Instructions Exopon solution for infusion 10 mg/ml container 100 ml No. 12
Composition
active ingredient: paracetamol;
1 ml of solution contains 10 mg of paracetamol;
Excipients: hydroxypropylbetadex, disodium edetate, sodium chloride, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate dihydrate, 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.
The exact mechanism of paracetamol's analgesic and antipyretic properties has not yet been established, and it may involve central and peripheral actions.
Paracetamol provides pain relief within 5-10 minutes of administration. The peak analgesic effect is reached within 1 hour, and the duration of this effect is usually 4-6 hours.
Paracetamol reduces body temperature within 30 minutes after administration, the antipyretic effect lasts for at least 6 hours.
Pharmacokinetics.
Adults.
Absorption.
After a single dose of up to 2 g and after repeated administration within 24 hours, the pharmacokinetics of paracetamol are linear.
Bioavailability after intravenous infusion of 1 g of paracetamol is the same as after administration of 2 g of propacetamol (containing 1 g of paracetamol). The maximum concentration (Cmax) in the blood plasma is reached at the end of a 15-minute infusion of 1 g of paracetamol and is 30 μg/ml.
Distribution.
The volume of distribution of paracetamol is approximately 1 l/kg. Paracetamol is poorly bound to plasma proteins. After administration of 1 g of paracetamol, significant concentrations (approximately 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 fraction (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.
Special patient groups.
Patients with renal failure.
In severe renal insufficiency (creatinine clearance 10-30 ml/min), the elimination of paracetamol is somewhat delayed, with a half-life of 2 to 5.3 hours. The rate of elimination of glucuronides and sulfates in patients with severe renal insufficiency is three times slower than in healthy volunteers. Therefore, in patients with severe renal insufficiency (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 or to other components of the drug.
Severe hepatocellular insufficiency.
Interaction with other medicinal products and other types of interactions
Probenecid causes an almost twofold decrease in paracetamol clearance by inhibiting its conjugation with glucuronic acid. In the case of concomitant use of paracetamol with probenecid, a reduction in the dose of paracetamol should be considered.
Salicylamide may prolong the half-life of paracetamol.
Caution should be exercised when using paracetamol simultaneously with enzyme-inducing substances (see section "Overdose").
Concomitant use of paracetamol (4 g daily for at least 4 days) with oral anticoagulants may lead to minor changes in the international normalized ratio (INR). In this case, increased monitoring of INR should be carried out during the period of concomitant use and for 1 week after discontinuation of paracetamol treatment.
When used simultaneously with hormonal contraceptives, the elimination of paracetamol from the body is accelerated and its analgesic effect may be reduced. Anticonvulsants (phenytoin, phenobarbital, methylphenobarbital, primidone) reduce the bioavailability of paracetamol and increase hepatotoxicity.
When used simultaneously with lamotrigine, the excretion of lamotrigine from the body is moderately increased.
When used simultaneously with metoclopramide or domperidone, an increase in the absorption of paracetamol in the small intestine is possible.
When used simultaneously with rifampicin, an increase in paracetamol clearance is possible due to increased metabolism in the liver.
There are reports of a possible increase in zidovudine toxicity (neutropenia, hepatotoxicity) when used simultaneously with paracetamol.
Caution should be exercised when using paracetamol with flucloxacillin, as concomitant administration has been associated with metabolic acidosis with an increased anion gap, especially in patients with risk factors (see section "Special warnings and precautions for use").
Application features
Prolonged or frequent use of the drug is not recommended. It is recommended to use appropriate oral analgesic therapy as soon as this route of administration becomes possible.
To avoid the risk of overdose, it should be checked whether other medicinal products administered do not contain paracetamol or propacetamol. Dosage may need to be adjusted (see section "Method of administration and dosage").
The use of the drug in doses exceeding the recommended ones carries a risk of serious liver damage. Clinical signs and symptoms of liver damage (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis) are usually observed only in the first 2 days after administration of the drug, with the peak of severity usually occurring after 4-6 days. Treatment with an antidote should be carried out as soon as possible (see section "Overdose").
Paracetamol can cause serious skin reactions. Patients should be informed of the early signs of serious skin reactions and the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. Caution is recommended when paracetamol and flucloxacillin are used concomitantly due to the increased risk of developing metabolic acidosis with a high anion gap, especially in patients with severe renal insufficiency, sepsis, malnutrition and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as in those taking maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.
After concomitant use of paracetamol and flucloxacillin, careful monitoring is recommended to detect the occurrence of acid-base disorders, namely: metabolic acidosis with a large anion gap.
Paracetamol should be prescribed with caution to patients with:
- hepatocellular insufficiency;
- severe renal insufficiency (creatinine clearance ≤ 30 ml/min (see sections “Pharmacokinetics” and “Method of administration and dosage”));
- chronic alcoholism;
- chronic malnutrition (low glutathione reserves in the liver);
- dehydration;
- Gilbert's syndrome;
- genetically determined glucose-6-phosphate dehydrogenase deficiency, hemolytic anemia may occur due to reduced glutathione availability after paracetamol administration.
