Skip to main content

Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: a cross-national survey among pharmacists and general practitioners

Abstract

Background

Benzydamine for oromucosal use is indicated in the relief of pain and irritation of the mouth and throat. It is an indazole derivative, non-steroidal anti-inflammatory drug, with combined local anesthetic and analgesic properties, and antiseptic activity, marketed under the brand name “Tantum Verde”. The aim of this study was to explore knowledge and prescriptive/advising attitudes among general practitioners (GPs) and pharmacists (PHs) with regard to the topical treatment of sore throat and other irritative/inflammatory conditions of the oropharynx, with a focus on benzydamine. These findings could be important to increase awareness on benzydamine efficacy in sore throat and stomatological conditions, and to reinforce knowledge on the characteristics of benzydamine and its mechanisms of action among healthcare professionals (pediatricians, otolaryngologists, oncologists, etc.).

Materials and methods

An online questionnaire survey was performed among PHs and GPs in four European countries (Italy, Germany, Russia and Poland).

Results

Both GPs and PHs proved to have an excellent knowledge and mastery of the constituents effective against oral symptoms. Among all the principles, benzydamine hydrochloride is the most recognized as certainly suitable for the topical treatment of sore throat symptoms and various inflammatory/irritative conditions of the oral cavity. It is recommended by about 90% of PHs and prescribed by 80% of GPs, mainly to solve the ailments caused by sore throats and stomatitis, especially for its anti-inflammatory, analgesic and anesthetic characteristics. Also in the pediatric field, benzydamine hydrochloride is recommended: among GPs, a high percentage (about 40%) prescribes it like the remedies based on dichlorobenzyl alcohol-sodium benzoate, which are instead more often recommended by PHs (44% against 37%).

Conclusion

Although the public has a lot of confidence in this treatment, GPs and PHs do not recommend/prescribe benzydamine as a first-line treatment of sore throat and other irritative/inflammatory conditions of the oropharynx. To increase the knowledge of benzydamine among these healthcare professionals, it would be important to emphasize its characteristics and the different irritative/inflammatory conditions of the oropharynx in which it can be used.

Peer Review reports

Introduction

Benzydamine is an indazole derivative, non-steroidal anti-inflammatory drug, with combined local anesthetic and analgesic properties, and antiseptic activity. It is an over-the-counter drug in Europe (except in Turkey) marketed under the brand name “Tantum Verde” [1].

In addition to its anti-inflammatory activity, benzydamine shows local an analgesic/anesthetic effects that in the topical route can be fully exploited and turned into competitive advantages over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) [2, 3]. In fact, its elective therapeutic use is the topical control of acute inflammation and pain. Benzydamine has its target indication in the symptomatic treatment of pain and irritative/inflammatory conditions of the oropharynx (gingivitis, stomatitis, pharyngitis), even when due to dental therapy.

Local application of benzydamine produces higher concentrations in the inflamed area than in the blood, as shown in studies performed in animals and humans [4, 5]. The ability of benzydamine to concentrate in the inflamed tissues, with low systemic exposure, is a clear advantage that limits potential systemic side effects [6].

The three main activities of benzydamine, anti-inflammatory, local analgesic, and anesthetic, all contribute to a highly specific and targeted efficacy, reducing symptoms related to a local inflammatory state.

Benzydamine hydrochloride has been studied and found to be effective for treating oral mucositis and oral ulcers, as well as for the prevention of post-operative sore throat following endotracheal intubation [7, 8]. Moreover, in some countries, it is also indicated for the symptomatic treatment of oromucosal inflammation, including oral mucositis due to radiotherapy + /chemotherapy in patients with Head and Neck Cancer (HNC) [9, 10].

Understanding the prescribing practice and attitudes among general practitioners (GPs) and community pharmacists (PHs) would help ascertain the degree of awareness of different active ingredients, including benzydamine hydrochloride, as topical treatments for irritative/inflammatory conditions of the oropharynx. These findings could be important to increase awareness on benzydamine efficacy in sore throat and stomatological conditions, and to reinforce knowledge on the characteristics of benzydamine and its mechanisms of action among healthcare professionals (pediatricians, otolaryngologists, oncologists, etc.).

Therefore, a survey among GPs and PHs in different European countries was performed with the aim of exploring knowledge, attitudes and prescriptive/advising behaviour of the respective study populations with regard to the topical treatment of sore throat and other irritative/inflammatory conditions of the oropharynx, with a focus on benzydamine.

Materials and methods

Study design

This study was carried out through an online questionnaire survey among PHs and GPs in four European countries (Italy, Germany, Russia and Poland) participating in the project. The questionnaire was sent out via e-mail by country-specific research marketing companies operating in the pharmaceutical sector and quality-certified (ISO 20252). The study was conducted between June and July 2021. In each country, 150 questionnaires were sent to GPs and 150 to community PHs, and the top 100 in each category were collected, amounting to a total of 802* completed questionnaires.

* One more questionnaire was collected from PHs in Poland and one more questionnaire was collected from GPs in Russia.

