Efficacy and Safety of an Oral Ambroxol Spray in the Treatment of Acute Uncomplicated Sore Throat

Abstract

Objective: Compare the efficacy and tolerability of oral spray formulations delivering 2.5, 5, and 10 mg ambroxol (AXS) per application (4 actuations/application) in relieving acute sore throat vs. spraying a matched placebo solution.

Design: Multi-centre, placebo-controlled, randomised, double-blind trial with up to 6 daily applications of the assigned medication for up to 3 days.

Patients: 511 outpatients with acute sore throat were enrolled, 494 were treated.

Treatments: Up to 6 spray applications per day as needed for up to 3 days.

Results: All treatments led to a reduction in pain intensity (PI); the mean cumulative PI-reductions over the first 2 h after the 1^st dose (SPIDnorm(0–2)) were 24.7, 26.6, 26.0, and 32.2% (SEM: 0.023) of the predose PI for treatment with placebo, and the 2.5, 5, and 10 mg AXS, respectively. These mean reductions were 2 (CI: −3.6; 7.5), 1.3 (CI: −4.3; 6.8), and 7.5 (CI: 2.0;13.1) percent points larger than for placebo. The 2.5 and 5 mg AXS were not distinguishable from placebo, but the 10 mg AXS was evidently superior. The numbers needed to treat (NNT) when comparing 10 mg AXS with placebo, were 9.5 and 8.8 for an average pain relief of 33 and 50% of the maximum achievable effect over the first 2 h.

Conclusions: 10 mg AXS showed a statistically significantly superior pain reduction relative to the placebo spray. Treatment with 10 mg AXS reaches an extent of pain relief that can be accepted to be clinically meaningful and was well tolerated.

Key words

sore throat - ambroxol - ambroxol spray - local anaesthetic

• References

• 1 Tyrakowski T, Greczko I, Sedlaczek A et al. Electrophysiological investigation of the effects of Ambroxol on the transepithelial Na+ ion transport pathway in airways. Pol J Pharmacol 1998; 50: 31-38
• 2 Weiser T, Wilson N. Inhibition of tetrodotoxin (TTX)-resistant and TTX-sensitive neuronal Na(+) channels by the secretolytic ambroxol. Mol Pharmacol 2002; 62: 433-438
• 3 Schutz A, Grund HJ, Pschorn U et al. Local anaesthetic properties of ambroxol hydrochloride lozenges in view of sore throat – Clinical proof of concept. Arzneim.-Forsch/Drug Res 2002; 52: 194-199
• 4 Fischer J, Pschorn U, Vix JM et al. Efficacy and tolerability of ambroxol hydrohloride lozenges in sore throat – Randomised, double-blind, placebo-controlled trials regarding the local anaesthetic properties. Arzneim.-Forsch/Drug Res 2002; 52: 256-263
• 5 de Mey C, Peil H, Kölsch S et al. Efficacy and safety of ambroxol lozenges in the treatment of acute uncomplicated sore throat. EBM-based clinical documentation. Arzneim.-Forsch/Drug Res 2008; 58: 557-568
• 6 Farrar JT, Berlin JA, Strom BL. Clinically important changes in acute pain outcome measures: a validation study. J Pain Symptom Manage 2003; 25: 406-411
• 7 Farrar JT. Advances in clinical research methodology for pain clinical trials. Nat Med 2010; 16: 1284-1293
• 8 Disse BG. The pharmacology of Ambroxol - review and new results. Eur J Respir Dis Suppl 1987; 153: 255-262
• 9 Disse BG, Ziegler HW. Pharmacodynamic mechanism and therapeutic activity of Ambroxol in animal experiments. Respiration 1987; 51 (Suppl 1) 15-22
• 10 Pfeifer S, Zissel G, Kienast K et al. Reduction of cytokine release of blood and broncheoalveolar mononuclear cells by Ambroxol. Eur J Med Res 1997; 2: 129-132
• 11 Gillissen A, Bartling A, Schoen S et al. Antioxidant function of Ambroxol in mononuclear and polymorphnuclear cells in vitro. Lung 1997; 175: 235-242
• 12 Felix K, Pairet M, Zimmermann R. The antioxidative activity of the mucoregulatory agents: Ambroxol, bromhexine and N-acetyl-L-cysteine. A pulse radiolysis study. Life Sci 1996; 59: 1141-1147
• 13 Lapenna D, de Gioia S, Ciofani G et al. Ambroxol is a scavenger of hypochlorous acid and monochloramine. Pharmacology 1994; 49: 132-135
• 14 Chenot JF, Weber P, Friede T. Efficacy of Ambroxol lozenges for pharyngitis: a meta-analysis. BMC Fam Pract 2014; 15: 45
• 15 Kieser M, Friede T, Gondan M. Assessment of statistical significance and clinical relevance. Stat Med 2013; 32: 1707-1719
• 16 Farrar JT, Young JP, LaMoreaux L et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain 2001; 94: 149-158
• 17 Cepeda MS, Africano JM, Polo R et al. What decline in pain intensity is meaningful to patients with acute pain?. Pain 2003; 105: 151-157
• 18 Bijur PE, Chang AK, Esses D et al. Problems with measurement of the minimum clinically significant difference in acute pain in elders. Acad Emerg Med 2011; 18: 135-139
• 19 Kendrick DB, Strout TD. The minimum clinically significant difference in patient-assigned numeric scores for pain. Am J Emerg Med 2005; 23: 828-832