Instructions Infulgan solution for infusions 1000 mg bottle 100 ml
Composition
active ingredient: paracetamol;
1 ml of solution contains 10 mg of paracetamol;
Excipients: citric acid monohydrate; sodium citrate; sorbitol (E 420); sodium sulfite anhydrous (E 221); water for injections.
Dosage form
Solution for infusion.
Main physicochemical properties: clear, colorless or slightly yellowish solution.
Pharmacotherapeutic group
Analgesics and antipyretics. ATX code N02B E01.
Pharmacological properties
Pharmacodynamics
Adults
Infulgan (paracetamol) has an analgesic and antipyretic effect. Paracetamol blocks cyclooxygenase (COX) I and II only in the central nervous system, affecting the centers of pain and thermoregulation. In excited tissues, cellular peroxidases neutralize the effect of paracetamol on COX, which explains the almost complete absence of anti-inflammatory effect. The lack of effect on the synthesis of prostaglandins in peripheral tissues determines the absence of a negative effect of the drug on water-salt metabolism (sodium and water retention) and the mucous membrane of the digestive tract.
Pharmacokinetics
Infulgan provides pain relief within 5-10 minutes after administration. The peak analgesic effect is reached within 1 hour, and the duration of this effect is usually 4-6 hours.
Infulgan reduces body temperature within 30 minutes after administration, the antipyretic effect lasts for at least 6 hours.
Absorption
After a single administration of up to 2 g of the drug and after repeated administration within 24 hours, the pharmacokinetics of paracetamol are linear.
Bioavailability after intravenous infusion of 500 mg and 1 g of paracetamol is the same as after administration of 1 g and 2 g of propacetamol (containing 500 mg and 1 g of paracetamol, respectively). The maximum concentration (Cmax) in the blood plasma is reached at the end of a 15-minute infusion of 500 mg or 1 g of paracetamol and is 15 μg/ml or 30 μg/ml, respectively.
Distribution
The volume of distribution of paracetamol is about 1 l/kg. Paracetamol is weakly bound to plasma proteins. After administration of 1 g of paracetamol, significant concentrations (about 1.5 μg/ml) were established in the cerebrospinal fluid 20 minutes after infusion.
Metabolism
Paracetamol is extensively metabolized in the liver by two main pathways: glucuronic acid conjugation and sulfuric acid conjugation. The latter pathway is rapidly saturated at doses exceeding therapeutic levels. A small portion (less than 4%) is metabolized by cytochrome P450 to form an intermediate metabolite (N-acetylbenzoquinoneimine), which under normal conditions is rapidly neutralized by reduced glutathione and excreted in the urine after binding to cysteine and mercaptopurine acid. However, in massive poisoning, the amount of this toxic metabolite increases.
Breeding
Paracetamol metabolites are excreted mainly in the urine. 90% of the administered dose is excreted within 24 hours, mainly as glucuronide (60-80%) and sulfate (20-30%). Less than 5% is excreted unchanged. The half-life is 2.7 hours, total clearance is 18 l/h.
Children
The pharmacokinetics of paracetamol in children is practically the same as in adults, except for a shorter plasma half-life (1.5-2 hours). In newborns, the half-life is longer than in infants - about 3.5 hours. Compared with adults, in children under 10 years of age, conjugation with glucuronic acid is significantly reduced and with sulfates is increased.
Table 1
Pharmacokinetic values according to age (standardized clearance, * CLstd/Foral.(l.h-1 70 kg-1))
| Age | Body weight (kg) | CLstd/Foral. (l.h-1 70 kg-1) |
| 40 weeks of age after conception | 3.3 | 5.9 |
| 3 months of postnatal age | 6 | 8.8 |
| 6 months of postnatal age | 7.5 | 11.1 |
| 1 year of postnatal age | 10 | 13.6 |
| 2 years of postnatal age | 12 | 15.6 |
| 5 years of postnatal age | 20 | 16.3 |
| 8 years of postnatal age | 25 | 16.3 |
*CLstd - patient group assessment of CL (clearance).
Special patient groups
Patients with renal insufficiency
In severe renal failure (creatinine clearance 10-30 ml/min) the elimination of paracetamol is somewhat delayed, and the half-life is from 2 to 5.3 hours. The rate of elimination of glucuronides and sulfates in patients with severe renal failure is three times slower than in healthy volunteers. Thus, in patients with severe renal failure (creatinine clearance ≤ 30 ml/min) the minimum interval between administrations should be increased to 6 hours.