The questionnaire

The questionnaire was designed by an interdisciplinary research team consisting of experienced GPs, otolaryngologists, a social scientist, and a statistician. The aforementioned team has a long standing experience in both practicing medicine and in research. An initial draft of the survey was reviewed by a general practitioner external to the research team to ensure it was easy to understand and could be completed in a few minutes. Two slightly different versions, according to the specific skills and tasks of the two target populations – community PHs and GPs—have been developed and then translated into the languages of the four countries involved. The questionnaire in English can be found in the appendix (see Additional file 1). It dealt with a total of 17 and 15 items to the GPs and PHs, respectively.

The main topics of the questionnaire can be summarized as follows. The first question regarded what the respondent – based on own knowledge – thinks about the usability of different active ingredients, including benzydamine hydrochloride, for the mouth and throat irritative symptoms. The next four items asked which of the active ingredients has been generally prescribed (if GP) or recommended (if PH), and what formulation, to adults and children, respectively. Then, focusing on those GPs and PHs who declared to prescribe and/or recommend benzydamine hydrochloride, a number of items inquired about which symptoms and mechanisms of action (anesthetic, analgesic, anti-inflammatory, antiseptic) it is mainly recommended for. PHs were asked to give an evaluation of the proportion of their customers acquiring the product based on benzydamine hydrochloride by themselves, that is an indicator of self-medication. The last items of the questionnaire collected information on demographic characteristics and the number of patients/customers usually followed by the respondent GP/PH.

Statistical analysis

All results are based on point estimations and hypothesis testing. Separately for GPs and PHs, frequencies for all data collected were reported. For presentation purposes, categorical data were presented as percentages and continuous data as means and standard deviations (SDs). Differences between categories of interest and countries were analyzed using chi-square tests and t tests. A value of P < 0.05 was considered statistically significant. All analyses were performed using R, a programming language and free software environment for statistical computing and graphics supported by the R Core Team and the R Foundation for Statistical Computing.

Results

Characteristics of respondents

Participant demographic details are shown in Table 1.

Table 1 Characteristics of GPs and PHs participating in the study

Among both pharmacists and general practitioners, men slightly outnumber women, and it is interesting to note that there are differences between countries: in Poland and Italy, the gender difference is more pronounced, especially among GPs. The overall mean age of the pharmacists is lower than general practitioners’: 49.6 (SD = 10.48) for PHs vs 52.5 (SD = 9.72) for GPs. On customers/patients base, approximately 90% of PHs have more than 300 customers with a mean of 533.3 (SD = 201.3), while for GPs the average number of patients is 1120.3 (SD = 278.6).

Benzydamine hydrochloride (Tantum Verde) and the other treatments

The vast majority of respondents, both GPs and PHs, reported the usability of all six active ingredients listed in the questionnaire as topical treatments for sore throat and inflammatory/irritative conditions of the mouth (Table 2).

Table 2 Reported usability in the survey of active ingredients for topical medication of sore throat and inflammatory/irritative conditions of the mouth (i.e. gingivitis or stomatitis)

Respondents showed an excellent knowledge of treatments for oral pain conditions in general and of benzydamine hydrochloride, in particular. In fact, among the six possible constituents listed in the questionnaire, benzydamine hydrochloride was the most frequently recognized effective treatment for sore throat and pain conditions in the mouth, with 92.3% of GPs and 95.3% of PHs declaring it as usable in such situations.

GPs and PHs concur in the usability of the active ingredients and their approach is similar for the other topical medications; the only remarkable difference is between natural extract and all the other treatments with an average difference of about 14% for PHs and 21% for GPs.

Regarding the usability of benzydamine, no differences between countries were found (Table 3): chi-square test state the equality of percentages of “yes” answers among the four countries analyzed for GPs (p-value = 0.758) and for PHs (p-value = 0.868). Looking at the differences between GPs and PHs within each country, the only statically significant result is in Italy (p-value = 0.0035) where PHs state usability of benzydamine in higher percentage (100% vs 89.10%).

Table 3 Reported usability in the survey of benzydamine for topical medication of sore throat and inflammatory/irritative conditions of the mouth (i.e. gingivitis or stomatitis) by country

Regarding prescribing, most respondents answered "yes" with a similar approach across treatments and between GPs and PHs, except for natural extracts (Table 4).

Table 4 Percentages of GPs and PHs that prescribe/recommend the active ingredients for topical treatment of symptoms of sore throat and various inflammatory/irritative conditions of the oral cavity such as gingivitis and stomatitis

The three constituents most recommended by PHs for the topical treatment of sore throat and other oral conditions are dichlorobenzyl alcohol-sodium benzoate (90.3%), ambroxolo hydrochloride (89.8%), and benzydamine hydrochloride (89.3%). Benzydamine hydrochloride is recommended by a very high percentage of GPs (80.8%) in the topical treatment of the oral cavity and is surpassed by dichlorobenzyl alcohol-sodium benzoate, which is prescribed by a slightly higher percentage of GPs (83.5%). Regarding approach to benzydamine between countries (Table 4), no statistical difference was found either for PHs (p-value = 0.5678) or for GPs (p-value = 0.3105). Within countries, there is a statistically significant difference between PHs and GPs only in Italy (p-value = 0.00737) and in Poland (p-value = 0.0357).

