Paracetamol S.A.L.F. solution for infusions 10 mg/ml bottle 100 ml

Instructions Paracetamol S.A.L.F. solution for infusions 10 mg/ml bottle 100 ml

Composition

active ingredient: paracetamol;

1 ml contains 10 mg of paracetamol;

Excipients: glucose monohydrate, sodium acetate trihydrate, acetic acid, sodium citrate dihydrate, hydrochloric acid, sodium hydroxide, water for injections.

Dosage form

Solution for infusion.

Main physicochemical properties: clear, colorless solution or slightly colored from amber-yellow to pink-pale orange (perception may vary).

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.

The drug reduces body temperature within 30 minutes after administration, the antipyretic effect lasts for at least 6 hours.

Pharmacokinetics.

Adults

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 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 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 mercaptopuric 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 insufficiency

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 after surgery.

Short-term treatment of fever when intravenous administration is clinically justified by the urgent need to treat pain or hyperthermia, and/or when 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 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 INR (international normalized ratio). 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.

When used simultaneously with chloramphenicol, the toxicity of chloramphenicol may be increased, possibly due to inhibition of its metabolism in the liver.

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 should discontinue use at the first appearance of skin rash or any other sign of hypersensitivity.

Caution is advised when using paracetamol concomitantly with flucloxacillin due to the increased risk of high anion gap metabolic acidosis (HAGMA). Patients at high risk of developing HAGMA include those with severe renal impairment, sepsis or malnutrition, especially when using the maximum daily dose of paracetamol.

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:

severe renal insufficiency (creatinine clearance ≤ 30 ml/min (see sections “Method of administration and dosage” and “Pharmacokinetics”));

Excipients.

This medicine contains less than 1 mmol sodium (23 mg) per 100 ml solution, i.e. essentially “sodium-free”.

Use during pregnancy or breastfeeding

Pregnancy

A significant 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.

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.

Ability to influence reaction speed when driving vehicles or other mechanisms

Does not affect.

Method of administration and doses

The drug should be administered intravenously.

Paracetamol S.A.L.F. should be used for adults, adolescents and children weighing more than 33 kg.

The dosage depends on the patient's body weight.

Table 1

* 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 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 free of visible particles. A solution containing visible foreign inclusions should not be used.

Any unused medicinal product remaining should be destroyed.

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

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.

Emergency measures

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.

Side effects

As with other paracetamol-containing products, adverse reactions occurred rarely (> 1/10,000 − < 1/1,000) or very rarely (< 1/10,000), frequency unknown (cannot be estimated from the available data), see Table 2.

In clinical studies, common (≥ 1/100 - < 1/10) adverse reactions were reported in patients at the injection site (pain and burning).

Table 2

*Very rare cases of hypersensitivity reactions such as anaphylactic shock, urticaria, and skin rashes requiring discontinuation of treatment have been reported.

**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.

Expiration date

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 °C, out of the reach of children. Do not refrigerate.

Incompatibility

Paracetamol S.A.L.F. should not be mixed with other medicines.

Packaging

100 ml in bottle No. 1.

100 ml in a bottle, 30 bottles in a cardboard box.

Vacation category

According to the recipe.

Producer

S.A.L.F. Spa. Laboratorio Pharmacologico.

Location of the manufacturer and address of its place of business.

Via G. Mazzini, 9, Senate Sotto, 24069, Italy.