[Evaluation of the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol versus a fixed-dose combination of bromhexine/guaifenesin/salbutamol in the treatment of productive cough in adult patients with acute bronchitis].

AIM: To evaluate the efficacy and safety of a combination drug containing ambroxol, guaifenesin, and levosalbutamol, oral solution, versus Ascoril Expectorant, syrup (combination of bromhexine, guaifenesin, and salbutamol) in the treatment of productive cough in adult patients with acute bronchitis. MATERIALS AND METHODS: This open-label, randomized, phase III study included patients with acute bronchitis who had a productive cough with difficulty in sputum expectoration. 244 patients were randomized in a 1:1 ratio and received 10 mL of the study drug or reference drug 3 times daily for 2 weeks. After 7 and 14 days of treatment, the physician evaluated patient's subjective complaints and the efficacy of therapy. The primary endpoint was the proportion of patients with high and very high efficacy. RESULTS: The primary endpoint was reached by 70 (0.5738) patients in the study drug group and 54 (0.4426) in the reference drug group (p=0.04). The intergroup difference was 0.1311 [95% confidence interval: 0.0057; 0.2566]. The lower limit of the 95% confidence interval was above zero, which confirms the superiority of therapy with the study drug over therapy with Ascoril Expectorant. The proportion of patients with a 1-point total score reduction and with complete resolution of all symptoms according to the Modified Cough Relief and Sputum Expectoration Questionnaire after 7 and 14 days was numerically higher in the study drug group versus the reference drug group. There were no statistically significant differences between the groups in the incidence of adverse events. CONCLUSION: The efficacy of a new combination drug containing ambroxol, guaifenesin, and levosalbutamol in the treatment of productive cough in adult patients with acute bronchitis is superior to the efficacy of Ascoril Expectorant. The safety profiles of the study drug and the reference drug were comparable.

Whole-genome methylation profiling of peripheral blood mononuclear cell for acute exacerbations of chronic obstructive pulmonary disease treated with corticosteroid.

OBJECTIVE: Although association studies in the general population may be relevant for determining susceptibility to chronic obstructive pulmonary disease (COPD), they may be less applicable for pharmacogenetics research in participants who have already acquired the disease. PATIENTS AND METHODS: A genome-wide methylation profiling (generated by HumanMethylation450 BeadChips study was performed on peripheral blood mononuclear cells of 24 patients with AECOPD (acute exacerbation COPD), with good and poor responsiveness to standard corticosteroid treatment. Pyrosequencing was used to replicate the selected CpG sites in 50 patients with AECOPD with standard corticosteroid treatment. RESULTS: The results showed the patients with AECOPD with good and poor response to standard corticosteroid treatment have a distinct DNA methylation pattern. A total of 23 CpG loci located in 19 known gene regions, including gene-body and promoter, appeared to be significantly differentially methylated. Replication by pyrosequencing revealed that one CpG site in PSMD8 showed the same trend of differential methylation and reached to statistical significance as the microarray result. CONCLUSION: Our preliminary findings provide evidence for molecular heterogeneity in patients with AECOPD, which may contribute to significant differences in their response to COPD treatment.

Generalized Bullous Fixed Drug Eruption due to Bromhexine.

We describe a patient with a generalized bullous form of Fixed Drug Eruption (FDE) induced by bromhexine, a commonly used drug for respiratory symptoms. This is a rare association and generalized bullous FDE is also very rare. We emphasize the importance of patch tests in identifying the culprit drug.

[Results of international multicentre non-interventional clinical study of the effectiveness and safety of ascoril expectorant for the treatment of cough in Kazakhstan and Uzbekistan].

This paper reports results of international multicentre non-interventional clinical study of the effectiveness and safety of ascoril expectorant for the treatment of cough in Kazakhstan and Uzbekistan. The study included 16312 patients examined in different cities during 2011-2012. It showed that ascoril expectorant (Glenmark) at a standard dose is an effective agent for the treatment of cough in children above 3 years and adults aged up to 78 years with ARVI and acute bronchitis, exacerbation of these conditions or grade I-II chronic obstructire pulmonary disease. Most patients reported good therapeutic effect within 1 day after intake. Ascoril expectorant caused no adverse reactions and was well tolerated by the patients. 91% of the attending physicians describe the drug as highly effective.

