PARACETAMOL REXIDOL. 600 mg Tablet. Analgesic-Antipyretic. Paracetamol 600 mg

Transcription

1 (Insert Text) UL Consumer Health PARACETAMOL REXIDOL 600 mg Tablet Analgesic-Antipyretic FORMULATION Each tablet contains: Paracetamol 600 mg PRODUCT DESCRIPTION Rexidol is a round, yellow, flat, bevel-edged tablet, bisected on one side and plain on the other side. CLINICAL PHARMACOLOGY Pharmacodynamics Paracetamol has analgesic and antipyretic properties with weak antiinflammatory activity. The mechanism behind its therapeutic effects has not been clearly explained although recent studies propose that paracetamol inhibits the peroxidase portion of cyclooxygenase, specifically targeting cyclooxygenase-3 (COX-3) enzyme, which is mainly responsible for the synthesis of prostaglandins in the brain cortex. Pharmacokinetics Paracetamol is rapidly and completely absorbed after oral administration. Peak plasma concentrations occur within 10 to 60 minutes. Following oral administration of a 500 mg conventional tablet, an average plasma paracetamol concentration of 2.1 mcg/ml occurs at 6 hours and only small amounts of the drug are detectable in plasma after 8 hours. 1 of 7

2 Paracetamol is rapidly and uniformly distributed into most body tissues. About 25% of paracetamol in blood is bound to plasma proteins. The apparent volume of distribution of paracetamol is approximately 0.7 to 1 L/kg in children and adults. Paracetamol crosses the placenta and small amounts are present in breastmilk. Paracetamol is primarily metabolized in the liver by glucuronide and sulfate conjugation. Small amounts (5 to 10%) of paracetamol are metabolized by cytochrome P-450 microsomal enzyme to a reactive intermediate metabolite (N-acetyl-p-benzoquinoneimine or NAPQI) which is further metabolized via conjugation with gluthathione and ultimately excreted in urine as mercapturic acid. However, hepatotoxic concentrations of NAPQI may accumulate with paracetamol overdosage and occasionally, with usual dosages in susceptible individuals (e.g., malnourished individuals, chronic ingestion of alcohol, those with predisposed medical conditions, or those with a genetic metabolic predisposition). The elimination half-life of paracetamol varies from 1.25 to 3 hours. Paracetamol s plasma half-life may be prolonged following toxic doses or in patients with liver damage. The administration of paracetamol to patients with moderate to severe renal impairment may result in accumulation of paracetamol conjugates. Paracetamol is excreted in urine primarily as paracetamol glucuronide with small amounts of paracetamol sulfate, mercaptate and unchanged drug. Approximately 85% of a paracetamol dose is excreted in urine as free and conjugated paracetamol within 24 hours after ingestion. INDICATIONS For the symptomatic relief of minor aches and pains such as headache, backache, menstrual cramps, muscular aches, minor arthritic pain, toothache, and pain due to the common cold and flu For the reduction of fever DOSAGE AND ADMINISTRATION Adults and Children 12 years old and above: 1 tablet every 4 to 6 hours as needed for pain and/or fever, or, as prescribed by a physician. 2 of 7

3 Do not use more than directed. Do not exceed 6 tablets in each 24-hour period. Do not use for more than 10 days unless directed by a doctor. CONTRAINDICATIONS Hypersensitivity to paracetamol or other ingredients in the medicine Repeated administration of paracetamol is contraindicated in patients with anemia, cardiac, pulmonary, renal, or hepatic disease Children below 12 years old WARNINGS AND PRECAUTIONS Liver Warning: Paracetamol has been associated with cases of acute liver failure. Patients are advised not to take more than 4 g (6 tablets), which is the maximum daily amount, in each 24-hour period. The risk of acute liver failure is higher in persons with an underlying liver disease and those who ingest alcohol while taking paracetamol. Overdose Warning: Taking more than the recommended dose can cause serious health problems, including liver damage. In case of overdosage, get medical help or contact a Poison Control Center right away. Quick medical attention is critical for adults as well as for children even if you do not notice any signs or symptoms. Alcohol Warning: Chronic, excessive consumption of alcohol may increase the risk of paracetamol-induced hepatotoxicity. If you consume 3 or more alcoholic drinks everyday, ask your physician if you should take paracetamol or other analgesics. Do not use with any other medicine containing paracetamol (prescription or nonprescription). If pregnant or breastfeeding, ask a health professional before use. Stop use and ask a doctor if: New symptoms occur Symptoms do not get better Headache is persistent Pain gets worse or lasts more than 10 days Fever gets worse or lasts more than 3 days 3 of 7

