Levodropropizine-Induced Anaphylaxis: Case Series and Literature Review

Levodropropizine is commonly used as an antitussive drug for acute and chronic cough. It is a non-opioid agent with peripheral antitussive action via the modulation of sensory neuropeptide levels in the airways. Thus, levodropropizine has a more tolerable profile than opioid antitussives. However, we experienced 3 cases of levodropropizine-induced anaphylaxis. Three patients commonly presented with generalized urticaria, dyspnea, and collapse after taking cold medication including levodropropizine. To find out the culprit drug, we performed skin tests, oral provocation tests (OPTs), and basophil activation tests (BATs). Two patients were confirmed as having levodropropizine-induced anaphylaxis by OPTs, and one of them showed positive to skin prick tests (SPTs). The other patient was confirmed by skin tests and BATs. When we analyzed pharmacovigilance data related to levodropropizine collected for 5 years, most cases (78.9%) had allergic reactions, such as rash, urticaria, angioedema, and anaphylaxis. Therefore, physicians should consider that levodropropizine can be a culprit drug, when anaphylaxis occurs after taking anti-cough or common cold medication.

Pathophysiology, Causes and Treatment of Chronic Cough in Adults: Literature Review / 대한이비인후과학회지

Chronic cough is a common symptom and the etiology of which can be challenging to diagnose. The key to successful management is to establish a diagnosis and to treat the cause of cough. Asthma, gastro-esophageal reflux, and postnasal drip syndrome have been thought to be most common causes of chronic cough. Various causes such as lung diseases (sarcoidosis, pertussis), obstructive sleep apnea, drug (angiotensin-converting enzyme inhibitor), and psychological status can induce chronic cough. However, many chronic cough patients do not have an identifiable cause. We need to understand the mechanisms underlying central and peripheral sensitization, how they interact with cough triggers and their relationship with the sensations that drive the urge to cough, and the subsequent motor cough response in chronic cough. Heightened cough reflex sensitivity is persistent and their cough is unexplained in many patients. In most patients who visited otorhinolaryngoloy clinics, it is possible to manage a majority of chronic cough patients successfully using a protocol based on presenting symptoms and therapeutic trials for the common causes of cough. However, there are few therapeutic options for patients with unexplained chronic cough. There is a pressing need to understand the physiological basis of unexplained chronic cough and to develop novel antitussive drugs that down regulate cough reflex sensitivity.

Drug therapy for the common cold

The common cold is an acute, self-limiting viral infection of the upper respiratory tract involving the nose, sinuses, pharynx and larynx. Drug therapies for the common cold are normally aimed at relieving the symptoms of the illness. Over-the-counter cough and cold medications should not be used in children younger than four years old because of potential harms and lack of benefit. Antibiotics, antitussives, anti-histamines, and inhaled corticosteroids are not effective in children. Products that may improve symptoms in children include expectorants, mucolytics, honey, vitamin C, zinc lozenges, geranium extract, and nasal saline irrigation. In adults, antihistamines, intranasal corticosteroids, codeine, intranasal ipratopium, and antibiotics are not effective. Decongestants, antihistamine/decongestant combi-nations, expectorants, and mucolytics may improve cold symptoms in adults. Nonsteroidal anti-inflammatory drugs and acetaminophen reduce pain secondary to upper respiratory tract infection in adults. Among complementary and alternative medicinetherapeutics, products containing vitamin C, zinc, or garlic may improve cold symptoms in adults. Prophylactic use of probiotics may decrease the frequency of colds in adults and children.

Antitussive and mucoactive drugs

Cough is the most frequent complaint from medical patients even though coughing is a protective reflex. The principle of relief from a cough is treatment of its underlying disease. However, when the treatment of the cause of coughing is not effective, cough suppression therapy just to relieve the symptom may be attempted. Antitussives and mucoactive drugs are used for this purpose. Unfortunately, the currently available agents are not consistently effective and frequently have intolerable side effects. Therefore, understanding the side effects and mechanism of action of these agents is definitely needed. This review provides a summary of the currently available antitussives and mucoactives.

The Efficacy of Inhaled Corticosteroid on Chronic Idiopathic Cough / 결핵및호흡기질환

BACKGROUND: The discomfort caused by chronic cough, that is persistent for more than 3 weeks, causes a number of patients to seek medical attention. However, the underlying disorder often remains undetermined despite thorough examinations, and is considered to be idiopathic. This study compared the efficacy of inhaled corticosteroid with conventional cough suppressants on chronic idiopathic cough. METHODS: Eligible patients with chronic idiopathic cough were randomly assigned to either the inhaled fluticasone group or the codeine plus levodropropizine oral administration group. The subjects in each group took their planned medication for 2 weeks. After the trial, comparative analyses of outcomes were performed in terms of the remnant cough (%) at the end of treatment, drug compliance, and adverse drug events. RESULTS: Seventy-seven patients were enrolled in this randomized trial; 38 to the inhaled fluticasone group and 39 to the codeine plus levodropropizine group. The remnant cough was 41.0+/-35.8% in the inhaled fluticasone group, and 32.4+/-32.0% in the codeine+levodropropizine group (p=0.288). Drug compliance was 95.4+/-7.4% and 81.8+/-18.6% in the inhaled fluticasone and the codeine+levodropropizine group, respectively (p<0.001). Nine patients had adverse drug events in the codeine+levodropropizine group compared to one in the inhaled fluticasone group (p<0.001). CONCLUSION: Short-term inhaled corticosteroid is not inferior to conventional antitussive agents in controlling chronic idiopathic cough without significant adverse events.

The Efficacy of Inhaled Corticosteroid on Chronic Idiopathic Cough / 결핵및호흡기질환

BACKGROUND: The discomfort caused by chronic cough, that is persistent for more than 3 weeks, causes a number of patients to seek medical attention. However, the underlying disorder often remains undetermined despite thorough examinations, and is considered to be idiopathic. This study compared the efficacy of inhaled corticosteroid with conventional cough suppressants on chronic idiopathic cough. METHODS: Eligible patients with chronic idiopathic cough were randomly assigned to either the inhaled fluticasone group or the codeine plus levodropropizine oral administration group. The subjects in each group took their planned medication for 2 weeks. After the trial, comparative analyses of outcomes were performed in terms of the remnant cough (%) at the end of treatment, drug compliance, and adverse drug events. RESULTS: Seventy-seven patients were enrolled in this randomized trial; 38 to the inhaled fluticasone group and 39 to the codeine plus levodropropizine group. The remnant cough was 41.0+/-35.8% in the inhaled fluticasone group, and 32.4+/-32.0% in the codeine+levodropropizine group (p=0.288). Drug compliance was 95.4+/-7.4% and 81.8+/-18.6% in the inhaled fluticasone and the codeine+levodropropizine group, respectively (p<0.001). Nine patients had adverse drug events in the codeine+levodropropizine group compared to one in the inhaled fluticasone group (p<0.001). CONCLUSION: Short-term inhaled corticosteroid is not inferior to conventional antitussive agents in controlling chronic idiopathic cough without significant adverse events.