End users appear very familiar with benzydamine hydrochloride, as evidenced by the fact that on average 40.03% of people require it as a self-medication (Table 5).

Table 5 Customer management of purchases of benzydamine hydrochloride (average percentage according to pharmacists)

The mechanisms of action and symptoms for which benzydamine hydrochloride is recommended

Based on pharmacists’ experience, the first two symptoms that prompt clients to seek advice are ache (14.57%) and cough (11.65%), followed by redness of the throat (9.37%), itchy throat and symptoms due to extraction therapy (Table 6).

Table 6 Average percentage of clients who seek for the advice of pharmacists by throat and oral symptoms

Clients behave very differently depending on the country (Table 6): for example, in Germany only an average of 8% of customers ask for advice if they have ache, while in Russia this percentage is almost double and in Italy almost triple. Even for cough, in Germany only 7.78% of customers ask for advice, while in Italy this percentage is double.

The vast majority of GPs (71.8%) and PHs (76.8%) recommend benzydamine hydrochloride to their patients/customers, with no significant difference in approach between GPs and PHs (p-value = 0.1246), as these proportions are not statistically different.

Benzydamine hydrochloride is prescribed for all four of its properties by both PHs and GPs who declared to prescribe/recommend benzydamine hydrochloride (Table 7). The most appreciated characteristic of benzydamine hydrochloride is its anti-septic features (71.60% for GPs and 74.10% for PHs), followed by the anti-inflammatory for PHs (68.20%) and anesthetic for GPs (60%).

Table 7 Percentage of GPs and PHs that top rank benzydamine hydrochloride by its characteristics

Sore throat is by far the pathological condition for which GPs (27.52%) and PHs (32.89%) more often recommend the use of benzydamine hydrochloride, followed by gingivitis (20.28% for PHs and 19.25% for GPs) (Table 8).

Table 8 Percentage of times benzydamine hydrochloride is recommended for each pathological condition

Essentially, there is the same approach at country level, with slight differences for GPs and PHs in Italy, where the former recommend benzydamine about 26.69% of the time, while the latter recommend it on average about 42.71% of the time.

Ache and cough are the symptoms for which the PHs more often suggest the use of benzydamine hydrochloride. Unlike PHs, the symptoms for which GPs most often give indications to use benzydamine are those related to extraction therapy (Table 9).

Table 9 Percentage of GPs and PHs who recommend benzydamine hydrochloride by client-reported symptoms

There are significant differences across symptoms (p-value < 0.001), but not between GPs and PHs (all p-values > 0.05).

The use of benzydamine hydrochloride in pediatrics

While natural extracts are much less recommended, both active ingredients, benzydamine and dichlorobenzyl alcohol-sodium benzoate, are prescribed/recommended for the treatment of sore throat in the pediatric population by GPs (39.7 and 40.6%) and PHs (36.9 and 44.4%) in a similar proportion (Table 10), with no statistical difference between treatments and between GPs and PHs (p-values > 0.05).

Table 10 Preference distribution for the active ingredients prescribed/recommended for the topical treatment of sore throat symptoms in children (order of preference: 1 = most preferred, 3 = least preferred)

Looking at countries in more detail, there are different approaches among countries and between GPs and PHs, and of note, benzydamine is by far the most recommended active ingredients by Italian GPs (60.4%) for topical treatment of sore throat symptoms in children (Table 10).

The three formulations, spray, hard candy and soft tub, are equally liked by GPs and by PHs. Regarding the preferred formulation, the spray treatment mode is the most recommended by both GPs (38.4%) and PHs (35.2%) for treating children (Table 11).

Table 11 Preference distribution for the formulations prescribed/recommended for the treatment of sore throat symptoms in children (order of preference: 1 = most preferred, 3 = least preferred)

Some differences emerge when looking more closely at the countries: for example, in Germany the spray is the preferred treatment, whereas in Poland both GPs and PHs prefer soft tablets over other formulations. In Italy, it is interesting to note a different approach between GPs and PHs: in fact, Italian GPs prefer spray, while PHs prefer soft tablets (Table 11).

Discussion

Comparison of benzydamine hydrochloride with other drugs

In this survey both GPs and PHs proved to have an excellent knowledge and mastery of the constituents effective against oral symptoms. Among all the principles, benzydamine hydrochloride is the most recognized as certainly suitable for the topical treatment of sore throat symptoms and various inflammatory/irritative conditions of the oral cavity such as gingivitis and stomatitis, with more than 92% of the interviewed GPs and more than 95% of the respondent PHs declaring it as usable in such situations.

