1 NAME OF THE MEDICINAL PRODUCT CETAMOL Oral Solution 120mg/5ml 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each 5ml contains Paracetamol 120mg. 3 PHARMACEUTICAL FORM Oral Solution. Clear colorless to pale yellow solution with characteristic odor and sweet taste. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications CETAMOL Solution is indicated as an analgesic and antipyretic. It is used in the treatment of mild to moderate pain, for the relief of symptoms of colds and influenza and to reduce fever, including post-vaccination fever in childhood. 4.2 Posology and method of administration Age Dose For post-vaccination fever for babies aged between 2 – 3 months 2.5mL If necessary, after 4 – 6 hours, give a second 2.5mL dose. o Do not give to babies less than 2 months of age. o Do not give more than 2 doses. o Leave at least 4 hours between doses. o If further doses are needed, talk to your doctor or pharmacist. Child’s Age How Much How often (in 24 hours) 3 – 6 months 2.5mL 4 times 6 – 24 months 5mL 4 times 2 – 4 years 7.5mL 4 times 4 – 6 years 10mL 4 times o Do not give more than 4 doses in any 24-hour period. o Leave at least 4 hours between doses. o Do not give this medicine to your child for more than 3 days without speaking to your doctor or pharmacist. 4.3 Contraindications Patients with rare hereditary problems of fructose intolerance should not take this medicine. Hypersensitivity to paracetamol or to any of the other constituents. Do not give to babies less than 2 months of age. 4.4 Special warnings and precautions for use Never give more medicine than shown in the table. Always use the syringe to measure the adequate required dose. Do not give to babies less than 2 months of age. For infants 2-3 months no more than two doses should be given. Do not give more than 4 doses in any 24-hour period. Leave at least 4 hours between doses. Prolonged use without medical supervision can be harmful. Do not give this medicine to your child for more than 3 days without speaking to your doctor or pharmacist. If symptoms persist consult your doctor. Do not give with any other paracetamol containing products. The product should be administered with caution to patients with known liver or renal impairment. Immediate medical advice should be sought in the event of an overdose, because of the risk of irreversible liver damage. As with all medicines, if your child is currently taking any medicine consult your doctor or pharmacist before taking this product. Keep out of the reach and sight of children. Caution is advised if paracetamol is administered concomitantly with flucloxacillin due to increased risk of high anion gap metabolic acidosis (HAGMA), particularly in patients with severe renal impairment, sepsis, malnutrition, and other sources of glutathione deficiency (e.g., chronic alcoholism), as well as those using maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended. CETAMOL contains 155 mg propylene glycol in each ml, If your child is less than 5 years old, talk to your doctor or pharmacist before giving them this medicine, in particular if they use other medicines that contain propylene glycol or alcohol. Co - administration with any substrate for alcohol dehydrogenase such as ethanol may induce adverse effects in children less than 5 years old. If you are pregnant or breast-feeding, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine. While propylene glycol has not been shown to cause reproductive or developmental toxicity in animals or humans, it may reach the foetus and was found in milk. As a consequence, administration of propylene glycol to pregnant or lactating patients should be considered on a case by case basis. If you suffer from a liver or kidney disease, do not take this medicine unless recommended by your doctor. Your doctor may carry out extra checks while you are taking this medicine. Various adverse events, such as hyperosmolality, lactic acidosis; renal dysfunction (acute tubular necrosis), acute renal failure; cardiotoxicity (arrhythmia, hypotension); central nervous system disorders (depression, coma, seizures); respiratory depression, dyspnoea; liver dysfunction; haemolytic reaction (intravascular haemolysis) and haemoglobinuria; or multisystem organ dysfunction, have been reported with high doses or prolonged use of propylene glycol. CETAMOL contains parabens which may cause allergic reactions “may be delayed”. 4.5 Interaction with other medicinal products and other forms of interactions Discontinue consumption of alcohol or products containing propylene glycol during and for at least three days after therapy with metronidazole. Use of oral metronidazole is associated with a disulfiram - like reaction to alcohol, including abdominal cramps, nausea, vomiting, headaches, and flushing. