Audigel

Audigel Uses, Dosage, Side Effects, Food Interaction and all others data.

Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Aceclofenac is a NSAID that inhibits both isoforms of COX enzyme, a key enzyme involved in the inflammatory cascade. COX-1 enzyme is a constitutive enzyme involved in prostacyclin production and protective functions of gastric mucosa whereas COX-2 is an inducible enzyme involved in the production of inflammatory mediators in response to inflammatory stimuli. Aceclofenac displays more selectivity towards COX-2 (IC50 of 0.77uM) than COX-1 (IC50 of >100uM), which promotes its gastric tolerance compared to other NSAIDs. The primary metabolite, 4'-hydroxyaceclofenac, also minimally inhibits COX-2 with IC50 value of 36uM . Although the mode of action of aceclofenac is thought to mainly arise from the inhibition of synthesis of prostaglandins (PGE2), aceclofenac also inhibits the production of inflammatory cytokines, interleukins (IL-1β, IL-6), and tumor necrosis factors (TNF) . It is also reported that aceclofenac also affects the cell adhesion molecules from neutrophils [A19763]. Aceclofenac also targets the synthesis of glycosaminoglycan and mediates chrondroprotective effects .

Although the precise mechanism of action of Capsaicin is not fully understood, current evidence suggests that Capsaicin exerts an analgesic effect by depleting and preventing reaccumulation of Substance P in peripheral sensory neurons. Substance P is thought to be the principal chemomediator of pain impulses from the periphery to the central nervous system.

Capsaicin is a TRPV1 receptor agonist. TRPV1 is a trans-membrane receptor-ion channel complex activated by temperatures higher than 43 degrees Celsius, pH lower than 6, and endogenous lipids. When activated by a combination of these factors, the channel can transiently open and initiate depolarization due to the influx of calcium and sodium ions. Because TRPV1 is commonly expressed in A-delta and mostly C fibers, depolarization results in action potentials which send impulses to the brain and spinal cord. These impulses result in capsaicin effects of warming, tingling, itching, stinging, or burning. Capsaicin also causes more persistent activation of these receptors compared to the environmental agonists, resulting in a loss of response to many sensory stimuli, described as "defunctionalization". Capsaicin is associated with many enzymatic, cytoskeletal, and osmotic changes, as well as disruption of mitochondrial respiration, impairing nociceptor function for extended periods of time.

Linseed oil is a rich source of α-Linolenic acid extracted from the dried, ripened seeds of the flax plant Linum usitatissimum. Other fatty acids contained in linseed oil include palmitic acid, stearic acid, oleic acid and linolenic acid. Linseed oil is particularly susceptible to polymerization reactions upon exposure to oxygen in air due to a high content of di- and triunsaturated esters. It is used in drying processes, and is used in other industrial and commercial applications. It is an indirect additive used in food contact substances.

Audigel
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Audigel
Generic	Aceclofenac + Capsaicin + Linseed Oil + Menthol + Methyl Salcylate
Type	Gel
Therapeutic Class
Manufacturer	Laborate Pharmaceuticals India Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Aceclofenac is used for the relief of pain and inflammation in both acute and chronic pain like osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, dental pain, post-traumatic pain, low back pain, gynaecological pain 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)

Audigel is also used to associated treatment for these conditions: Ankylosing Spondylitis (AS), Osteoarthritis (OA), Rheumatoid ArthritisArthritis, 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 Audigel works

Through COX-2 inhibition, aceclofenac downregulates the production of various inflammatory mediators including prostaglandin E2 (PGE2), IL-1β, and TNF from the arachidonic acid (AA) pathway. Inhibition of IL-6 is thought to be mediated by diclofenac converted from aceclofenac . Suppressed action of inflammatory cytokines decreases the production of reactive oxygen species. Aceclofenac is shown to decreased production of nitrous oxide in human articular chondrocytes . In addition, aceclofenac interferes with neutrophil adhesion to endothelium by decreasing the expression of L-selectin (CD62L), which is a cell adhesion molecule expressed on lymphocytes . Aceclofenac is proposed to stimulate the synthesis of glycosaminoglycan in human osteoarthritic cartilage which may be mediated through its inhibitory action on IL-1 production and activity . The chrondroprotective effects are generated by 4'-hydroxyaceclofenac which suppresses IL-1 mediated production of promatrix metalloproteinase-1 and metalloproteinase-3 and interferes with the release of proteoglycan from chrondrocytes .

