Benzydamine is a locally-acting NSAID indicated for the symptomatic relief of pain in acute sore throat and for the symptomatic relief of oropharyngeal mucositis caused by radiation therapy.

Brand Names
Pharixia, Tantum
Generic Name
DrugBank Accession Number

Benzydamine (also known as Tantum Verde or Difflam), available as the hydrochloride salt, is a locally-acting nonsteroidal anti-inflammatory drug (NSAID) with local anaesthetic and analgesic properties. It is used topically for pain relief and anti-inflammatory treatment of the mouth, throat, or muscoskeletal system.

Although the indazole analogue benzydamine is a non-steroidal anti-inflammatory drug (NSAID), it has various physicochemical properties and pharmacologic activities that are different from those of traditional aspirin-like NSAIDs but facilitate benzydamine's mechanism of action as an effective locally-acting NSAID with local anaesthetic and analgesic properties. Moreover, unlike aspirin-like NSAIDs which are acids or metabolised to acids, benzydamine is in fact a weak base.

Small Molecule
Average: 309.413
Monoisotopic: 309.184112373
Chemical Formula
  • Bencidamina
  • Benzydamine
  • Benzydaminum



Available predominantly as a liquid mouthwash, oromucosal spray, or topical cream, benzydamine is most frequently employed as a locally acting analgesic and anti-inflammatory treatment for the relief of painful inflammatory conditions.

When formulated as a mouthwash or spray, benzydamine may be used to treat traumatic conditions like pharyngitis following tonsillectomy or the use of a naso-gastric tube, inflammatory conditions like pharyngitis, aphthous ulcers and oral ulceration due to radiation therapy, dentistry operations and procedures, or more general conditions like sore throat, sore tongue, sore gums, mouth ulcers, or discomfort caused by dentures. 6

When used as a topical cream, benzydamine may be employed to relieve symptoms associated with painful inflammatory conditions of the muscolo-skeletal system including acute inflammatory disorders such as myalgia and bursitis or traumatic conditions like sprains, strains, bruises, sore muscles, stiff joints, or even the after-effects of fractures. 7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Symptomatic treatment ofAcute sore throat••••••••••••
Used in combination to treatGingivitisCombination Product in combination with: Cetylpyridinium (DB11073)••••••••••••••••••
Used in combination to treatGingivitisCombination Product in combination with: Cetylpyridinium (DB11073)•••••••••••••••••••••• •••••• ••••••• •••••••
Used in combination to treatInflammation of mouthCombination Product in combination with: Cetylpyridinium (DB11073)••••••••••••••••••
Used in combination to treatInflammation of mouthCombination Product in combination with: Cetylpyridinium (DB11073)•••••••••••••••
Associated Therapies
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Benzydamine is a non-steroidal anti-inflammatory drug (NSAID) designed to elicit local anesthetic and analgesic effects mainly for the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, oedema, or granuloma. Typically applied topically, the drug demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Moreover, benzydamine exhibits analgesic properties and local anaesthetic activity if pain is caused by an inflammatory condition. Benzydamine can be absorbed into the oral mucosa and intact skin. Once absorbed in the local area of pain or inflammation, benzydamine binds selectively to local inflamed tissues, usually allowing it to act with few adverse systemic effects. On average a period of 2 to 4 hours is necessary for the substance to reach peak plasma concentration. 5

Benzydamine can be synthesized with the reaction of the N-benzyl derivative from methyl anthranilate with nitrous acid to give N-nitoso derivative. This is next reduced by sodium thiosulfate to give transient hydrazine. This hydrazine can then undergo spontaneous internal hydrazide formation. Treating this resultant enolate with 3-chloro-1-dimethylamkino propane ultimately yields benzydamine.