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased bleeding; occasional doses have no significant effect. The rate of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine. Chronic alcohol intake can increase the hepatotoxicity of paracetamol overdose. Acute alcohol intake may diminish an individual's ability to metabolize large doses of paracetamol, the plasma half-life of which can be prolonged. The use of drugs that induce hepatic microsomal enzymes, such as anticonvulsants and oral contraceptives, may increase the extent of metabolism of paracetamol, resulting in reduced plasma concentrations of the drug and a faster elimination rate. Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risks factors (see section 4.4). 4.6 Fertility, pregnancy and lactation Pregnancy A large amount of data on pregnant women indicates neither malformities, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency. Lactation Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data does not contraindicate breast feeding. 4.7 Effects on ability to drive and use machines None. 4.8 Undesirable effects Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. Very rare cases of serious skin reactions have been reported. There have been a few reports of blood dyscrasias including thrombocytopenia and agranulocytosis. Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year and liver damage has been reported after daily ingestion of excessive amounts for shorter periods. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol nor was the control of the disease improved after paracetamol withdrawal. Nephrotoxic effects following therapeutic doses of paracetamol are uncommon. Papillary necrosis has been reported after prolonged administration. Reporting of suspected adverse reactions: • Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: • e-mail for reporting: pv.followup@edaegypt.gov.eg • Website for reporting: www.edaegypt.gov.eg • Hotline: 15301 • Scan QR code: 4.9 Overdose Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors, including the following ones: Risk factors a) long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes, or b) regular consumption of ethanol in excess of recommended amounts, or c) likely glutathione depletion, e.g., eating disorders, cystic fibrosis, HIV infection, starvation, cachexia. Symptoms Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, hematuria, and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported. Treatment Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage. Management should be in accordance with established treatment guidelines. Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour. Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol, however, the maximum protective effect is obtained up to 8 hours' post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with a liver unit. 5 PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Analgesic, Antipyretic Paracetamol is an antipyretic and analgesic proven in pediatric use. Paracetamol produces antipyresis through action on the hypothalamic heat-regulation center and analgesia by elevation of the pain threshold. Paracetamol has analgesic and antipyretic actions similar to those of aspirin but it has no useful anti-inflammatory properties. 5.2 Pharmacokinetic properties Paracetamol has analgesic and antipyretic actions but only weak anti-inflammatory properties. Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations occur within 30 to 60 minutes, with slightly faster absorption of liquid preparations. Usual analgesic doses produce total serum concentrations of 5 to 20micrograms/ml. A good correlation between serum concentration and analgesic effect has not been found. Paracetamol is distributed into most body tissues; it crosses the placenta and it is present in breast milk. Serum protein binding varies from 20% to 50% at toxic serum concentrations. Paracetamol is metabolized predominantly in the liver and excreted in the urine mainly as glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 3 hours and is prolonged in neonates and in patients with hepatic impairment. Total body clearance of paracetamol is reduced in neonates and increases with age. 6 PHARMACEUTICAL PARTICULARS 6.1 List of excipients Methyl paraben, Propyl Paraben, Sugar, Propylene Glycol, Glycerin, Saccharine Sodium, Tutti Frutti, Water. 6.2 Incompatibilities Not applicable. 6.3 Shelf life 36 Months (3 years). 6.4 Special precautions for storage Store at temperature not exceeding 30°C. 6.5 Nature and contents of container Carton box containing amber glass bottle (type III) containing 120 ml syrup closed with aluminum cap lined with LDPE foam liner with inner leaflet. 7 MARKETING AUTHORISATION HOLDER AND MANUFACTURER Memphis for pharmaceuticals & chemical Industries, Cairo-Egypt.
