Each mL of Ifimol IV contains paracetamol 10 mg and water for injection to make 1 mL.
Pharmacology: Pharmacokinetics: Absorption: Paracetamol pharmacokinetics is linear up to 2 g after single administration and after repeated administration during 24 hrs. The maximal plasma concentration (Cmax) of paracetamol is observed at the end of 15 min. 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 to plasma proteins of paracetamol (about 1.5 mcg/mL) were observed in the cerebrospinal fluid at and after the 20th min following infusion.
Metabolism: Paracetamol is metabolised 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 metabolised by cytochrome P450 to a reactive intermediate (N-acetyl benzoquinone imine), which under normal conditions uses, 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 hrs, mainly in glucuronide (60-80%) and sulphate (20-30%) conjugates. Less than 5% is eliminated unchanged. Plasma half-life (t½) is 2.7 hrs 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 t½ that is slightly shorter (1.5-2 hrs) than in adults. In neonates, the plasma t½ is longer than in infants ie, around 3.5 hrs. 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 t½ ranging from 2-5.3 hrs 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 hrs.
Elderly: The pharmacokinetics and the metabolism of paracetamol is not modified in elderly subjects. No dose adjustment is required in this population.
Short-term treatment of moderate pain, especially following surgery and for the short-term treatment of fever, when administration by IV route is clinically justified by an urgent need to treat pain or hyperthermia and/or when other routes of administration are not possible.
For IV use.
The 100 mL is restricted to adults, adolescent and children weighing >33 kg (approximately 11 years).
Adolescents and Adults Weighing >50 kg: 1 g ie, 1.5 mL/kg. Maximum Dose: 4 g daily.
Children Weighing >33 kg (Approximately 11 years), Adolescent and Adults Weighing <50 kg: 15 mg/kg ie, 1.5 mL/kg. Maximum Dose: 60 mg/kg (without exceeding 3 g) daily.
Children Weighing >33 kg (Approximately 11 years) and Weighing <33 kg: 15 mg/kg ie, 1.5 mL/kg. Maximum Dose: 60 mg/kg (without exceeding 2 g) daily.
Children Weighing <10 kg (up to approximately 1 year); Term Newborn, Infants, Toddlers: 7.5 mg/kg ie, 0.75 mL/kg. Maximum Dose: 30 mg/kg daily.
All doses to be taken 4 times daily and must have a minimum interval between administration of 4 hrs.
There is a risk of poisoning, particularly in elderly subjects, in patients with liver disease, in cases of chronic alcoholism, in patient with chronic malnutrition and in patients receiving enzyme inducers. Overdosing may be fatal in these cases. Symptoms generally appear within the first 24 hrs and comprise: Nausea, vomiting, anorexia, pallor and abdominal pain. Overdose, paracetamol ≥7.5 g in adults or 140 mg/kg body weight in children in a single administration, 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 [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], lactate dehydrogenase and bilirubin are observed together with decreased prothrombin levels that may appear 12-48 hrs after administration. Clinical symptoms of liver damage are usually evident after 2 days.
Treatment: Immediate hospitalization.
Before beginning treatment, take blood sample for plasma paracetamol assay, as soon as possible after overdose. The treatment includes administration of the antidote, N-acetylcysteine (NAC) by IV or oral route if possible before the 10th hr. N-acetylcysteine can, however, give some degree of protection even after 10 hrs but in these cases, prolonged treatment is given.
Symptomatic Treatment: Hepatic test must be carried out at the beginning of treatment and repeated every 24 hrs. In most cases, hepatic transaminases return into normal in 1-2 weeks with full return of normal liver function. In very severe cases, however, liver transplantation may be necessary.
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.
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.
As with all paracetamol products, adverse reactions are rare (>1/1000 to <1/100) or very rare (<1/1000).
General: Rare: Malaise. Very Rare: Hypersensitive reaction.
Cardiovascular: Rare: Hypotension.
Liver: Rare: Increased hepatic transformation level.
Platelet/Blood: Very Rare: Thrombocytopenia, leukopenia, neutropenia.
Very rare cases of hypersensitivity reaction from simple skin rash or urticaria to anaphylactic shock have been reported and require discontinuation of treatment.
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 t½ 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 normalised rate (INR) values. In this case, increased monitoring of INR values should be conducted during the period of concomitant use as for 1 week after paracetamol treatment has been discontinued.
Store at temperatures not exceeding 30°C. Do not freeze.
N02BE01 - paracetamol ; Belongs to the class of anilide preparations. Used to relieve pain and fever.
Ifimol IV soln for infusion 10 mg/mL
100 mL x 1's;50 mL x 1's
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