Mechanism of action

Despite being categorized as a non-steroidal anti-inflammatory drug (NSAID), benzydamine demonstrates various mechanisms of action that differ from those of traditional aspirin-like NSAIDs. In particular, benzydamine predominantly acts by inhibiting the synthesis of pro inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) without largely affecting other pro inflammatory cytokines (ie. such as IL-6 and IL-8) or anti-inflammatory cytokines (ie. like IL-10 or IL-1 receptor antagonist). 3,5

Moreover, benzydamine is largely a weak inhibitor of prostaglandin synthesis as it has been shown to effectively inhibit cyclooxygenase (COX) and lipoxygenase enzyme activity only at concentrations of 1mM or greater. Considering most contemporary usages of benzydamine are topical applications that are generally not well absorbed through the skin and/or non-specialized mucosae, benzydamine does not often achieve the kind of absorption or blood concentrations necessary to cause any extraneous distant systemic effects or COX inhibition, allowing it to localize its action. 3,5

Additionally, it is also hypothesized that benzydamine is capable of inhibiting the oxidative burst of neutrophils and membrane stabilization. These actions are exhibited by the substance’s ability to inhibit the release of granules from neutrophils and to stabilize lysosomes. 3,5

Furthermore, benzydamine is capable of a local anaesthetic effect that may be related to its capability for inhibiting the release of inflammatory mediators like substance P and calcitonin gene related peptide from sensory nerve endings. Since substance P is capable of causing the release of histamine from mast cells, benzydamine’s prevention of substance P release further contributes to an anti-inflammatory effect. 3,5

Benzydamine also demonstrates a non-specific antibacterial activity against various bacterial strains that are resistant to broad-spectrum antibiotics such as ampicillin, chloramphenicol, and tetracycline at concentrations of about 3 mmol/L. Combinatorial use of benzydamine and other antibiotics like tetracycline and chloramphenicol are also synergistic against antibiotic resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa. 3


Oral doses of benzydamine are well absorbed and plasma drug concentrations reach a peak fairly rapidly and then decline with a half-life of approximately 13 hours. When applied topically, although the local drug concentrations are relatively large, the systemic absorption of topically applied benzydamine is relatively low compared to oral doses. This low topical absorption contributes to a decreased potential for any systemic drug side-effects when benzydamine is administered in this way. 6

Volume of distribution

The volume of distribution of benzydamine is 10 L 1,3.

Protein binding

Benzydamine exhibits < 20% plasma protein binding after oral administration 6,3.


Benzydamine is primarily metabolized by oxidation, dealkylation, and conjugation into hydroxy, dealkylated, and N-oxide metabolites 6,3.

In general, however, when used at the recommended doses the levels at which benzydamine is absorbed or exposed into the body are usually not sufficient to produce systemic pharmacological effects [L

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Route of elimination

The relatively high lipid solubility of the weak base benzydamine is thought to be associated with considerable passive resorption within the renal tubule, which suggests that only approximately 5% of benzydamine is excreted unchanged in the urine 1. At the same time however, other studies have suggested that considerably larger amounts (50-65%) of the drug is excreted unchanged in urine 4.

While several inactive oxidized metabolites of benzydamine are excreted in urine, the benzydamine N-oxide metabolite can remain in plasma and demonstrate a half-life that is longer than the parent benzydamine compound 1.

Nevertheless, it is generally believed that excretion occurs mainly through urine and is mostly in the form of inactive metabolites or conjugation products 8.


Approximately 13 h after oral administration 6, with a terminal half life of about 7.7 h 3.


Benzydamine demonstrateas a systemic clearance of 170 ml/min 3.

Adverse Effects
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A possible adverse reaction associated with the use of the mouthwash or oromucosal spray formulations of benzymadine is potential numbness and/or stinging in the mouth and/or throat 5,6.

Some possible adverse reactions that tend to be associated more with topical cream formulations of benzymadine include increased sensitivity to sunlight, and localized itching, skin rash, redness, or swelling 7.

The prescribing information for all formulations of benzymadine however, warn against the possibility of severe allergic reaction (anaphylaxis) associated with swelling of the throat and mouth, difficulty in swallowing, speaking, and breathing, or wheezing 5,6,7.

As benzydamine is a non-steroidal anti-inflammatory drug (NSAID), it is necessary to determine if a patient is allergic to NSAIDs before considering its use 5,6,7.

Intoxication is expected as a consequence of accidental ingestion of large quantities of benzydamine (over 300 mg ingestion). Other symptoms associated with overdose of ingested benzydamine include gastrointestinal and central nervous system symptoms like nausea, vomiting, abdominal pain, oesophageal irritation, dizziness, hallucinations, agitation, anxiety, and irritability 6.