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

Audigel dosage

Adults: The maximum recommended dose is 200 mg daily, taken as two separate 100 mg doses, one tablet in the morning and one in the evening.

Children: There is no clinical data on the use of aceclofenac in children.

Elderly: The pharmacokinetics of aceclofenac are not altered in elderly patients, therefore it is not considered necessary to modify the dose and dose frequency.

Renal insufficiency: There is no evidence that the dosage of aceclofenac needs to be modified in patients with mild renal impairment.

Hepatic insufficiency: The dose of aceclofenac should be reduced in patients with hepatic impairment. An initial daily dose of 100 mg should be administered.

Aceclofenac SR tablet:

The recommended dose is 200 mg once daily.

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

Generally aceclofenac is well tolerated. The majority of side effects observed have been reversible and of a minor nature and include gastrointestinal disorders (dyspepsia, abdominal pain, nausea and diarrhoea) and occasional occurance of dizziness. Dermatological side effects including pruritus and rash. Abnormal hepatic enzyme levels and raised serum creatinine have occasionally been reported.

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

Some common adverse effects include gastro-intestinal disorders (dyspepsia, abdominal pain, nausea), rash, ruber, urticaria, symptoms of enuresis, headache, dizziness, and drowsiness . Oral LD50 value in rats is 130 mg/kg .

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

Aceclofenac should be administered with caution to patients with symptoms indicative of gastrointestinal disorders, with a history of peptic ulceration, ulcerative colitis, Crohn\'s disease, hepatic porphyria, and coagulation disorders. Patients suffering from severe hepatic impairment must be monitored.

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.

Interaction

Lithium and Digoxin: Aceclofenac, like many NSAIDs may increase plasma concentrations of lithium and Digoxin.

Diuretics: Aceclofenac, like other NSAIDs, may interact the activity of diuretics.

Anticoagulants: Like other NSAIDs, Aceclofenac may enhance the activity of anticoagulant. Close monitoring of patients on combined anticoagulants and Aceclofenac therapy should be undertaken.

Methotrexate: Caution should be exercised if NSAIDs and Methotrexate are administered within 24 hours of each other, since NSAIDs may increase Methotrexate plasma levels, resulting in increased toxicity.

Volume of Distribution

The volume of distribution is approximately 25 L .

Elimination Route

Aceclofenac is rapidly and completely absorbed from the gastrointestinal tract and circulates mainly as unchanged drug following oral administration. Peak plasma concentrations are reached around 1.25 to 3 hours post-ingestion, and the drug penetrates into the synovial fluid where the concentration may reach up to 60% of that in the plasma . There is no accumulation in regular dosing, with similar maximum plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax) after single and multiple doses .

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

The mean plasma elimination half-life is approximately 4 hours .

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

The mean clearance rate is approximately 5 L/h .

Elimination Route

The main route of elimination is via the urine where the elimination accounts for 70-80% of clearance of the drug . Approximately two thirds of the administered dose is excreted via the urine, mainly as glucuronidated and hydroxylated forms of aceclofenac . About 20% of the dose is excreted into feces .

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

Pregnancy: There is no information on the use of aceclofenac during pregnancy. Aceclofenac should not be administered during pregnancy, unless there are compelling reasons for doing so. The lowest effective dose should be administered.

Lactation: There is no information on the secretion of aceclofenac in breast milk. The use of aceclofenac should therefore be avoided during lactation unless the potential benefits to the mother outweigh the possible risks to the children.

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

Contraindication

Aceclofenac should not be administered to patients with active or suspected peptic ulcer or gastro-intestinal bleeding. It should not be given to patients with moderate to severe renal impairment. Close medical surveillance is also imperative in patients suffering from severe impairment of hepatic function. It should not be prescribed during pregnancy, unless there are compelling reasons for doing so. The lowest effective dosage should be used. Aceclofenac should not be administered to patients previously sensitive to Aceclofenac or in whom aspirin or NSAIDs precipitate attacks of asthma, acute rhinitis or urticaria or who are hypersensitive to these drugs.

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

There is no human data available on the consequences of aceclofenac overdosage. After overdosage, following therapeutic measures to be taken: absorption should be prevented as soon as possible by means of gastric lavage and treatment with activated charcoal. Supportive and symptomatic treatment should be given for complications.

Sufficient information on overdose of Capsaicin is not available.