Diclofenac diethylamine, Menthol.
Inflaryl gel contains Diclofenac Diethylamine BP 1.16% w/w equivalent to Diclofenac Sodium 1% w/w and Menthol USP 2% w/w as active ingredients in Gel Base q.s.
Excipients/Inactive Ingredients: It also contains Carbopol-980 BP, Propylene Glycol BP, Benzyl Alcohol BP, Triethanolamine BP, Hydroxyethyl Cellulose NF, Disodium Edetate BP, Fragrance SSY-DO- 1201 IHS & Purified Water BP as inactive ingredients.
Pharmacology: Pharmacodynamics: Diclofenac is a nonsteroidal anti-inflammatory agent with potent anti-inflammatory, analgesic, and antipyretic properties. Chemically it is a phenylacetic acid derivative. Diclofenac is a potent inhibitor of cyclooxygenase activity, which causes a sharp reduction in the formation of prostaglandin, prostacyclin and thromboxane product, all of which are mediators of inflammation. In addition, diclofenac also regulates the lipoxygenase pathway. Proinflammatory cytokine IL-6 and substance P levels in synovial fluid and plasma of 24 patients with rheumatoid arthritis were reduced after seven days of treatment with diclofenac compared to placebo, suggesting that these are factors in NSAID anti-inflammatory mechanism of action.
Diclofenac has been found to decrease the signs and symptoms of ocular inflammation following cataract removal. It may prevent the effects of prostaglandins on eye structures.
PREVENTION OF COLORECTAL CANCER: In vitro, animal, clinical and epidemiological studies lend support for the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing colorectal cancer. Four mechanisms have been proposed for the chemopreventative effects of NSAIDs: (1) cyclooxygenase (COX)-mediated carcinogen activation, (2) cell proliferation, (3) apoptosis and (4) immune surveillance. Some mechanisms are believed to occur independently of cyclooxygenase inhibition. COX-1 or COX-2 or both may initiate carcinogenesis by the following mechanisms: (1) direct activation of carcinogens, (2) production of MDA, a mutagen and carcinogen and (3) production of peroxyl radicals. NSAIDs inhibit the first 2 of the previously mentioned processes. In addition, colon carcinogens increase COX-1 and COX-2 expression which may increase carcinogen activation. In all tissues, a balance exists between cell renewal and cell loss which is lost in neoplasia. In cell culture, NSAIDs inhibit cell division and alter cell cycle phase distribution of colon cancer cells; it has NOT been definitively determined whether prostaglandin synthesis is necessary for this effect. Apoptosis, programmed cell death, is inhibited during development of colorectal cancer. NSAIDs induce apoptosis in the colon and rectum. In clinical studies, use of sulindac restored normal apoptosis in the flat rectal mucosa of patients with familial adenomatous polyposis. In cell culture and animal models, colon tumors produce increased quantities of prostaglandin E2 which reduces gene expression of HLA antigens and recognition by immune cells. NSAIDs increase gene expression in colon cancer cells which increases recognition by immune cells.
Pharmacokinetics: Onset of Duration: ONSET: Analgesia, immediate release: 30 minutes.
DRUG CONCENTRATION LEVELS: BIOAVAILABILITY (F): Oral, delayed release: 50% after first-pass metabolism.
Oral, immediate release: 50% after first-pass metabolism.
Intramuscular, regular release: complete.
Ophthalmic drops: minimal.
Rectal suppositories: complete.
Topical gel: 6% percutaneous absorption.
Distribution: TOTAL PROTEIN BINDING: 99.7%.
OTHER DISTRIBUTION SITES: SYNOVIAL FLUID, 70%: The synovial fluid concentration was 70% of the plasma concentration 2 hours after injecting diclofenac 75 mg. At 4 hours and beyond, synovial fluid concentrations were higher than plasma concentrations. Accumulation may occur after multiple doses, with synovial fluid concentrations rising 3 to 5 times higher than plasma.
Distribution Kinetics: VOLUME OF DISTRIBUTION (Vd): 550 mL/kg.
Metabolism: METABOLISM SITES AND KINETICS: Liver, extensive.
Diclofenac undergoes first-pass metabolism which decreases systemic bioavailability to 50%.
METABOLITES: Aromatic hydroxylated metabolite, inactive. Conjugated metabolite, inactive.
Excretion: BREAST MILK: BREASTFEEDING: Unknown.
Limited data from two studies indicate that diclofenac is undetectable in breast milk. However, the presence or absence of diclofenac metabolites in breast milk was not assessed.
KIDNEY: RENAL EXCRETION: 65%.
Diclofenac is eliminated primarily by the kidney as conjugated metabolites; little unchanged drug is detected in the urine.
Other: OTHER EXCRETION: Bile, 35%.
Little or no unchanged diclofenac is excreted in the bile.
Half-Life: PARENT COMPOUND: ELIMINATION HALF-LIFE: 2 hours.
