Each film-coated tablet contains: Aceclofenac 100 mg, Paracetamol 500 mg.
Pharmacology: Pharmacodynamics: Aceclofenac relieves pain and inflammation through a variety of mechanisms and in addition exert 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.
lL-1 B, lL-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-1B and suppresses cartilage degeneration by inhibiting IL-1B 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' hydroxy-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 concentration (Cmax) occurring about 10 to 60 minutes after oral administration. Plasma proteins and binding is negligible at usual therapeutic concentration but increases with increasing concentration. Acetaminophen is relatively uniformly distributed throughout most body fluids. The plasma half life (t1/2) is 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.
Treatment of pain and inflammation in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, low back pain, dental pain, gynaecological pain and inflammatory conditions of ear, nose, and throat.
The recommended dose of aceclofenac and paracetamol is 1 tablet in the morning and 1 tablet in the evening, maximum of 2 tablets a day. Or as prescribed by the physician.
Overdosage may cause nausea, vomiting, pain in 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.
Aceclofenac and Paracetamol is contraindicated in patients with history of hypersensitivity to the drugs, aspirin and other NSAID's or to any of the excipients of the products, patients with active or suspected peptic ulcer or GI bleeding or bleeding disorder, patients with severe heart failure, hypertension, hepatic or renal impairment, pregnancy.
The combination of aceclofenac and paracetamol may cause dizziness. Driving or operating machinery should be avoided. Individuals receiving long term treatment should be regularly monitored for renal function tests, liver function test and blood count. It is used with caution in hepatic porphyria, coagulation disorder, history of peptic ulcer, ulcerative colitis, Crohn's disease 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.
Regular use of Dolowin Plus during pregnancy and lactation should be avoided, unless the unless the potential benefits outweigh the risks.
The commonest adverse effects occuring during therapy with NSAID's are gastrointestinal disturbances (dyspepsia, abdominal pain, nausea, and diarrhoea); most frequent being dyspepsia, abdominal pain and rise in hepatic enzymes. Others rare side effects include dizziness, constipation, vomiting, ulcerative stomatitis, rash, dermatitis, headache, fatigue, allergic reaction, 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.
Drug interactions associated with Aceclofenac are similar to those observed with other NSAIDs. Aceclofenac may increase the plasma concentration of lithium & digitoxin and methotrexate. Concominant use with diuretics may inhibit the activity of diuretics. The activity of anticoagulant may be entranced when used concomitantly with aceclofenac. Convulsion may occur due to interaction between quinolones and NSAID's. Coadministration of aceclofenac with other NSAID's 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, antiepileptic drugs and antiviral drugs is to be avoided. Metoclopromide may increase the absorption of paracetamol where as excretion and plasma concentration may be altered when co administered with probenecid. Cholestyramine also reduces the absorption of paracetamol.
Store at temperatures not exceeding 30°C.
N02BE51 - paracetamol, combinations excl. psycholeptics ; Belongs to the class of anilide preparations. Used to relieve pain and fever.