Difflam plus ANAESTHETIC Sore Throat Lozenges (Sugar Free) Menthol and Eucalyptus Flavour

2,4 Dichlorobenzyl Alcohol
Benzydamine
Lignocaine

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

Not Available

Description

Not Available

Indication

Not Available

Mechanism of Action

Not Available

Pharmacodynamics

Not Available

Pharmacokinetics

Absorption:

Not Available

Distribution:

Not Available

Metabolism:

Not Available

Elimination:

Not Available

Half-life

Not Available

Clearance

Not Available

Toxicity

Not Available

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

Benzydamine | Benzydamine |

Description

Benzydamine (also known as Tantum Verde and branded in some countries as Difflam), available as the hydrochloride salt, is a locally-acting nonsteroidal anti-inflammatory drug (NSAID) with local anaesthetic and analgesic properties for pain relief and anti-inflammatory treatment of typically topical inflammatory conditions associated with the mouth, throat, or muscoskeletal locations. 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.

Indication

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. [L1121] 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. [ L1123]

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). [A31528, L1120] 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. [A31528, L1120] 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. [A31528, L1120] 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. [A31528, L1120] 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*. [A31528]

Pharmacodynamics

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. [L1120] 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.

Pharmacokinetics

Absorption:

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. [L1121]

Distribution:

The volume of distribution of benzydamine is 10 L [A27273, A31528].

Metabolism:

Benzydamine is primarily metabolized by oxidation, dealkylation, and conjugation into hydroxy, dealkylated, and N-oxide metabolites [L1121, A31528]. 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

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 [A27273]. At the same time however, other studies have suggested that considerably larger amounts (50-65%) of the drug is excreted unchanged in urine [A31530]. 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 [A27273]. Nevertheless, it is generally believed that excretion occurs mainly through urine and is mostly in the form of inactive metabolites or conjugation products [L2466].

Half-life

Approximately 13 h after oral administration [L1121], with a terminal half life of about 7.7 h [A31528].

Clearance

Benzydamine demonstrateas a systemic clearance of 170 ml/min [A31528].

Toxicity

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 [L1120, L1121]. 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 [L1123]. 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 [L1120, L1121, L1123]. 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 [L1120, L1121, L1123]. 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 [L1121]. The official prescribing information for benzydamine generally suggest that benzydamine mouthwashes and sprays should not be used in pregnancy [L1121, L1123] . 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 [L1121, L1123]. 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 [L1120]. 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 [L1120]. Additionally, there is no evidence of teratogenic effects in animal studies [L1121].

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

2-(Diethylamino)-2',6'-acetoxylidide | 2-(Diethylamino)-N-(2,6-dimethylphenyl)acetamide | alpha-diethylamino-2,6-dimethylacetanilide | Lignocaine | α-diethylamino-2,6-dimethylacetanilide | Lidocaine |

Description

A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [PubChem]

Indication

For production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks.

Mechanism of Action

Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action. Lidocaine alters signal conduction in neurons by blocking the fast voltage gated sodium (Na+) channels in the neuronal cell membrane that are responsible for signal propagation. With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anaesthetic effect by not merely preventing pain signals from propagating to the brain but by aborting their birth in the first place.

Pharmacodynamics

Lidocaine is an anesthetic agent indicated for production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Lidocaine appears to be similar to that of procaine, procainamide and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected. In contrast to the latter 3 drugs, Lidocaine in therapeutic doses does not produce a significant decrease in arterial pressure or in cardiac contractile force. In larger doses, lidocaine may produce circulatory depression, but the magnitude of the change is less than that found with comparable doses of procainamide.

Pharmacokinetics

Absorption:

Information derived from diverse formulations, concentrations and usages reveals that lidocaine is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent.

Distribution:

* 0.7 to 2.7 L/kg [healthy volunteers]

Metabolism:

Primarily hepatic.

Elimination:

Lidocaine and its metabolites are excreted by the kidneys.