In addition, GPs and PHs agree on the usability of other active ingredients, recognizing Non Steroidal Anti-Inflammatory Drugs (NSAIDs) such as flurbiprofen and ketoprofen, the mucolytic agent ambroxol, and the active ingredients dichlorobenzyl alcohol and sodium benzoate with local antiseptic action of the oropharyngeal cavity as effective medications for sore throats and inflammatory/irritative conditions of the mouth. Moreover, natural remedies could also be helpful with products capable of exerting an anti-inflammatory action towards the throat.

Dichlorobenzyl Alcohol-Sodium Benzoate is the most widely prescribed by GPs and recommended by PHs for the topical treatment of sore throat and other oral conditions, followed by ambroxol hydrochloride and benzydamine hydrochloride in a slightly lower percentage.

As for benzydamine hydrochloride, it is recommended by about 90% of PHs and prescribed by 80% of GPs, with no significant differences between countries. There are no data in the literature to support these preferred recommendations. These findings represent clinical practice and real-life data from the countries that participated in the survey.

Moreover, end users appear very familiar with benzydamine hydrochloride, as evidenced by the fact that on average 40% of people require it as a self-medication. This is confirmed across nations, so regardless of the country most customers ask for the benzydamine on a self-management basis. This attitude can be explained by the fact that benzydamine is an over-the-counter (OTC) drug and does not require a prescription from a healthcare professional. Moreover, the high rate of self-management shows that patients/customers are confident with benzydamine and also very satisfied with the therapeutic outcome.

The lower rate of pharmacist advice for benzydamine compared to medical advice (17% vs 24%) may be explained by the fact that doctors and physician cover different roles. Generally customers prefer to follow their doctor's prescription, while those who seek advice from the pharmacist have already chosen the self-management route. Pharmacists should offer reassurance and advice on appropriate treatment to increase the chances of optimum symptomatic relief and satisfaction [11]. In addition, the pharmacist can leverage on a plethora of treatment for sore throat and it is worth considering that treatment decisions are not only influenced by medical factors; non-medical factors such as cultural issues or patient expectations and pressures also influence the prescribing approach [12].

The mechanisms of action and symptoms for which Benzydamine Hydrochloride is recommended

The first two symptoms that prompt clients to seek advice to the pharmacist are ache and cough, followed by redness of the throat, itchy throat and symptoms due to extraction therapy. However, clients behave very differently depending on the country: this different attitude reflects the cultural and social characteristics of the country and can also be influenced by a different healthcare system.

The great majority of PHs (77%) recommend benzydamine hydrochloride to their customers and the 72% of the interviewed GPs usually prescribe it, mainly to solve the disorders caused by sore throat, followed by gingivitis and stomatitis.

It is important to consider that while the etiology of gingivitis or stomatitis is clearly defined, sore throat is an inflammatory condition characterized by pain, redness, heat and swelling that has different causes [13]. Sore throat is a term often used to describe pharyngitis, tonsillitis and laryngitis that occur for a short period of time, which result from inflammation of the upper respiratory tract. Tonsillitis is inflammation due to infection of the tonsils, whereas pharyngitis is inflammation of the oropharynx only but, in practice, the distinction between the two can be unclear and they can occur simultaneously. Laryngitis is used when there is hoarseness with soreness lower down in the throat [14].

The non-infective causes of sore throat are usually due to environmental variations, such as temperature changes, low humidity, second hand smoking, air pollution and a reaction to allergens [15]. Only a small proportion of sore throat cases are caused by bacterial infection, such as group A beta-hemolytic streptococcus, and up to 80% of sore throats are caused by viruses, such as influenza A, respiratory syncytial virus, severe acute respiratory syndrome corona virus, and rhinovirus [16, 17]. Therefore, antibiotics are ineffective in most cases and are not recommended as the first line of treatment for acute sore throat in the EU [18, 19]. However, irrespective of causative pathogen, there is a need for symptom relief. Most patients with acute sore throat present with symptoms which include pain on swallowing, headache and cough, and flu-like symptoms.

This survey shows that ache and cough are the symptoms for which the PHs more often suggest the use of benzydamine hydrochloride (12,68% and 10,43%, respectively). Differently from the PHs, the symptom for which GPs most often give indications to use benzydamine are those related to extraction therapy (14,38%). However, the symptoms for which GPs and PHs recommend benzydamine vary depending on the country, probably reflecting a different clinical practice experience.

Benzydamine hydrochloride is prescribed/recommend for all four of its properties (anti-inflammatory, analgesic, anesthetic, and antiseptic) by both GPs and PHs. The most appreciated characteristics of benzydamine hydrochloride are its anti-inflammatory features, followed by the anesthetic ones for both GPs and PHs.

In fact, the pharmacological activity of benzydamine is mainly related to the inhibition of proinflammatory cytokine synthesis, although it also shows anesthetic activity by modulating neuronal excitability.

