Sanmol

Sanmol

paracetamol

Manufacturer:

PT Sanbe Farma

Distributor:

Macropharma Corp
Full Prescribing Info
Contents
Paracetamol.
Description
Each 100 mL contains: Paracetamol 1 g.
Action
Pharmacology: PARACETAMOL (SANMOL) Infusion provides onset of pain relief within 5-10 minutes after the start of administration. The peak analgesic effect is obtained in 1 hour and the duration of this effect is usually 4-6 hours. PARACETAMOL (SANMOL) Infusion reduces fever within 30 minutes after the start of administration with a duration of the antipyretic effect of at least 6 hours.
Pharmacokinetics: Adults: Absorption: Paracetamol pharmacokinetics are linier after a single administration of up to 2 g and after repeated administration during 24 hours.
The bioavailability of paracetamol following infusion of 1 g of Paracetamol 10 mg/mL is similar to that observed following infusion of 2 g propacetamol (containing 1 g of paracetamol). For both these products, peak plasma concentration is obtained as and from the end of infusion. The maximum plasma concentration (Cmax) of paracetamol observed following intravenous infusion of 1 g Paracetamol 10 mg/mL is about 30 μg/mL. About 15 minutes is required to obtain the maximal plasma concentration (Tmax).
The bioavailability of paracetamol following infusion of 500 mg of Paracetamol 10 mg/mL, solution for infusion is similar to that observed following infusion of 1 g propacetamol (containing 500 mg paracetamol). The maximum plasma concentration (Cmax) of paracetamol observed at the end of 15-minutes intravenous infusion of 500 mg of Paracetamol 10 mg/mL, solution for infusion is about 15 μg/mL.
The pharmacokinetics of oral paracetamol (500 mg) and intravenous propacetamol (1 g) were compared in a randomised, double-blind, 2-period crossover study in 12 healthy male subjects. As expected, plasma concentrations of intravenous were significantly higher and obtained earlier, compared to oral administration, however after the first hour and up to 24 hours the plasma concentrations remained similar. (See Figure 1 and Table 1 as follows.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Distribution: The volume of distribution of paracetamol is approximately 1 L/kg.
Paracetamol is not extensively bound to plasma proteins.
Following infusion of 2 g propacetamol (equivalent to 1 g of paracetamol) significant concentrations of paracetamol (about 1.5 μg/mL) were observed in the cerebrospinal fluid 20 minutes after infusion.
Metabolism: Paracetamol is metabolised mainly in the liver following two major hepatic pathways: glucuronic acid conjugation and sulphuric acid conjugation. The latter route is rapidly saturable at doses that exceed the therapeutic doses. A small fraction (less than 4%) is metabolised by cytochrome P450 to a reactive intermediate (N-acetyl benzoquinone imine) which, under normal conditions of use, is rapidly detoxified by reduced glutathione and eliminated in the urine after conjugation with cysteine and mercapturic acid. However, during massive overdosing, the quantity of this toxic metabolite is increased. At therapeutic doses, CYP3A4, the major isoform of P450 in human liver, contributes to the production of the cytotoxic metabolite. For very high, supratherapeutic plasma concentrations (1500 mg/L) of paracetamol, the 2E1 and 1A2 isoforms may also be involved.
Elimination: The metabolites of paracetamol are mainly excreted in the urine. 90% of the dose administered is excreted in 24 hours, mainly as glucuronide (60-80%) and sulphate (20-30%) conjugates. Less than 5% is eliminated unchanged. Plasma half-life is 2.7 hours and total body clearance is 18 L/h.
Neonates and Infants <6 Months of Age: Clinical Trials examining the pharmacokinetics of Paracetamol in neonates and infants <6 months of age are limited. The safety and efficacy of Paracetamol in premature neonates has not been established. In a trial of 12 children between 1 and 232 days of age, which included 5 children less than 10 days of age the pharmacokinetics results for Paracetamol were as follows: See Figure 2 and Table 2.