The official prescribing information for benzydamine generally suggest that benzydamine mouthwashes and sprays should not be used in pregnancy 6,7 . Similarly, the official prescribing information for benzydamine also generally suggest that benzydamine mouthwashes and sprays should not be used during lactation unless considered essential by a physician 6,7.

The prescribing information for topical cream formulations of benzydamine note that benzydamine cream should not be used in pregnancy or lactation unless considered necessary by the physician 5.

Overall, non-clinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated toxicity, genotoxicity, cardiogenic potential, and toxicity to reproduction 5. Additionally, there is no evidence of teratogenic effects in animal studies 6.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
AbacavirBenzydamine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Benzydamine is combined with Abciximab.
AcebutololBenzydamine may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Benzydamine.
AcemetacinThe risk or severity of adverse effects can be increased when Benzydamine is combined with Acemetacin.
Food Interactions
No interactions found.


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Product Ingredients
IngredientUNIICASInChI Key
Benzydamine hydrochlorideK2GI407R4Q132-69-4HNNIWKQLJSNAEQ-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PharixiaMouthwash0.15 % w/vBuccalPendopharm Division Of Pharmascience Inc1996-12-02Not applicableCanada flag
Pharixia Alcohol FreeMouthwash0.15 % w/vBuccalPendopharm Division Of Pharmascience Inc2020-07-13Not applicableCanada flag
Sun-benz - Liq 0.15%Liquid.15 %Dental; OralSun Pharmaceutical Industries Inc.1997-04-032011-07-29Canada flag
TantumMouthwash0.15 % w/vBuccalBausch Health, Canada Inc.1993-12-31Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-benzydamine Oral RinseMouthwash0.15 %BuccalApotex Corporation1998-11-09Not applicableCanada flag
Novo-benzydamineMouthwash; Solution1.5 mg / mLBuccal; OralNovopharm Limited2008-06-032018-05-17Canada flag
Novo-benzydamine - Oral RinseLiquid; Mouthwash1.5 mg / mLBuccal; OralNovopharm Limited1997-02-062015-10-26Canada flag
Nu-benzydamine Oral RinseLiquid0.15 %BuccalNu Pharm IncNot applicableNot applicableCanada flag
Odan-benzydamineMouthwash0.15 % w/vBuccalOdan Laboratories Ltd2017-08-11Not applicableCanada flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Difflam Forte Anti-Inflammatory Throat SpraySpray3.0 mg/mLBuccalINOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED2009-02-04Not applicableSingapore flag
DIFFLAM LOZENGE 3 mgLozenge3 mgOralINOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED1993-04-29Not applicableSingapore flag
DIFFLAM SOLUTION 22.5 mg/15 mlMouthwash22.5 mg/15mlOralINOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED1990-04-23Not applicableSingapore flag
Difflam? Anti-Inflammatory Throat SpraySpray1.5 mg/mLBuccalINOVA PHARMACEUTICALS (SINGAPORE) PTE. LIMITED2009-02-04Not applicableSingapore flag
ดีโทรท สเปรย์ 0.3% (กลิ่นมิ้นท์)Spray3 mg/1mlOralบริษัท อินเตอร์ไทย ฟาร์มาซูติเคิ้ล แมนูแฟคเจอริ่ง จำกัด จำกัด2017-12-02Not applicableThailand flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ANDOREX %0.15+%0.12 GARGARA, 200 MLBenzydamine hydrochloride (22.5 mg/15mL) + Chlorhexidine gluconate (18 mg/15mL)RinseOralHUMANİS SAĞLIK A.Ş.2003-01-24Not applicableTurkey flag
ANDOREX %0.15+%0.12 SPREY, ÇÖZELTİ 30 MLBenzydamine hydrochloride (0.3 mg/0.2mL) + Chlorhexidine gluconate (0.24 mg/0.2mL)SprayOralHUMANİS SAĞLIK A.Ş.2003-01-24Not applicableTurkey flag
BENZIRIN ® VERDE ASEPTICBenzydamine hydrochloride (0.15 g) + Cetylpyridinium chloride (0.05 g)SolutionBuccal; OralTECNOFAR TQ S.A.S2015-03-12Not applicableColombia flag
BUCALIV® ULTRABenzydamine hydrochloride (0.15 g) + Cetylpyridinium chloride (0.05 g)SolutionBuccal; OralLABORATORIO FRANCO COLOMBIANO - LAFRANCOL S.A.S.2018-03-162023-10-08Colombia flag
BUCOXOL® FORTE TRIPLE ACCION SOLUCION ORAL SABOR COOL MINT. MIEL LIMON Y FRUTOS ROJOSBenzydamine hydrochloride (0.3 g) + Cetylpyridinium chloride (0.2 g)SolutionOralPHARMETIQUE S.A.2013-09-18Not applicableColombia flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
TANTUM %5 JEL, 100 GBenzydamine (5 %)GelTopicalANGELİNİ İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
TANTUM %5 JEL, 50 GBenzydamine (5 %)GelTopicalANGELİNİ İLAÇ SAN. VE TİC. A.Ş.2013-01-29Not applicableTurkey flag
TANTUM VERDE % 0,15 120 ML GARGARABenzydamine hydrochloride (180 mg/120ml)RinseOralANGELİNİ İLAÇ SAN. VE TİC. A.Ş.2013-01-29Not applicableTurkey flag
TANTUM VERDE 0,045 GR 30 ML SPREYBenzydamine hydrochloride (0.045 g/30ml)RinseOralANGELİNİ İLAÇ SAN. VE TİC. A.Ş.2013-01-29Not applicableTurkey flag