Bromhexine Hydrochloride Tablets for the Treatment of Moderate COVID-19: An Open-Label Randomized Controlled Pilot Study.

This open-label randomized controlled pilot study aimed to test the study feasibility of bromhexine hydrochloride (BRH) tablets for the treatment of mild or moderate coronavirus disease 2019 (COVID-19) and to explore its clinical efficacy and safety. Patients with mild or moderate COVID-19 were randomly divided into the BRH group or the control group at a 2:1 ratio. Routine treatment according to China's Novel Coronavirus Pneumonia Diagnosis and Treatment Plan was performed in both groups, whereas patients in the BRH group were additionally given oral BRH (32 mg t.i.d.) for 14 consecutive days. The efficacy and safety of BRH were evaluated. A total of 18 patients with moderate COVID-19 were randomized into the BRH group (n = 12) or the control group (n = 6). There were suggestions of BRH advantage over placebo in improved chest computed tomography, need for oxygen therapy, and discharge rate within 20 days. However, none of these findings were statistically significant. BRH tablets may potentially have a beneficial effect in patients with COVID-19, especially for those with lung or hepatic injury. A further definitive large-scale clinical trial is feasible and necessary.

[Skin reactions attributed to the use of bromhexine]. / Huidreacties toegeschreven aan het gebruik van broomhexine.

Since 1972, the Netherlands Centre for Monitoring of Adverse Reactions to Drugs has received 22 reports of skin reactions attributed to use of bromhexine. The reports concerned II men and II women. The ages ranged between 5 months and 88 years. The skin reactions occurred within one to 30 days after starting the use of bromhexine. Most skin reactions consisted of generalised urticaria. Other reports concerned once an angioedema and once an anaphylactic reaction. Most patients recovered completely after cessation of bromhexine without further treatment.

Stevens-Johnson syndrome presumably induced by bromhexine. A case report.

The Stevens-Johnson syndrome is a serious form of erythema multiforme, an acute inflammatory pathology with an autoimmune pathogenesis. Its etiology is unknown, although it is thought to have multifactorial causes; nonetheless, many drugs are thought to induce such an immune response. The clinical symptomatology is mainly muco-cutaneous, with a remarkable oral involvement. The authors describe here a case of Stevens-Johnson syndrome involving the ocular, oral, and genital areas, presumably induced by the bromhexine administered to the patient for a viral syndrome.

Acute generalized exanthematous pustulosis associated with polysensitivity to paracetamol and bromhexine: the diagnostic role of in vitro interferon-gamma release test.

We report a patient with acute generalized exanthematous pustulosis (AGEP), which occurred 3 days after ingesting paracetamol and bromhexine. Both were immediately stopped and the rash resolved rapidly. To determine the offending drug responsible for AGEP, an in vitro drug-induced interferon (IFN)-gamma release test was performed using an ELISA technique. Increased IFN-gamma release was observed following in vitro challenge of the patient's lymphocytes with paracetamol or bromhexine (110% and 157% increase, respectively). In vitro challenge with paracetamol or bromhexine in a control patient, treated with paracetamol and bromhexine, did not induce an increase in IFN-gamma. These findings suggest that the patient with AGEP may have polysensitivity to both drugs. The ELISA assessment also demonstrates the relevance of in vitro cytokine release tests in the investigation of such dermatoses.

[Hemostatic disorders with secretolytics? A contribution to drug safety]. / Hämosasestörungen bei Sekretolytika? Ein Beitrag zur Arzneimittelsicherheit

Based on literature and on the results of this open clinical trial we conclude, that there is no connection between application of the above named group of drugs and the change in parameters of haemostasis function, which might lead to a manifest haemorrhagic diathesis. Within the period surveyed of 14 days no case of induced coagulopathy and particularly no thrombocytopenia was seen. The substances under consideration themselves did not exert any anticoagulatory effect nor did they potentiate or inhibit the effect of a concurrently given cumarin derivative.

Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo.