Although benzydamine is a nonsteroidal anti-inflammatory agent, it possesses a different mechanism of action that distinguishes it from conventional NSAIDs. Unlike NSAIDs that act by inhibiting prostaglandin synthesis, the anti-inflammatory activity of benzydamine has been related to its ability to inhibit the release of pro-inflammatory cytokines (TNFa, IL-1β, and MCP-1), without affecting other inflammatory cytokines (IL-6, IL-8), and, importantly, anti-inflammatory cytokines (IL-10, IL-1ra) [20].

However, it also exerts other activities that may contribute to the modulation of the inflammatory status, i.e. reduction of vascular permeability produced by histamine, acetylcholine, serotonin and epinephrine, inhibition of platelet aggregation, thrombus formation, degranulation of human polymorphonuclear leukocytes, and migration of human monocytes.

The local anesthetic properties of benzydamine are most likely due to its structural features. Unlike other NSAIDs, it does not associate with steroid structure and it shares with local anesthetics an aromatic (hydrophobic) ring structure linked to a basic tertiary amine group (hydrophilic) by a short alkyl chain [21]. Therefore, benzydamine like local anesthetics, reversibly blocks nerve conduction when applied topically in appropriate concentrations.

The results of a study showed that benzydamine blocks voltage-gated Na + currents in Dorsal Root Ganglion (DRG) neurons, and suggest that it can be a modulator of nociceptor excitability [22]. Indeed, benzydamine attenuates the local transmission of the pain stimulus by preventing the generation and propagation of action potentials through the blockade of Nav channels expressed in sensory neurons. In a clinical trial performed on 87 healthy subjects, benzydamine, applied topically to normal mucosa for 60 s, was found to exert a remarkable anesthetic activity superior to control (cetylpyridinium hydrochloride 0.025%) and placebo mouthwashes, also showing a long lasting effect (more than 90 min). The local anesthetic activity of benzydamine has been shown to be extremely useful in the treatment of painful conditions of the mouth and throat, primarily due to rapid pain relief [2].

The use of benzydamine hydrochloride in pediatrics

Also in the pediatric field, benzydamine hydrochloride is indicated for the topical treatment of sore throat symptoms. Among GPs, a high proportion (about 40%) prescribe benzydamine in a similar proportion to other remedies based on dichlorobenzyl alcohol, which is slightly preferred by PHs instead (44% vs 37%). Looking at countries in more detail, except for Italian physicians who prescribe mostly benzydamine (60%), both GPs and PHs prefer dichlorobenzyl alcohol for topical treatment of sore throat symptoms in children.

Dichlorobenzyl alcohol (DCBA) is a mild antiseptic used as an active ingredient in several marketed OTC throat lozenges, typically in combination with Amylmetacresol (AMC), another antiseptic, for the symptomatic relief of mouth and throat infections, and acute sore throat due to upper respiratory tract infections (URTIs) [23, 24].

Lozenges containing AMC/DCBA have been reported in several clinical trials in adults and have proven to produce significantly greater improvement for symptomatic and pain relief, such as difficulty swallowing and throat numbness, and a reduction in the severity of throat soreness in patients with URTIs [23, 25]. AMC/DCBA throat lozenges have been shown to be safe and efficient in relieving of acute sore throat symptoms, and it produces an immediate symptomatic relief [26, 27]. Moreover, in-vitro evidence has demonstrated the virucidal effect of lozenges containing AMC and DCBA on a number of viruses associated with the common cold such as RSV, influenza A virus, and a member of the coronavirus family, SARS-CoV; a reduction in viral load is believed to have benefits in reducing the symptoms [28].

The characteristics of this active ingredient, at the country level, might justify the greater preference for dichlorobenzyl alcohol over benzydamine. However, there are no clinical studies that have compared these two active ingredients for the topical treatment of sore throat symptoms.

Although in a smaller percentage, natural extracts are prescribed/recommended by GPs and PHs, respectively. This trend can be explained by the influence of parents who sometimes prefer to avoid "chemical" drugs and are more prone to give their children natural products. This is an obstacle that should be overcome by convincing these parents that there are effective and safe pharmacologic alternatives for sore throat symptoms in children.

The three formulations, spray, hard candy and soft tub, are equally liked by physicians and by pharmacists. Regarding the preferred formulation, the spray treatment mode is the most recommended by both GPs (38.4%) and PHs (35.2%) for treating children. However, the choice of drug formulation in pediatrics also depends on the age of the children and the preferences of the parents, and on the safety profile. Children, for example, prefer the sweet effect of a candy, while parents the convenience of a spray because they can control the mode of application. Moreover, the palatability of medications is an important factor in determining medication adherence and completion of drug therapy in young children, and should be an important part in the choice of pediatric formulations [29].

There are clear differences between the topical delivery systems in the onset of action and the amount of active ingredients present in the mouth and throat [30]. Advantages of a spray include delivery of a full dose immediately at the site of pain and inflammation, whereas lozenges slowly dissolve to release the active ingredients directly onto the irritated mucosal tissues [31].

In conclusion, benzydamine can be considered an effective treatment in children and can be administered as a spray in localized forms such as in the treatment of inflamed gum in dental eruption or as soft tab for a more generalized sore throat.