ATC Codes
A01AD02 — BenzydamineM01AX07 — BenzydamineM02AA05 — BenzydamineG02CC03 — BenzydamineR02AX03 — Benzydamine
Drug Categories
Chemical TaxonomyProvided by Classyfire
This compound belongs to the class of organic compounds known as indazoles. These are compounds containing an indazole, which is structurally characterized by a pyrazole fused to a benzene.
Organic compounds
Super Class
Organoheterocyclic compounds
Sub Class
Direct Parent
Alternative Parents
Alkyl aryl ethers / Benzene and substituted derivatives / Pyrazoles / Heteroaromatic compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzopyrazole / Ether / Heteroaromatic compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

CAS number
InChI Key


General References
  1. Baldock GA, Brodie RR, Chasseaud LF, Taylor T, Walmsley LM, Catanese B: Pharmacokinetics of benzydamine after intravenous, oral, and topical doses to human subjects. Biopharm Drug Dispos. 1991 Oct;12(7):481-92. [Article]
  2. Silvestrini B, Barcellona PS, Garau A, Catanese B: Toxicology of benzydamine. Toxicol Appl Pharmacol. 1967 Jan;10(1):148-59. [Article]
  3. Quane PA, Graham GG, Ziegler JB: Pharmacology of benzydamine. Inflammopharmacology. 1998;6(2):95-107. doi: 10.1007/s10787-998-0026-0. [Article]
  4. Catanese B, Grasso A, Silverstrini B: Studies on the absorption and elimination of benzydamine in the mouse, rat, dog, and man. Arzneimittelforschung. 1966 Oct;16(10):1354-7. [Article]
  5. Electronic Medicines Compedium Difflam (Benzydamine Hydrochloride) Spray Monograph [Link]
  6. Electronic Medicines Compedium Benzydamine Hydrochloride 0.15% w/v Mouthwash Monograph [Link]
  7. Electronic Medicines Compedium Difflam (Benzydamine Hydrochloride) 3% Cream Monograph [Link]
  8. Benzydamine - Tantum Verde [Link]
PubChem Compound
PubChem Substance
Download (343 KB)

Clinical Trials

Clinical Trials
4CompletedOtherIntubation; Complication1
4CompletedPreventionPost Operative Nausea and Vomiting (PONV) / Sore Throat1
4CompletedPreventionSore Throat1
4CompletedSupportive CarePain / Quality of Life (QOL)1
4CompletedTreatmentAcute Sore Throat1


