AMNOFEN-P Tablet

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 and throat.

Dosage

1 tablet twice daily.

Generally, no dose adjustment is necessary in elderly patients and those with mild renal impairment.

Safety and efficacy has not been established in children.

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.

Most of the adverse events are minor and reversible with treatment discontinuation.

The majority of side effects are related to gastrointestinal system (dyspepsia, abdominal pain, nausea and diarrhea), most frequent being dyspepsia, abdominal pain and rise in hepatic enzymes.

Other rare side-effects include dizziness, constipation, vomiting, ulcerative stomatitis, rash, dermatitis, headache, fatigue, allergic reactions, anemia, granulocytopenia, thrombocytopenia, neutropenia, oedema, palpitation, leg cramps, flushing, purpura, paraesthesia, tremors, gastrointestinal bleeding, gastrointestinal ulceration, pancreatitis interstitial nephritis, depression, abnormal dreaming, somnolence, insomnia, vasculitis, hypoglycemia, rise in blood urea, serum creatinine and serum potassium. As with other NSAIDs, severe mucocutaneous skin reactions may occur.

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 nephrotoxicity and precipitate convulsions when coadministered with quinolone antibiotics. Coadministration 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 hepatotoxic drugs or drugs that induce hepatic microsomal enzymes. Coadministration of Paracetamol with rifampicin, isoniazid, chloramphenicol, anti-epileptic drugs and antiviral drugs is to be avoided. Metoclopramide may increase the absorption of Paracetamol whereas excretion and plasma concentration may be altered when coadministered with probenecid. Cholestyramine also reduces the absorption of Paracetamol.

Third trimester of pregnancy: Contraindicated.

This medicine may cause dizziness. Driving or operating machinery are 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.

Mechanism of action 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 and COX-2) after intracellular metabolism to 4’hydroxy-aceclofenac and diclofenac in human rheumatoid synovial cells and other inflammatory cells.

IL-10, 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-10 and suppresses cartilage degeneration by inhibiting IL-10 mediated promatrix metalloproteinase production and proteoglycan release. Paracetamol is a clinically proven analgesic an 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.