Important information about excipients
This medicinal product contains less than 1 mmol sodium (23 mg) per 100 ml solution, i.e. essentially 'sodium-free'.
Use during pregnancy or breastfeeding
Pregnancy: A large amount of data on the use of the drug in pregnant women confirms the absence of malformative effects or fetal/neonatal toxicity.
Epidemiological studies of the development of the nervous system in children exposed to paracetamol in utero have not yielded conclusive results. Animal reproduction studies with intravenous paracetamol have not been conducted. However, studies with the oral form have not demonstrated malformations or fetotoxic effects. However, paracetamol should be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus or child and if clinically necessary. In this case, it should be used at the lowest effective dose, for the shortest possible period of time and with the lowest frequency of use.
Breastfeeding. 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. Therefore, paracetamol can be used by breastfeeding women.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no significant impact.
Method of administration and doses
The drug Exopon should be administered intravenously.
Paracetamol should be used for adults and children weighing more than 33 kg.
The dosage depends on the patient's body weight.
Table 1
| Patient body weight | Single dose | Volume per dose | Maximum volume of medicinal product (10 mg/ml) per dose according to upper limits of body weight for the group (ml)** | Maximum daily dose * |
| > 33 kg – ≤ 50kg | 15 mg/kg | 1.5 ml/kg | 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 development hepatotoxicity | 1 g | 100 ml | 100 ml | 4 g |
* Maximum daily dose: the maximum daily dose is intended for patients not receiving other paracetamol-containing medicines and should be adjusted accordingly when taking such medicines.
** Patients with lower body weight require smaller volumes.
Paracetamol solution should be administered by intravenous infusion over 15 minutes. The minimum interval between administrations should be 4 hours. The course of treatment usually does not exceed 4 infusions within 24 hours.
The minimum interval between doses in patients with severe renal insufficiency should be at least 6 hours.
Before administration, it is necessary to ensure that the solution is clear and does not contain visible particles. A solution containing visible foreign inclusions should not be used. For disposal, the so-called “waste collection system” should be used, if available. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Patients of special groups.
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, Gilbert's syndrome, with a body weight of less than 50 kg.
The maximum daily dose should not exceed 3 g.
Elderly patients.
Elderly patients usually do not require dose adjustment.
Children.
Do not use in children weighing less than 33 kg.
Overdose
Symptoms: There is a risk of liver damage (including fulminant hepatitis, hepatic failure, cholestatic hepatitis, cytolytic hepatitis), especially in the elderly, young children, patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in those with reduced enzyme 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, in children - 140 mg / kg body weight. This leads to the development of liver cytolysis, liver failure, metabolic acidosis, encephalopathy, 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 2 days and reach a maximum after 4-6 days. Doses exceeding 20-25 g are potentially fatal.
Treatment. Emergency measures:
- immediate hospitalization;
- determination of paracetamol concentration in blood plasma as soon as possible after overdose before starting treatment;
- intravenous or oral administration of the antidote, N-acetylcysteine (NAC), if possible no later than 10 hours after the overdose. NAC can be administered later than 10 hours after the 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 medicines containing paracetamol, adverse reactions occurred rarely (> 1/10,000 -
In clinical trials, common (≥ 1/100 -
Table 2
| Organ systems | Often | Rarely | Very rare | Frequency unknown |
| Blood and lymphatic system disorders | thrombocytopenia, leukopenia, neutropenia | | | |
| On the part of the immune system | hypersensitivity reaction*, anaphylactic shock* | | | |
| Cardiovascular system | arterial hypotension | tachycardia, hot flashes | | |
| Liver and biliary tract | increased liver transaminase levels | | | |
| Skin and subcutaneous tissue disorders | serious skin reactions *** | rash*, urticaria* | | |
| General disorders and administration site conditions | pain and burning sensation | malaise | erythema, hyperemia, itching | |
| From the side of metabolism, metabolism | high anion gap metabolic acidosis (HAGMA) ** | | | |
**In the post-marketing period, with simultaneous use of paracetamol with flucloxacillin; usually in the presence of risk factors.
***Very rare cases of serious skin reactions requiring discontinuation of treatment have been reported.
Reporting of suspected adverse reactions
Reporting adverse reactions after the registration of a medicinal product is important. This allows monitoring of the benefit/risk ratio of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua
Expiration date
2 years.
Storage conditions
Store in original packaging at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Incompatibility.
Paracetamol should not be mixed with other medicines.
Packaging
100 ml of solution in a container in a protective bag; 12 containers in a protective bag in a cardboard box.
Vacation category
According to the recipe.
Producer
UNI-PHARMA KLEON CETIS PHARMACEUTICAL LABORATORIES SA.
Location of the manufacturer and address of its place of business.
14th km of National Road 1 Building A and Building B, Kato Kifisia Attica, 14564, Greece.