Strengths and limitations of the study

In this survey, benzydamine hydrochloride is the most recognized as certainly suitable for the topical treatment of sore throat symptoms and various inflammatory/irritative conditions of the oral cavity. It is recommended by about 90% of PHs and prescribed by 80% of GPs mainly to resolve complaints caused by sore throat and stomatitis, with no significant differences between countries. These results are interesting because no recommendations on the use of benzydamine for the symptomatic treatment of sore throat appear in most European guidelines on the management of acute sore throat [13, 32,33,34,35]. Therefore, these results represent clinical practice and real-life data from the countries that participated in the survey, providing an updated picture of benzydamine use compared with other drugs in adult and pediatric populations.

However, there were several limitations to this study.

The first limitation is that the active ingredients compared in the study, though OTC drugs and freely available, may have slightly different therapeutic indications in each country. This may explain the different prescription rates in the countries involved in the survey. In particular, although benzydamine for oromucosal use is indicated in the relief of pain and irritation of the mouth and throat, the approved indication differs slightly among countries.

The second is that we used a self-reported survey so it is possible that GPs and PHs answered the questions in a way that reflected professional desirability rather than their practices.

Third, the different healthcare systems in each country involved in the study should be considered to explain some differences in the results; for example, in Germany, patients do not have to go to a general practitioner and then be referred to a specialist, and pharmacies are still owned by individual pharmacists. Therefore, the way to reinforce knowledge of benzydamine should differ depending on the market and healthcare system in the individual country.

Conclusions

This study suggests that interventions to improve knowledge of GPs and PHs about topical treatment of sore throat and other irritative/inflammatory conditions of the oropharynx, particularly benzydamine, are warranted.Although customers/patients have a lot of confidence in this treatment, these specialists do not recommend/prescribe benzydamine as a first-line treatment. To fill this gap it should be fundamental to increase knowledge of benzydamine among these healthcare professionals, emphasizing its characteristics and the different irritative/inflammatory conditions of the oropharynx in which it can be used. In particular, it would be useful to improve knowledge of among pharmacists, who are in contact with the public, about the efficacy of benzydamine and its mechanisms of action, so that they can proactively recommend it in the treatment of sore throat and thus reduce the burden on the healthcare system and the workload of general practitioners.

Several projects are currently underway to collect new data on the use of benzydamine in the treatment of sore throat and to thoroughly investigate its mechanisms of action. Of note, a recently completed phase IV study (BePaiR study) -results not yet published- evaluated the efficacy and speed of relief provided by a single application of benzydamine hydrochloride (0.30% spray or lozenges) in patients with acute sore throat (NCT04941976).

In conclusion, the results of this study are important because they represent clinical practice and real-life data from the countries that participated in the survey, providing an updated picture of benzydamine use in the treatment of inflammatory and irritative condition of the throat and mouth compared with other drugs in adult and pediatric populations.

Availability of data and materials

The data that support the findings of this study are available as supplementary materials.

References

  1. Turnbull RS. Benzydamine Hydrochloride (Tantum) in the management of oral inflammatory conditions. J Can Dent Assoc. 1995;61(2):127–34.

    CAS  PubMed  Google Scholar 

  2. Simard-Savoie S, Forest D. Topical anaesthetic activity of benzydamine. Curr Ther Res. 1978;23:734–45.

    Google Scholar 

  3. Griswold DE, Hillegass LM, Breton JJ, Esser KM, Adams JL. Differentiation in vivo of classical non-steroidal anti-inflammatory drugs from cytokine suppressive anti-inflammatory drugs and other pharmacological classes using mouse tumour necrosis factor alpha production. Drugs Exp Clin Res. 1993;19(6):243–8.

    CAS  PubMed  Google Scholar 

  4. Lisciani R, Barcellona PS, Silvestrini B. Researches on the topical activity of benzydamine. Eur J Pharmacol. 1968;3(2):157–62.

    CAS  Article  Google Scholar 

  5. Landry RG, Turnbull RS, Howley T. Effectiveness of benzydamine HCl in the treatment of periodontal post-surgical patients”. Res Clin Forums. 1988;10(8):105–11.

    Google Scholar 

  6. Turnbul RS. Benzydamine Hydrochloride (Tantum) in the management of oral inflammatory conditions. Journal Can Den Assoc. 1995;61(2):127–34.

    Google Scholar 

  7. Karavana SY, Güneri P, Ertan G. Benzydamine hydrochloride buccalbioadhesive gels designed for oral ulcers: preparation, rheological, textural, mucoadhesive and release properties. Pharm Dev Technol. 2009;14(6):623–31.

    CAS  Article  Google Scholar 

  8. Agarwal A, Nath SS, Goswami D, Gupta D, Dhiraaj S, Singh PK. An evaluation of the efficacy of aspirin and benzydamine hydrochloride gargle for attenuating postoperative sore throat: a prospective, randomized, singleblind study. Anesth Analg. 2006;103(4):1001–3.