Elderly patients
The pharmacokinetics and metabolism of paracetamol are not altered in elderly patients. No dose adjustment is required.
Indication
Short-term treatment of moderate pain, especially in the postoperative period, and short-term treatment of hyperthermic reactions when intravenous administration is clinically justified or other routes of administration are unacceptable.
Contraindication
Hypersensitivity to paracetamol, propacetamol hydrochloride (precursor of paracetamol) or other components of the drug. Severe hepatocellular insufficiency.
Interaction with other medicinal products and other types of interactions
Probenecid halves the clearance of paracetamol by blocking its binding to glucuronic acid, so the dose of paracetamol should be reduced during combination therapy with probenecid.
Salicylates may increase the half-life of paracetamol from the body.
Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) can contribute to the development of severe intoxications even with a small overdose.
Concomitant use of paracetamol (4 g per day for at least 4 days) with oral anticoagulants may lead to minor changes in the international normalized ratio (INR). In this case, the INR should be monitored during treatment and for 1 week after the end of treatment with Infulgan.
Application features
The risk of developing liver damage during treatment with Infulgan increases in patients with alcoholic hepatosis.
The use of Infulgan may negatively affect the results of laboratory tests for the quantitative determination of glucose and uric acid in blood plasma.
During long-term treatment, monitoring of peripheral blood counts and liver function is required.
Dosage errors due to confusion between milligrams (mg) and milliliters (mL) must be avoided, which can lead to accidental overdose and death.
It is recommended to use oral paracetamol if this route of administration is possible.
To avoid the risk of overdose, it is necessary to be sure that other prescribed medicines do not contain paracetamol or propacetamol.
The risk of liver damage increases when Infulgan is administered in doses higher than recommended. Clinical symptoms of liver damage (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis) are usually first observed two days after administration of the drug, reaching a peak after 4-6 days. The use of an antidote should be prescribed as soon as possible.
The drug should be used with caution if the patient has:
hepatocellular insufficiency; severe renal insufficiency (creatinine clearance less than 30 ml/min); chronic alcoholism; nutritional depletion (decreased glutathione reserve in the liver); dehydration.
Ability to influence reaction speed when driving vehicles or other mechanisms
Does not affect.
Use during pregnancy or breastfeeding
Pregnancy
Clinical experience with intravenous paracetamol is limited. However, epidemiological data on therapeutic doses of oral paracetamol indicate no adverse effects on pregnancy or on the health of the foetus/newborn.
Prospective data on overdose during pregnancy do not indicate an increased risk of malformations.
Animal reproduction studies with intravenous paracetamol have not been conducted. Studies with oral administration have not shown any fetotoxic effects.
However, Infulgan should be used during pregnancy only after careful assessment of the benefit/risk ratio, and the instructions should be followed exactly when calculating the dosage and duration of treatment.
Breast-feeding
After oral administration, paracetamol is excreted in breast milk in small quantities. No adverse effects have been observed in infants when paracetamol is used during breastfeeding.
Method of administration and doses
Infulgan is administered intravenously.
For adults, adolescents and children weighing more than 33 kg, the solution is used in 100 ml bottles.
For children weighing less than 33 kg, the solution is available in 20 ml and 50 ml bottles.
The dosage depends on the patient's body weight.
Table 2
| Patient body weight | Single dose | Volume per dose | Maximum volume of Infulgan (10 mg/ml) per dose according to upper body weight limits for the group (ml)** | Maximum daily dose *** |
| ≤ 10 kg * | 7.5 mg/kg | 0.75 ml/kg | 7.5 ml | 30 mg/kg |
| > 10 kg – ≤ 33 kg | 15 mg/kg | 1.5 ml/kg | 49.5 ml | 60 mg/kg, not to exceed 2 g |
| > 33 kg – ≤ 50kg | 15 mg/kg | 1.5 ml/kg | 75 ml | 60 mg/kg, not to exceed 3 g |
| > 50 kg, in the presence of risk factors for hepatotoxicity | 1 g | 100 ml | 100 ml | 3 g |
| > 50 kg, in the absence of risk factors for hepatotoxicity | 1 g | 100 ml | 100 ml | 4 g |
* Premature neonates: Safety and efficacy data in premature neonates are not available.