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

In neonates, the plasma half-life is longer than infant's i.e. around 3.5 hours. Neonates and infants excrete significantly less glucuronide and more sulphate conjugates than adults. The potential effect of immaturity in metabolic and elimination pathways of paracetamol should be considered when administering paracetamol to neonates and children <6 months age.
Infants and Children >6 Months of Age: The pharmacokinetic parameters of paracetamol observed in infants and children are similar to those observed in adults, except for the plasma half-life that is slightly shorter (1.5 to 2 h) than in adults.
Indications/Uses
Paracetamol infusion is indicated for the short-term treatment of moderate pain, especially following surgery and for the short-term treatment of fever, when administration by intravenous route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of administration are not possible.
Dosage/Direction for Use
Intravenous Route: The 100 mL bottle is restricted to adults, adolescents and children weighing more than 33 kg (approximately 11 years old).
Adolescents and Adults Weighing More Than 50 kg: Paracetamol 1 g per administration, i.e. one 100 mL bottle, up to four times a day. The minimum interval between each administration must be 4 hours. The maximum daily dose must not exceed 4 g.
Children Weighing More Than 33 kg (Approximately 11 Years Old), Adolescents and Adults Weighing Less Than 50 kg: Paracetamol 15 mg/kg per administration, i.e. 1.5 mL solution per kg up to four times a day. The minimum interval between each administration must be 4 hours. The maximum daily dose must not exceed 60 mg/kg (without exceeding 3 g).
Children Weighing More Than 10 kg (Approximately 1 Year Old) and Weighing Less Than 33 kg: Paracetamol 15 mg/kg per administration, i.e. 1.5 mL solution per kg up to four times a day. The minimum interval between each administration must be 4 hours. The maximum daily dose must not exceed 60 mg/kg (without exceeding 2 g).
Severe Renal Insufficiency: It is recommended, when giving Paracetamol to patients with severe renal impairment (creatinine clearance ≤30 mL/min), to increase the minimum interval between each administration to 6 hours.
Administration: The paracetamol solution is administered as a 15-minute intravenous infusion. It can also be diluted in a 0.9% sodium chloride solution or a 5% glucose solution up to one tenth. In this case, use the diluted solution within the hour following its proportion (infusion time included). As for all solutions for infusion presented in glass bottle, it is reminded that a close monitoring is needed notably at the end of the infusion, regardless the administration route. This monitoring at the end of the perfusion applies particularly for central route infusion, in order to avoid embolism.
Overdosage
There is a risk of liver injury (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis) particularly in elderly subjects; in young children, in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzyme inducers. Overdosing may be fatal in these cases.
Symptoms generally appear within the first 24 hours and comprise of: Nausea, vomiting, anorexia, pallor, abdominal pain.
Overdose, 7.5 g or more of Paracetamol in a single administration in adults and 140 mg/kg of body weight in a single administration in children, causes hepatic cytolysis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis and encephalopathy which may lead to coma and death. Simultaneously, increased levels of hepatic transaminases (AST and ALT), lactate dehydrogenase and bilirubin are observed together with decreased prothrombin levels that may appear 12 to 48 hours after administration. Clinical symptoms of liver damage are usually evident initially after two days, and reach a maximum after 4 to 6 days.
Emergency Measures: Immediate hospitalization.
Before beginning treatment, take a tube of blood for plasma Paracetamol assay, as soon as possible after overdose.
The treatment includes administration of the antidote, N-acetylcysteine (NAC), by the i.v. or oral route, if possible before the 10th hour. NAC can, however, give some degree protection even after 10th hour, but in these cases prolonged treatment is given.
Symptomatic treatment.
Hepatic tests must be carried out at the beginning of treatment and repeated every 24 hours. In most cases hepatic transaminases return to normal in one to two weeks with full restitution of liver function. In very severe cases, however, liver transplantation may be necessary.
Contraindications
Hypersensitivity to paracetamol or to propacetamol hydrochloride (prodrug of paracetamol) or to any of the excipients. Severe hepatocellular insufficiency. Patients with hepatic failure or active liver disease.
Special Precautions
Warnings: It is recommended to use a suitable analgesic oral treatment as soon as this administration route is possible. In order to avoid the risk of overdose, check that other medicines administered do not contain Paracetamol. Doses higher than the recommended entails risk for very serious liver damage.
Clinical symptoms and signs on liver damage are usually seen first after two days with a maximum usually after 4-6 days. Treatment with antidote should be given as soon as possible (see Overdosage).
Precautions for Use: Paracetamol should be used with caution in cases of: Hepatocellular insufficiency. Severe renal insufficiency (creatinine clearance ≤30 mL/min). Chronic alcoholism. Chronic malnutrition (low reserves of hepatic glutathione). Dehydration.
Use in Pregnancy: Paracetamol should only be used during pregnancy after a carefully benefit-risk assessment. In this case, the recommended posology and duration must be strictly observed.
Use in Lactation: After oral administration, Paracetamol is excreted into breast milk in small quantities. No undesirable effects on nursing infants have been reported. Consequently, Paracetamol may be used in breastfeeding women.
Adverse Reactions
Dizziness, headache, dystonia, nausea, vomiting, constipation. Simple skin rash or urticaria to anaphylactic shock have been occurred and require discontinuation of treatment. Malaise. Hypersensitivity reaction. Hypotension. Increased level of hepatic transaminases. Thrombocytopenia, leucopenia, neutropenia.
Caution For Usage
Incompatibilities: Paracetamol infusion should not be mixed with other medicinal product.
Storage
Store below 30°C, away from light. Do not refrigerate or freeze. Before administration, the product should be visually inspected for any particulate matter and discoloration. For single use only. The product should be used immediately after opening and any unused solution should be discarded. If diluted in 0.9% sodium chloride or 5% glucose, the solution should be used immediately. However, if the solution is not used immediately, store below one hour (infusion time included).
Shelf-Life: 24 months
ATC Classification
N02BE01 - paracetamol ; Belongs to the class of anilide preparations. Used to relieve pain and fever.
Presentation/Packing
Soln for infusion (vial) 1 g/100 mL x 100 mL x 1's.
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