COMPOSITION :

PHARMACOLOGY : Pharmacodynamics:
Aceclofenac relieves pain and inflammation through a variety of mechanisms and in addition exerts stimulatory effects on cartilage matrix synthesis. Anti-inflammatory activity: The anti-inflammatory effects of Aceclofenac have been shown in both acute and chronic inflammation. It inhibits various mediators of pain and inflammation including:

• PGE2 via cyclooxygenase inhibition (COX-1 & COX-2) after intracellular metabolism to 4’ hydroxy-aceclofenac and diclofenac in human rheumatoid synovial cells and other inflammatory cells.
• IL-1β, IL-6 and tumor necrosis factor in human osteoarthritic synovial cells and human articular chondrocytes.
• Reactive oxygen species (which plays a role in joint damage) has also been observed in patients with osteoarthritis of knee.
• Expression of cell adhesion molecules (which is implicated in cell migration and inflammation) has also been shown in human neutrophils.

Stimulatory effects on cartilage matrix synthesis: Aceclofenac stimulates glycosaminoglycan synthesis in human osteoarthritic cartilage by inhibition of IL-1β and suppresses cartilage degeneration by inhibiting IL-1β mediated promatrix metalloproteinase production and proteoglycan release. Paracetamol is a clinically proven analgesic and antipyretic agent with weak anti-inflammatory effect.

Analgesic action: The central analgesic action of Paracetamol resembles that of aspirin. It produces analgesia by raising pain threshold.

Antipyretic effect: The antipyretic effect of Paracetamol is attributed to its ability to inhibit COX in the brain where peroxide tone is low. Recent evidence suggests inhibition of COX-3 (believed to be splice variant product of the COX-1 gene) could represent a primary central mechanism by which Paracetamol decreases pain and possibly fever.

Pharmacokinetics: Aceclofenac is well absorbed from gastrointestinal tract and peak plasma concentrations (Cmax) are reached 1-3 hours after an oral dose. The drug is more than 99% bound to plasma proteins and the volume of distribution (VD) is approximately 25 liters. The presence of food reduced rate of absorption (increased tmax) but not the extent of absorption (Cmax or AUC). In patients with knee pain and synovial fluid effusion, the plasma concentration of Aceclofenac was twice that in synovial fluid after multiple doses of the drug. Aceclofenac is metabolized mainly to 4’ hydroxyl aceclofenac. The drug is eliminated primarily through renal excretion with 70-80% of administered dose found in urine as glucoronides and rest being excreted in faeces. The plasma elimination half life of Aceclofenac is approximately 4 hours.

Paracetamol is rapidly and almost completely absorbed from gastrointestinal tract with peak plasma concentrations (Cmax) occurring about 10 to 60 minutes after oral administration. Plasma protein binding is negligible at usual therapeutic concentration but increases with increasing concentrations. Acetaminophen is relatively uniformly distributed throughout most body fluids. The plasma half life (t1/2) 2-3 hours and the effect after oral dose lasts for 3-5 hours. Paracetamol is metabolized predominantly in liver and excreted in the urine mainly as glucuronide and sulfate conjugate. Less than 5% is excreted unchanged.

INDICATIONS

VEXIPAR-AC is indicated for relief from severe pain and inflammation in Osteoarthritis, Rheumatoid arthritis, Ankylosing spondylitis, Low back pain, Dental pain, Gynaecological pain and Painful & Inflammatory conditions of ear, nose & throat.

DOSAGE AND METHOD OF ADMINISTRATION

VEXIPAR-AC tablets are supplied for oral administration in adults. The maximum recommended dose of VEXIPAR-AC is two tablets daily, taken as one tablet in the morning and one in the evening.

CONTRAINDICATIONS

VEXIPAR-AC is contraindicated in the following situations:

• Patients sensitive to Aceclofenac, Paracetamol or to any of the excipients of the product.
• Patients in whom aspirin or other NSAIDs precipitate attacks of bronchospasm, acute rhinitis or urticaria or patients hypersensitive to these drugs.
• Patients with active or suspected peptic ulcer or gastrointestinal bleeding or bleeding disorders.
• Patients with severe heart failure, hypertension, hepatic or renal insufficiency Third trimester of pregnancy.

WARNINGS AND PRECAUTIONS

VEXIPAR-AC may cause dizziness. Driving or operating machinery is to be avoided. Individuals receiving long-term treatment should be regularly monitored for renal function tests, liver function tests and blood counts. It is to be used with caution in hepatic porphyria, coagulation disorders, history of peptic ulcers, ulcerative colitis, Crohn’s disease, SLE, cerebrovascular bleeding, pregnancy and lactation.

Caution should be exercised in patients with mild to moderate impairment of cardiac, hepatic or renal function and in elderly patients who are more likely to be suffering from these conditions. Caution is also required in patients on diuretic therapy or otherwise at risk of hypovolemia.

DRUG INTERACTIONS

Drug interactions associated with Aceclofenac are similar to those observed with other NSAIDs. Aceclofenac may increase the plasma concentrations of lithium, digoxin and methotrexate. It may increase the activity of anticoagulants, inhibit the activity of diuretics, enhance cyclosporine nehrotoxicity and precipitate convulsions when co administered with quinolone antibiotics. Co administration of Aceclofenac with other NSAIDs and corticosteroids are to be avoided due to increased incidence of side-effects. The risk of Paracetamol toxicity may be increased in patients receiving other potentially heatotoxic drugs or drugs that induce hepatic microsomal enzymes. Co administration of Paracetamol with rifampicin, isoniazid, chloramphenicol, antiepileptic drugs and antiviral drugs is to be avoided. Metoclopromide may increase the absorption of Paracetamol whereas excretion and plasma concentration may be altered when co administered with probenecid. Cholestyramine also reduces the absorption of Paracetamol

Pregnancy The drug in not recommended in pregnant women.
Lactation The drug in not recommended in breast-feeding women.

OVERDOSE Over dosage may cause nausea, vomiting, pain abdomen, dizziness, somnolence, headache, sweating, pancreatitis, hepatic failure and acute renal failure. Treatment, if required, includes gastric lavage, activated charcoal and other symptomatic measures as per medical advice.

SHELF-LIFE: 2 years.

PACKAGING INFORMATION: VEXIPAR-AC is available in a strip of 10 tablets.