** Patients with lower body weight require smaller volumes.
The minimum interval between administrations should be 4 hours. The course of treatment usually does not exceed 4 infusions in one day.
*** Maximum daily dose: The maximum daily dose is intended for patients not receiving other paracetamol-containing medicinal products and should be adjusted accordingly when taking such medicinal products.
Patients with severe renal insufficiency
When prescribing paracetamol to patients with severe renal insufficiency (creatinine clearance ≤ 30 ml/min), it is recommended to increase the minimum interval between doses to 6 hours.
Patients with hepatocellular insufficiency, chronic alcoholism, patients who are chronically malnourished (low hepatic glutathione stores), patients with dehydration
The maximum daily dose should not exceed 3 g.
Paracetamol solution is administered as a 15-minute intravenous infusion.
Patients with body weight ≤ 10 kg
The Infulgan bottle is not suspended for infusion due to the small volume of medication that must be administered.
The required volume of the drug is drawn from the bottle using a syringe and used undiluted or diluted in 0.9% sodium chloride solution or 5% glucose solution in a ratio of one part of the drug to nine parts of the dilution solution and administered to the patient within 15 minutes.
The diluted solution should be used within 1 hour of preparation (including infusion time).
A 5 or 10 ml syringe should be used to measure the required dose according to the child's weight. However, this dose should not exceed 7.5 ml.
Be sure to follow dosage recommendations.
Children
It is used from the first days of life. Do not use in premature newborns.
Overdose
The risk of liver damage (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis) is increased in the elderly, young children, patients with liver disease, in cases of chronic alcoholism, in the presence of alimentary dystrophy and in individuals with reduced enzymatic activity. In these cases, overdose can be fatal.
Symptoms appear within the first 24 hours and are manifested by nausea, vomiting, anorexia, pallor, and abdominal pain.
Overdose in adults can occur with a single administration of 7.5 g or more, in children - at a dose of 140 mg / kg body weight. In this case, liver cytolysis, liver failure, metabolic acidosis, encephalopathy develop, which can lead to coma and death of the patient. Within 12-48 hours, the level of hepatic transaminases (alanine aminotransferase, aspartate aminotransferase), lactate dehydrogenase, bilirubin increases and the level of prothrombin decreases.
Clinical symptoms of liver damage appear after two days and reach a maximum after 4−6 days.
Emergency measures
immediate hospitalization; determination of paracetamol plasma concentration as soon as possible after overdose before initiating treatment; intravenous or oral administration of the antidote, N-acetylcysteine (NAC), if possible, no later than 10 hours after overdose. NAC can be administered later than 10 hours after overdose, but treatment should be continued for longer; symptomatic treatment.
Liver function tests should be performed before starting treatment and repeated every 24 hours. In most cases, liver transaminase levels return to normal within one to two weeks with full recovery of liver function. In some cases, liver transplantation may be required.
Adverse reactions
As with other paracetamol-containing products, adverse reactions occurred rarely (> 1/10,000 −
Table 3
| Organ systems | Rarely | Very rare |
| General disorders | Malaise | Hypersensitivity reactions |
| Cardiac disorders | Arterial hypotension | |
| Hepatobiliary system disorders | Increased hepatic transaminase levels | |
| Blood and lymphatic system disorders | Thrombocytopenia, leukopenia, neutropenia | |
In clinical studies, common adverse reactions were reported in patients at the injection site (pain and burning).
Very rarely, hypersensitivity reactions have been observed: from simple rash or urticaria to anaphylactic shock, requiring discontinuation of treatment.
Cases of erythema, redness, itching and tachycardia have also been reported.
Expiration date
2 years. Do not use after the expiry date stated on the packaging.
Storage conditions
Keep out of reach of children.
Store in a place protected from light at a temperature not exceeding 25 ° C. Do not freeze.
Packaging
100 ml in a bottle. 1 bottle in a pack.
Vacation category
According to the recipe.
Producer
LLC "Yuria-Pharm".
Location of the manufacturer and its business address
Ukraine, 18030, Cherkasy region, Cherkasy city, Kobzarska st., 108.
