Infulgan

1 mL of the solution contains paracetamol 10 mg.
Excipients/Inactive Ingredients: Citric acid monohydrate, sodium citrate, sorbitol (E420), sodium sulfite anhydrous (E 221), water for injections.

Pharmacotherapeutic Group: Analgesics and antipyretics. ATC Code: N02BE01.
Pharmacology: Pharmacodynamics: Infulgan (paracetamol) exhibits analgesic and antipyretic properties. Paracetamol affects the site of pain and the heat-regulating center by blocking cyclooxygenase (COX) I and II only in central nervous system. Cell peroxidase neutralizes paracetamol effect on COX in irritated tissues that results in complete absence of any anti-inflammatory effect. No effect on prostaglandin synthesis in peripheral tissues stipulates the absence of negative impact on water-salt metabolism and gastrointestinal mucosa.
Pharmacokinetics: Concentration of paracetamol in plasma reaches its peak in 15 minutes. Maximum concentration is 15-30 µg/mL. Distribution volume is 1 L/kg. Plasma protein binding of paracetamol is negligible. Paracetamol passes blood-brain barrier. It is metabolised in the liver by conjugation to glucuronides and sulphates. A small amount (4%) is metabolised by cytochrome P450 to an intermediate metabolite (N-acetyl benzoquinon imine) which is rapidly detoxified by reconstituted glutathione and eliminated with urine after conjugation with cysteine and mercapturic acid under the normal conditions. However, in case of massive overdosing the quantity of this toxic metabolite grows. Elimination half-life is 2.7 hours in adult, 1.5 to 2 hours in children, and 3.5 hours in infants. Total body clearance is 18 L/h. Paracetamol is mainly eliminated with urine. 90% of the administrated dose is excreted by kidneys within 24 hours as glucuronide (60-80%) and sulphate (20-30%) predominantly. Less than 5% is excreted unchanged. Paracetamol elimination is slightly delayed in patients with severe renal insufficiency (creatinine clearance less than 10-30 mL/min). Elimination half-life in this case varies from 2 to 5.3 hours. Elimination rate of glucuronide and sulphate in patients with severe renal insufficiency is 3 times slower than in healthy volunteers.
Pediatric pharmacokinetics is generally similar to that in adults except for the plasma elimination half-life that is slower (1.5-2 hours). Conjugation to glucuronic acid is significantly reduced and conjugation to sulphate is increased in children up to 10 years compared to adults.

Adults: Short-term treatment of moderate pain syndrome, especially following surgery; short-term treatment of hyperthermic response.
Pediatric: Symptomatic treatment of pain and hyperthermia in the post-surgical period.

Infulgan is used for rapid relief of pain and/or hyperthermic syndrome in case of overriding necessity for intravenous route of administration of the preparation.
For pediatric use excess amount of the solution should be withdrawn from the bottle before infusion to get the volume required for a single dose administration.
Duration of intravenous infusion must be 15 minutes.
Adults and Adolescents Weighing More Than 50 kg: The maximum single dose is 1000 mg of paracetamol.
The maximum daily dose is 4 g.
The minimum interval between each administration must be not less than 4 hours.
1 to 4 infusions are commonly used during the first 24 hours since the onset of pain syndrome (following surgery). Treatment duration may be extended if necessary but should not exceed the total duration of 72 hours (3 days) and total of 12 infusions.
Children Weighing from 33 kg to 50 kg: Paracetamol 15 mg/kg per administration, i.e. 1.5 mL/kg. Maximum daily dose must not exceed 60 mg/kg of body weight. Minimum interval between each administration must be not less than 4 hours. Treatment duration must not exceed 4 infusions per 1 day.
Children Weighing from 10 kg to 33 kg: Paracetamol 15 mg/kg per administration, i.e. 1.5 mL/kg. Maximum daily dose must not exceed 60 mg/kg of body weight. Minimum interval between each administration must be not less than 4 hours. Treatment duration must not exceed 4 infusions per 1 day.
Interval between each administration in patients with renal insufficiency (creatinine clearance ≤30 mL/min) must be increased up to 6 hours and treatment duration must not exceed 48 hours.

The risk of paracetamol toxicity is increased in elderly and pediatric patients, in patients with hepatic insufficiency, chronic alcoholism, present nutritional dystrophy, and reduced enzyme activity. Overdosing may be fatal in these cases.
Symptoms generally become apparent within the first 24 hours and comprise nausea, vomiting, anorexia, pallor, abdominal pain.
Overdose may occur after a single administration of 7.5 g or more of paracetamol in adults and a single administration of 140 mg/kg of body weight in children. It causes hepatic cytolysis, hepatic insufficiency, metabolic acidosis, encephalopathy which may result in coma and death. Levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin may increase, and levels of prothrombin may reduce within 12 to 48 hours after administration.
Clinical symptoms of liver damage generally become evident 2 days after, and reach a maximum after 4 to 6 days.
Treatment: Administration of sulphydryl-group donors and precursors of glutathione-methionine synthesis in 8-9 hours after the overdose, and administration of N-acetylcysteine after 10 hours. The decision to perform additional therapeutic measures (further administration of methionine, intravenous administration of N-acetylcysteine) should be made based on serum concentration of paracetamol and the time that has passed since the overdose.

Hypersensitivity to paracetamol or to any of the other ingredients of the preparation. Severe hepatocellular insufficiency.
Due to the content of sodium sulfite. Drug should not be prescribed to patients with bronchial asthma and hypersensitivity to sulfite.

Special caution should be exercised in patients with: Hepatocellular insufficiency; severe renal insufficiency (creatinine clearance less than 30 mL/min); chronic alcoholism; nutritional dystrophy (reduced reserves of hepatic gluthatione); dehydration.
Risk of developing liver damage during the treatment with Infulgan increases in patients with alcoholic liver disease.
Administration of Infulgan may affect laboratory test results by altering the levels of serum glucose and serum uric acid.
Liver function monitoring and peripheral blood cell count are recommended in case of prolonged treatment.
Effect on the Ability to Drive and Operate Machinery: No effect.
Use in Children: Infulgan may be used in infants weighing more than 10 kg for symptomatic treatment of pain and hyperthermia in the post-surgical period only.

There are no data on fetotoxicity or negative effect of paracetamol for intravenous administration on fetus. However, it should be used during pregnancy only after a careful benefit/risk assessment and the pregnant woman should be carefully monitored during the treatment.
Paracetamol can be excreted into breast milk. Breast feeding should be discontinued during treatment with the preparation.

(See Table.)

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Isolated cases of skin eruption or urticaria were reported. One case each of anaphylactic shock and thrombocytopenia was reported.

Probenecid causes 2-fold reduction in clearance of paracetamol by inhibiting its conjugation with glucuronic acid. Thus, paracetamol dose should be reduced in case of combined treatment with probenecid.
Salicylates may prolong elimination half-life of paracetamol.
Liver microsomal oxidation inducing agents (such as phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) may enhance development of severe toxicity following even insignificant overdose.

Store below 30ºC protected from light. Do not freeze.
Shelf-Life: 2 years.

Analgesics (Non-Opioid) & Antipyretics

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

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