The effectiveness of bromhexine in the treatment of patients with bronchiectasis, in a stage of clinical exacerbation, was assessed in a double-blind, placebo-controlled trial involving 88 in-patients. Bronchiectasis was diagnosed by bronchography and/or CT scan. Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os. Ceftazidine, 1 g i.m., was given to all patients once a day for the first week only. Bromhexine seemed to improve the clinical picture, with significantly positive trends for expectoration, quantity of sputum and auscultatory findings. It also increased the FEV1 and was well-tolerated. Both patients and investigators judged it efficacious.

Efficacy and safety of Ascoril in the management of cough--National Study Group report.

A total of 768 patients were recruited by 81 physicians and paediatricians all over the country in this National Study Group of 'Ascoril + Expectorant'. The results of this first large scale study of a cough formula indicates that 'Ascoril + Expectorant' is effective in controlling cough, breathlessness and decreasing the volume of sputum. No serious adverse events were noted. Ascoril was well accepted by the patients and its efficacy was rated very high by the physician. The National Study Group concludes that 'Ascoril + Expectorant' is highly effective in the management of cough associated with lower respiratory tract infection and COPDs.

Clinical effectiveness of a combination of bromhexine and amoxicillin in lower respiratory tract infection. A randomized controlled trial.

A multicenter double-blind randomized trial was performed in 22 teaching hospitals to compare the clinical effectiveness of the combination of amoxicillin (CAS 26787-78-0) plus bromhexine (CAS 3572-43-8) versus amoxicillin alone given 4 times a day for 5 to 7 days in the treatment of clinically diagnosed community-acquired bacterial lower respiratory tract infections. 392 adult patients diagnosed clinically to have acute bronchitis or pneumonia of bacterial etiology were recruited for the study with 192 subjects given amoxicillin (250 mg) plus bromhexine (8 mg) (Drug AB) and 200 receiving amoxicillin (250 mg) (Drug AA) alone 4 times a day for 5 to 7 days. Clinical response, improvement in symptom scores using a visual analogue scale, and bacteriologic response were monitored at Days 3, 5 and 7 of treatment. Results showed that although 180/192 (94%) given Drug AB and 185/200 (93%) given Drug AA had favorable clinical response at the end of treatment, the infection was completely resolved for 89/192 (46%) among the Drug AB group and in 67/200 (34%) of patients on Drug AA (p = 0.022). Also, patients given Drug AB had significantly greater reduction of their symptom scores at Day 3 for symptoms of cough discomfort, cough frequency, ease of expectoration and sputum volume. Among the subset of patients with pneumonia, the cure rates for Drug AB and Drug AA were 24/50 (47%) and 11/50 (22%), respectively (p = 0.008). A respiratory pathogen was cultured in only 72/392 (18%) of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy and safety of Ascoril expectorant and other cough formula in the treatment of cough management in paediatric and adult patients--a randomised double-blind comparative trial.

The present study was undertaken to study the comparative safety and efficacy of two cough formulas viz, Ascoril expectorant and other cough formula in the management of cough associated with respiratory disorders. Fifty patients having cough associated with various respiratory disorders like bronchitis and upper or lower respiratory tract infections were randomly divided into 2 equal groups and were treated with one of the two cough formulas viz, Ascoril cough formula and other cough formula in double-blind manner over a period of 15 days. The evaluation of improvement was carried out by a rating scale using three clinical parameters--cough, sputum and breathlessness. The physicians were asked to rate the effectiveness of the therapy and patients were asked to rate the acceptability of therapy using pre-defined operational criteria. It was observed that the improvement and symptom relief was almost immediate, quicker and better in the group receiving Ascoril as compared to other group. On effectiveness parameter, 96% of the physicians rated Ascoril as having either 'very high effectiveness or high effectiveness' as opposed to only 34% of the physicians who rated other cough formula as having 'high' or 'very high effectiveness'. While on parameter of acceptability, 96% of the patients rated acceptability of Ascoril as 'high' or 'good' as opposed to only 24% of the patients who rated other cough formula 'high' or 'good'. The findings of this study suggests that Ascoril cough formula has better efficacy as well as better patient acceptability. Thus, Ascoril cough formula is superior to other cough formula in management of cough associated with respiratory disorders.