    CAS  Article  Google Scholar 

  9. Kin-Fong Cheng K, KaTsuiYuenet J. A pilot study of chlorhexidine and benzydamine oral rinses for the prevention and treatment of irradiation mucositis in patients with head and neck cancer. Cancer Nurs. 2006;29(5):423–30.

    Article  Google Scholar 

  10. Rastogi M, Khurana R, Revannasiddaiah S, Jaiswal I, Nanda SS, Gupta P, et al. Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (>50 Gy) with or without chemotherapy. Support Care Cancer. 2017;25(5):1439–43.

    Article  Google Scholar 

  11. Thomas M, Del Mar C, Glasziou P. How effective are treatments other than antibiotics for acute sore throat? Br J Gen Pract. 2000;50(459):817–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. van Driel ML, De Sutter A, Deveugele M, Peersman W, Butler CC, De Meyere M, et al. Are sore throat patients who hope for antibiotics actually asking for pain relief? Ann Fam Med. 2006;4(6):494–9.

    Article  Google Scholar 

  13. Pelucchi C, Grigoryan L, Galeone C, Esposito S, Huovinen P, Little P, et al. Guideline for the management of acute sore throat. Clin Microbiol Infect. 2012;18(Suppl 1):1–28.

    CAS  Article  Google Scholar 

  14. Marshall S. Giving advice on sore throats. Pharm J. 2008;280:127–30.

    Google Scholar 

  15. Roxas M, Jurenka J. Colds and influenza: a review of diagnosis and conventional botanical and nutritional considerations. Altern Med Rev. 2007;12(1):25–48.

    PubMed  Google Scholar 

  16. Summers A. Sore throats. Accid Emerg Nurs. 2005;13(1):15–7.

    Article  Google Scholar 

  17. Worrall GJ. Acute sore throat. Can Fam Physician. 2007;53(11):1961–2.

    PubMed  PubMed Central  Google Scholar 

  18. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2006;2013(4):CD000023.

    Google Scholar 

  19. Centre for Clinical Practice at NICE (UK) Respiratory Tract Infections - Antibiotic Prescribing: Prescribing of Antibiotics for Self-Limiting Respiratory Tract Infections in Adults and Children in Primary Care. London: National Institute for Health and Clinical Excellence (UK); 2008. National Institute for Health and Clinical Excellence: Guidance. Available from: https://www.nice.org.uk/guidance/cg69

  20. Sironi M, Massimiliano L, Transidico P, Pinza M, Sozzani S, Mantovani A, et al. Differential effect of benzydamine on pro- versus anti-inflammatory cytokine production: lack of inhibition of interleukin-10 and interleukin-1 receptor antagonist. Int J Clin Lab Res. 2000;30(1):17–9.

    CAS  Article  Google Scholar 

  21. Mangano G, Apicella C, Vitiello M, Milanese C, Polenzani L. Benzydamine Local Anesthetic Activity And [3H]-Batrachotoxin Binding Sites. Poster presented to 31st National Congress of the Italian Society of Pharmacology, Trieste, Italy, 26–29 June, 2003. Available from: https://www.pharmtox.org/sif_unito/archivio/cong31/absweb/mangano_g.pdf.

  22. Mathivanan S, de la Torre-Martinez R, Wolf C, Mangano G, Polenzani L, Milanese C, et al. Effect of econazole and benzydamine on sensory neurons in culture. J Physiol Pharmacol. 2016;67(6):851–8.

    CAS  PubMed  Google Scholar 

  23. McNally D, Shephard A, Field E. Randomised, double-blind, placebo-controlled study of a single dose of an amylmetacresol/2,4-dichlorobenzyl alcohol plus lidocaine lozenge or a hexylresorcinol lozenge for the treatment of acute sore throat due to upper respiratory tract infection. J Pharm Pharm Sci. 2012;15(2):281–94.

    CAS  Article  Google Scholar 

  24. Tan TW, Chen BC, Tan HL, Chang CM. Effectiveness of amylmetacresol and 2,4-dichlorobenzyl alcohol throat lozenges in patients with acute sore throat due to upper respiratory tract infection: a systematic review protocol. JBI Database System Rev Implement Rep. 2017;15(4):862–72.

    Article  Google Scholar 

  25. Wade AG, Morris C, Shephard A, Crawford GM, Goulder MA. A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/ DCBA Cool lozenge in the relief of acute sore throat. BMC Fam Pract. 2011;12(6):1–14.

    Google Scholar 

  26. Thomas MJ, ACP Journal Club. Amylmetacresol and 2,4- dichlorobenzyl alcohol lozenges were better than placebo lozenges for relief of acute sore throat. Ann Intern Med. 2010;153(4):JC2-6.

    Article  Google Scholar 

  27. McNally D, Simpson M, Morris C, Shephard A, Goulder M. Rapid relief of acute sore throat with AMC/DCBA throat lozenges: randomized controlled-trial. Int J Clin Pract. 2010;64(2):194–207.