4 INTERACTIONS WITH OTHER MEDICAMENTS CONCOMITANT DRUG Alcohol Anticonvulsants (e.g., phenytoin, barbiturates, carbamazepine) Aspirin Cholestyramine Isoniazid Metoclopramide, Domperidone Phenothiazines Warfarin EFFECT Increased risk of paracetamol-induced hepatotoxicity Increased conversion of paracetamol to hepatotoxic metabolites; increased risk of paracetamol-induced hepatotoxicity Paracetamol does not seem to inhibit the antiplatelet effect of aspirin Cholestyramine reduces the speed of absorption of paracetamol if given within one hour of paracetamol Possible increased risk of hepatotoxicity The speed of absorption of paracetamol may be accelerated Possible increased risk of severe hypothermia Increased anticoagulation effect of warfarin; monitoring of prothrombin time (PT) and international normalized ratio (INR) is needed STATEMENT ON USAGE FOR HIGH-RISK GROUPS PREGNANCY AND LACTATION Pregnancy Pregnancy Category B. Paracetamol crosses the placenta but the drug has been widely used as an analgesic in pregnancy and no adverse fetal effects have been recorded. Lactation Paracetamol is distributed into breast milk but has not been detected in the urine of breastfed infants. Paracetamol is compatible with breastfeeding. USE IN CHILDREN Paracetamol is recommended as an antipyretic and analgesic in children. 4 of 7

5 USE IN THE ELDERLY Caution is advised in elderly patients with liver or kidney disease. UNDESIRABLE EFFECTS Paracetamol has a low incidence of side effects when used within therapeutic doses. Minor gastrointestinal disturbances have been reported. Dermatologic and Sensitivity Reactions: pruritic maculopapular rash, urticaria, laryngeal edema, angioedema, anaphylactoid reactions Hematologic: thrombocytopenia, thrombocytopenia purpura, leucopenia, pancytopenia, neutropenia, agranulocytosis Hepatic: hepatotoxicity, acute liver failure; elevations in alanine aminotransferase (ALT) occurred after receiving 4 g of paracetamol daily for 2 weeks Paracetamol very rarely aggravates bronchospasm in patients who are sensitive to aspirin and other non-steroidal anti-inflammatory drugs. Although paracetamol does not normally produce methemoglobinemia or hemolysis even after overdosage or in patients with glucose-6-phosphate dehydrogenase deficiency, there have been isolated reports of these complications. OVERDOSE AND TREATMENT Paracetamol toxicity may result from a single toxic dose, from repeated ingestion of large dose of paracetamol or from chronic ingestion of the drug. Dosedependent, hepatic necrosis is the most serious acute toxic effect associated with overdosage and is potentially fatal Paracetamol toxicity usually involves 4 phases: (1) anorexia, nausea, vomiting, malaise, and diaphoresis, which may inappropriately prompt administration of additional paracetamol; (2) right upper quadrant pain or tenderness, liver enlargement, elevated bilirubin and hepatic enzyme concentrations, prolongation of prothrombin time, and occasionally oliguria; (3) anorexia, nausea, vomiting, and malaise recur and signs of hepatic failure (e.g., jaundice) and possibly renal failure and cardiomyopathy develop; (4) recovery or progression to fatal complete liver failure 5 of 7

6 In adults, hepatotoxicity may occur following ingestion of greater than 7.5 to 10 g over a period of 8 hours or less. Fatalities are infrequent (less than 3-4% of untreated cases) and have rarely been reported with overdoses of less than 15 grams. Management of acute paracetamol overdosage includes determination of the magnitude of the ingestion, classification of risk, and measures to reduce morbidity and mortality. Early recognition and treatment of overdosage are essential to prevent morbidity and mortality. If paracetamol has been recently ingested, activated charcoal may reduce paracetamol absorption and should be administered as soon as possible, preferably within 1 hour of ingestion. Other methods of gastric decontamination (e.g., syrup of ipecac) are less effective and generally are not recommended. The preferred method to assess the risk of toxicity after paracetamol ingestion is the measurement of plasma or serum paracetamol concentrations. Plasma or serum paracetamol concentrations should be determined as soon as possible, but no sooner than 4 hours after ingestion. N-acetylcysteine (NAC) therapy is initiated as soon as possible with an oral or IV loading dose in adult and pediatric patients. Results are optimal if NAC therapy is given within 8-16 hours of ingestion, but it is effective when given more than 24 hours after ingestion. STORAGE CONDITION Keep the product out of reach and sight of children. Store at temperatures not exceeding 30C. AVAILABILITY CAUTION Food, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription. 6 of 7

7 NAME AND ADDRESS OF MANUFACTURER/MARKETING AUTHORIZATION HOLDER DATE OF REVISION OF THE PACKAGE INSERT Note to ULCH: Package insert revision date should be the date when the insert is approved by the Food and Drug Administration (FDA). 7 of 7