Tantum C

Uses

Benzydamine Hydrochloride mouthwash is used to treat many painful conditions affecting the throat or mouth including: Sore throat, Sore tongue or gums, Mouth ulcers, Discomfort caused by dentures, Pain after dental surgery etc.

Capsaicin is indicatd for- Rheumatoid arthritis, Osteoarthritis, Pain due to diabetic neuropathy, Joint pain, Post-herpetic neuralgia, Post-surgical neuropathic pain, Nerve Pain, Back pain, Muscle pain, Fibromyalgia, Bursitis, Pruritis (itching)

Tantum C is also used to associated treatment for these conditions: Acute Sore Throat, Gingivitis, Inflammation of Mouth, Laryngitis, Mouth irritation, Mucositis of the oro-pharyngeal, Orofacial Pain, Pain, Pharyngitis, Sore gums, Throat irritation, Traumatic Injuries caused by Dental Prosthesis, Gum irritation, Oral Hygiene, Tooth Extractions, Oral antisepsisArthritis, Back Pain Lower Back, Backache, Bursitis, Contusions, Inflammatory Reaction caused by Rheumatism, Muscle Cramps, Musculoskeletal Pain, Osteoarthritis (OA), Periarthritis, Post-Herpetic Neuralgia (PHN), Rheumatic Pain, Soft Tissue Injury, Tendinitis, Acute nonspecific tenosynovitis

How Tantum C works

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).

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.

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.

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.

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.

Capsaicin has been shown to reduce the amount of substance P associated with inflammation - however this is not believed to be its main mechanism in the relief of pain . Capsaicin's mechanism of action is attributed to "defunctionalization" of nociceptor fibers by inducing a topical hypersensitivity reaction on the skin. This alteration in pain mechanisms is due to many of the following: temporary loss of membrane potential, inability to transport neurotrophic factors leading to altered phenotype, and reversible retraction of epidermal and dermal nerve fiber terminals.

Dosage

Tantum C dosage

15 ml of Benzydamine mouthwash should be rinsed or gargled every 1.5-3 hours or as required, for 20-30 seconds. If stinging occurs, it can be diluted with an equal volume of water.

18 years of age and older:Apply a thin film of Capsaicin cream to affected area 3 to 4 times daily. A burning sensation may occur upon application, but generally disappears with regular use. Application schedules of 3 to 4 times a day for 2 weeks provides optimum pain relief.

Side Effects

Benzydamine Hydrochloride mouthwash can cause side effects, although not everybody gets them. Side effects are generally minor.

• Severe allergic reaction which may include a red and lumpy skin rash, difficulty breathing, swelling of face, mouth, lips or eyelids, unexplained high temperature (fever) and feeling faint. If the swelling affects throat and makes breathing difficult and swallowing difficult, patients should be hospitalized
• Itchy rash, sometimes with pale, raised areas of skin with red edges (urticaria).
• A feeling of numbness in mouth.
• A stinging feeling in mouth- the mouthwash may be diluted with water if you experience stinging. This should help to reduce the stinging effect.

Capsaicin may cause transient burning on application. This burning is observed more frequently when the application schedules are more than 3-4 times daily. The burning can be enhanced if too much cream is used and if it is applied just before or after a bath or shower.

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 .

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 .

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 .

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 .

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 .

The official prescribing information for benzydamine generally suggest that benzydamine mouthwashes and sprays should not be used in pregnancy . 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 .

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 .

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 . Additionally, there is no evidence of teratogenic effects in animal studies .

Acute oral LD50 and dermal LD50 in mouse are 47.2 mg/kg and >512 mg/kg, respectively . Capsaicin is shown to be mutagenic for bacteria and yeast .

