Fevere

Paracetamol (Fevere) 10 mg/mL (1 g/100 mL) Solution for Injection (IV Infusion) is a clear and transparent pale yellow liquid injection in colorless and transparent plastic container for infusion.
Each mL contains: Paracetamol 10 mg.

Analgesic/Anti-Pyretic (Anilide).
Pharmacology: Pharmacodynamics: Paracetamol solution for infusion provides onset of pain relief within 5 to 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 to 6 hours. Paracetamol 10 mg/mL solution for infusion reduces fever within 30 minutes after the start of administration with a duration of the anti-pyretic effect of at least 6 hours.
Pharmacokinetics: Absorption: Paracetamol pharmacokinetics is linear up to 2 g after single administration and after repeated administration during 24 hours. The maximal plasma concentration (Cmax) of Paracetamol is observed at the end of 15 minutes. Intravenous infusion of 500 mg and 1 g is about 15 mcg/mL and 30 mcg/mL, respectively.
Distribution: The volume of distribution of Paracetamol is approximately 1 L/kg. Paracetamol is not extensively bound to plasma proteins. Following infusion of 1 g to plasma protein of Paracetamol (about 1.5 mcg/mL) were observed in the cerebrospinal fluid after the 20th minute following infusion.
Metabolism: Paracetamol is metabolized mainly in the liver following 2 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 (<4%) is metabolized 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.
Elimination: The metabolites of Paracetamol are mainly excreted in the urine. Ninety percent (90%) of the dose administered is excreted within 24 hours, mainly in glucuronide (60-80%) and sulphate (20-30%) conjugates. Less than 5% is eliminated unchanged. Plasma half-life (t1/2) is 2.7 hours and total body clearance is 18 L/hr.
Special Population: Neonates, Infants and Children: The pharmacokinetic parameters of Paracetamol observed in infants and children are similar to those observed in adults, except for the plasma t1/2 that is slightly shorter (1.5-2 hours) than in adults. In neonates, the plasma t1/2 is longer than in infants i.e. around 3.5 hours. Neonates, infants and children up to 10 years excrete significantly less glucuronide and more sulphate conjugates than adults.
Renal Insufficiency: In cases of severe renal impairment (creatinine clearance (CrCl) 10-30 mL/min), the elimination of Paracetamol is slightly delayed, the elimination t1/2 ranging from 2-5.3 hours. For the glucuronide and sulphate conjugates, the elimination rate is 3 times slower in subjects with severe renal impairment than in healthy subjects. Therefore, when giving Paracetamol to patients with severe renal impairment (≤CrCl 30 mL/min), the minimum interval between each administration should be increased to 6 hours.
Elderly: The pharmacokinetics and the metabolism of Paracetamol is not modified in elderly subjects. No dose adjustment is required in this population.

Paracetamol (Fevere) 10 mg/mL (1 g/100 mL) Solution for Injection (IV 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.

Paracetamol (Fevere) 10 mg/mL (1 g/100 mL) Solution for Injection (IV Infusion) is given by intravenous infusion to adults and children over 10 kg in weight as follows: Patients weighing over 50 kg, single doses of 1 g every 4 or more hours, to a maximum of 4 g daily; from 33 to 50 kg, single doses of 15 mg/kg every 4 or more hours, to a maximum of 60 mg/kg or 3 g daily (whichever is less); between 10 and 33 kg, single dose of 15 mg/kg or 2 g daily (whichever is less).
The Paracetamol solution is administered as a 15-minute intravenous infusion.
Posology: See table.

Click on icon to see table/diagram/image

Symptoms of overdosage may include nausea, vomiting, abdominal pain, diaphoresis, generalized weakness and lethargy. If an ovedosage of Paracetamol is suspected, blood should be withdrawn immediately for Paracetamol plasma assay, without regards to the presence or absence of symptomology.
Treatment: The acute hepatotoxicity and nephrotoxicity of Paracetamol can be overcome by administration of sulphydryl donors e.g., N-Acetylcysteine which should be given as soon as possible after congestion. Treatment after 12 hours is not effective. Paracetamol overdosage should be treated with gastric lavage if the patient is seen within 24 hours of ingestion of the drug.

Hypersensitivity to Paracetamol and Propacetamol HCl (prodrug of Paracetamol).
Severe hepatocellular insufficiency.

It is recommended that a suitable analgesic oral treatment be used as soon as this route of administration is possible. Doses higher than those recommended entail risk of very serious liver damage. Clinical sign and symptoms of liver damage are not usually seen until 2 days and up to maximum of 4-6 days after administration.
Treatment with antidote should be given as soon as possible.

Hepatocellular insufficiency, severe renal insufficiency (creatinine clearance (CrCl) ≤30 mL/min), chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), dehydration.
Use in lactation: After oral administration, Paracetamol is excreted into breast milk in small quantities. No adverse effects on nursing infants have been reported.
Consequently, Paracetamol may be used in breastfeeding women.
Use in children: No safety and efficacy data are available for premature neonates.

Paracetamol is generally considered to be the analgesic of choice in pregnant patients. However, the frequent use of Paracetamol (defined as most days or daily use) in late pregnancy may be associated with an increased risk of persistent wheezing in the infant. The authors emphasized that the number of pregnant women taking frequent doses was very small and they recommended that infrequent Paracetamol should remain the analgesic of choice in pregnancy.
Breast feeding: No adverse effects have been observed in breast-feeding infants whose mothers were receiving Paracetamol, and the American Academy of Pediatrics considers that it is therefore usually compatible with breastfeeding. The British National Formulary also considers that the amount of Paracetamol distributed into breast milk is too small to be harmful to a breast-fed infant.
Pharmacokinetic studies in 12 nursing mothers given a single dose of Paracetamol showed that peak Paracetamol concentrations in breast milk of 10 to 15 micrograms/mL were achieved in 1 to 2 hours. Plasma concentrations were determined in 2 mothers; a breast milk/plasma ratio of about 1 was reported. Similar findings have been reported from other studies.

Paracetamol has rarely been found to produce any side effects in therapeutic doses and is usually well tolerated by aspirin sensitive patients. Toxicity may result from a single toxic dose of the drug or from chronic ingestion. The following adverse reactions have been reported: skin eruption, hematological toxicity e.g., thrombocytopenia and leucopenia, methemoglobinemia which can result in cyanosis, and on long-term use, renal damage can result.

Probenecid causes almost 2-fold reduction in clearance of Paracetamol by inhibiting its conjugation with glucuronic acid. A reduction in the Paracetamol dose should be considered if it is to be used concomitantly with probenecid.
Salicylamide may prolong the elimination t1/2 of Paracetamol.
Caution should be taken with concomitant intake of enzyme-inducing substances.
Concomitant use of Paracetamol (4 g daily for at least 4 days) with oral anticoagulants may lead to slight variation of international normalized rate (INR) values. In this case, increased monitoring of INR values should be conducted during the period of concomitant use for 1 week after Paracetamol treatment has been discontinued.

Instructions and special precautions for handling and disposal: Any unused product or waste material should be disposed in accordance with local requirements.

Store at temperatures not exceeding 30°C.
Parenteral products should be inspected visually for particulate matter and discoloration prior administration, whenever solution and container permit.

Analgesics (Non-Opioid) & Antipyretics

N02BE01 - paracetamol ; Belongs to the class of anilide preparations. Used to relieve pain and fever.

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