PurposeAn extended-release (ER) formulation of the expectorant guaifenesin has recently been launched in India for the treatment of productive cough accompanied by mucus (phlegm). Although the safety profile of ER guaifenesin marketed in the USA is well documented, there were limited safety data available in the Indian population. The aim of this study was to further elucidate the safety profile of ER guaifenesin in patients with acute upper respiratory tract infection (URTI).Patients and methodsA prospective, post-marketing surveillance study enrolled 552 adults with cough, thickened mucus and chest congestion due to URTI, who took ER guaifenesin 1200 mg (Mucinex®, Reckitt Benckiser; two 600 mg tablets) every 12 hrs for 7 days. Adverse events (AEs) were recorded and questionnaires administered to patients and investigators.ResultsA total of 29 treatment-emergent AEs were recorded in 28/552 patients, including gastrointestinal (n = 11), nervous system (n = 8), psychiatric (n = 3), respiratory, thoracic and mediastinal (n = 2), skin and subcutaneous tissue (n = 2), and general disorders (n = 3). All AEs were mild in severity and no serious AEs or deaths occurred. The majority of both patients and investigators were either satisfied or very satisfied with improvements in treatment outcomes.ConclusionThis study found that ER guaifenesin was well tolerated and had a favorable safety profile in otherwise healthy patients suffering from symptoms of cough, thickened mucus and chest congestion associated with URTI. Registered trial NCT03725085 (ClinicalTrials.gov) and CTRI/2014/07/004730 (ctri.nic.in).