Capsaicin can cause serious irritation, conjunctivitis and lacrimation via contact with eyes. It induces a burning sensation and pain in case of contact with eyes and skin. As it is also irritating to the respiratory system, it causes lung irritation and coughing as well as bronchoconstriction. Other respiratory effects include laryngospasm, swelling of the larynx and lungs, chemical pneumonitis,respiratory arrest and central nervous system effects such as convulsions and excitement . In case of ingestion, gastrointestinal tract irritation may be observed along with a sensation of warmth or painful burning . Symptoms of systemic toxicity include disorientation, fear, loss of body motor control including diminished hand-eye coordination, hyperventilation, tachycardia, and pulmonary oedema . Careful early decontamination is recommended and medical intervention should be initiated for any life-threatening symptoms. In case of contact, individual must be removed from the source of exposure and the contacted skin and mucous membranes should be thoroughly washed with copious amounts of water .

Precaution

Capsaicin cream should not be applied to broken or irritated skin. Applied area should not be tightly bandaged. Do not get on mucous membranes and into eyes or on contact lenses. If this occurs, rinse the affected area thoroughly with water. Do not apply the cream on the heat treated area as this may increase the burning sensation. In case of accidental ingestion, seek physician advice immediately.

Volume of Distribution

The volume of distribution of benzydamine is 10 L .

Elimination Route

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.

Oral: Following oral administration, capsaicin may be absorbed by a nonactive process from the stomach and whole intestine with an extent of absorption ranging between 50 and 90%, depending on the animal . The peak blood concentration can be reached within 1 hour following administration . Capsaicin may undergo minor metabolism in the small intestine epithelial cells post-absorption from the stomach into the small intestines. While oral pharmacokinetics information in humans is limited, ingestion of equipotent dose of 26.6 mg of pure capsaicin, capsaicin was detected in the plasma after 10 minutes and the peak plasma concentration of 2.47 ± 0.13 ng/ml was reached at 47.1 ± 2.0 minutes .

Systemic: Following intravenous or subcutaneous administration in animals, the concentrations in the brain and spinal cord were approximately 5-fold higher than that in blood and the concentration in the liver was approximately 3-fold higher than that in blood .

Topical: Topical capsaicin in humans is rapidly and well absorbed through the skin, however systemic absorption following topical or transdermal administration is unlikely . For patients receiving the topical patch containing 179 mg of capsaicin, a population analysis was performed and plasma concentrations of capsaicin were fitted using a one-compartment model with first-order absorption and linear elimination. The mean peak plasma concentration was 1.86 ng/mL but the maximum value observed in any patient was 17.8 ng/mL .

Half Life

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

Following oral ingestion of equipotent dose of 26.6 mg of pure capsaicin, the half life was approximately 24.9 ± 5.0 min . Following topical application of 3% solution of capsaicin, the half-life of capsaicin was approximately 24 h . The mean population elimination half-life was 1.64 h following application of a topical patch containing 179 mg of capsaicin .

Clearance

Benzydamine demonstrateas a systemic clearance of 170 ml/min .

Elimination Route

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 . At the same time however, other studies have suggested that considerably larger amounts (50-65%) of the drug is excreted unchanged in urine .

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 .

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

It is proposed that capsaicin mainly undergoes renal excretion, as both the unchanged and glucuronide form. A small fraction of unchanged compound is excreted in the feces and urine. In vivo animal studies demonstrates that less than 10 % of an administered dose was found in faces after 48 h .

Pregnancy & Breastfeeding use

The safety of Benzydamine has not been established in pregnant patients. Risk to benefit ratio should be established if this drug is to be used in these patients.

The safety of Capsaicin during pregnancy or lactation has not been established in either humans or animals.

Contraindication

Patients allergic (hypersensitive) to Benzydamine or other component of mouthwash should not use the preparation. Contact with eye should be avoided. If accidentally get into eyes, they should be immediately washed with cold water.

Capsaicin cream is contraindicated on broken or irritated skin. It is also contraindicated in patients with known hypersensitivity to capsaicin or any of the excipients used in this product.

Acute Overdose

Sufficient information on overdose of Capsaicin is not available.

Storage Condition

Keep away from light, store in cool and dry place under 30º C. Keep out of reach of children.

Keep at cool and dry place, away form light. Keep out of the reach of children.

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