The synovial fluid half-life is 3 times longer than the plasma half-life.
Toxicology: Preclinical Safety Data: Preclinical Data reveal no special hazard for humans based on conventional studies of pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
INFLARYL GEL is indicated for the treatment of pain and inflammation in muscle and joint injuries, e.g. sprains, strains and bruises, rheumatic aches and pains, ankylosing spondylitis, osteoarthritis, painful post-operative and post-traumatic inflammation, swelling and soft tissue rheumatism.
POSOLOGY: Apply Inflaryl Gel 2-3 times daily and gently massage the gel into the area of pain or stiffness until the gel has been absorbed.
Method of Administration: Topical application.
History of hypersensitivity precipitated by aspirin or other NSAIDs.
Do not apply on wounds and broken skin. Do not apply near eyes, on mucus membrane or on inflamed skin.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: NONE.
Diclofenac should be avoided in late pregnancy (during third trimester) due to the effects of prostaglandin inhibition on the fetal cardiovascular system.
Rashes, local irritation, erythema, photosensitivity.
DRUG INTERACTIONS: DRUG-DRUG COMBINATIONS: ACENOCOUMAROL: Concomitant diclofenac and oral anticoagulant therapy with acenocoumarol presents an increased risk of serious bleeding, particularly from the gastrointestinal tract.
ALENDRONATE: Because both NSAID and alendronate use has been associated with gastrointestinal irritation, caution should be exercised with concomitant administration.
ANGIOTENSIN CONVERTING ENZYME INHIBITORS: NSAIDs may decrease the antihypertensive and natriuretic effect of ACE inhibitors, particularly in low renin hypertensive patients.
ANISINDIONE: Concomitant diclofenac and oral anticoagulant therapy with anisindione presents an increased risk of serious bleeding, particularly from the gastrointestinal tract.
ASPIRIN: Concomitant administration of aspirin and diclofenac results in aspirin displacing diclofenac from its binding sites. This leads to reduced diclofenac plasma concentrations, peak plasma levels, and area under the concentration-time curve (AUC) values.
BETA-ADRENERGIC BLOCKERS: The concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) and beta-adrenergic blockers has been reported to result in increase in blood pressure and interference with blood pressure control.
CALCIUM CHANNEL BLOCKERS: Calcium channel blockers may be associated with an increased risk of gastrointestinal hemorrhage. Caution is advised if NSAIDs and calcium channel blockers are used concomitantly. Monitor for signs and symptoms of gastrointestinal hemorrhage, such as weakness, nausea and blood in the stool. The antihypertensive effects of calcium channel blockers may be antagonized by concomitant administration of NSAIDs.
CHOLESTYRAMINE: It decreases diclofenac absorption in the gastrointestinal tract.
COMFREY: Elevated liver transaminases with or without concomitant hepatic damage.
Comfrey is a known hepatotoxin and should be avoided.
CYCLOSPORINE: The concurrent use of nonsteroidal anti-inflammatory agents (NSAIDs) and cyclosporine has resulted in increases in cyclosporine levels, nephrotoxicity and increased plasma creatinine concentrations.
DICUMAROL: Concomitant diclofenac and oral anticoagulant therapy with dicumarol presents an increased risk of serious bleeding, particularly from the gastrointestinal tract.
DIGOXIN: Increased digoxin serum concentrations have been reported during concurrent therapy with digoxin and diclofenac.
ENALAPRIL/FELODIPINE: Calcium channel blockers may be associated with an increased risk of gastrointestinal hemorrhage.
EPTIFIBATIDE: Concurrent administration of nonsteroidal anti-inflammatory agents and eptifibatide may produce enhanced anticoagulation, leading to an increased risk of internal and superficial hemorrhage.
EUCALYPTUS: Increased risk of hepatotoxicity. Avoid use of eucalyptus while taking drugs with potential for hepatoxicity.
FEVERFEW: Theoretically, concomitant use of feverfew with a nonsteroidal anti-inflammatory agent (NSAID) may predispose the patient to more adverse effects (e.g., gastropathy, increased risk of bleeding and nephropathy).
GERMANDER: Elevated liver transaminases with or without concomitant hepatic damage.
GINKGO: Avoid concomitant use of Ginkgo with any medicine which can inhibit platelet aggregation or coagulation, including non-steroidal anti-inflammatory agents.
GOSSYPOL: Gossypol may cause tissue congestion, mucosal sloughing, mucosal necrosis and intestinal wall hemorrhage.
Instructions for Use, Handling and Disposal: For External use only. Store at a temperature below 30°C. Do not freeze.
Store at a temperature below 30°C. Do not freeze.
Shelf Life: 36 Months from the date of Manufacturing.
M01AB55 - diclofenac, combinations ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.
Topical gel 30 g (white, translucent smooth gel with a mild, pleasant odour) x 1's.