Not Available
Not Available
Dosage Forms
MouthwashBuccal0.15 %
CreamTopical5.00 g
SolutionBuccal0.150 g
SolutionBuccal; Oral150 mg
SolutionBuccal0.1500 g
RinseOral120 ml
SprayOral0.15 %
GelTopical50 gr
Tablet, coated50 mg
RinseOral1.5 mg/ml
CreamTopical3 %
GelTransmucosal0.5 %
Paste, dentifriceDental5 mg/g
SolutionOral0.15 %
SprayTransmucosal0.15 %
SolutionTopical0.15 g
TabletTransmucosal3 MG
Tablet, film coatedOral50 mg
TabletBuccal3 mg
TabletOral3 mg
SolutionBuccal; Oral
PowderTopical; Vaginal0.498 g
PowderTopical; Vaginal5.3 g
SolutionBuccal; Oral0.3 g
CreamVaginal0.5 g
SolutionTopical; Vaginal100 mg
SolutionTopical; Vaginal10000000 mg
SolutionBuccal; Oral0.15 g
GelTopical5.00 g
SprayOral1.5 mg/ml
SprayOral3 mg/ml
SolutionBuccal; Oral15000000 mg
GelCutaneous5.000 g
LozengeOral3 mg
SprayBuccal3.0 mg/mL
Spray, meteredOral0.3 %w/v
GelSubmucosal10 mg/g
LozengeOral1.2 mg
MouthwashOral22.5 mg/15ml
LozengeOral3.0 mg
SprayBuccal1.5 mg/mL
LozengeOral1.5 mg
RinseOral0.15 %
CreamTopical5 %
GelTopical5 %
GelTopical5 G
Injection, solutionIntramuscular5 mg/5ml
OintmentTopical3 %
OintmentTopical5 G
Pill50 MG
Solution / dropsOral3 %
SuppositoryRectal100 MG
SuppositoryRectal25 mg
SuppositoryRectal50 MG
Powder, for solutionVaginal
CreamVaginal0.5 %
DoucheVaginal100 mg/100ml
Granule, for solutionVaginal500 MG
SolutionVaginal0.1 %
SolutionVaginal500 MG/10ML
Tablet, solubleOral
SolutionOral0.15 g
Mouthwash; solutionBuccal; Oral1.5 mg / mL
Liquid; mouthwashBuccal; Oral1.5 mg / mL
LiquidBuccal0.15 %
MouthwashBuccal0.15 % w/v
Spray, meteredOral
SolutionVaginal1 mg/ml
Granule, for solutionVaginal0.5 g/9.44g
TabletTransmucosal3 mg/1mg
LiquidDental; Oral.15 %
MouthwashOral0.15 %
RinseOral180 mg/120ml
RinseOral0.045 g/30ml
PastilleOral3 mg
Paste, dentifriceDental0.5 %
GelTopical50 g
SolutionOral1.5 MG/ML
PasteBuccal0.500 g
SolutionVaginal5.000 g
CreamCutaneous5.000 g
PowderVaginal500 MG
SprayOral1.5 mg/1ml
SprayOral3 mg/1ml
LozengeOral3 mg
Not Available
Not Available


Experimental Properties
melting point (°C)320°FMSDS
water solubilityMiscibleMSDS
Predicted Properties
Water Solubility0.0491 mg/mLALOGPS
pKa (Strongest Basic)9.26Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area30.29 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity105.56 m3·mol-1Chemaxon
Polarizability35.62 Å3Chemaxon
Number of Rings3Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available


Mass Spec (NIST)
Not Available
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0006-9220000000-be226c37efcc0d490030
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-1009000000-c1979aa04235f7aae62e
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-6dcfc71c55d35e02845f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-9038000000-3d6ea7c9003842ca7479
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a59-2595000000-859a510f09f6024f0999
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9010000000-43ad2972d65e3271029f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-1900000000-8c64d511b7d3a35b9c11
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
DarkChem Lite v0.1.0
DeepCCS 1.0 (2019)
DarkChem Lite v0.1.0
DeepCCS 1.0 (2019)
DarkChem Lite v0.1.0
DeepCCS 1.0 (2019)

Drug created at September 15, 2015 19:55 / Updated at May 29, 2024 19:09