asthma, Aspirin-Induced; Bronchial Spasm; Case-Control Studies; Cyclopropanes; Drug Hypersensitivity; Female; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Quinolines; Republic of Korea; Sulfides; Young Adult

Patients with previous adverse contrast reactions occasionally present with ST-segment elevation myocardial infarction. Whether they can undergo catheterization safely using current contrast and medications is unknown. We reviewed catheterization laboratory records of all 501 patients (January 2005 to December 2006) presenting with ST-segment elevation myocardial infarction who underwent emergency coronary angiography. Six patients (1.2%) reported a previous contrast reaction including rash, acute bronchospasm, or anaphylaxis. All received a combination of intravenous steroids and H1 and H2 blockers in the emergency department or catheterization laboratory before catheterization. None of these had complications or evidence of allergy in any patient. In conclusion, some patients with previous contrast reaction may undergo emergency catheterization without adverse consequences, although the safety of this approach has not been proved.

Topics: Acetates; Angioplasty, Balloon, Coronary; Anti-Inflammatory Agents; Antiemetics; Cimetidine; Contrast Media; Cyclopropanes; Drug Hypersensitivity; Drug Therapy, Combination; Emergency Medical Services; Heart Conduction System; Histamine H2 Antagonists; Humans; Leukotriene Antagonists; Methylprednisolone; Myocardial Infarction; Prochlorperazine; Quinolines; Sulfides; Time Factors

Topics: Acetaminophen; Acetates; Adult; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclopropanes; Drug Hypersensitivity; Female; Follow-Up Studies; Humans; Quinolines; Sulfides

Topics: Acetates; Adrenal Cortex Hormones; Aged; Albuterol; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Arthritis; Asthma; Cyclopropanes; Depression; Drug Hypersensitivity; Drug Therapy, Combination; Epinephrine; Female; Humans; Hypersensitivity; Hypertension; Methylprednisolone; Omalizumab; Quinolines; Rhinitis; Salmeterol Xinafoate; Seizures; Sulfides; Syncope

Nonsteroidal anti-inflammatory drug (NSAID)-sensitivity is a frequent condition in patients with chronic urticaria and/or asthma. The physiopatologic process underlying respiratory and cutaneous reactions probably involves an increased production of cysteinyl leukotrienes. Cyclooxygenase 2 (COX-2) selective inhibitor, has been proposed as the main alternative to control pain and inflammatory diseases in these patients. However, a small percentage of patients with NSAID-induced skin reactions does not even tolerate COX-2 selective inhibitors. We report a very infrequent case of a patient with NSAID, paracetamol and COX-2 selective inhibitors sensitivity in whom we induced tolerance to paracetamol and celecoxib using the leukotriene receptor antagonist montelukast prior to oral challenges.

Topics: Acetates; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Cyclopropanes; Drug Hypersensitivity; Female; Humans; Middle Aged; Quinolines; Sulfides

There is a high incidence of post-surgical recurrences of nasal polyps (NP) in patients suffering from the ASA Syndrome. The numerous theories as to the pathogenesis of the ASA Syndrome include an increase in lipoxygenase-mediated arachidonic acid metabolism, with the subsequent hyperproduction of leukotrienes (LT), and an inhibition of the cycloxygenase. Therefore, based on the information acquired on the immunobiological action mechanism of montelukast, a cysteinyl-LT receptor antagonist, it appeared worth testing the effectiveness of this substance in preventing post-surgical NP recurrences in a group of ASA Syndrome patients. After taking a case history, filling out a questionnaire scoring nasal symptoms, undergoing rhinoendoscopy and rhinomanometry, 40 patients suffering from ASA-Syndrome and NP (age range 30-72 years) were recruited for the study. They were uniformly classified according to Lund and Mackay using high resolution CT of the nose and paranasal sinuses performed after at least 1 month of nasal medical treatment. All the patients underwent microendoscopic anterior-posterior ethmoidectomy and bilateral maxillary antrostomy. After removing the nasal packing, the only treatment administered was 10 mg of montelukast/die for 6 months, with the drug suspended for 1 months after the first 3 months of treatment. The monthly follow-up included rhinoendoscopy, rhinomanometry and the questionnaire to score symptoms. After the seventh month a new CT was performed and compared with the pre-operative CT. In a control group of subjects, homogeneous with the test group, momethasone furoate nasal spray was administered at a dose of 100 mcg per nostril/die and loratadin tablets 10 mg/die. The results obtained in the patients treated with montelukast were analogous with those obtained in the second group, and during follow-up all patients showed total absence of any local recurrence, good nasal patency and no significant nasal symptom score on the questionnaire. In no case did the comparative CT, performed after the seventh month, show any signs of recurrence. The patients taking the montelukast reported a significant reduction in the use of steroids and bronchodilator inhalants during the course of the study than did the second group; indeed the number of asthmatic episodes dropped and they reported an improvement in the quality of life. Based on these results, the authors suggest that the use of montelukast in the treatment of post-surgical NP recurrences

Topics: Acetates; Adult; Aged; Aspirin; Asthma; Cyclopropanes; Drug Hypersensitivity; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Nasal Polyps; Neoplasm Recurrence, Local; Quinolines; Sulfides; Syndrome

Topics: Acetates; Anti-Asthmatic Agents; Asthma; Autoimmune Diseases; Chromones; Churg-Strauss Syndrome; Cyclopropanes; Drug Hypersensitivity; Eosinophilia; Humans; Indoles; Leukotriene Antagonists; Leukotrienes; Lupus Erythematosus, Systemic; Phenylcarbamates; Quinolines; Sulfides; Sulfonamides; Th2 Cells; Tosyl Compounds

Topics: Acetates; Adult; Anaphylaxis; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclopropanes; Diclofenac; Drug Hypersensitivity; Humans; Leukotriene Antagonists; Male; Quinolines; Sulfides; Treatment Failure