Instructions Paramol solution for infusion 1000 mg/100 ml container 100 ml No. 1
Composition
active ingredient: paracetamol;
100 ml of solution (1 container) contains 1000 mg of paracetamol;
Excipients: mannitol (E 421), disodium phosphate dihydrate, water for injections.
Dosage form
Solution for infusion.
Main physicochemical properties: clear liquid from colorless to light yellow.
Pharmacotherapeutic group
Analgesics and antipyretics. ATX code N02B E01.
Pharmacological properties
Pharmacodynamics
Paracetamol has analgesic and antipyretic effects. The mechanism of action is to block 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 its negative effect on water-salt metabolism (sodium and water retention) and the mucous membrane of the digestive tract.
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 single or repeated administration of the drug within 24 hours at a dose of up to 2 g, 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 plasma concentration (Cmax) 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 poorly 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. At the same time, 90% of the administered dose is excreted by the kidneys within 24 hours, mainly in the form of glucuronide (60-80%) and sulfate (20-30%). Less than 5% is excreted unchanged. The half-life is 2.7 hours, the total clearance is 18 l/hour.
Newborns, infants and children.
The pharmacokinetics of paracetamol in children is almost 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 from conception | 3.3 | 5.9 |
postnatal age: 3 months | 6 | 8.8 |
| 6 months | 7.5 | 11.1 |
| 1 year | 10 | 13.6 |
| 2 years | 12 | 15.6 |
| 5 years | 20 | 16.3 |
| 8 years | 25 | 16.3 |
*CLstd - patient group assessment of CL (clearance).
Special patient groups.
Patients with renal failure.
In severe renal insufficiency (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 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 propacetamol hydrochloride (a prodrug of paracetamol) or to any of the excipients. Severe hepatocellular insufficiency.
Interaction with other medicinal products and other types of interactions
Probenecid halves the clearance of paracetamol by inhibiting its conjugation with glucuronic acid, therefore, in combination therapy with probenecid, the dose of paracetamol should be reduced.
Salicylamide may increase the half-life of paracetamol from the body.
Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) may increase the risk of developing severe liver disorders even with a minor overdose (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). Therefore, the INR should be monitored during the period of concomitant use and for one week after cessation of paracetamol treatment.
Application features
The risk of developing liver damage during treatment with paracetamol increases in patients with alcoholic hepatosis.
The use of paracetamol may adversely 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.
As soon as possible, further treatment with oral analgesics is recommended.
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 with paracetamol overdose in doses higher than recommended. Clinical symptoms of liver damage (including liver failure, hepatitis, including fulminant, cholestatic, cytolytic) are usually first observed from the 2nd day after the start of the drug and reach a maximum on the 4th-6th day. It is necessary to prescribe an antidote as soon as possible (see section "Overdose").
Paramol, solution for infusion 1000 mg/100 ml, contains less than 1 mmol (23 mg) sodium per 100 ml of solution, i.e. essentially sodium-free.
Use the drug with caution in the case of:
hepatocellular insufficiency; severe renal insufficiency (creatinine clearance less than 30 ml/min); chronic alcoholism; chronic malnutrition (reduced 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 the use of therapeutic doses of oral paracetamol indicate no adverse effects on pregnancy or on the health of the fetus/newborn.
Prospective data on overdose during pregnancy do not indicate an increased risk of fetal malformations.
Studies on the effects of intravenous paracetamol on reproductive function in animals have not been conducted. Similar studies with oral administration have not demonstrated fetotoxic effects.
But paracetamol during pregnancy should only be used after a careful assessment of the benefit/risk ratio, at the lowest effective dose for the shortest time and at the lowest possible frequency.
Breastfeeding period.
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.
Method of administration and doses
Paramol, solution for infusion 1000 mg/100 ml, is administered intravenously.
The dosage depends on the patient's body weight.
Dosage for adults, adolescents and children weighing more than 33 kg (see Table 2).
Table 2
| Patient body weight | Single dose | Volume per dose | Maximum volume of drug 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 | 75 ml | 60 mg/kg, but not more than 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 |
* Patients with lower body weight require smaller volumes.
The minimum interval between administrations should be at least 4 hours. The course of treatment usually does not exceed 4 infusions in one day.
The minimum interval between administrations in patients with severe renal insufficiency should be at least 6 hours.
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 who are chronically malnourished (have low hepatic glutathione reserves), dehydrated, with hepatocellular insufficiency, chronic alcoholism: the maximum daily dose should not exceed 3 g.
CAUTION! In order to avoid dosing errors due to the discrepancy between milligrams (mg) and milliliters (ml), it is necessary to carefully calculate the doses when prescribing and administering PARAMOL solution for infusion. Such a discrepancy can lead to accidental overdose and even death. When writing prescriptions, the total dose should be indicated in both mg and ml.
Paracetamol solution is administered by intravenous infusion over 15 minutes.
The product should be used immediately after opening the package.
Any unused infusion solution should be discarded.
Do not use if the seal is broken or the contents of the container are opaque.
Children
PARAMOL, solution for infusion, is used for children weighing more than 33 kg.
Do not use in premature newborns.
Overdose
The risk of liver damage (including fulminant hepatitis, cholestatic hepatitis, cytolytic hepatitis, hepatic failure) is increased in the elderly, young children, patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in individuals with reduced enzymatic activity. In these cases, overdose can be fatal.
Symptoms usually appear within the first 24 hours and include nausea, vomiting, anorexia, pallor, abdominal pain. Overdose in adults can occur with a single dose of 7.5 g or more, in children - at a dose of 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 two days and reach a maximum on days 4–6.
Urgent measures:
immediate hospitalization; determination of paracetamol plasma concentration 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 overdose. NAC can be used later than 10 hours after overdose, but in this case the treatment will be longer; symptomatic treatment. Liver 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
General disorders: malaise.
From the cardiovascular system: arterial hypotension, tachycardia.
On the part of the hepatobiliary system: increased levels of hepatic transaminases.
From the blood and lymphatic system: thrombocytopenia, leukopenia, neutropenia.
Immune system: hypersensitivity reactions (rash, urticaria; anaphylactic shock, which may require discontinuation of treatment).
Injection site reactions: pain and burning, erythema, flushing, itching.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions after the marketing authorisation of a medicinal product is important. This allows for continuous monitoring of the benefit-risk balance of this medicinal product. Healthcare professionals are asked to report any suspected adverse reactions in accordance with local requirements.
Expiration date
18 months.
Storage conditions
Store at a temperature not exceeding 25 ºС in the original packaging.
Do not refrigerate. Do not freeze.
Keep out of reach of children.
Packaging
100 ml of the drug in a polypropylene container. 1 container in a cardboard box.
Vacation category
According to the recipe.
Producer
Subsidiary company "Pharmatrade".
Location of the manufacturer and its business address
Ukraine, 82111, Lviv region, Drohobych, Sambirska st., 85.