    CAS  Article  Google Scholar 

  28. Oxford JS, Lambkin R, Gibb I, Balasingam S, Chan C, Catchpole A. A throat lozenge containing amylmetacresol and dichlorobenzyl alcohol has a direct virucidal effect on respiratory syncytial virus influenza A and SARs-CoV. Antivir Chem Chemother. 2005;16(2):129–34.

    CAS  Article  Google Scholar 

  29. Thompson A, Reader S, Field E, Shephard A. Open-label taste-testing study to evaluate the acceptability of both strawberry-flavored and orange-flavored amylmetacresol/2,4-dichlorobenzyl alcohol throat lozenges in healthy children. Drugs R D. 2013;13(2):101–7.

    Article  Google Scholar 

  30. Limb M, Connor A, Pickford M, Church A, Mamman R, Reader S, et al. Scintigraphy can be used to compare efficacy of sore throat formulations. Int J Clin Pract. 2009;63(4):606–12.

    CAS  Article  Google Scholar 

  31. Schachtel BP, Homan HD, Gibb IA, Christian J. Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model. Clin Pharmacol Ther. 2002;71(5):375–80.

    CAS  Article  Google Scholar 

  32. Krüger K, Töpfner N, Berner R, Windfuhr J, Oltrogge JH. Clinical practice guideline: sore throat. Dtsch Arztebl Int. 2021;118:188–94.

    PubMed Central  Google Scholar 

  33. Scottish Intercollegiate Guidelines Network (SIGN). Management of sore throat and indications for tonsillectomy. A national clinical guideline 2010. Available from: https://www.sign.ac.uk/media/1055/sign117.pdf

  34. Reinholdt KB, Rusan M, Hansen PR, Klug TE. Management of sore throat in Danish general practices. BMC Fam Pract. 2019;20(1):75.

    Article  Google Scholar 

  35. Farah B, Visintini S. Benzydamine for acute sore throat: A review of clinical effectiveness and guidelines. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Sep 21.CADTH Rapid Response Reports. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537954/

Download references

Acknowledgements

The authors want to thank all participating general practitioners and pharmacists for taking the time to contribute to this study despite their demanding work.

Funding

The editorial and publication work has been realized thank to the support of Angelini Pharma.

Author information

Authors and Affiliations

Authors

Contributions

All authors conceived, read and approved the manuscript.

Corresponding author

Correspondence to Desiderio Passali.

Ethics declarations

Ethics approval and consent to participate

The study was carried out in accordance with the European Data Protection Rules with informed consent from all participants. According to the article 1, paragraph 1, of the legislative decree n. 211 of 2003 (legislation implementing the European Directive 2001/20 / EC on the application of good clinical practice in the execution of clinical trials of medicinal products for clinical use) and according to the Sect. 1.3 of the EphMRA (European Pharmaceutical Market Research Association) Code of Conduct, no formal ethics approval was needed since no research on human tissue or other biological material was performed, as stated by the research marketing company that conducted the survey. The participating general practitioners and pharmacists were informed about the use and publication of their anonymized data for this study. Participation in the study was voluntary. Returning the completed questionnaire was interpreted as informed consent to participate in the study. No incentives were offered.

Consent for publication

Not applicable.

Competing interests

Prof. Dr. Mösges reports personal fees from Angelini Pharma, during the conduct of the study; personal fees from ALK, grants from ASIT biotech, personal fees from allergopharma, personal fees from Allergy Therapeutics, grants and personal fees from Bencard, grants from Leti, grants, personal fees and non-financial support from Lofarma, non-financial support from Roxall, grants and personal fees from Stallergenes, grants from Optima, personal fees from Friulchem, personal fees from Hexal, personal fees from Servier, personal fees from Klosterfrau, non-financial support from Atmos, personal fees from Bayer, non-financial support from Bionorica, personal fees from FAES, personal fees from GSK, personal fees from MSD, personal fees from Johnson&Johnson, personal fees from Meda, personal fees and non-financial support from Novartis, non-financial support from Otonomy, personal fees from Stada, personal fees from UCB, non-financial support from Ferrero, grants from BitopAG, grants from Hulka, personal fees from Nuvo, grants and personal fees from Ursapharm, personal fees from Menarini, personal fees from Mundipharma, personal fees from Pohl-Boskamp, grants from Inmunotek, grants from Cassella-med GmbH & Co. KG, personal fees from Laboratoire de la Mer, personal fees from Sidroga, grants and personal fees from HAL BV, personal fees from Lek, personal fees from PRO-AdWise, outside the submitted work.

Passali D., Arezzo M. F., De Rose A., De Simone G., Forte G., Jablko-Musial M. declares no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Passali, D., Arezzo, M.F., De Rose, A. et al. Benzydamine hydrochloride for the treatment of sore throat and irritative/inflammatory conditions of the oropharynx: a cross-national survey among pharmacists and general practitioners. BMC Prim. Care 23, 154 (2022). https://doi.org/10.1186/s12875-022-01762-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12875-022-01762-3

Keywords

  • Sore throat
  • Benzydamine
  • Oropharynx
  • General practitioner