PHARMACOKINETICS
SAFENAC-P is a fixed dose combination of Aceclofenac and Paracetamol. Aceclofenac belongs to a group of Non Steroidal Anti-inflammatory Drugs (NSAIDs) used to treat various painful inflammatory conditions. Aceclofenac has an outstanding anti-inflammatory profile mediated primarily through inhibition of cyclooxygenase (COX) activity and suppression of PGE2 synthesis. Paracetamol is a safe and effective analgesic-antipyretic agent with minimal effect on cardiovascular, respiratory and GI system. Paracetamol or acetaminophen is the deethylated active metabolite of phenacetin. Chemically, Paracetamol is N-acetyl-p-aminophenol.

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’ hydroxyaceclofenac. 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
SAFENAC-P 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
The recommended dose of SAFENAC-P is 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.
ADVERSE REACTION
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.

CONTRDICTIONS
SAFENAC-P 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