Half-life

109 minutes

Clearance

* 0.64 +/- 0.18 L/min

Toxicity

The oral LD 50 of lidocaine HCl in non-fasted female rats is 459 (346-773) mg/kg (as the salt) and 214 (159-324) mg/kg (as the salt) in fasted female rats. Symptoms of overdose include convulsions, hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest.

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank

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Approval Information

Difflam plus ANAESTHETIC Sore Throat Lozenges (Sugar Free) Menthol and Eucalyptus Flavour was registered with Health Science Authority of Singapore by INOVA PHARMACEUTICALS (SINGAPORE) PTE LIMITED. It is marketed with the registration number of SIN15584P with effective from 2018-11-29.

This product contains 1.2mg of 2,4 Dichlorobenzyl Alcohol, 3mg of Benzydamine, and 4mg of Lignocaine in the form of LOZENGE.

The medicine was manufactured by Unique Pharmaceutical Laboratories (A Division of J.B.Chemicals & Pharmaceuticals Ltd.) in INDIA

It is a Pharmacy Only Medicine which can be obtained from a pharmacist at a retail pharmacy.

Anatomical Therapeutic Chemical (ATC) Classification

Products Containing as Single Ingredient

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1DEXTROMETHORPHAN LINCTUS 15mg/5mlDextromethorphanP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
22ZENMOLIN SYRUP 2mg/5mlSalbutamolP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
41APO-PROPRANOLOL TABLET 40mgPropranololPOMPHARMAFORTE SINGAPORE PTE LTDActive
42APO-DIAZEPAM TABLET 2mgDiazepamPOMPHARMAFORTE SINGAPORE PTE LTDActive
44APO-DIAZEPAM TABLET 5mgDiazepamPOMPHARMAFORTE SINGAPORE PTE LTDActive
45APO-DIAZEPAM TABLET 10mgDiazepamPOMPHARMAFORTE SINGAPORE PTE LTDActive
46APO-PROPRANOLOL TABLET 10mgPropranololPOMPHARMAFORTE SINGAPORE PTE LTDActive
55APO-ISDN TABLET 10mgIsosorbide DinitratePOMPHARMAFORTE SINGAPORE PTE LTDActive
63DIAPO TABLET 10mgDiazepamPOMBEACONS PHARMACEUTICALS PTE LTDActive
64FURMIDE TABLET 40mgFurosemidePOMBEACONS PHARMACEUTICALS PTE LTDActive

Products Containing as Mixture Ingredient

Drug IDTrade NameActive IngredientsForensic ClassRegistrantStatus
4DIPHENHYDRAMINE EXPECTORANTAmmonium Chloride|Diphenhydramine|Sodium CitrateP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
5DIPHENHYDRAMINE EXPECTORANT PAED.Ammonium Chloride|Diphenhydramine|Sodium CitrateP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
400FAKTU SUPPOSITORYCinchocaine|PolicresulenP OnlyTAKEDA PHARMACEUTICALS (ASIA PACIFIC) PTE LTDActive
407TRIMAXAZOLE TABLETSulfamethoxazole|TrimethoprimPOMBEACONS PHARMACEUTICALS PTE LTDActive
435APO-SULFATRIM TABLETSulfamethoxazole|TrimethoprimPOMPHARMAFORTE SINGAPORE PTE LTDActive
508APO-SULFATRIM PEDIATRIC TABLETSulfamethoxazole|TrimethoprimPOMPHARMAFORTE SINGAPORE PTE LTDActive
526B.S. SUSPENSIONSulfamethoxazole|TrimethoprimPOMAPEX PHARMA MARKETING PTE LTDActive
583CO-TRIMEXAZOLE SUSPENSIONSulfamethoxazole|TrimethoprimPOMBEACONS PHARMACEUTICALS PTE LTDActive
676BANEOCIN OINTMENTBacitracin|NeomycinPOMNOVARTIS (SINGAPORE) PTE LTDActive
678BANEOCIN POWDERBacitracin|NeomycinPOMNOVARTIS (SINGAPORE) PTE LTDActive